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Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Fr ont of B ook > E ditor s
Editors Adel K. Afifi M. D. , M. S. Prof essor of Pediat rics Neurol ogy, and Anatomy and Cel l Bi ol ogy, Uni versi ty of Iowa, Col l ege of Medi ci ne, Iowa Ci ty, Iowa Ronald A. Bergman Ph. D. Prof essor Emerit us of Anat omy and Cell Biology Uni versi ty of Iowa, Col l ege of Medi ci ne, Iowa Ci ty, Iowa
Secondary Editors T his book was set in Adobe G aramond by MidAtlantic Books and Journals. Isabel Nogueira Edit or Janet Foltin Edit or Jason Malley Edit or Lester A. Sheinis Edit or Richard C. Ruzycka Product ion Supervisor Eve Siegel Text Designer Charissa Baker I llust rat ion Manager Maria T. Magtoto I llust rat ion Coordinat or Janice Bielawa Cover Designer Alexandra Nickerson I ndexer Q uebecor Dubuque was printer and binder
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Fr ont of B ook > D edic ation
Dedication To our f amilies and t o t he memories of our parent s and Mohammed A. Sow eid, Samih Y. Alami, and Ramez and Nabih K. Af if i
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Fr ont of B ook > Notic e
Notice Medicine is an ever-changing science. As new research and clinical experience broaden our know ledge, changes in t reat ment and drug t herapy are required. The aut hors and t he publisher of t his w ork have checked w it h sources believed t o be reliable in t heir eff ort s t o provide inf ormat ion t hat is complet e and generally in accord w it h t he st andards accept ed at t he t ime of publicat ion. How ever, in view of t he possibilit y of human error or changes in medical sciences, neit her t he aut hors nor t he publisher nor any ot her part y w ho has been involved in t he preparat ion or publicat ion of t his w ork w arrant s t hat t he inf ormat ion cont ained herein is in every respect accurat e or complet e, and t hey disclaim all responsibilit y f or any errors or omissions or f or t he result s obt ained f rom use of t he inf ormat ion cont ained in t his w ork. Readers are encouraged t o conf irm t he inf ormat ion cont ained herein w it h ot her sources. For example and in part icular, readers are advised t o check t he product inf ormat ion sheet included in t he package of each drug t hey plan t o administ er t o be cert ain t hat t he inf ormat ion cont ained in t his w ork is accurat e and t hat changes have not been made in t he recommended dose or in t he cont raindicat ions f or administ rat ion. This recommendat ion is of part icular import ance in connect ion w it h new or inf requent ly used drugs.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Fr ont of B ook > P r efac e
Preface The at t ract ive f eat ures of t he second edit ion are t he same as t hose of t he f irst edit ion, namely: limit ed aut horship, consist ent and easy-t o-read st yle, complet e and balanced but nonexhaust ive coverage of neuroanat omy, emphasis on human neuroanat omy, simplif ied schemat ics t o illust rat e neural pat hw ays, clinical correlat ion chapt ers, key concept s f or easy pre-exam review, derivat ion of t erms and hist orical perspect ive of common eponyms, and an ext ensive at las of spinal cord and brain sect ions as w ell as magnet ic resonance images (MRI ) in t hree planes. I n t his edit ion, all chapt ers have been updat ed t o ref lect t he current st at e of know ledge. f our new chapt ers are added: t w o are relat ed t o t he ret icular Format ion, Wakef ulness and Sleep; one on t he Cont rol of Post ure and Movement , and one on The Approach t o t he Pat ient w it h Neurologic Disorder. The illust rat ions have been improved and several new illust rat ions have also been added. The Key Concept s have been placed at t he beginning of each chapt er and can easily be ident if ied by t his icon . New ref erences have been added t o t he Suggest ed Readings at t he end of each chapt er. t he t ext in t he margins of t he pages has been expanded and relocat ed f or more eff icient use of space. Boldf ace emphasis of some t erms in t he t ext has been removed t o allow easier f low of t ext . These t erms are now list ed in t he Terminology sect ion at t he end of each chapt er and are highlight ed in blue color in t he t ext . Leaders in t he At las have been improved t o make it easier f or t he reader t o ident if y t he int ended st ruct ures. We are grat ef ul t o t he many colleagues and st udent s w ho w rot e review s and/ or made comment s or suggest ions about t he f irst edit ion. t heir comment s and suggest ions w ere helpf ul in developing t he second edit ion. We w ant in part icular t o acknow ledge t he f ollow ing colleagues and st udent s: St even Anderson, Nadia Bahut h, Ant oine Becharea, Daniel Bont hius, Deema Fat t al, Aleyamma Fenn, Tiny jaent sch, Jean Jew, Kokoro O zaki, Paul Reimann, Ergun Uc, and G ary Van Hoesen. We w ant t o t hank Karen Boat man w ho w as inst rument al in t yping addit ions t o t he chapt ers and t he new chapt ers. Her inquisit ive int erest in t he subject made it a pleasure t o w ork w it h her. Karolyn Leary assist ed us in t yping some of t he t ext and relieved Karen f rom many ot her off ice t asks t o allow her t o devot e t ime t o
t he book. Special t hanks t o t he st aff of McG raw -Hill and in part icular t o isabel Nogueira w ho init iat ed t he proposal f or t he second edit ion and provided valuable advice and guidance during t he early phase of it s preparat ion; Janet Folt in, Jason Malley, and Lest er A. Sheinis w ho most ably oversaw t he t edious edit orial t ask of it s product ion; Richard C. Ruzycka, product ion supervisor; Eve Siegel, t ext designer; Charissa Baker, illust rat ion manager; Maria T. Magt ot o, illust rat ion coordinat or; Janice Bielaw a, cover designer; Alexandra Nickerson, indexer; and Keit h Donnellan, of Dovet ail Cont ent Solut ions, w ho direct ed t he copyedit ing of t he manuscript . Adel K. Af if i M. D. , M. S. Ronald A. Bergman Ph. D.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 1 - Neur ohis tology
1 Neurohistology
T he Cells and T heir Unique Characteristics Overview of Neurons Perikaryon Axon (Axis cylinder, Remak's band) Dendrites Neuroglia Ganglia Craniospinal Ganglia Autonomic Ganglia Nerve Fibers Myelinated Nerve Fibers Unmyelinated Nerve Fibers Conduction of Nerve Impulses Axonal Transport Synapse Neuromuscular Junction Receptor Organs of Sensory Neurons Free (Nonencapsulated) Nerve Endings Encapsulated Nerve Endings Reaction of Neurons to Injury Cell Body and Dendrites Axon Nerve Growth Factors
Clinical Correlation Neuronal Plasticity KEY CONCEPTS A neuron consists of a perikaryon (cell body) and its processes (axon and dendrites). Neurons vary in size and shape, and each neuron has one axon and many dendrites. Perikaryal organelles that are found in axons include mitochondria, microtubules, microfilaments, neurofilaments, neurotubules, smooth endoplasmic reticulum, lysosomes, and vesicles. Dendrites contain all the perikaryal organelles except the Golgi complex. Neuroglia are the supporting elements of the central nervous system. They include macroglia (astrocytes and oligodendroglia), microglia, and ependymal cells. Astrocytes are metabolic intermediaries for nerve cells. Fibrous astrocytes also serve a repair function after neural injury. Oligodendroglia elaborate central nervous system myelin. Microglia play a role in repair of the central nervous system. Craniospinal ganglia include the dorsal root ganglia and the ganglia of cranial nerves V, VII, VIII, IX, and X. Peripheral nerves are surrounded by three connective tissue sheaths. Endoneurium invests individual axons, perineurium invests groups of axons
in fascicles, and epineurium invests the whole nerve. Two types of axonal transport occur in axons: anterograde and retrograde. On the basis of their function, synapses are classified into excitatory and inhibitory. Sensory receptor organs are classified according to their location (skin or joints), structure (encapsulated or free), function (nociceptor or mechanoreceptor), adaptive properties (slowly or quickly adapting), or a combination of these categories. Neurons react to injury by undergoing characteristic changes that occur proximal (chromatolysis) and distal (wallerian degeneration) to the site of the injury. Clinically, nerve injury is classified according to the degree of severity into conduction block (neurapraxia), loss of axonal continuity (axonotmesis), and loss of nerve trunk continuity (neurotmesis).
The cells of t he nervous syst em can be divided int o t w o groups: nerve cells (neurons) and support ing cells (glia). Nerve cells are all associat ed w it h each ot her as a f unct ional syncyt ium, a complex net w ork somew hat like t hat f ound in a t elephone company sw it ch board. Neurons communicat e w it h each ot her t hrough specialized areas of neuronal cont act called synapses. The complexit y of t he synapt ic relat ionships among billions of neurons f orms t he basis f or t he behavioral complexit y of humans.
THE CELLS AND THEIR UNIQUE CHARACTERISTICS Overview of Neurons
A neuron, or nerve cell (t he t erms may be used int erchangeably), has a cell body, or perikaryon (t he part cont aining t he nucleus), and all it s processes (axon and dendrit es). The names given t o neurons w ere suggest ed by t heir size, shape, appearance, f unct ional role, or presumed discoverer [ e. g. , Purkinje cell (neuron) of t he cerebellum] . The size and shape of neuronal cell bodies are remarkably variable. The diamet er of t he cell body may be as small as 4 ľm (granule cell of t he cerebellum) or as large as 125 ľm (mot or neuron of t he spinal cord). Nerve cells may have a pyramidal, f lask, st ellat e, or granular shape (Figure 1-1). An addit ional f eat ure of t hese perikarya is t he number and organizat ion of t heir processes. Some neurons have f ew dendrit es, w hile ot hers have numerous dendrit ic project ions. Wit h t w o know n except ions (t he axonless amacrine cell of t he ret ina and t he granule cells of t he olf act ory bulb), all neurons have at least one axon and one or more dendrit es. I n general, t hree basic t ypes of neurons are recognized: 1. Unipolar or pseudounipolar neurons (e. g. , sensory [ or dorsal root ] ganglion cells) have a spherical cell body w it h single process t hat bif urcat es (Figure 1-1H). 2. Bipolar neurons (e. g. , cochlear and vest ibular peripheral ganglia and olf act ory and ret inal recept or cells) are spindle-shaped, w it h one process at each end of t he cell (Figure 1-1I). 3. Mult ipolar neurons (e. g. , aut onomic ganglia and t he enormous populat ion of cells in t he cent ral nervous syst em) have one axon and many dendrit ic processes (Figure 1-1 A G ). The most int erest ing f eat ure of t he neurons is t heir processes. I n humans, t he axon of a neuron, t he eff ect or part of t he cell, may be a met er or more in lengt h, ext ending f rom t he spinal cord t o t he f ingers or t oes or f rom t he neurons of t he cerebral cort ex t o t he dist al ext ent of t he spinal cord. The dendrit es, t he primary recept or area of t he cell, are variable in number and in branching pat t ern, w hich in some cases enormously increases a neuron's surf ace area.
Fi gure 1-1. Schemat ic diagram illust rat ing variat ions in neuronal size, shape, and processes. A. Pyramidal neuron. B. Flask-shaped Purkinje neuron. C.
St ellat e neuron. D. G ranular neuron. E. Mult ipolar ant erior horn neuron. F. Mult ipolar sympat het ic ganglion neuron. G . Mult ipolar parasympat het ic ganglion neuron. H. Pseudounipolar dorsal root ganglion neuron. I. Bipolar neuron. cb, cell body; Ax, axon.
Fi gure 1-2. Schemat ic diagram of mot or neuron and it s organelles. A. Neuronal cell body and it s processes. B. G olgi apparat us. C. Neurof ilament s. D. Lipochrome pigment . E. Melanin pigment .
Perikaryon The perikaryon, or cell body, cont ains t he nucleus and a number of organelles (Figure 1-2). The nucleus is usually round and cent rally locat ed. The nucleoplasm is t ypically homogeneous and st ains poorly w it h basic dyes (nuclear st ains). This indicat es t hat t he deoxyribonucleic acid (DNA) is dispersed and is in it s f unct ionally act ive f orm. The nucleoplasm is said t o be in it s euchromat ic f orm. I n st ark cont rast , each nucleus cont ains one deeply st ainable (w it h basic dyes) nucleolus,
composed in part of ribonucleic acid (RNA), w hich normally is present w it hin t he nucleus. The nuclear cont ent s are enclosed in a dist inct nuclear membrane. The cyt oplasm surrounding t he nucleus is f illed w it h a variet y of organelles and inclusions. The most dramat ic organelle is t he so-called chromophil subst ance (because of it s aff init y f or basic dyes), or Nissl bodies (af t er it s discoverer). Nissl bodies (Figure 1-2A) are part icularly prominent in somat ic mot or neurons, such as t hose f ound in t he ant erior horn of t he spinal cord or in some mot or cranial nerve nuclei (in t his case, t he t erm nucl ei ref ers t o a clust er of cell bodies in t he cent ral nervous syst em rat her t han t he nuclei of neurons). Nissl bodies, w hich are dist inct ive in shape and abundant , are composed of membrane-bound ribonucleoprot eins (also know n as granular endoplasmic ret iculum). The role of t he nucleus, nucleolus, and cyt oplasmic RNA in prot ein synt hesis is w ell est ablished. Thus, t he cell body synt hesizes cyt oplasmic prot eins and ot her essent ial const it uent s, w hich are dist ribut ed t hroughout t he neuron f or maint enance and t he f unct ional act ivit ies t hat w ill be discussed below. Nissl bodies are f ound not only in t he cell body but also in dendrit es. Hence, t hey t oo are involved in synt het ic act ivit y. The presence of Nissl bodies in dendrit es conf irms t heir ident it y as dendrit es, somet hing t hat ot herw ise w ould be impossible in t he st udy of t he dense mix of dendrit es and axons in t he neuropil. Nissl bodies are absent f rom t he axon hillock (part of t he perikaryon f rom w hich t he axon arises). Nissl bodies undergo charact erist ic changes (chromat olysis) in response t o axonal injury (see below ). Numerous mit ochondria dispersed t hroughout t he cyt oplasm play a vit al role in t he met abolic act ivit y of t he neuron. The G olgi apparat us (Figure 1-2B), w hich originally w as discovered in neurons, is a highly developed syst em of f lat t ened vesicles and small oval and/ or round agranular vesicles. The G olgi apparat us is t hought t o be t he region of t he cell t hat receives t he synt het ic product s of t he Nissl subst ance t o allow addit ional synt het ic act ivit y. I t is t hought t hat t he G olgi area is t he sit e w here carbohydrat es are linked t o prot ein in t he synt hesis of glycoprot eins. The small vesicles arising f rom t his organelle may be t he source of synapt ic vesicles and t heir cont ent s, w hich are f ound in axon t erminals. Neurof ibrils (Figure 1-2C) are f ound in all neurons and are cont inuous t hroughout all t heir processes. They are composed of subunit s (neurof ilament s) t hat are 7. 5 t o 10 nm in diamet er and t hus are below t he limit of resolut ion of t he light microscope. Aggregat es of abnormal neurof ibrils (neurof ibrillary t angles) accumulat e in neurons in Alzheimer's disease. I n addit ion t o neurof ilament s, t here are neurot ubules w it h an ext ernal diamet er of about 25 nm; t hese st ruct ures are similar t o t hose f ound in cells t hat are not neuronal. Neurot ubules are concerned w it h t he rapid t ransport of prot ein molecules synt hesized in t he
cell body, w hich are carried t hrough t he dendrit es and axon. Neuronal perikarya also cont ain 5- t o 8-nm neurof ilament s or act in f ilament s, w hich f orm a net w ork under t he plasma membrane. Most large nerve cells cont ain lipochrome pigment granules (Figure 1-2D). These granules apparent ly accumulat e w it h age and are more evident during t he advancing age of t he organism. I n addit ion, cert ain nerve cells f ound in specif ic locat ions of t he brain cont ain black (melanin pigment ) granules (Figure 1-2E). All t hese organelles and inclusions are f eat ures of t he perikaryon, marking it as t he neuron's t rophic cent er. The separat ion of a process (axon or dendrit e) f rom t he perikaryon result s in t he disint egrat ion of t he process.
Axon (Axis Cylinder, Remak's Band) A single axon arises f rom t he cell body. The point of depart ure of t he axon is know n as t he axon hillock. The axon may be very long (120 cm or more) and is unif ormly cylindrical. The diamet er of axons is also variable and is relat ed t o t heir f unct ion. The origin of t he axon is t he axon hillock, a small part of t he cell body t hat is devoid of Nissl subst ance. Beneat h t he neuronal membrane at t he axon hillock is a dense layer of granular mat erial about 200 Ĺ t hick. I n addit ion, t here is a conf luence of microt ubules t hat exhibit clust ering and cross-linkage. The area bet w een t he perikaryon (and axon hillock) and t he axon is called t he init ial segment . This segment is short , narrow, and devoid of myelin. I t is at t his segment t hat t he nerve impulse or act ion pot ent ial is init iat ed. Just beyond t he init ial segment , many axons become myelinat ed; t his increases t heir diamet er in a unif orm manner unt il an axon t erminat es at it s end organ. The axoplasm cont ains many organelles, such as mit ochondria, microt ubules, microf ilament s, neurof ilament s, neurot ubules, smoot h endoplasmic ret iculum, lysosomes, and vesicles of various sizes (Figure 1-3). The axon, unlike t he cell body, does not have any st ruct ures associat ed w it h prot ein synt hesis or assembly (ribosomes, rough endoplasmic ret iculum [ Nissl subst ance] , and t he G olgi complex). The smallest axoplasmic component s are t he microf ilament s, w hich are paired helical chains of act in. The microf ilament s usually are locat ed in t he cort ical zone near t he axolemma; t heir prot ein, act in (associat ed w it h t he cont ract ile process), may play a role in int raaxonal t ransport . Neurof ilament s (7. 5 t o 10 nm in diamet er) are larger t han microf ilament s and more prevalent . They are scat t ered t hroughout t he axoplasm, but not in a recognizable pat t ern. Neurof ilament s are composed of t hree prot eins w it h a molecular mass of 68 t o 200 kDa, subunit s of t he prot ein t ubulin. They are readily disassembled by int rinsic prot eases and disappear rapidly in damaged axons. Microt ubules are axially arranged hollow cylinders t hat measure 23 t o 25 nm in diamet er and are of indef init e lengt h. The number of microt ubules w it hin an axon varies in direct relat ion t o axonal mass and t he t ype of nerve; t hey are
more numerous in unmyelinat ed axons.
Fi gure 1-3. Schemat ic diagram show ing part of neuronal perikaryon, it s axon hillock, and axon.
Mit ochondria vary in number in an inverse rat io t o axonal cross-sect ional area. They are of t en t opographically relat ed t o one or more microt ubules. Smoot h endoplasmic ret iculum (SER) provides secret ory vesicles along t he axon. SER is f unct ionally concerned w it h axonal t ransport . Secret ory vesicles range in size f rom 40 t o 100 ľm. Concent rat ions of vesicles are f ound in associat ion w it h nodes of Ranvier (see below ) and w it hin nerve t erminals. Lysosomes usually are f ound near nodes of Ranvier and accumulat e rapidly during t he degenerat ion of nerves af t er an injury. Axons ret ain a unif orm diamet er t hroughout t heir lengt h. Axons may have collat eral branches proximally and usually branch ext ensively at t heir dist al ends (t elodendria) bef ore t erminat ing by synapt ic cont act w it h dendrit es and cell bodies of ot her neurons or on eff ect or organs (muscles and glands). Axons may be myelinat ed or unmyelinat ed (Figure 1-4). I n bot h cases, how ever, t he axons are ensheat hed by support ing cells: Schw ann cells in t he peripheral nervous syst em and oligodendroglia cells in t he cent ral nervous syst em. Myelinat ed axons are f ormed w hen t hey become w rapped (Figure 1-5) in mult iple layers of Schw ann or oligodendroglia plasmalemma (cell membrane). The process of myelinat ion is discussed lat er in t his chapt er. The myelin sheat h is discont inuous at t he dist al ends of each cell (Schw ann or
oligodendroglia) involved in t he ensheat hing process. The area of discont inuit y bet w een cells is know n as a node of Ranvier (Figure 1-6) and is t he sit e of volt age-gat ed sodium channels and ot her ionic displacement s involved in impulse conduct ion (act ion pot ent ials). The elect ric impulse f low s across a myelinat ed axon by jumping f rom node t o node. This t ype of impulse conduct ion is know n as salt at ory conduct ion; it t ends t o increase t he conduct ion speed of t he act ion pot ent ial. The nodes of Ranvier are not lined up w it h t hose of adjacent axons, and t he myelin sheat hs serve as elect ric insulat ion; hence, t here is lit t le if any spurious act ivat ion of axons.
Fi gure 1-4. Schemat ic diagram of cross sect ions of a peripheral nerve st ained t o show myelin sheat hs (A) and axons (B)
Myelin, w hich is composed of a variable number of t ight w rappings of cell membrane around axons, is a lipid-prot ein complex. When it is prepared f or light microscopy, lipid is ext ract ed or lost during t issue preparat ion, leaving behind in t he sect ioned t issue a resist ant prot eolipid art if act know n as neurokerat in. I n addit ion t o myelin sheat hs, peripheral nerve f ibers are surrounded by connect ive t issue, t he endoneurium. Connect ive t issues are cont inuous w it h each ot her t hroughout t he nerve, but t hey are named diff erent ly according t o t heir locat ions. The t issue covering individual axons is know n as endoneurium, t hat
surrounding a grouping of axons is know n as perineurium, and t hat covering t he ent ire nerve (a recognizable mult ibundle of axons) is know n as t he epineurium. The perineurium const it ut es a barrier prevent ing cert ain subst ances f rom ent ry t o t he axons.
Fi gure 1-5. Schemat ic diagram of t he process of f ormat ion of myelin sheat hs. A and B show f ormat ion of myelin sheat h by concent ric double layers of Schw ann cell (SC) membranes w rapping t hemselves around t he axon (Ax). C show s how prot oplasmic surf aces of t he membrane become f used t oget her t o f orm t he major dense lines. D show s how several unmyelinat ed axons are cont ained w it hin t he inf oldings of a single Schw ann cell.
Fi gure 1-6. Schemat ic diagram of t he st ruct ure of a myelin-at ed peripheral nerve.
Myelinat ed axons vary in diamet er f rom 1 t o 20 ľm, w hereas unmyelinat ed axons are not larger t han 2 ľm. The size of t he nerve f iber (t he axon plus it s myelin) has a direct relat ionship t o t he rat e of impulse conduct ion; large myelinat ed f ibers conduct nerve impulses at a f ast er rat e t han do small unmyelinat ed axons.
Dendrites Neurons possess a single axon but usually have more t han one dendrit e, alt hough t here are except ions (see below ). Dendrit es may increase t he recept ive surf ace area of t he cell body enormously. Anot her met hod of increasing t he recept ive surf ace area of dendrit es involves numerous project ions f rom t he dendrit es know n as spines or gemmules, w hich represent sit es of synapt ic cont act by axon t erminals f rom ot her neurons. Dendrit es cont ain all t he organelles f ound in t he neuroplasm of t he perikaryon except t he G olgi apparat us. Neurons t hat receive axon t erminal or synapt ic cont act s f rom a variet y of cent ral nervous syst em sources may have an ext remely complex dendrit ic organizat ion. An out st anding example of t his complexit y is f ound in Purkinje cells in t he cerebellum. Cells of t he cent ral nervous syst em and aut onomic ganglia have dendrit es ext ending f rom t heir perikarya. Cells w it h mult iple dendrit es are called mult ipolar; t hose w hich possess only axonlike processes ext ending f rom each end of t he cell are named bipolar neurons. Bipolar neurons are f ound only in t he ret ina of t he eye, olf act ory recept ors, and t he peripheral ganglia of t he vest ibulocochlear nerve (cranial nerve VI I I ). Sensory neurons in t he dorsal root ganglia of spinal neurons are ref erred t o as pseudounipolar because only a single process leaves t he cell body bef ore bif urcat ing t o f orm proximal and dist al segment s. The processes of bipolar and pseudounipolar neurons are axonlike in st ruct ure; t hey have a limit ed or specif ic recept ive capacit y. These neurons of t he peripheral nervous syst em usually ret ain t he diversif ied t erminal axonal branching w hen t hey ent er t he cent ral nervous syst em (brain and spinal cord). A unique and unusual cell f ound in t he ret ina, t he amacrine cell, is regarded as an axonless neuron.
Neuroglia The support ing cells bet w een t he neurons of t he cent ral nervous syst em are ref erred t o as neuroglia (Figure 1-7). There are several variet ies, w hich may be organized as f ollow s: 1. Ast rocyt es a. Fibrous b. Prot oplasmic 2. O ligodendroglia 3. Ependymal cells 4. Microglia
Ast rocyt es and oligodendroglia are also know n as t he macroglia.
A. ASTROCYTES (ASTROGLIA) Ast rocyt es are t he largest of t he neuroglia. They are branched st ellat e cells. The nuclei of t hese cells are ovoid, are cent rally locat ed, and st ain poorly because t hey lack signif icant amount s of het erochromat in and have no nucleoli. The nuclei do cont ain euchromat in, w hich does not st ain w it h t ypical nuclear st ains and is charact erist ic of act ive nuclear act ivit y in it s cellular f unct ion. The cyt oplasm of ast rocyt es may cont ain small round granules and glial f ilament s composed of glial f ibrillary acidic prot ein (G FAP). The processes of ast roglia at t ach t o and complet ely cover t he out er surf ace of capillaries (perivascular end f eet or f oot plat es) as w ell as t he pia mat er (glia limit ans). During development , ast rocyt es (radial glia) provide a f ramew ork w hich guides neuronal migrat ion.
1. Fibrous astrocytes. Fibrous ast rocyt es (Figure 1-7C) have t hin, spindly processes t hat radiat e f rom t he cell body and t erminat e w it h dist al expansions or f oot plat es, w hich are also in cont act w it h t he ext ernal w alls of blood vessels w it hin t he cent ral nervous syst em. The f oot processes f orm a cont inuous glial sheat h, t he so-called perivascular limit ing membrane, surrounding blood vessels. The cyt oplasm of f ibrous ast rocyt es cont ains f ilament s t hat ext end t hroughout t he cell as w ell as t he usual (t he generic group of ) cyt oplasmic organelles. Fibrous ast rocyt es, w hich are f ound primarily w it hin t he w hit e mat t er, are believed t o be concerned w it h met abolit e t ransf erence and t he repair of damaged t issue (scarring).
2. Protoplasmic astrocytes. Prot oplasmic ast rocyt es (Figure 1-7A, B) have t hicker and more numerous branches. They are in close associat ion w it h neurons and may part ially envelop t hem; t hus, t hey are know n as sat ellit e cells. Since t hey have a close relat ionship t o neurons, t hey are locat ed primarily in t he gray mat t er, w here t he cell bodies are f ound. Their f unct ion is not ent irely clear, but t hey serve as a met abolic int ermediary f or nerve cells.
B. OLIGODENDROGLIA O ligodendroglia (Figure 1-7D) have f ew er and short er branches t han do ast rocyt es. Their nuclei are round and have condensed, st ainable (het erochromat in) nucleoplasm. The cyt oplasm is densely f illed w it h
mit ochondria, microt ubules, and ribosomes but is devoid of neurof ilament s. O ligodendroglia cells are f ound in bot h gray and w hit e mat t er. They usually are seen lying in row s among axons in t he w hit e mat t er. Elect ron microscopic st udies have implicat ed t he oligodendroglia in myelinat ion w it hin t he cent ral nervous syst em in a manner similar t o t hat of Schw ann cells in t he peripheral nervous syst em. Wit hin t he gray mat t er, t hese cells are closely associat ed w it h neurons (perineuronal sat ellit e cells), as are t he prot oplasmic ast rocyt es.
Fi gure 1-7. Schemat ic diagram of t ypes of neuroglia show ing t he t hick and numerous processes of prot oplasmic ast rocyt es and t he slender and f ew processes of microglia (A), prot oplasmic ast rocyt es in close proximit y t o neurons (B), f ibrous ast rocyt e w it h processes in cont act w it h a blood vessel (C), oligodendroglia in close proximit y t o a neuron (D), and ependymal cells
lining cent ral canal of t he spinal cord (E).
C. EPENDYM AL CELLS Ependymal cells (Figure 1-7E) line t he cent ral canal of t he spinal cord and t he vent ricles of t he brain. They vary f rom cuboidal t o columnar in shape and may possess cilia. Their cyt oplasm cont ains mit ochondria, a G olgi complex, and small granules. These cells are involved in t he f ormat ion of cerebrospinal f luid. A specialized f orm of ependymal cell is seen in some areas of t he nervous syst em, such as t he subcommissural organ.
D. M ICROGLIA The microglia (Figure 1-7A), unlike ot her nerve and glial cells, are of mesodermal origin and ent er t he cent ral nervous syst em early in it s development . Their cell bodies are small, usually w it h lit t le cyt oplasm, but are densely st aining and have somew hat f lat t ened and elongat ed nuclei. These cells have f ew processes, occasionally t w o, at eit her end. The processes are spindly and bear small t horny spines. Normally, t he f unct ion of t he microglia is uncert ain, but w hen dest ruct ive lesions occur in t he cent ral nervous syst em, t hese cells enlarge and become mobile and phagocyt ic. Thus, t hey become t he macrophages, or scavenger cells, of t he cent ral nervous syst em. G lial cells have been described as t he elect rically passive element s of t he cent ral nervous syst em. How ever, it has been show n t hat glial cells in cult ure can express a variet y of ligand- and volt age-gat ed ion channels t hat previously w ere believed t o be propert ies of neurons. Alt hough numerous ion channels have been described s odium, calcium, chloride, and pot assium t heir f ull f unct ional signif icance is uncert ain. O ligodendrocyt es have been show n t o quickly change t he pot assium gradient across t heir cell membranes, giving rise t o a pot ent ial change; t hus, t hey serve as highly eff icient pot assium buff ers. Recept ors f or numerous neurot ransmit t ers and neuromodulat ors, such as gamma-aminobut yric acid (G ABA), glut amat e, noradrenaline, and subst ance P, have been demonst rat ed on glia cells, part icularly ast rocyt es. Pat ch clamp st udies have revealed t hat t hese glial recept ors are similar in many respect s t o t hose on neurons.
GANGLIA G anglia are def ined as collect ions of nerve cell bodies locat ed out side t he cent ral nervous syst em. There are t w o t ypes of ganglia: craniospinal and aut onomic.
Craniospinal Ganglia
The craniospinal ganglia (Figure 1-1H) are locat ed in t he dorsal root s of t he 31 pairs of spinal nerves and in t he sensory root s of t he t rigeminal (cranial nerve V), f acial (cranial nerve VI I ), vest ibulocochlear (cranial nerve VI I I ), glossopharyngeal (cranial nerve I X), and vagus (cranial nerve X) nerves. The dorsal root ganglia and t he cranial nerve ganglia are concerned w it h sensory recept ion and dist ribut ion. They receive st imulat ion f rom t he ext ernal and int ernal environment s at t heir dist al ends and t ransmit nerve impulses t o t he cent ral nervous syst em. The ganglion cells of t he spinal group are classif ied as pseudounipolar neurons, w hereas t he ganglion cells of t he vest ibular and cochlear nerves are bipolar neurons (Figure 1-1I). Craniospinal ganglion cells vary in size f rom 15 t o 100 ľm. I n general, t hese cells f all int o t w o size groups. The smaller neurons have unmyelinat ed axons, w hereas t he larger cells have myelinat ed axons. Each ganglion cell is surrounded by connect ive t issue and support ing cells (t he perineuronal sat ellit e cells or capsule cells). From each cell, a single process arises t o bif urcat e and by doing so f orms an invert ed T or Y shape (Figure 1-1H). This axonlike st ruct ure ext ends t o appropriat e proximal and dist al locat ions. The int racapsular process may be coiled (so-called glomerulus) or relat ively st raight . The bipolar ganglion cells of t he vest ibular and cochlear cranial nerves are not , how ever, encapsulat ed by sat ellit e cells.
Autonomic Ganglia Aut onomic ganglia are clust ers of neurons f ound f rom t he base of t he skull t o t he pelvis, in close associat ion w it h and bilat erally arranged adjacent t o vert ebral bodies (sympat het ic ganglia), or locat ed w it hin t he organ t hey innervat e (parasympat het ic ganglia). I n cont rast t o cranial-spinal ganglia, t he ganglion cells of t he aut onomic nervous syst em (sympat het ic and parasympat het ic) are mult ipolar (Figure 1-1F, G) and receive synapt ic input f rom various areas of t he nervous syst em. Aut onomic ganglion cells are surrounded by connect ive t issue and small perineuronal sat ellit e cells t hat are locat ed bet w een t he dendrit es and are in close associat ion w it h t he cell body. Aut onomic cells range in diamet er f rom 20 t o 60 ľm and have clear (euchromat ic) spherical or oval nuclei, w it h some cells being binucleat e. The cyt oplasm cont ains neurof ibrils and small aggregat es of RNA, a G olgi apparat us, small vesicles, and t he ubiquit ous mit ochondria. The dendrit ic processes of t w o or more adjacent cells of t en appear t angled and may f orm dendrit ic glomeruli; such cells usually are enclosed in a single capsule. The t erminal arborizat ions of t he ganglionic axons synapse on t hese dendrit ic glomeruli as w ell as on t he dendrit es of individual ganglion cells. I n general, t he preganglionic arborizat ion of a single axon brings t hat axon int o synapt ic cont act w it h numerous ganglion cells. The axons of t hese ganglion cells are small in diamet er (0. 3 t o 1. 3 ľm). Aut onomic ganglion cells w it hin t he viscera (int ramural,
parasympat het ic ganglia) may be f ew in number and w idely dist ribut ed. They are not encapsulat ed but are cont ained w it hin connect ive t issue sept a in t he organ t hat is innervat ed. The cells of t he aut onomic ganglia innervat e visceral eff ect ors such as smoot h muscle, cardiac muscle, and glandular epit helium.
NERVE FIBERS A peripheral nerve is composed of nerve f ibers (axons) t hat vary in size, are myelinat ed or unmyelinat ed, and t ransmit nerve impulses eit her t o or f rom t he cent ral nervous syst em. Peripheral nerves are of t en mixed nerves because t hey usually are composed of bot h mot or and sensory f ibers. Nerves cont aining only sensory f ibers are called sensory nerves; t hose w hich cont ain only mot or f ibers are called mot or nerves. The st ruct ural organizat ion changes along t he lengt h of t he nerve because of t he repeat ed division and union of diff erent nerve f ascicles, result ing in complex f ascicular f ormat ions. The nerve f ibers t hat make up a peripheral nerve have been classif ied according t o size and ot her f unct ional charact erist ics (Table 1-1). Axons designat ed as A alpha axons range in size f rom 12 t o 22 ľm; A bet a, f rom 5 t o 12 ľm; A gamma, f rom 2 t o 8 ľm; and A delt a, f rom 1 t o 5 ľm. Preganglionic sympat het ic f ibers t hat are less t han 3 ľm in diamet er are designat ed as B f ibers. All t hese st ruct ures are myelinat ed nerve f ibers. The smallest axons (0. 1 t o 3 ľm in diamet er) are designat ed C f ibers and are unmyelinat ed. Tabl e 1-1. Some Properties of Mammalian Peripheral Nerve
Nerve fiber type
Num ber Function designation and/or source
Ia A alpha (α)
Proprioception, stretch (muscle, spindle, annulospiral receptor), and motor to skeletal muscle fibers
Fiber size (ľm )
Myelinati
12 2 2
++
(extrafusal)
A beta (β)
A gamma (γ)
A delta (δ)
B
Ib
Contractile force (Golgi tendon organ)
12 2 2
++
II
Pressure, stretch (muscle spindle, flower spray receptor), touch, and vibratory sense
5 1 2
++
II
Motor to muscle spindle (intrafusal muscle fibers)
2 8
++
III
Some nerve endings serving pain, temperature, and touch
1 5
+
-
Sympathetic preganglionic axons
Table of C ontents > P ar t I - Text > 3 - S pinal C or d
3 Spinal Cord
External Topography Derm atom es and Myotom es Meninges Cross-Sectional Topography Microscopic Anatom y Gray Matter W hite Matter Spinal Cord Neurotransmitters and Neuropeptides Spinal Reflexes Micturition Pathway and Bladder Control Functional Overview of the Spinal Cord Blood Supply KEY CONCEPTS The spinal cord comprises 31 segments defined by 31 pairs of spinal nerves. Each spinal nerve is formed by union of a dorsal (sensory) and a ventral (motor) root. The first cervical segment has only a ventral root. Dermatomes are areas of skin supplied by a single posterior (dorsal) nerve root. M yotome refers to a group of muscles innervated by a single spinal cord segment.
The internal structure of the spinal cord consists of central, H-shaped, gray matter and surrounding white matter. The former contains neurons, and the latter contains ascending and descending fiber tracts. Autonomic sympathetic neurons are located in thoracic and upper lumbar spinal cord segments, whereas autonomic parasympathetic neurons are located in sacral spinal cord segments. Alpha motor neurons in the ventral horn are somatotopically organized. Posterior funiculus tracts convey conscious proprioceptive sensory modalities, especially those actively explored by the individual perceived at cortical level. Pain and thermal sensations are conveyed by the lateral and anterior spinothalamic tracts. Corticospinal tracts are essential for skilled and precise movements. Autonomic innervation of the urinary bladder is related to specific nerve cells in the lower thoracic, upper lumbar, and midsacral region of the spinal cord. Somatic innervation of the urinary bladder originates in the nucleus of Onufrowicz in the ventral horn of midsacral spinal cord segments. Segmental control of bladder function is modified by suprasegmental influences in the pons, midbrain, hypothalamus, and cerebral cortex. The blood supply of spinal cord is provided by anterior and posterior spinal arteries derived from vertebral and segmental (radicular) arteries. Some spinal cord segments are particularly susceptible to reduction in blood supply.
EXTERNAL TOPOGRAPHY The spinal cord of adult humans ext ends f rom t he f oramen magnum t o t he level of t he f irst or second lumbar vert ebra. Approximat ely 45 cm long in males and 42 cm in f emales, it has a cylindrical shape in t he upper cervical and t horacic segment s and an oval shape in t he low er cervical and lumbar segment s, w hich are sit es of t he brachial and lumbosacral nerve plexuses, respect ively. I n t he early st ages of f et al development , t he cord occupies t he w hole lengt h of t he vert ebral canal; in t he t erm new born, it ext ends dow n t o t he low er border of t he t hird lumbar vert ebra; in lat e adolescence, t he spinal cord at t ains it s adult posit ion, t erminat ing at t he level of t he int ervert ebral disk bet w een t he L-1 and L-2 vert ebrae (Figure 3-1). The level at w hich t he cord t erminat es changes w it h development because t he vert ebral column grow s f ast er t han t he spinal cord. The lengt h of t he ent ire adult vert ebral column is 70 cm. The spinal cord exhibit s t w o enlargement s: cervical (t hird cervical t o second t horacic segment s) and lumbar (f irst lumbar t o t hird sacral segment s). These are sit es of neurons t hat innervat e t he upper and low er ext remit ies, respect ively. The caudal end of t he cord is t apered t o f orm t he conus medullaris, f rom w hich a pial-glial f ilament , t he f ilum t erminale, ext ends and at t aches t o t he coccyx t o anchor t he spinal cord. The spinal cord is also anchored t o t he dura by t w o lat eral series of dent iculat e ligament s, pial f olds t hat st ret ch f rom t he surf ace of t he cord t o t he dural sheat h midw ay bet w een t he dorsal and vent ral root s. Dent iculat e ligament s serve as usef ul landmarks f or t he neurosurgeon in ident if ying t he ant erolat eral segment of t he cord w hen perf orming operat ions such as cor-dot omies f or t he relief of int ract able pain. There are 20 or 21 pairs of dent iculat e ligament s ext ending bet w een t he f irst lumbar and f irst cervical vert ebrae.
Fi gure 3-1. Schemat ic diagram show ing t he relat ionships of spinal cord segment s and spinal nerves t o vert ebral column levels.
The human spinal cord comprises 31 segment s (8 cervical, 12 t horacic or dorsal, 5 lumbar, 5 sacral, and 1 coccygeal), each of w hich, except t he f irst cervical segment , has a pair of dorsal and vent ral root s and a pair of spinal nerves. The f irst cervical segment has only a vent ral root . The dorsal and vent ral root s join in t he int ervert ebral f oramina t o f orm t he spinal nerves. Just proximal t o it s junct ion w it h t he vent ral root in t he int ervert ebral f oramen, each dorsal root has an oval sw elling: t he dorsal root (spinal) ganglion cont aining pseudounipolar sensory neurons. At t he point w here t he dorsal nerve root ent ers t he spinal cord, glial support ing t issue f rom t he spinal cord ext ends a short dist ance int o t he nerve root t o meet t he Schw ann cell and t he collagenous support ing t issue of t he peripheral nervous syst em. The junct ion zone bet w een t he t w o t ypes of t issues is quit e sharp hist ologically. I t is called t he O berstei ner-Redl i ch space af t er t w o Aust rian neurologist s, Heinrich O berst einer and Emil Redlich. The 31 pairs of
spinal nerves are divided int o 8 cervical nerves, 12 t horacic nerves, 5 lumbar nerves, 5 sacral nerves, and 1 coccygeal nerve (Figure 3-1). The f ourt h and f if t h sacral nerves and t he coccygeal nerve arise f rom t he conus medullaris. Spinal nerves leave t he vert ebral canal t hrough t he int ervert ebral f oramina. The f irst cervical nerve emerges above t he at las; t he eight h cervical nerve emerges bet w een t he sevent h cervical (C-7) and t he f irst t horacic (T-1) vert ebrae. All ot her spinal nerves exit beneat h t he corresponding vert ebrae (Figure 3-1). Because of t he diff erent ial rat e of grow t h of t he spinal cord and vert ebral column, spinal cord segment levels do not correspond t o t hose of t he vert ebral column (Table 3-1). Thus, in t he cervical region, t he t ip of t he vert ebral spine corresponds t o t he level of t he succeeding cord segment ; t hat is, t he sixt h cervical spine corresponds t o t he level of t he sevent h spinal cord segment . I n t he upper t horacic region, t he t ip of t he spine is t w o segment s above t he corresponding cord segment ; t hat is, t he f ourt h t horacic spine corresponds t o t he sixt h cord segment . I n t he low er t horacic and upper lumbar regions, t he diff erence bet w een t he vert ebral and cord level is t hree segment s; t hat is, t he t ent h t horacic spine corresponds t o t he f irst lumbar cord segment . Because of t his, t he root f ilament s of spinal cord segment s have t o t ravel progressively longer dist ances f rom cervical t o sacral segment s t o reach t he corresponding int ervert ebral f oramina f rom w hich t he spinal nerves emerge (Figure 3-1). The crow ding of lumbosacral root s around t he f ilum t erminale is know n as t he cauda equina. Tabl e 3-1. Relationship of Spinal Cord Segments and Vertebral Spines.
Cord segm ents Vertebral spines C-1
C-1
C-7
C-6
T-6
T-4
L-1
T-10
S-1
T-12 to L-1
DERM ATOM ES AND M YOTOM ES The area of skin supplied by a single post erior (dorsal) nerve root const it ut es a dermat ome. Familiarit y w it h dermat omal maps (Figure 3-2) is essent ial f or localizat ion of t he level of lesion in t he spinal cord. Few dermat omes are part icularly usef ul in localizat ion of lesion (Table 3-2). A viral disorder t hat charact erist ically present s w it h dermat omal dist ri-but ion of pain and vesicular lesions is herpes zost er (shingles). G roups of muscles innervat ed f rom a single spinal cord segment const it ut e a myot ome. Familiarit y w it h clinically relevant myo-t omes is usef ul in localizat ion of t he level of lesion in t he spinal cord (Table 3-3).
M ENINGES The spinal cord is covered by t hree meningeal coat s; t hese are t he pia, arachnoid, and dura mat er. The pia mat er is composed of an inner membranous layer, t he int ima pia, and an out er superf icial layer, t he epipia. The int ima pia is int imat ely adherent t o t he surf ace of t he spinal cord. The epipia carries blood vessels t hat supply and drain t he spinal cord. I t also f orms t he dent iculat e ligament s. The arachnoid is closely adherent t o t he dura mat er. The space bet w een t he dura and arachnoid (subdural space) is a very narrow (pot ent ial) space visible w it h t he aid of a microscope in hist ologic preparat ions in normal condit ions. Bridging veins course across t his space. Rupt ure of t hese veins result s in accumulat ion of blood and expansion of t his space, a condit ion know n as subdural hematoma. The space bet w een t he arachnoid and pia (subarachnoid space), in cont rast , is w ider and cont ains t he cerebrospinal f luid. The spinal dura mat er, unlike t he dura w it hin t he skull, is f irmly at t ached t o bone only at t he margin of t he f oramen magnum. Elsew here, t he spinal dura is separat ed f rom t he vert ebral periost eum by t he epidural space. The spinal epidural space cont ains adipose t issue and a venous plexus and is largest at t he level of t he second lumbar vert ebra. The spinal epidural space is used f or inject ion of local anest het ics t o produce paravert ebral nerve block know n as epi dural anesthesi a f or relief of pain during obst et rical delivery. The epidural space is also used t o inject drugs (e. g. , cort isone) t o relieve back pain. The spinal dura mat er ensheat hes t he dorsal and vent ral root s, t he dorsal root ganglia, and proximal port ions of spinal nerves, and t hen it becomes cont inuous w it h t he epineurium of spinal nerves at t he level of t he int ervert ebral f oramen. The spinal cord t erminat es at t he level of t he L-1 and L-2 vert ebrae, w hereas t he dura mat er ext ends dow n t o t he level of t he S-1 and S-2 vert ebrae. Below t he sit e of spinal cord t erminat ion (conus medullaris), a sac f illed w it h cerebrospinal f luid and devoid of spinal cord f orms in t he subarachnoid space. This sac is a f avorable sit e f or clinicians t o int roduce a special spinal needle t o obt ain cerebrospinal f luid f or examinat ion or t o inject drugs or dyes int o t he subarachnoid space f or purposes of t reat ment or diagnosis. This procedure is called l umbar puncture or spi nal tap.
Fi gure 3-2. Dermat omal map show ing body landmarks and corresponding spinal cord segment s.
Tabl e 3-2. Body Landmarks and Corresponding Dermatomes.
Body landm ark
Derm atom e
Back of head
C-2
Shoulder
C-4
Thumb
C-6
Middle finger
C-7
Small finger
C-8
Nipple
T-4, T-5
Umbilicus
T-10
Inguinal region
L-1
Big toe
L-4, L-5
Small toe
S-1
Genitalia and perianal region
S-4, S-5
CROSS-SECTIONAL TOPOGRAPHY I n cross sect ion, t he spinal cord is composed of a cent rally placed but t erf lyor H-shaped area of gray mat t er surrounded by w hit e mat t er. The t w o w ings of t he but t erf ly are connect ed across t he midline by t he dorsal and vent ral gray commissures above and below t he cent ral canal, respect ively (Figure 3-3). The gray mat t er of t he cord cont ains primarily t he cell bodies of neurons and glia. The w hit e mat t er of t he cord cont ains primarily f iber t ract s. Tabl e 3-3. Clinically Relevant Myotomes.
Myotom e
Spinal cord segm ent
Deltoid
C-5
Biceps
C-6
Triceps
C-7
Hypothenar muscle
T-1
Quadriceps femoris
L-4
Extensor hallucis
L-5
Gastrocnemius
S-1
Rectal sphincter
S-3, S-4
The t w o halves of t he spinal cord are separat ed by t he dorsal (post erior) median sept um and t he vent ral (ant erior) median f issure (Figure 3-3). The sit e of ent rance of dorsal root f ibers is marked by t he dorsolat eral (post erolat eral) sulcus; similarly, t he sit e of exit of vent ral root s is marked by t he vent rolat eral (ant erolat eral) sulcus (Figure 3-3). These landmarks divide t he w hit e mat t er of each half of t he cord int o a dorsal (post erior) f uniculus, a lat eral f uniculus, and a vent ral (ant erior) f uniculus (Figure 3-3). Furt hermore, in cervical and upper t horacic spinal cord segment s, t he dorsal (post erior) f uniculus is divided int o t w o unequal part s by t he dorsal (post erior) int ermediat e sept um (Figure 3-3). The H-shaped gray mat t er is also divided int o a smaller dorsal (post erior) horn or column and a larger vent ral (ant erior) horn or column. The t horacic and upper lumbar cord segment s, in addit ion, exhibit a w edge-shaped int ermediolat eral horn or column (Figure 3-3). The spinal cord is asymmet ric in about 75 percent of humans, w it h t he right side being larger in 75 percent of t he asymmet ries. The asymmet ry is due t o more descending cort icospinal t ract f ibers on t he larger side. I t has been show n t hat more f ibers in t he lef t medullary pyramid cross t o reach t he right half of t he spinal cord and more f ibers f rom t he right medullary pyramid remain uncrossed t o descend in t he right half of t he spinal cord. These t w o occurrences result in a larger complement of cort icospinal f ibers in t he right half of t he cord. I n essence, t hen, t he right side of t he spinal cord receives more f ibers f rom t he cort ex t han t he lef t side. This has no relat ion t o handedness. The amount of uncrossed f ibers may be relat ed t o t he occurrence of t he ipsilat eral hemiplegia (w eakness) report ed in pat ient s w it h lesions in t he int ernal capsule. I f most f ibers do not cross, t hen t he hemiplegia w ill be most ly ipsilat eral.
M ICROSCOPIC ANATOM Y The microscopic anat omy of t he spinal cord varies in t he diff erent regions of t he cord. The charact erist ics of microscopic anat omy in t he diff erent regions help def ine t he level of sect ion (Figure 3-4). As one ascends f rom low sacral segment s t o high cervical segment s, t he volume of w hit e mat t er increases progressively because t he number of nerve f ibers, bot h ascending t o higher
levels and descending t o low er levels, is larger in t he high cervical sect ions and diminishes progressively at more caudal levels. Some t ract s are not present at cert ain levels. The dorsal spinocerebellar t ract appears f irst at t he second lumbar segment and is not present below t his segment . This is because neurons t hat give rise t o t his t ract f irst appear at t he level of L-2 and are not present below t his level. The cuneat e t ract (f asciculus) appears above t he sixt h t horacic spinal cord segment and is not pres-ent below t his level. I t f ollow s t hat t he dorsal (post erior) int ermediat e sulcus, w hich separat es t he gracile and cuneat e t ract s, is only present above t he T-6 segment . Diff erent spinal cord regions also demonst rat e dist inct ive gray mat t er f eat ures. The int ermedio-lat eral cell column and t he nucleus dorsalis of Clarke ext end bet w een t he C-8 and L-2 segment s and are not seen eit her below or above t hese levels. The cervical and lumbar enlargement s of t he cord are charact erized by voluminous vent ral horns because of t he presence of mot or neurons t hat supply limb musculat ure at t hese t w o levels.
Fi gure 3-3. Phot omicrograph of spinal cord show ing division int o gray and w hit e mat t er, t he sulci and f issures, gray mat t er columns, and w hit e mat t er f uniculi.
Fi gure 3-4. Schemat ic diagram show ing variat ions in spinal cord segment s at diff erent levels.
Gray Matter A. OLDER TERM INOLOGY Prior t o 1952, t he organizat ion of t he gray mat t er of t he spinal cord w as present ed in t he f ollow ing w ay. Dorsal horn The dorsal (post erior) horn or column receives axons of t he dorsal root ganglia via t he dorsal root s and cont ains cell clust ers concerned w it h sensory f unct ion. These cell clust ers are t he post eromarginal nucleus, t he subst ant ia gelat inosa, and t he nucleus proprius. Intermedi ol ateral horn The int ermediolat eral horn or column is limit ed t o t he t horacic and upper lumbar segment s of t he cord. I t cont ains preganglionic neurons of t he sympat het ic nervous syst em, t he axons of w hich f orm t he preganglionic nerve f ibers and leave t he spinal cord via t he vent ral root . Alt hough no dist inct int ermediolat eral horn is present in t he sacral spinal cord, a dorsal out pouching of t he vent ral horn in S-2 t o S-4 spinal cord segment s cont ains preganglionic parasympat het ic
neurons. Ventral horn The vent ral horn or column cont ains mult ipolar mot or neurons, axons of w hich const it ut e t he major component of t he vent ral root . Intermedi ate zone This zone cont ains t he nucleus dorsalis of Clarke and a large number of int erneurons. The preceding organizat ional pat t ern is illust rat ed diagrammat ically in Figure 35.
B. REXED TERM INOLOGY I n 1952, Rexed invest igat ed t he cyt oarchit ect onics, or cellular organizat ion, of t he spinal cord in t he cat and f ound t hat cell clust ers in t he cord are arranged w it h ext raordinary regularit y int o t en zones or laminae. His observat ions subsequent ly have been conf irmed in ot her species, including humans. Figure 3-6 is a diagrammat ic represent at ion of t he locat ion of t he t en laminae of Rexed. Table 3-4 compares t he older t erminology w it h t he more recent Rexed t erminology. Laminae I t o I V are concerned w it h ext erocept ive sensat ions, w hereas laminae V and VI are concerned primarily w it h propriocept ive sensat ions, alt hough t hey respond t o cut aneous st imuli. Lamina VI I act s as a relay bet w een midbrain and cerebellum. Lamina VI I I modulat es mot or act ivit y, most probably via gamma neurons. Lamina I X is t he main mot or area of t he spinal cord. I t cont ains large alpha and smaller gamma mot or neurons arranged in columns (dorsolat eral, vent rolat eral, vent romedial, and cent ral). The axons of t hese neurons supply ext raf usal and int raf usal muscle f ibers, respect ively. Alpha mot or neurons in lamina I X of cord segment s C-3 t o C-5 const it ut e t he phrenic nucleus. Axons of t hose neurons innervat e t he diaphragm and t hus are essent ial f or breat hing. From segment s S-1, S-2 t o S-4, a supplement ary column of alpha mot or neurons appears in lamina I X. This is t he O nuf 's (O nuf row icz) nucleus, w hich lies at t he most vent ral border of t he vent ral horn. The nucleus is divided int o a dorsomedial cell group innervat ing t he bulbocavernosus and ischiocavernosus muscles and a vent rolat eral cell group innervat ing ext ernal anal and uret hral sphinct ers. The dorsomedial port ion of O nuf 's nucleus cont ains signif icant ly more neurons in males t han in f emales. Mot or neurons in O nuf 's nucleus are charact erist ically spared in mot or neuron disease (amyot rophic lat eral sclerosis), in marked cont rast t o mot or neurons elsew here in t he spinal cord and brain st em.
Fi gure 3-5. Cross-sect ional diagram of t he spinal cord show ing t he major nuclear groups w it hin t he gray columns.
Alpha mot or neurons in lamina I X are somat ot opically organized in such a w ay t hat neurons supplying f lexor muscle groups are locat ed dorsally, w hereas neurons supplying ext ensor muscle groups are locat ed vent rally. I n addit ion, neurons supplying t runk musculat ure are placed medially w hereas neurons supplying ext remit y musculat ure are placed lat erally (Figure 3-7). Mot or neurons in lamina I X receive direct input f rom dorsal root s (f or spinal ref lexes) as w ell as f rom descending pat hw ays concerned w it h mot or cont rol. Physiologic st udies have demonst rat ed t w o t ypes of alpha mot or neurons, t onic and phasic. Tonic neurons are charact erized by a low er rat e of impulse f iring and slow er axonal conduct ion. They innervat e t he slow muscle f ibers. Phasic neurons exhibit f ast axonal conduct ion and innervat e t he f ast muscle f ibers. No anat omic crit eria are available t o dist inguish t onic f rom phasic alpha mot or neurons.
Fi gure 3-6. Schemat ic diagram of half of t he spinal cord show ing t he locat ion of Rexed laminae.
Physiologic st udies also have demonst rat ed t w o t ypes of gamma mot or neurons, st at ic and dynamic. The st at ic variet y is relat ed t o t he nuclear chain t ype of int raf usal muscle f iber, w hich is concerned w it h t he st at ic response of t he muscle spindle, w hereas t he dynamic variet y is relat ed t o t he nuclear bag t ype of int raf usal muscle f iber, w hich is concerned w it h t he dynamic response of t he spindle. As is t he case w it h alpha mot or neurons, no anat omic crit eria are available t o diff erent iat e st at ic f rom dynamic gamma mot or neurons. I n addit ion t o alpha and gamma mot or neurons, lamina I X cont ains int erneurons. O ne of t hese int erneurons, t he Renshaw cell, has received part icular at t ent ion f rom neuroscient ist s. The Renshaw cell is int erposed bet w een t he recurrent axon collat eral of an alpha mot or neuron and t he dendrit e or cell body of t he same alpha mot or neuron. The axon collat eral of t he alpha mot or neuron excit es t he Renshaw cell. The axon of t he Renshaw cell inhibit s (recurrent inhibit ion) t he parent alpha mot or neuron and ot her mot or neurons. Through t his f eedback loop, an alpha mot or neuron may inf luence it s ow n act ivit y. Recent st udies have show n t hat Renshaw cell axons project t o nearby as w ell as dist ant sit es, including laminae I X, VI I I , and VI I . The f unct ional consequences of Renshaw cell inhibit ion are t o curt ail t he mot or out put f rom a part icular collect ion of mot or neurons and t o highlight t he out put of mot or neurons t hat are st rongly act ivat ed. The inhibit ory neurot ransmit t er used by t he Renshaw cells is probably glycine. Tabl e 3-4. Cellular O rganization of Spinal Cord.
Rexed term inology
Older term inology
Lamina I
Posteromarginal nucleus
Lamina II
Substantia gelatinosa
Laminae III, IV
Nucleus proprius
Lamina V
Neck of posterior horn
Lamina VI
Base of posterior horn
Lamina VII
Intermediate zone, intermediolateral horn
Lamina VIII
Commissural nucleus
Lamina IX
Ventral horn
Lamina X
Grisea centralis
Fi gure 3-7. Schemat ic diagram of t he spinal cord show ing somat ot opic organizat ion of vent ral horn (lamina I X) mot or neurons.
Q uant it at ive st udies of t he dendrit ic organizat ion of spinal mot or neurons have show n t hat dendrit es f orm approximat ely 80 percent of t he recept ive area of a neuron. Alt hough dendrit es ext end up t o 1000 ľm f rom t he cell body, t he proximal t hird of each dendrit e cont ains most of t he synapses and t hus is t he most eff ect ive in t he recept ion and subsequent t ransmission of incoming st imuli. Lamina X surrounds t he cent ral canal and cont ains neuroglia. Neurons in t he gray mat t er of t he spinal cord are of t w o t ypes, principal neurons and int erneurons. The f ormer have been classif ied int o t w o general cat egories on t he basis of t heir axonal course. Tract (project ion) neurons have axons t hat
cont ribut e t o t he f ormat ion of a t ract . Examples of such neurons include t he dorsal nucleus of Clarke, w hich gives rise t o t he dorsal spinocerebellar t ract , and neurons in t he dorsal (post erior) horn t hat give rise t o t he spinot halamic t ract . I n cont rast , root neurons have axons t hat cont ribut e t o t he f ormat ion of t he vent ral root . Examples of such neurons include alpha and gamma mot or neurons in t he vent ral (ant erior) horn and t he aut onomic (sympat het ic and parasympat het ic) neurons in t he int ermediolat eral horn and S-2 t o S-4 spinal cord segment s, respect ively.
White Matter The w hit e mat t er of t he spinal cord is organized int o t hree f unic-uli (Figure 3-3): 1. Post erior (dorsal) f uniculus 2. Lat eral f uniculus 3. Ant erior (vent ral) f uniculus Each of t hese f uniculi cont ains one or more t ract s or f asciculi (Tables 3-5 and 36). A tract is composed of nerve f ibers sharing a common origin, dest inat ion, and f unct ion. I n general, t he name of a t ract denot es it s origin and dest inat ion; f or example, t he spino-cerebellar t ract connect s t he spinal cord and cerebellum and t he cort icospinal t ract connect s t he cerebral cort ex and spinal cord.
A. POSTERIOR FUNICULUS Nerve f ibers in t his f uniculus are concerned w it h t w o general modalit ies relat ed t o conscious propriocept ion. These are kinest hesia (sense of posit ion and movement ) and discriminat ive t ouch (precise localizat ion of t ouch, including t w o-point discriminat ion). Lesions of t his f uniculus t heref ore w ill be manif est ed clinically as loss or diminut ion of t he f ollow ing sensat ions: 1. Vibrat ion sense 2. Posit ion sense 3. Tw o-point discriminat ion 4. Touch 5. Form recognit ion
Tabl e 3-5. Spinal Cord Ascending Tracts
Tract nam e
Origin
Location
Extent
Te
Gracile
Ipsilateral dorsal root ganglion
Medial in posterior funiculus
Throughout spinal cord
Ips gra nu me
Cuneate
Ipsilateral dorsal root ganglion
Lateral in posterior funiculus
Above sixth thoracic segment
Ips cu nu me
Dorsal spinocerebellar
Ipsilateral nucleus dorsalis of Clarke
Lateral funiculus
Above second lumbar segment
Ips ce
Ventral spinocerebellar
Contralateral dorsal horn
Lateral funiculus
Throughout spinal cord
Co ce
Spinocervical thalamic (Morin's)
Ipsilateral dorsal root ganglion
Throughout spinal cord
Ips lat ce nu
Throughout spinal cord
Ips tha (ve po nu
Lateral spinothalamic
Contralateral dorsal horn
Lateral funiculus
Lateral funiculus
Lateral
Ips
Anterior spinothalamic
Contralateral (largely) dorsal horn
and anterior funiculi
Throughout spinal cord
tha (ve po nu
Tabl e 3-6. Spinal Cord Descending Tr
Tract nam e
Origin
Location
Extent
Lateral corticospinal
Contralateral cerebral cortex
Lateral funiculus
Througho spinal co
Anterior cortico-spinal (bundle of Türck)
Ipsilateral cerebral cortex (largely)
Anterior funiculus
Variable
Tract of Barnes
Ipsilateral cerebral cortex
Lateral funiculus
Througho spinal co
Lateral funiculus
Througho spinal co
Rubrospinal
Contralateral red nucleus
(midbrain)
Lateral vestibulospinal
Ipsilateral lateral vestibular nucleus
Lateral funiculus
Througho spinal co
Medial vestibulospinal
Ipsi- and contralateral medial vestibular nuclei
Anterior funiculus
Cervical spinal co
Reticulospinal
Medullary and pontine reticular formation, bilaterally
Lateral and anterior funiculi
Througho spinal co
Tectospinal
Contralateral superior colliculus (midbrain)
Anterior funiculus
Cervical spinal co
Descending
Ipsilateral
Anterolateral
Througho
autonomic
hypothalamus
funiculus
spinal co
Monoaminergic
Raphe nucleus, locus ceruleus, periaqueductal gray
Lateral and anterior funiculi
Througho spinal co
The presence or absence of t hese diff erent sensat ions is t est ed by t he neurologist as f ollow s: 1. Vibrat ion is t est ed by placing a vibrat ing t uning f ork over a bony prominence. 2. Posit ion sense is t est ed by moving t he t ip of t he pat ient 's f inger or t oe dorsally and vent rally and asking t he pat ient (w it h eyes closed) t o ident if y t he posit ion of t he part moved. 3. Tw o-point discriminat ion is t est ed by simult aneously pricking or t ouching t he pat ient in t w o adjacent areas of skin. Under normal condit ions, a person is able t o recognize t hese t w o simult aneous st imuli as separat e st imuli if t he dist ance bet w een t hem is not less t han 5 mm on t he f ingert ips using pins and not less t han 10 cm on t he shin using f ingert ips. 4. Touch is t est ed by placing a cot t on ball gent ly over t he skin. 5. Form recognit ion is t est ed by asking t he pat ient t o ident if y an object placed in t he hand (w it h eyes closed) based on w eight , size, f orm, and t ext ure percept ion. The nerve f ibers t hat cont ribut e t o t he post erior f uniculus have t heir cell bodies in t he dorsal root ganglia. Peripheral recept ors cont ribut ing t o t his syst em are (1) cut aneous mechanorecept ors (hair f ollicle and t ouch pressure recept ors) t hat convey t he sensat ions of t ouch, vibrat ion, hair movement , and pressure and (2) propriocept ive recept ors (muscle spindle, G olgi t endon organ, and joint recept ors). Muscle recept ors (muscle spindles and G olgi t endon organs) are t he primary recept ors conveying posit ion sense. Joint recept ors may be concerned w it h signaling joint movement but not joint posit ion.
Nerve f ibers of t he post erior f uniculus are t hickly myelinat ed and occupy t he dorsolat eral part of t he dorsal root . Those t hat ent er t he spinal cord below t he sixt h t horacic segment are locat ed medially in t he post erior f uniculus and f orm t he gracile t ract (t ract of G oll). Fibers t hat ent er t he spinal cord above t he sixt h t horacic segment are locat ed more lat erally and f orm t he cuneat e t ract (Burdach column). Thus t he nerve f ibers in t he post erior f uniculus are laminat ed or layered in such a w ay t hat t hose arising f rom t he sacral region are most medial, w hereas t hose f rom t he cervical region are most lat eral (Figure 3-8). I t should be point ed out t hat t he laminat ion in t he post erior f uniculus is bot h segment al (sacral, lumbar, t horacic, cervical) and modalit y orient ed. Physiologic st udies have show n t hat f ibers conduct ing impulses f rom hair recept ors are superf icial and are f ollow ed by f ibers mediat ing t act ile and vibrat ory sensat ions in successively deeper layers. The f ibers f orming t he post erior f uniculus ascend t hroughout t he spinal cord and synapse on t he post erior (dorsal) column nuclei (nucleus gracilis and nucleus cuneat us) in t he medulla oblongat a. Axons of t hese nuclei t hen cross in t he midline t o f orm t he medial lemniscus, w hich ascends t o t he t halamus (vent ral post erolat eral nucleus) and f rom t here t o t he primary sensory (somest het ic) cort ex (Figure 3-9). Approximat ely 85 percent of ascending f ibers in t he post erior f uniculus are primary aff erent s. These have cell bodies in t he dorsal root ganglia and are act ivat ed by st imulat ion of mechanorecept ors (unimodal aff erent s). Approximat ely 15 percent of f ibers in t he post erior f uniculus are nonprimary aff erent s. These have cell bodies in t he dorsal root ganglion, est ablish synapses in laminae I I I t o V in t he post erior (dorsal) horns of t he cervical and lumbar enlargement s, and are act ivat ed by st imulat ion of bot h mechanorecept ors and nocicept ors (polymodal aff erent s). Some of t he f ibers in t he post erior f uniculus send collat eral branches t hat t erminat e on neurons in t he post erior horn gray mat t er. Such collat erals give t he post erior f uniculus a role in modif ying sensory act ivit y in t he post erior horn. As discussed lat er, t his role is inhibit ory t o pain impulses. Lesions in t he post erior f uniculus decrease t he t hreshold t o painf ul st imuli and augment all f orms of sensat ions conveyed by t he spinot halamic (pain) pat hw ays. Thus nonpainf ul st imuli become painf ul, and painf ul st imuli are t riggered by low er st imulat ion t hresholds. St imulat ion of t he post erior f uniculus has been used in t he t reat ment of chronic pain. I n one large st udy, 47 percent of t reat ed pat ient s responded init ially t o t his st imulat ion, but t he percent age dropped t o 8 percent af t er 3 years. None of t he pat ient s st udied had complet e relief f rom pain. Report s in t he lit erat ure describe lesions in t he post erior f uniculus in humans and animals w it hout concomit ant def icit in t he sensory modalit ies presumably carried
by t his syst em. This is explained by t he presence of anot her syst em, t he spinocervical t halamic, locat ed in t he lat eral f uniculus, w hich may compensat e f or some post erior f uniculus def icit s. The role of t he dorsal (post erior) column syst em in sensory t ransmission and appreciat ion has been st udied ext ensively in bot h humans and experiment al animals (Table 3-7). Sensory st imuli conduct ed via t he post erior column are generally of t hree t ypes: (1) t hose t hat are impressed passively on t he organism, (2) t hose t hat have t emporal or sequent ial f act ors added t o a spat ial cue, and (3) t hose t hat cannot be recognized w it hout manipulat ion and act ive explorat ion by t he digit s. The f irst t ype, st imuli t hat are impressed passively on t he organism (e. g. , vibrat ing t uning f ork, t w o-point discriminat ion, t ouch w it h a piece of cot t on), are t ransmit t ed by t he dorsal column. How ever, much t he same inf ormat ion is t ransmit t ed by a number of parallel pat hw ays such as t he spinocervical t halamic t ract . Thus such passive t ypes of sensat ions remain int act in t he absence of t he dorsal column. The second t ype, st imuli w it h t emporal or sequent ial f act ors added t o a spat ial cue (e. g. , det erminat ion of t he direct ion of lines t hat are draw n on t he skin), are det ect ed by t he dorsal column. The dorsal column has t he inherent f unct ion of t ransmission t o higher cent ral nervous syst em cent ers inf ormat ion concerning t he changes in a peripheral st imulus over a period of t ime. The t hird t ype, st imuli t hat cannot be recognized w it hout manipulat ion and act ive explorat ion by t he digit s (e. g. , det ect ion of shapes and pat t erns), are appreciat ed only by t he dorsal column. I n addit ion t o it s role in sensory t ransmission, t he dorsal column has a role in cert ain t ypes of mot or cont rol. Many movement s involving t he ext remit ies depend on sensory inf ormat ion t hat is f ed back t o t he brain f rom peripheral sensory organs such as muscle spindles, joint recept ors, and cut aneous recept ors. Many of t hese f eedback input s t ravel via t he dorsal column. The dorsal column t ransmit s t o t he mot or cort ex of t he brain (via t he t halamus) inf ormat ion necessary t o plan, init iat e, program, and monit or t asks t hat involve manipulat ive movement s by t he digit s. The t halamic nucleus (vent ral post erolat eral) t hat receives input f rom t he dorsal column syst em has been show n t o project not only t o t he primary somest het ic (post cent ral gyrus) sensory cort ex but also t o t he primary mot or cort ex in t he precent ral gyrus. I n addit ion, t he primary sensory cort ex project s t o t he primary mot or cort ex.
Fi gure 3-8. Schemat ic diagram of t he spinal cord show ing spat ial arrangement of f ibers in t he post erior f uniculus.
Fi gure 3-9. Schemat ic diagram of t he post erior column pat hw ay.
A f requent ly report ed observat ion in lesions of t he post erior column is t he discrepancy in loss of vibrat ion and posit ion sense. A possible explanat ion f or t his diff erent ial loss is t hat diff erent pat hw ays are used f or t ransmission of t he t w o modalit ies. I n experiment al animals it has been show n t hat cut aneous mechanorecept ors in f orelimbs and hindlimbs (conveying t ouch, vibrat ion, hair movement , and pressure) t ransmit t heir impulses via t he dorsal columns (cuneat e and gracile t ract s, respect ively) and t he spino-cervical t halamic t ract (Figure 310). I n cont rast , propriocept ive sensat ions (f rom muscle spindle and G olgi t endon organ [ posit ion sense] and joint recept ors) f rom t he f orelimbs ut ilize t he dorsal column (cuneat e t ract ), w hile t hose f rom t he hindlimb t ravel w it h t he gracile t ract t o t he level of t he dorsal nucleus of Clarke. From t here t hey leave
t he gracile t ract , synapse in t he nucleus dorsalis of Clarke, and t ravel w it h t he dorsal spinocerebellar f ibers t o t erminat e on t he nucleus of Z (of Brodal and Pompeiano), a small collect ion of cells in t he most rost ral part of nucleus gracilis in t he medulla. From t here t he f ibers join t he medial lemniscus t o reach t he t halamus (Figure 3-10). Tabl e 3-7. Dorsal Column System Function.
Dorsal colum n
Type of stim ulus
Transm its
Essential for
Passively impressed (vibration, two-point discrimination, touch)
Yes
No
Temporal or sequential (direction of line drawn on skin)
Yes
Yes
Actively explored and manipulated (detection of shapes and patterns)
Yes
Yes
B. LATERAL AND ANTERIOR FUNICULI Whereas t he post erior f uniculus (Table 3-5) cont ains only one ascending t ract or f iber syst em (t he post erior column syst em), t he lat eral and ant erior f uniculi cont ain several ascending and descending t ract s (Tables 3-5 and 3-6). O nly t hose t ract s w it h est ablished f unct ional or clinical relevance w ill be discussed.
C. ASCENDING TRACTS All t he f ollow ing t ract s have t heir cells of origin in dorsal root ganglia (Table 35).
1. Dorsal Spinocerebellar Tract. This ascending f iber syst em conveys t o t he cerebellum propriocept ive impulses
f rom recept ors locat ed in muscles, t endons, and joint s. The impulses arising in muscle spindles t ravel via I a and I I nerve f ibers, w hereas t hose arising in G olgi t endon organs t ravel via I b nerve f ibers. Cent ral processes of neurons in dorsal root ganglia ent er t he spinal cord via t he dorsal root and eit her ascend or descend in t he post erior f uniculus f or a f ew segment s bef ore reaching t he spinal nucleus, or t hey may reach t he nucleus direct ly. Nerve cells, t he axons of w hich f orm t his t ract , are locat ed in t he nucleus dorsalis of Clarke (also know n as Clarke's column, nucleus t horacicus, t horacic nucleus, St illing column, or St illing nucleus) w it hin lamina VI I of Rexed (see Figure 3-12). This nucleus is not f ound t hroughout t he ext ent of t he spinal cord but is limit ed t o t he spinal cord segment s bet w een t he eight h cervical (C-8) and second lumbar (L-2). Because of t his, t he dorsal spinocerebellar t ract is not seen below t he second lumbar segment . Nerve f ibers belonging t o t his syst em and ent ering below L-2 ascend t o t he L-2 level, w here t hey synapse w it h cells locat ed in t he nucleus. Similarly, nerve f ibers ent ering above t he upper limit of t he nucleus ascend in t he cuneat e t ract t o reach t he accessory cuneat e nucleus in t he medulla oblongat a, w hich is homologous t o t he nucleus dorsalis (Figure 3-11). Fibers in t his t ract are segment ally laminat ed in such a w ay t hat f ibers f rom low er limbs are placed superf icially. The f ibers in t his t ract reach t he cerebellum via t he inf erior cerebellar peduncle (rest if orm body) (Figure 3-12) and t erminat e on t he rost ral and caudal port ions of t he vermis. The dorsal spinocerebellar t ract conveys t o t he cerebellum inf ormat ion pert aining t o muscle cont ract ion, including phase, rat e, and st rengt h of cont ract ion. There is evidence t o suggest t hat some of t he f ibers f orming t his t ract arise f rom neurons in laminae V and VI of Rexed, as w ell as f rom t he nucleus dorsalis of Clarke.
2. Ventral Spinocerebellar Tract. This f iber syst em (Figure 3-12) conveys impulses almost exclusively f rom G olgi t endon organs via I b aff erent s. Dorsal root f ibers dest ined f or t his t ract synapse w it h neurons in laminae V t o VI I of Rexed. Axons arising f rom t hese neurons t hen cross t o f orm t he vent ral spinocerebellar t ract , w hich ascends t hroughout t he spinal cord, medulla oblongat a, and pons bef ore ent ering t he cont ralat eral cerebellum via t he superior cerebellar peduncle (brachium conjunct ivum). Thus t he f ibers of t his t ract cross t w ice, once in t he spinal cord and again bef ore ent ering t he cerebellum. Most f ibers in t his t ract t erminat e in t he vermis and int ermediat e lobe, most ly homolat eral t o t he limb of origin but also cont ralat eral. The vent ral spinocerebellar t ract t ransmit s, t o t he cerebellum, inf ormat ion relat ed t o int erneuronal act ivit y and t he eff ect iveness of t he descending pat hw ays.
Fi gure 3-10. Schemat ic diagram show ing t he diff erent pat hw ays f or cut aneous and propriocept ive sensat ions f rom f ore- and hindlimbs.
Unlike t he post erior column, w hich conveys conscious propriocept ion t o t he cerebral cort ex, t he dorsal and vent ral spinocerebellar t ract s t erminat e in t he cerebellum and t hus convey unconscious propriocept ion. I n addit ion t o t he preceding classic spinocerebellar pat hw ays, t here are at least t w o ot her indirect pat hw ays f rom t he spinal cord t o t he cerebellum:
1. The spino-olivo-cerebellar pat hw ay, w it h an int ermediat e st at ion at t he inf erior olive in t he medulla oblongat a 2. The spino-ret iculo-cerebellar pat hw ay, w it h an int ermediat e synapse in t he lat eral ret icular nucleus of t he medulla The impulses t raveling via t he indirect spinocerebellar pat hw ays reach t he cerebellum af t er a longer lat ency t han t hat observed w it h t he more direct spinocerebellar pat hw ays. I t is post ulat ed t hat impulses t raveling via t he classic direct pat hw ay reach t he cerebellum sooner and w ill condit ion it f or t he recept ion of impulses arriving lat er via t he indirect pat hw ays.
3. Spinocervical Thalamic Tract (Morin's Tract). Nerve f ibers dest ined t o f orm t he spinocervical t halamic t ract are cent ral processes of dorsal root ganglia. They ent er t he spinal cord w it h t he t hickly myelinat ed f ibers of t he medial division of t he dorsal root . They t ravel w it hin t he post erior f uniculus f or several segment s bef ore ent ering t he post erior horn gray mat t er t o synapse on neurons t here. Axons of neurons in t he post erior horn ascend in t he lat eral f uniculus t o t he upper t w o or t hree cervical segment s, w here t hey synapse on neurons of t he lat eral cervical nucleus. Axons of t his nucleus cross t o t he opposit e lat eral f uniculus and ascend t o t he t halamus (Figure 3-10). The lat eral cervical nucleus is organized somat ot opically (similar t o t he post erior column nuclei) and similarly receives an input f rom t he cerebral cort ex.
Fi gure 3-11. Schemat ic diagram of t he spinal cord show ing t he homology of t he accessory cuneat e nucleus and t he nucleus dorsalis of Clarke.
The spinocervical t halamic t ract account s f or t he presence of kinest hesia and discriminat ive t ouch af t er t ot al int errupt ion of t he post erior f uniculus. Alt hough t his t ract has not been demonst rat ed in humans, it s presence has been assumed because of t he persist ence of post erior f uniculus sensat ions af t er t ot al post erior f uniculus lesions. Thus t he older concept of t he necessit y of t he post erior f uniculus f or discriminat ory sensat ion is being challenged. I nst ead, a new er concept is evolving t hat at t ribut es t o t he post erior f uniculus a role in t he discriminat ion of t hose sensat ions t hat an animal must explore act ively and t o t he spinocervical t halamic syst em a role in t he discriminat ion of sensat ions t hat are impressed passively on t he organism (Table 3-7).
4. Lateral Spinothalamic Tract. This ascending f iber t ract is locat ed medial t o t he dorsal and vent ral spinocerebellar t ract s (Figure 3-13) and is concerned w it h t ransmission of pain and t emperat ure sensat ions. Root f ibers cont ribut ing t o t his t ract (C-f ibers and A-delt a f ibers) have t heir cell bodies in dorsal root ganglia. They are unmyelinat ed and t hinly myelinat ed f ibers t hat generally occupy t he vent rolat eral region of t he dorsal root as it ent ers t he spinal cord. C-f ibers conduct slow ly at 0. 5 t o 2 m/ s. A-delt a f ibers conduct f ast er at 5 t o 30 m/ s. I ncoming root f ibers est ablish synapses in laminae I t o VI of Rexed. A-delt a and C-f ibers t erminat e in laminae I t o I I I ; A-delt a f ibers t erminat e in addit ion in deep layer V. Axons of neurons in t hese laminae in t urn est ablish synapses w it h neurons in laminae V t o VI I I . Axons of t ract neurons in laminae V t o VI I I , as w ell as some axons arising f rom neurons in lamina I , cross t o t he opposit e lat eral f uniculus in t he ant erior w hit e commissure w it hin one t o t w o segment s above t heir ent ry level t o f orm t he lat eral spinot halamic t ract . A small number of f ibers st ay uncrossed. Fibers of sacral origin are locat ed most lat erally and t hose of cervical origin more medially in t he crossed t ract . This segment al laminat ion is usef ul clinically in diff erent iat ing lesions w it hin t he spinal cord f rom t hose compressing t he spinal cord f rom out side. I n t he f ormer, t he cervical f ibers are aff ect ed early, w hereas t he sacral f ibers are aff ect ed eit her lat e or not at all. This condit ion, know n clinically as sacral spari ng, is charact erized by preservat ion of pain and t emperat ure sensat ions in t he sacral dermat omes and t heir loss or diminut ion in ot her dermat omes. I n addit ion t o t his segment al laminat ion, t he lat eral spinot halamic t ract exhibit s modalit y laminat ion, in w hich f ibers conveying pain sensat ions are locat ed ant eriorly and t hose conveying t hermal sense are locat ed most post eriorly (Figure 3-14). This segregat ion of f ibers in a modalit y pat t ern, how ever, is incomplet e. O nce f ormed, t his t ract ascends t hroughout t he lengt h of t he spinal cord and brain st em t o reach t he t halamus, w here it s axons synapse
on neurons in t he vent ral post erolat eral nucleus. Third-order neurons project f rom t here by means of t he post erior limb of t he int ernal capsule t o t he primary somat osensory cort ex (Figure 3-15). Lesions of t his t ract result in loss of pain and t hermal sensat ion in t he cont ralat eral half of t he body beginning one or t w o segment s below t he level of t he lesion. I n cont rast t o t his pat t ern of pain and t hermal loss, lesions of t he dorsal root result in segment al (dermat omal) loss of sensat ion ipsilat eral t o t he lesion, w hereas lesions of t he crossing f ibers in t he ant erior w hit e commissure result in bilat eral segment al loss of pain and t emperat ure sensat ion in dermat omes corresponding t o t he aff ect ed spinal segment s. This last pat t ern is of t en not ed in syringomyelia, a disease in w hich t he cent ral canal of t he spinal cord encroaches on, among ot her sit es, t he ant erior w hit e commissure. The lat eral spinot halamic t ract may be sect ioned surgically f or t he relief of int ract able pain. I n t his procedure, know n as cordot omy, t he surgeon uses t he ligament um dent iculat um of t he spinal meninges as a landmark and orient s t he knif e ant erior t o t he ligament t o reach t he t ract . Because of t he segregat ion of pain and t hermal f ibers in t he lat eral spinot halamic t ract , cordot omies can select ively ablat e pain f ibers, leaving t hermal sensat ions int act . There has been increased int erest in pain pat hw ays and pain mechanisms in recent years. These ext ensive st udies have show n t hat t he lat eral spinot halamic t ract is only one of several pat hw ays carrying pain impulses. O t her pat hw ays conveying t his modalit y include a mult isynapt ic pat hw ay associat ed w it h t he ret icular syst em and a spinot ect al pat hw ay. These st udies also have developed t he concept of an inhibit ory input int o t he post erior horn f rom t he t hickly myelinat ed f ibers of t he dorsal root and post erior column. This has led clinicians t o st imulat e t hese inhibit ory f ibers t raveling in t he post erior column in an at t empt t o relieve int ract able pain. O ut of t hese st udies on pain mechanisms has evolved t he gat e-cont rol t heory of pain, proposed by Melzack and Wall (Figure 3-16). According t o t his t heory, t w o aff erent input s relat ed t o pain ent er t he spinal cord. O ne input is via small f ibers t hat are t onic and adapt slow ly w it h a cont inuous f low of act ivit y, t hus keeping t he gat e open. I mpulses along t hese f ibers w ill act ivat e an excit at ory mechanism t hat increases t he eff ect of arriving impulses. The second input is via large, t hickly myelinat ed f ibers t hat are phasic, adapt rapidly, and f ire in response t o a st imulus. Bot h t ypes of f ibers project int o lamina I I of Rexed, w hich suggest s t hat t his lamina is t he modular cent er f or pain. The t hin f ibers inhibit , w hereas t he t hick f ibers f acilit at e, neurons in t his lamina. Bot h t ypes of f ibers also project int o laminae I and I V t o VI I I of Rexed, w here t ract cells are locat ed. Bot h t hin and t hick f ibers f acilit at e neurons in t hese laminae. Furt hermore, axons of neurons in lamina I I have a presynapt ic inhibit ory eff ect on bot h small and large axons project ing on t ract neurons. These diff erent relat ionships (Figure 3-16) can be summarized as f ollow s:
Fi gure 3-12. Schemat ic diagram show ing t he f ormat ion, course, and t erminat ion of t he dorsal (post erior) and vent ral (ant erior) spinocerebellar t ract s.
1. O ngoing act ivit y t hat precedes a st imulus is carried by t he t onic, slow ly adapt ing f ibers t hat t end t o keep t he gat e open. 2. A peripheral st imulus w ill act ivat e bot h small and large f ibers. The discharge of t he lat t er init ially w ill f ire t he t ract cells (T cells) t hrough t he direct rout e and t hen part ially close t he gat e t hrough t heir act ion via lamina I I (f acilit at ion of presynapt ic inhibit ion).
3. The balance bet w een large- and small-f iber act ivat ion w ill det ermine t he st at e of t he gat e. I f t he st imulus is prolonged, large f ibers w ill adapt , result ing in a relat ive increase in small-f iber act ivit y t hat w ill open t he gat e f urt her and increase T-cell act ivit y. How ever, if large-f iber act ivit y is increased by a proper st imulus (vibrat ion), t he gat e w ill t end t o close, and Tcell act ivit y w ill diminish. Since it s publicat ion, t he gat e-cont rol t heory has been modif ied and f urt her clarif ied. I t is now recognized t hat inhibit ion occurs by bot h presynapt ic and post synapt ic input s f rom t he periphery, as w ell as by descending cort ical inf luences. While it is generally agreed t hat a gat e cont rol f or pain exist s, it s f unct ional role and det ailed mechanism need f urt her explorat ion. O ngoing research in pain mechanisms has given rise in recent years t o much int erest ing dat a, some of w hich are summarized below : 1. Tw o t ypes of pain recept ors have been ident if ied: unimodal nocicept ors responding t o nocicept ive st imuli and polymodal nocicept ors responding t o nocicept ive, chemical, and mechanical st imuli. 2. Three t ypes of spinot halamic neurons have been ident if ied in t he dorsal horn: low -t hreshold mechanorecept ors in laminae VI t o VI I , high-t hreshold, nocicept ive-specif ic nocicept ors in lamina I , and w ide-dynamic-range neurons in laminae I V and V responding t o bot h mechanorecept or and nocicept or st imulat ion. The w ide-dynamic-range neurons receive input s f rom bot h low -t hreshold mechanorecept ors and high-t hreshold nocicept ors and are probably concerned w it h visceral and ref erred pain.
Fi gure 3-13. Schemat ic diagram show ing t he f ormat ion of t he lat eral spinot halamic t ract .
3. O nly t he nocicept or neurons are inhibit ed by serot onergic f ibers f rom t he nucleus raphe magnus of t he medulla. 4. Several neurot ransmit t er subst ances have been ident if ied in t he dorsal horn: norepinephrine and serot onin in t he subst ant ia gelat inosa and subst ance P, somat ost at in, and enkephalins in laminae I t o I I I . Subst ance P has been f ound t o be excit at ory, w hereas enkephalins are inhibit ory.
Fi gure 3-14. Schemat ic diagram show ing t he segment al and modalit y laminat ion of t he lat eral spinot halamic t ract . S, sacral; L, lumbar; T,
t horacic (dorsal); C, cervical. St ippled area denot es t hermal f ibers. Clear area denot es pain f ibers.
Fi gure 3-15. Schemat ic diagram of t he f ormat ion, course, and t erminat ion of t he lat eral spinot halamic t ract .
5. C-f ibers ent ering via t he dorsal root t erminat e on lamina I , lamina I I , and lamina I I I neurons. They excit e neurons in all t hese laminae via axodendrit ic synapses. Axons of lamina I I neurons in t urn inhibit neurons of lamina I via axosomat ic synapses. 6. A-delt a f ibers est ablish excit at ory synapses on laminae I I and I V neurons. Some t erminat e on laminae I , I I I , and V. Since lamina I I neurons inhibit
lamina I neurons, repet it ive st imulat ion of A-delt a f ibers can inhibit lamina I neurons signif icant ly. I n common pract ice, t his is probably w hat happens w hen pain f rom a cut on t he f inger is reduced by local pressure (st imulat ion of A-delt a f ibers). 7. About 24 percent of sacral and 5 percent of lumbar originat ing f ibers in t he lat eral spinot halamic t ract project t o t he ipsilat eral t halamus.
5. Anterior Spinothalamic Tract. This t ract carries light t ouch st imuli. Fibers cont ribut ing t o t his t ract in t he dorsal root est ablish synapses in laminae VI t o VI I I . Axons of neurons in t hese laminae cross in t he ant erior w hit e commissure over several segment s and gat her in t he lat eral and ant erior f uniculi t o f orm t he t ract . Somat ot opic organizat ion in t his t ract is similar t o t hat in t he lat eral spinot halamic t ract . The course of t his t ract in t he spinal cord and brain st em is similar t o t hat of t he lat eral spinot halamic t ract . Recent evidence about t his t ract suggest s t he f ollow ing: (1) I t conveys pain impulses in addit ion t o t ouch. (2) Some of it s f ibers ascend ipsilat erally all t he w ay t o t he midbrain, w here t hey cross in t he post erior commissure and project primarily on int ralaminar neurons in t he t halamus, w it h some f ibers reaching t he periaqueduct al gray mat t er in t he midbrain. (3) I t is believed t o convey aversive and mot ivat ional nondiscriminat ive pain sensat ions, in cont rast t o t he lat eral spinot ha-lamic t ract , w hich is believed t o convey t he w ell-localized discriminat ive pain sensat ions. The exist ence of t his t ract as a separat e ent it y has been quest ioned. Most aut hors include t his f iber syst em w it h t he lat eral spinot halamic t ract . Physiologist s t end t o ref er t o t he t w o t ract s as t he anterol ateral system.
Fi gure 3-16. Schemat ic diagram of t he gat e-cont rol t heory of pain.
6. Other Ascending Tracts. O t her ascending t ract s of less clinical signif icance include t he spino-olivary, spinot ect al, and spinocort ical t ract s. The f unct ional signif icance of t hese mult isynapt ic pat hw ays is not very w ell delineat ed; t hey may play a role in f eedback cont rol mechanisms.
D. DESCENDING TRACTS Whereas all t he ascending t ract s originat e in dorsal root ganglia neurons (Table 3-5), t he descending t ract s, in cont radist inct ion, originat e f rom several sit es (Table 3-6). As w it h t he ascending t ract s, only t he descending t ract s of clinical or f unct ional signif icance w ill be discussed.
1. Corticospinal Tract. The cort icospinal t ract has t he highest level of development in higher primat es, especially in humans. The cells of origin of t his t ract are locat ed in t he cerebral cort ex. The primary mot or cort ex (Brodmann's area 4) and t he premot or cort ex (area 6) cont ribut e 80 percent of t he t ract . From t heir sit e of origin, axons of t he cort icospinal t ract descend t hroughout t he w hole lengt h of t he neuraxis (brain st em and spinal cord) (Figure 3-17). Approximat ely one million axons compose t he cort icospinal t ract on each side. At t he caudal end of t he medulla oblongat a, t he majorit y of cort icospinal f ibers cross (pyramidal decussat ion) t o f orm t he
l ateral corti cospi nal tract, locat ed in t he lat eral f uniculus of t he spinal cord (Figure 3-18). Fibers in t he lat eral cort icospinal t ract are organized somat ot opically. The cervical f ibers are most medial, f ollow ed lat erally by t he t horacic, lumbar, and sacral f ibers (Figure 3-19). The uncrossed f ibers remain in t he ant erior f uniculus as t he anteri or corti cospi nal tract (bundle of Türck) (Figure 3-18). They, in t urn, cross at segment al levels t o t erminat e on cont ralat eral mot or neurons (Figure 3-18). A crossed component of t he ant erior cort icospinal t ract has been described, how ever. I t is locat ed in t he post erolat eral part of t he ant erior f uniculus close t o t he vent ral (ant erior) horn. The crossed lat eral cort icospinal t ract ext ends t hroughout t he spinal cord. The ext ent of t he uncrossed component of t he ant erior cort icospinal t ract depends on it s size, w hich is variable. When large, it ext ends t hroughout t he spinal cord. The crossed component of t he ant erior cort icospinal t ract ext ends t o t he sixt h or sevent h cervical segment s only. About 2 t o 3 percent of t he cort icospinal f ibers remain uncrossed (Figure 3-18) in t he lat eral f uniculus (tract of Barnes) and inf luence ipsilat eral mot or neurons. Most f ibers in t he cort icospinal t ract are small in caliber, ranging in diamet er f rom 1 t o 4 ľm. O nly about 3 percent of t he f iber populat ion consist s of large-caliber f ibers ( Table of C ontents > P ar t I - Text > 6 - Medulla O blongata: C linic al C or r elates
6 Medulla Oblongata: Clinical Correlates
Medial Medullary Syndrom e (Dejerine's Anterior Bulbar Syndrom e) Lateral Medullary Syndrom e Babinski-Nageotte Syndrom e Dorsal Medullary Syndrom e Collet-Sicard Syndrom e Pseudobulbar Palsy KEY CONCEPTS Vascular lesions of the medulla oblongata are designated by the anatomic region affected rather than by the arte-rial supply. The clinical signs of the medial medullary syndrome include contralateral weakness of the upper motor neuron type, contralateral loss of kinesthesia and discriminative touch, and ipsilateral tongue weakness of the lower motor neuron type. The clinical signs of the lateral medullary syndrome include loss of pain and temperature sense in the ipsilateral face and the contralateral half of the body, ipsilateral loss of the gag reflex, hoarseness, dysphagia, dysarthria, ataxia, vertigo, ipsilateral
Horner's syndrome, nystagmus, and ocular lateropulsion. The clinical signs of combined lateral and medial medullary syndromes constitute the BabinskiNageotte syndrome. The clinical signs of the dorsal medullary syndrome include ipsilateral ataxia, nystagmus, vomiting, and vertigo. The Collet-Sicard syndrome results from an extraaxial lesion affecting cranial nerves IX to XII. Bilateral interruption of the corticobulbar or corticoreticulobulbar fibers results in the pseudobulbar syndrome.
Vascular lesions in t he medulla oblongat a are best suit ed t o anat omicoclinical correlat ion. I n t he past , t hese syndromes w ere designat ed by t he art ery of supply (e. g. , ant erior spinal art ery syndrome, post erior inf erior cerebellar art ery syndrome, vert ebral art ery syndrome). Because of variat ions in t he source of blood supply, how ever, t hese syndromes are current ly designat ed by t he anat omic region aff ect ed by t he lesion. Tw o such syndromes are part icularly illust rat ive: t he medial medullary syndrome and t he lat eral medullary syndrome.
M EDIAL M EDULLARY SYNDROM E (DEJERINE'S ANTERIOR BULBAR SYNDROM E) The medial medullary syndrome (Figure 6-1) is caused by occlusion of t he ant erior spinal art ery or t he paramedian branches of t he vert ebral art ery. The aff ect ed area usually includes t he f ollow ing st ruct ures: 1. Medial lemniscus 2. Pyramid 3. Root let s of t he hypoglossal nerve or it s nucleus w it hin t he medulla The neurologic signs result ing f rom t he involvement of t hese areas are as f ollow s:
1.
Cont ralat eral loss of kinest hesia and discriminat ive t ouch result ing f rom involvement of t he medial lemniscus
2. Cont ralat eral paralysis of t he upper mot or neuron t ype (w eakness, hyperact ive ref lexes, Babinski's sign, clonus, and spast icit y) w it h sparing of t he f ace caused by involvement of t he pyramid 3. Low er mot or neuron paralysis of t he homolat eral half of t he t ongue (w eakness, at rophy, and f ibrillat ion) and deviat ion of t he prot ruded t ongue t o t he at rophic side caused by involvement of t he hypoglossal nucleus or nerve The medial medullary syndrome may occur bilat erally, result ing in bilat eral upper mot or neuron w eakness or paralysis (w it h f acial sparing), bilat eral paralysis of t he t ongue of t he low er mot or neuron t ype, and bilat eral loss of kinest hesia and discriminat ive t ouch.
Fi gure 6-1. Schemat ic diagram of medullary st ruct ures involved in t he medial medullary syndrome, and t he result ing clinical manif est at ions.
LATERAL M EDULLARY SYNDROM E The lat eral medullary syndrome (Figure 6-2) is caused by occlusion of t he vert ebral art ery or, less f requent ly, t he medial branch of t he post erior inf erior cerebellar art ery w hen t his art ery supplies t he lat eral medulla. I t is also know n as t he post erior inf erior cerebellar art ery (PI CA) syndrome or Wallenberg's syndrome. The aff ect ed area usually includes t he f ollow ing st ruct ures: 1. Spinal nucleus of t he t rigeminal nerve and it s t ract 2. Adjacent spinot halamic t ract
3. Nucleus ambiguus or it s axons 4. Base of t he inf erior cerebellar peduncle (rest if orm body) 5. Vest ibular nuclei 6. Descending sympat het ic f ibers f rom t he hypot halamus 7. O livocerebellar f ibers The neurologic signs and sympt oms result ing f rom t he involvement of t hese areas include t he f ollow ing: 1.
Loss of pain and t emperat ure sensat ions f rom t he ipsilat eral f ace as a result of involvement of t he spinal nucleus of t he t rigeminal nerve and it s t ract .
2. Loss of pain and t emperat ure sensat ion over t he cont ralat eral half of t he body because of involvement of t he spinot halamic t ract . 3. Loss of t he gag ref lex, diff icult y sw allow ing (dysphagia), hoarseness, and diff icult y in art iculat ion (dysart hria) caused by paralysis of muscles supplied by t he nucleus ambiguus ipsilat eral t o t he medullary lesion. 4. I psilat eral loss of coordinat ion (at axia) result ing f rom involvement of t he base of t he inf erior cerebellar peduncle. 5. Hallucinat ion of t urning (vert igo) result ing f rom involvement of t he vest ibular nuclei.
Fi gure 6-2. Schemat ic diagram of medullary st ruct ures involved in t he lat eral medullary syndrome, and t he result ing clinical manif est at ions.
6. Horner's syndrome caused by involvement of t he descending sympat het ic f ibers f rom t he hypot halamus. This syndrome consist s of a small pupil (miosis), slight drooping of t he upper eyelid (pt osis), and w arm dry skin of t he f ace (anhidrosis), all ipsilat eral t o t he lesion. 7. Vomit ing, nyst agmus, and nausea result ing f rom involvement of t he vest ibular nuclei. 8. Hiccuping t hat is of uncert ain cause but usually is at t ribut ed t o involvement of t he respirat ory cent er in t he ret icular f ormat ion of t he medulla. 9. O cular lat eropulsion occurs almost universally in t his syndrome. I t consist s of a t endency t ow ard saccadic eye movement overshoot or hypermet ria t ow ard t he side of t he lesion and a t endency t ow ard hypomet ria aw ay f rom t he lesion. O cular lat eropulsion is believed t o result f rom involvement of olivocerebellar f ibers relat ed t o ocular movement t raveling in t he lat eral medulla or t o a concomit ant cerebellar lesion. 10. Diff icult y pursuing cont ralat eral moving t arget s as a result of involvement of t he vest ibular pat hw ays t o nuclei of ext raocular movement . Alt hough credit f or t he descript ion of t he lat eral medullary syndrome in 1895 is of t en given t o Adolph Wallenberg, as evidenced by t he t erm Wal l enberg's syndrome, t he Sw iss physician G aspard Vieusseux provided an account in 1810, report ing in det ail his ow n st roke t o t he Medical and Surgical Societ y of London. Clinical manif est at ions of t he lat eral medullary syndrome may vary depending on t he caudal-rost ral level of t he lesion. Dysphagia, hoarseness, and ipsilat eral f acial paresis are more common in pat ient s w it h lesions in t he rost ral medulla. G ait at axia, vert igo, and nyst agmus are more common in pat ient s w it h caudal medullary lesions. The ipsilat eral f acial paresis report ed in rost ral medullary lesions is at t ribut ed t o involvement of aberrant cort ico-bulbar f ibers in t he medulla or ext ension of t he medullary lesion t o t he pons. The sensory pat t ern in t he lat eral medullary syndrome has been show n t o vary w it h t he rost ral-caudal and lat eral-medial ext ent of t he lesion. The f ollow ing sensory pat t erns (Figure 6-3) have been described (Table 6-1): 1. Loss of pain and t hermal sense in t he ipsilat eral f ace and cont ralat eral body (classical pat t ern). This pat t ern has been report ed in 26 percent of pat ient s. The lesion is in t he post erolat eral part of t he caudal-middle medulla and involves t he spinot halamic t ract and spinal t rigeminal t ract and nucleus. 2. Loss of pain and t hermal sense in t he f ace bilat erally and in t he cont ralat eral body. This pat t ern occurs in 24 percent of pat ient s. The lesion is usually large in t he post erolat eral and vent romedial part s of t he middle-rost ral medulla. I n addit ion t o t he spinot halamic t ract and spinal t rigeminal t ract and
nucleus, t he t rigeminot halamic t ract (secondary t rigeminal) is involved. 3. Loss of pain and t hermal sense in t he cont ralat eral f ace and body. This pat t ern report edly occurs in 18 percent of pat ient s. The lesion spares most of t he post erolat eral part of t he medulla and select ively involves t he spinot halamic and t rigeminot halamic t ract s. 4. Loss of pain and t hermal sense in t he cont ralat eral body. The f ace is spared. This pat t ern occurs in 20 percent of pat ient s. The lesion is small and superf icial in t he lat eral medulla, involving only t he spinot halamic t ract . 5. Loss of pain and t hermal sense in t he ipsilat eral f ace. This pat t ern has been report ed t o occur in 8 percent of pat ient s. The lesion is usually small, more post eriorly localized, and involves only t he spinal t rigeminal t ract and nucleus. 6. No sensory loss. This pat t ern has been report ed in 4 percent of pat ient s. The lesion is small and spares all sensory st ruct ures. Dissociat ion of spinot halamic sensat ion (loss of t hermal sense and maint enance of pain sensat ion) in t he cont ralat eral body has been report ed in t he lat eral medullary syndrome. This pat t ern is at t ribut ed t o a small superf icial lesion t hat t ransect s t he lat eral spinot halamic t ract , t hus aff ect ing t hermal f ibers and sparing pain f ibers. Propriocept ive (vibrat ion, posit ion) def icit s have been report ed in lat eral medullary syndrome w hen t he lesion is in t he caudal medulla and involves t he post erior column nuclei.
Fi gure 6-3. Lat eral medullary syndrome pat t erns.
Tabl e 6-1. Lateral Medullary Syndrome Patt
Face
B
Pattern Ipsilateral Contralateral Bilateral Ipsilateral
1
X
2
X
3
X
4
`
5
X
Chronic f acial pain has been report ed in some pat ient s w it h lat eral medullary syndrome. This rare manif est at ion has been at t ribut ed t o a lesion t hat aff ect s t he rost ral spinal t rigeminal nucleus (pars oralis and int erpolaris) and t ract , and t hat spares t he caudal spinal t rigeminal nucleus (pars caudalis), w here most nocicept or neurons are locat ed. Deaff erent at ion of t he pars caudalis result s in abnormal neuronal act ivit y, w hich is t ransmit t ed t o t he t halamus and beyond, leading t o chronic neuropat hic pain. Besides Wallenberg's syndrome, occlusion of t he medial branch of PI CA can present w it h a pseudolabyrint hine syndrome charact erized by cerebellar and vest ibular signs (vert igo, dysmet ria, at axia, and axial lat eropulsion) t hat overshadow t he medullary signs. O cclusion of t he medial branch of t he post erior inf erior cerebellar art ery also may result in a silent inf arct t hat is det ect ed only at aut opsy. There are no clinical report s of occlusion of t he lat eral branch of t he post erior inf erior cerebellar art ery. Silent inf arct s have been report ed as a chance aut opsy f inding.
BABINSKI-NAGEOTTE SYNDROM E The Babinski-Nageot t e syndrome, also know n as medullary t egment al paralysis, is a combined lat eral and medial medullary syndrome. The lesion is
at t he pont omedullary junct ion. Manif est at ions include ipsilat eral Horner's syndrome (aut onomic sympat het ic f ibers); ipsilat eral w eakness of t he sof t palat e, pharynx, larynx (nucleus ambiguus), and t ongue (hypoglossal nucleus); loss of t ast e in t he post erior t hird of t he t ongue (nucleus solit arius); cerebellar at axia (rest if orm body) and nyst agmus (vest ibular nuclei); and cont ralat eral hemiparesis (pyramid) and hemianest hesia (medial lemniscus).
DORSAL M EDULLARY SYNDROM E The dorsal medullary syndrome is caused by occlusion of t he medial branch of t he post erior inf erior cerebellar art ery. Aff ect ed st ruct ures include t he vest ibular nuclei and t he rest if orm body (inf erior cerebellar peduncle). The associat ed neurologic signs include t he f ollow ing: 1. I psilat eral limb or gait at axia result ing f rom involvement of t he rest if orm body 2. Vert igo, vomit ing, and ipsilat eral gaze-evoked nyst agmus result ing f rom involvement of t he vest ibular nuclei
COLLET-SICARD SYNDROM E Described by t he French ot olaryngologist Frederick Collet in 1915 and t w o years lat er by t he French radiologist and neurologist Jean-At henase Sicard, t his syndrome consist s of loss of t ast e in t he post erior t hird of t he t ongue, paralysis of vocal cords and palat e, w eakness of st ernomast oid and t rapezius muscles, and hemianest hesia of palat e, t ongue, and pharyngeal w all, all ipsilat eral t o t he lesion. The syndrome is associat ed w it h unilat eral ext ra-axial injury of t he glossopharyngeal (cranial nerve I X), vagus (cranial nerve X), accessory (cranial nerve XI ), and hypoglossal (cranial nerve XI I ) nerves.
PSEUDOBULBAR PALSY Pseudobulbar palsy is a clinical syndrome caused by t he int errupt ion of t he cort icobulbar f ibers t o mot or nuclei of t he cranial nerves. Most cranial nerve nuclei in t he brain st em receive bilat eral input s f rom t he cerebral cort ex arising primarily f rom t he precent ral cort ex. The majorit y of t hese f ibers reach cranial nerve nuclei via t he ret icular f ormat ion (cort icoret iculobulbar syst em). Some cranial nerve nuclei, how ever, receive cort icobulbar f ibers direct ly. These nuclei include t he sensory and mot or t rigeminal nuclei, t he nucleus solit arius, t he f acial mot or nucleus, t he spinal accessory (supraspinal) nucleus, and t he hypoglossal nucleus. Bilat eral int errupt ion of t he indirect cort icoret iculobulbar or direct cort icobulbar f ibers in t he brain st em result s in t he syndrome of pseudobulbar palsy. The neurologic manif est at ions of t his syndrome include t he f ollow ing:
1. Weakness (upper mot or neuron variet y) of muscles supplied by t he corresponding cranial nerve nuclei 2. I nappropriat e out burst s of laught er and crying
TERM INOLOGY Anhidrosis (G reek an, n egative ; hi dros, s weat ) . Absence or def iciency of sw eat ing. Babinski's sign. An upper mot or neuron lesion sign charact erized by dorsif lexion of t he big t oe and f anning out of t he rest of t he t oes upon painf ul st imulat ion or st roking of t he sole. The sign w as described a s t he phenomenon of t he t oes by Josef -FrançoisFelix Babinski (1857 1 932), a French neurologist , in 1896. The phenomenon had previously been not ed by Hall and Remak. Babinski invest igat ed t he phenomenon in dept h in papers published bet w een 1896 and 1903. Clonus (G reek kl onos, t urmoil ) . Alt ernat e muscular cont ract ion of agonist and ant agonist muscle groups in rapid succession in response t o sudden st ret ching of t he muscle t endon. Usually seen in an upper mot or neuron lesion caused by t he loss of suprasegment al inhibit ion of t he local spinal ref lex arc. The t erm w as originally used by G reek physicians f or t he convulsing movement s of epilept ics. Dejerine, Joseph-Jules (1849 1 917). A French neurologist w ho described, among ot her syndromes, t he medial medullary syndrome. Dysmetria (G reek dys, d ifficult ; metron, m easure ) . I mproper measuring of dist ance, dist urbed cont rol of range of movement . A sign of cerebellar disease. Fibrillation. Local involunt ary cont ract ion of muscle t hat is invisible under t he skin and is recorded by elect romyography af t er t he placement of a recording needle in t he muscle. A sign of denervat ion. Hemianesthesia (G reek hemi , h alf ; an, n egative ; ai sthesi s, s ensation ) . Loss of f eeling or sensat ion in half t he body. Hemiparesis (G reek hemi , h alf ; paresi s, r elaxation ) . Weakness of one side of t he body. Hiccup. An involunt ary spasmodic cont ract ion of t he diaphragm t hat causes a beginning of inspirat ion, w hich is suddenly checked by closure of t he glot t is, causing a
charact erist ic sound. Also called singult us. Horner's syndrome. Drooping of t he eyelid (pt osis), const rict ion of t he pupil (miosis), ret ract ion of t he eyeball (enopht halmos), and loss of sw eat ing on t he f ace (anhidrosis) const it ut e a syndrome described by Johann Friedrich Horner, a Sw iss opht halmologist , in 1869. The syndrome is due t o int errupt ion of descending sympat het ic f ibers. Also know n as Bernard-Horner syndrome and oculosympat het ic palsy. The syndrome w as described in animals by François du Pet it in 1727. Claude Bernard in France in 1862 and E. S. Hare in G reat Brit ain in 1838 gave precise account s of t he syndrome bef ore Horner. Lateropulsion (Latin l atero, s ide ; pel l ere, t o drive ). An involunt ary t endency t o go t o one side. A charact erist ic sign of a cerebellar or lat eral medullary lesion. Nageotte, Jean (1866 1 948). A French neurologist w ho w it h Babinski described t he combined lat eral and medial medullary syndrome (medullary t egment al paralysis). Nucleus ambiguus (Latin, c hangeable, doubtful ). So called because it s boundaries are indist inct . Nystagmus (G reek nystagmos, d rowsiness, nodding ). Nodding or closing of t he eye in a sleepy person. The modern use of t he t erm ref ers t o involunt ary rhyt hmic oscillat ion of t he eyes. Wallenberg's (lateral medullary) syndrome. Also know n as t he lat eral bulbar syndrome and t he post erior inf erior cerebellar art ery syndrome. A syndrome consist ing of vert igo, vomit ing, hiccups, dysart hria, dysphagia, hoarseness, at axia, Horner's syndrome, and crossed sensory loss. The syndrome w as described in det ail by Adolph Wallenberg, a G erman neurologist , in 1895. An earlier account of t he syndrome w as provided by t he Sw iss physician G aspard Vieusseux in 1810.
SUGGESTED READINGS Amarenco P et al: I nf arct ion in t he t errit ory of t he medial branch of t he post erior inf erior cerebellar art ery. J Neurol Neurosurg Psychi atry 1990; 53: 731 7 35. Arai M: I solat ed t hermoanest hesia associat ed w it h a midlat eral medullary inf arct ion. Neurol ogy 2002; 58: 1695 1 696. Brazis PW: The localizat ion of lesions aff ect ing t he brainst em. I n Brazis PW et al (eds): Local i zati on i n Cl i ni cal Neurol ogy. Bost on, Lit t le, Brow n, 1985: 225 2 38.
Brochier T et al: Dorsolat eral inf arct ion of t he low er medulla: Clinical MRI st udy. Neurol ogy 1999; 52: 190 1 93. Fit zek S et al: Mechanisms and predict ors of chronic f acial pain in lat eral medullary inf arct ion. Ann Neurol 2001; 49: 493 5 00. Kim JS et al: Spect rum of lat eral medullary syndrome. Correlat ion bet w een clinical f indings and magnet ic resonance imaging in 33 subject s. Stroke 1994; 25: 1405 1 410. Kim JS et al: Pat t erns of sensory dysf unct ion in lat eral medullary inf arct ion. Clinical M RI correlat ion. Neurol ogy 1997; 49: 1557 1 563. Milandre L et al: Bilat eral inf arct ion of t he medullary pyramids. Neurol ogy 1990; 40: 556. Norrving B, Cronquist S: Lat eral medullary inf arct ion: Prognosis in an unselect ed series. Neurol ogy 1991; 41: 244 2 48. Pryse-Phillips W: Compani on to Cl i ni cal Neurol ogy. Bost on, Lit t le, Brow n, 1995. Romano J, Merrit t HH: The singular aff ect ion of G aspard Vieusseux: An early descript ion of t he lat eral medullary syndrome. Bul l Hi st Med 1941; 9: 72 7 9. Sacco RL et al: Wallenberg's lat eral medullary syndrome: Clinical-magnet ic resonance imaging correlat ions. Arch Neurol 1993; 50: 609 6 14. Troost BT: Signs and sympt oms of st roke syndromes of t he brain st em. I n Hoff erbert h B et al (eds): Vascul ar Brai n Stem Di seases. Basel, Karger, 1990: 112 1 24. Vieusseux G : An early descript ion of t he lat eral medullary syndrome. Bul l Hi st Med 1941; 9: 72 7 9. Vuilleumier P et al: I nf arct ion of t he low er brainst em: Clinical, aet iological and MRI -t opographical correlat ions. Brai n 1995; 118: 1013 1 025. Waepse W, Wichmann W: O culomot or dist urbances during visual vest ibular int eract ions in Wallenberg's lat eral medullary syndrome. Brai n 1990; 113: 821 8 46.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 7 - P ons
7 Pons
Gross Topography Ventral Surface Dorsal Surface Microscopic Structure Basis Pontis (Ventral) Tegmentum (Dorsal) Pontine Reticular Form ation Parabrachial and Pedunculopontine Nuclei Parabrachial Nucleus Pedunculopontine Nucleus Cranial Nerve Nuclei Cochleovestibular Nerve (Cranial Nerve VIII) Facial Nerve (Cranial Nerve VII) Abducens Nerve (Cranial Nerve VI) Trigeminal Nerve (Cranial Nerve V) KEY CONCEPTS The ventral surface of the pons shows the basilar artery in the pontine sulcus and four cranial nerves: the abducens at the medullary pontine junction, the facial and cochleovestibular in the cerebellopontine angle, and the trigeminal at the midpontine level. The dorsal surface of the pons forms the rostral
floor of the fourth ventricle, in which the facial colliculi are seen. Coronal sections of the pons reveal two components: a ventral and phylogenetically newer basis pontis and a dorsal and phylogenetically older tegmentum. The basis pontis contains pontine nuclei and the following nerve fiber bundles: corticospinal, corticobulbar, and corticopontocerebellar (the largest). The tegmentum contains the following nerve fiber bundles: medial lemniscus, trigeminal lemniscus, spinothalamic, trap-ezoid body, central tegmental tract, medial longitudinal fasciculus, tectospinal, and descending sympathetic fibers. The parabrachial nucleus plays an important role in autonomic regulation. The pedunculopontine nucleus plays roles in locomotion, motor learning, reward system, arousal, and saccadic eye movements. Cochlear nerve fibers terminate selectively on neurons in the dorsal or ventral cochlear nuclei. Reciprocal feedback circuits exist throughout the extent of the auditory pathways. Reflex eye and neck movements to sound are carried out via two pathways: from the inferior colliculus to the superior colliculus and then via the tectobulbar and tectospinal tracts to the nuclei of eye and neck muscles and from the superior olive to the abducens nucleus and then via the medial longitudinal fasciculus to the nuclei of extraocular movements. Vestibular nerve fibers terminate selectively on four ves-tibular nuclei: medial (Schwalbe's principal),
inferior (spinal), lateral (Deiters'), and superior (Bechterew's). Some fibers project directly to the cerebellum. The output of vestibular nuclei is to the following areas: spinal cord, cerebellum, thalamus, nuclei of extraocular movement, vestibular cortex, and vestibular end organ. Vestibular projections to the nuclei of extraocular movement play important roles in controlling conjugate eye movements. The sensory facial nuclei are the spinal trigeminal nucleus (exteroceptive sensation) and the nucleus solitarius (taste). The motor facial nuclei are the facial motor nucleus (somatic motor) and the superior salivatory nucleus (visceral motor). Cortical input to the facial motor nucleus is bilateral to the upper face motor neurons and only contralateral to the lower face motor neurons. Characteristic conglomerate clinical signs occur in lesions of the facial nerve at or distal to the stylomastoid foramen, distal to the geniculate ganglion, and proximal to the geniculate ganglion. Lesions of the abducens nerve outside the neuraxis result in ipsilateral lateral rectus paralysis. Lesions of the abducens nucleus result in paralysis of ipsilateral lateral gaze. The motor nucleus of the trigeminal nerve supplies the muscles of mastication, the tensor tympani, the tensor palati, the mylohyoideus, and the anterior belly of the digastric. The sensory nuclei of the trigeminal nerve are the
spinal (pain, temperature, touch), principal (main) sensory (touch), and mesencephalic (proprioception). Dorsal and ventral trigeminothalamic tracts link the main sensory and spinal trigeminal nuclei, respectively, with the thalamus. Blood supply to the pons is provided by the basilar artery via three branches: paramedian, short circumferential, and long circumferential.
GROSS TOPOGRAPHY The pons is t he part of t he brain st em t hat lies bet w een t he medulla oblongat a caudally and t he midbrain rost rally. The cerebral peduncles and t he superior pont ine sulcus mark it s rost ral boundary, t he middle cerebellar peduncles (brachium pont is) mark it s lat eral boundary, and t he inf erior pont ine sulcus marks it s caudal boundary. The dorsal surf ace of t he pons is covered by t he cerebellum.
Ventral Surface The vent ral surf ace (Figure 7-1) of t he pons f orms a bulge know n as t he pont ine prot uberance. I n t he middle of t his prot uberance is t he pont ine sulcus, w hich cont ains t he basilar art ery. Several cranial nerves leave t he vent ral surf ace of t he pons. The abducens nerve (cranial nerve VI ) emerges f rom t he boundary bet w een t he pons and t he medulla oblongat a. I n t he angle bet w een t he caudal pons, t he rost ral medulla, and t he cerebellum (t he cerebellopont ine angle), t he f acial (cranial nerve VI I ) and cochleovest ibular (cranial nerve VI I I ) nerves appear. From t he lat eral and rost ral part s of t he pons emerge t he t w o component s of t he t rigeminal nerve (cranial nerve V): t he larger sensory port ion (port io major) and t he smaller mot or port ion (port io minor). The crow ding of t he f acial and cochleovest ibular nerves in t he cerebellopont ine angle explains t he early involvement of t hese t w o nerves in t umors (acoust ic neuromas) t hat arise in t his angle.
Fi gure 7-1. Schemat ic diagram of t he vent ral surf ace of t he brain st em show ing t he major st ruct ures on t he vent ral surf ace of t he pons.
Dorsal Surface The dorsal surf ace (see Figure 5-3) of t he pons f orms t he rost ral port ion of t he f loor of t he f ourt h vent ricle. This part of t he f loor f eat ures t he f acial colliculi, one on each side of t he midline sulcus (median sulcus). These colliculi represent t he surf ace landmarks of t he genu of t he f acial nerve and t he underlying nucleus of t he abducens nerve.
M ICROSCOPIC STRUCTURE Coronal sect ions of t he pons reveal a basic organizat ional pat t ern made of t w o part s: a vent ral basis pont is and a dorsal t egment um.
Basis Pontis (Ventral) The basis pont is (Figure 7-2) corresponds t o t he pont ine prot uberance described in G ross Topography, earlier. I t cont ains t he pont ine nuclei and mult idirect ional nerve f iber bundles. The mult idirect ional nerve f iber bundles in t he basis pont is belong t o t hree f iber syst ems. 1. Cort icospinal f ibers f rom t he cerebral cort ex t o t he spinal cord pass t hrough t he basis pont is and cont inue caudally as t he pyramids of t he medulla oblongat a.
2. Cort icobulbar f ibers f rom t he cerebral cort ex t o t he cranial nerve nuclei of t he brain st em. Some of t hese f ibers project direct ly on t he nuclei of cranial nerves (cort icobulbar); t he majorit y, how ever, synapse on an int ermediat e ret icular nucleus bef ore reaching t he cranial nerve nucleus (cort icoret iculobulbar). Cort icobulbar and cort icoret iculobulbar f ibers usually arise f rom bot h cerebral hemispheres. 3. Cort icopont ocerebellar f ibers const it ut e t he largest group of f ibers in t he basis pont is. This f iber syst em originat es f rom w ide areas of t he cerebral cort ex, project s on ipsilat eral pont ine nuclei, and crosses t he midline on it s w ay t o t he cerebellum via t he middle cerebellar peduncle. I t is est imat ed t hat in humans t his f iber syst em cont ains approximat ely 19 million f ibers on each side. The number of pont ine neurons in humans is est imat ed t o be approximat ely 23 million in each half of t he pons. Thus, t he rat io of cort icopont ine f ibers t o pont ine neurons is approximat ely 1: 1. Alt hough t he cort icopont ine project ion is believed t o arise f rom w ide areas of t he cerebral cort ex, it arises principally f rom t he prerolandic and post rolandic sensorimot or cort ices w it h minor t o moderat e cont ribut ions f rom t he pariet al and t emporal associat ion cort ices, t he premot or and pref ront al associat ion cort ices, and t he cingulat e gyrus. The f act t hat cort ical input t o t he pont ine nuclei arises chief ly f rom primary cort ical areas suggest s t hat t he cort icopont ocerebellar f iber syst em is concerned w it h t he rapid correct ion of movement s. The f unct ional signif icance of t he cingulopont ine f iber connect ion is not know n, but it may represent t he anat omic subst rat e f or t he eff ect of emot ion on mot or f unct ion. The input f rom t he associat ion cort ices suggest s a role f or t his f iber syst em in behavioral and cognit ive processes. A cort ical region usually project s t o more t han one cell column of t he pont ine nuclei, and some pont ine columns receive project ions f rom more t han one cort ical region. Like t he cort icoolivocerebellar syst em, t he cort icopont ocerebellar syst em is somat ot opically organized. Thus, t he prerolandic cort ex (primary mot or cort ex) project s t o medial pont ine nuclei, t he post rolandic cort ex (primary somat osensory cort ex) t o lat eral pont ine nuclei, t he arm area of t he sensorimot or cort ex t o dorsal pont ine nuclei, and t he leg area t o vent ral pont ine nuclei. The project ion f rom t he cingulat e gyrus also has been show n t o be somat ot opically organized, w it h t he ant erior cingulat e cort ex project ing t o t he medial pont ine nuclei and t he post erior cingulat e cort ex project ing t o t he lat eral pont ine nuclei. The pont ocerebellar project ion is primarily crossed; how ever, it has been est imat ed t hat 30 percent of t he pont ine project ion t o t he cerebellar vermis and 10 percent of t he project ion t o t he cerebellar hemisphere are ipsilat eral. The densit y of project ion t o t he cerebellar hemispheres is t hree t imes t hat t o t he vermis. Like t he cort icopont ine project ion, t he pont ocerebellar project ion is somat ot opically organized, w it h t he caudal half of t he pons project ing t o t he ant erior lobe of t he cerebellum and t he rost ral half project ing t o t he post erior
lobe. The basilar port ion of t he pons is t he phylogenet ically new er part and is present only in animals w it h w ell-developed cerebellar hemispheres.
Tegmentum (Dorsal) The t egment um is t he phylogenet ically older part of t he pons and is composed largely of t he ret icular f ormat ion. Lesions t hat dest roy more t han 25 percent of t he t egment um may result in loss of consciousness. I n t he basal part of t he t egment um, t he medial lemniscus (w hich maint ains a vert ical orient at ion on each side of t he midline in t he medulla) becomes f lat t ened in a mediolat eral direct ion (Figure 7-3). Fibers originat ing f rom t he cuneat e nucleus are locat ed medially; gracile f ibers are lat erally placed. Lat eral t o t he medial lemniscus lies t he t rigeminal t ract , w hich conveys sensat ions of pain, t emperat ure, t ouch, and propriocept ion f rom t he cont ralat eral f ace. The spinot halamic t ract is lat eral t o t he t rigeminal t ract and carries pain and t emperat ure sensat ions f rom t he cont ralat eral half of t he body. Thus, in t he basal part of t he t egment um lies t he specif ic sensory lemniscal syst em, w hich includes t he medial lemniscus, t rigeminal lemniscus, and spinot ha-lamic t ract .
Fi gure 7-2. Schemat ic diagram of t he pons show ing it s major divisions int o t egment um and basis pont is, and t ypes of f iber bundles t raversing t he basis pont is.
I nt ermingled w it h t he ascending f ibers of t he lemniscal syst em are t ransversely orient ed f ibers of t he t rapezoid body. These f ibers arise f rom t he cochlear nuclei, course t hrough t he t egment um, and gat her in t he lat eral port ion of t he pons t o f orm t he lat eral lemniscus. This f iber syst em w ill be discussed lat er in connect ion w it h t he cochlear division of t he cochleovest ibular nerve (cranial nerve VI I I ). Dorsal t o t he medial lemniscus is t he cent ral t egment al t ract , w hich originat es in t he basal ganglia and midbrain and project s on t he inf erior olive. I t shif t s posit ion in t he t egment um of t he pons and lies dorsal t o t he lat eral part of t he medial lemniscus in t he caudal pons (Figure 7-3). The medial longit udinal f asciculus and t he t ect ospinal t ract ret ain t he same dorsal and paramedian posit ions t hey occupied in t he medulla just beneat h t he f loor of t he f ourt h vent ricle (Figure 7-3). O t her t ract s coursing t hrough t he t egment um of t he pons include t he rubrospinal t ract medial t o t he spinal t rigeminal nucleus and t he vent ral spinocerebellar t ract medial t o t he rest if orm body. The vent ral spinocerebellar t ract ent ers t he superior cerebellar peduncle t o reach t he cerebellum. The t egment um of t he pons also cont ains descending sympat het ic f ibers f rom t he hypot halamus; t hese f ibers are locat ed in t he lat eral part of t he t egment um. I nt errupt ion of t hese f ibers produces Horner's syndrome (Chapt er 5). Cort icobulbar f ibers and cort icoret iculo-bulbar f ibers on t heir w ay f rom t he basis pont is t o cranial nerve nuclei also pass t hrough t he t egment um (Figure 7-2). I n t he rost ral pons, lying dorsally in t he t egment um, is t he nucleus locus ceruleus (group A-6 of primat es). I t cont ains on each side an average of 16, 000 t o 18, 000 melanin-cont aining neurons t hat are involved in Parkinson's disease, Alzheimer's disease, and Dow n syndrome. I t is t he major source of t he w idespread noradrenergic innervat ion t o most cent ral nervous syst em regions. This nucleus is subdivided int o f our subnuclei: cent ral (largest ), ant erior (rost ral end), t he nucleus subceruleus (caudal and vent ral), and a small post erior and dorsal nucleus. The nucleus spans a rost ral-caudal dist ance of 11 t o 14 mm. Rost rally, t he nucleus begins at t he level of t he inf erior colliculus (midbrain), w here it is sit uat ed vent ral and lat eral t o t he cerebral aqueduct (aqueduct of Sylvius) in t he periaqueduct al gray mat t er of t he midbrain. Caudally, at t he junct ion of t he cerebral aqueduct and t he f ourt h vent ricle, t he nucleus is displaced lat erally. The number of cells in t he nucleus increases f rom rost ral t o caudal. Tw o project ion bundles emanat e f rom t he nucleus: a dorsal ascending bundle t o t he hypot halamus, hippocampus, neocort ex, and cerebellum and a descending bundle t o t he spinal cord. Cell loss in t he nucleus is generalized in Parkinson's disease, w hereas it is limit ed t o t he rost ral port ion of t he nucleus (w hich project s mainly t o t he cerebral cort ex) in Alzheimer's disease and Dow n syndrome.
Fi gure 7-3. Schemat ic diagram of t he pons show ing t he major t ract s t raversing t he t egment um.
PONTINE RETICULAR FORM ATION The pont ine ret icular f ormat ion const it ut es t he major part of t he t egment al port ion of t he pons and is a rost ral cont inuat ion of t he medullary ret icular f ormat ion. The organizat ion and connect ions of t he pont ine ret icular f ormat ion are discussed in Chapt er 32. Lesions involving t he pont ine ret icular nuclei in t he t egment um and cort icospinal f ibers in t he basis pont is are associat ed w it h t he syndrome of anosognosia f or hemiplegia in w hich t he pat ient s are unaw are of t heir mot or def icit . A similar syndrome occurs in lesions of t he nondominant pariet al lobe.
PARABRACHIAL AND PEDUNCULOPONTINE NUCLEI Parabrachial Nucleus At t he level of t he ist hmus, in t he dorsolat eral pons, bet w een t he lat eral edge of t he brachium conjunct ivum (superior cerebellar peduncle) and t he lat eral lemniscus, is t he parabrachial nucleus, a synapt ic st at ion f or gust at ory (t ast e) pat hw ays. I n humans t he parabrachial nucleus has been show n t o have neuromelanin-cont aining cat echolamine neurons. The pigment ed neurons in t he nucleus are rat her small (compared w it h neuromelanin-cont aining neurons in t he locus ceruleus or t he subst ant ia nigra), and t heir granules have a very delicat e appearance; t his may explain w hy pigment ed neurons in t his nucleus have been overlooked in report s on t he dist ribut ion of cat echolamine neurons in t he human brain. I n humans t he parabrachial nucleus is subdivided int o lat eral and medial segment s. Pigment ed neurons are
more abundant in t he lat eral segment . Pigment ed neurons in t he parabrachial nucleus undergo a signif icant reduct ion in number in pat ient s w it h Parkinson's disease. The parabrachial nucleus has f iber connect ions w it h t he hypot halamus, amygdala, st ria t erminalis, and brain st em nuclei, including t he nucleus of t he solit ary t ract and t he dorsal raphe nucleus. I t is believed t hat t he parabrachial nucleus plays an import ant role in aut onomic regulat ion, and it s involvement in parkinsonism may explain t he aut onomic dist urbances t hat occur in t hat disease. St udies in animals and man suggest t hat t he parabrachial nucleus is a relay st at ion in t he brainst em pat hw ay f or t ast e.
Pedunculopontine Nucleus Bet w een t he spinal lemniscus, brachium conjunct ivum, and medial lemniscus is t he parabrachial pedunculopont ine nucleus. The pedunculopont ine nucleus is t he brain st em cont rol cent er f or somat ic mot or and cognit ive behaviors, including locomot ion, mot or learning, and t he rew ard syst em. Accumulat ed evidence point s t o a role f or t he nucleus in t he sleep w ake arousal syst em and t he muscle coordinat ion mechanism as w ell as in oculomot or f unct ion including init iat ion of saccadic eye movement s. The nucleus cont ains t w o populat ions of neurons, cholinergic and glut amat ergic. The complex and w idely dist ribut ed eff erent s of t he cholinergic populat ion allow t he nucleus t o part icipat e in a variet y of f unct ions. The glut amat ergic populat ion project s caudally t o t he pont ine and medullary ret icular f ormat ion responsible f or locomot ion. I t receives direct excit at ory cort ical input f rom mult iple mot or-relat ed areas of t he f ront al lobe and an inhibit ory input f rom t he basal ganglia (int ernal segment of globus pallidus and subst ant ia nigra pars ret iculat a). The nucleus sends direct excit at ory out put t o t he basal ganglia (mainly t o subt ha-lamic nucleus and subst ant ia nigra pars compact a, w it h a smaller project ion t o bot h segment s of globus pallidus) and t o t he int ralaminar nuclei of t halamus. The nucleus sends indirect out put t o t he spinal cord (via t he gigant ocellular ret icular nucleus of t he medulla oblongat a) (Figure 7-4). The nucleus is believed t o possibly have t w o f unct ional roles: (1) relay bet w een t he cerebral cort ex and spinal cord serving as cont rol cent er f or int erlimb coordinat ion in locomot ion and (2) modulat ory cent er t hat receives excit at ory drive f rom t he cerebral cort ex and governs act ivit y of dopaminergic neurons in t he subst ant ia nigra pars compact a, t hus inf luencing mot or learning and t he rew ard syst em as w ell as volunt ary mot or cont rol.
CRANIAL NERVE NUCLEI Cochleovestibular Nerve (Cranial Nerve VIII) The cochleovest ibular nerve has t w o divisions: cochlear and vest ibular. The t w o divisions t ravel t oget her f rom t he peripheral end organs in t he inner ear t o t he pons, w here t hey separat e; each t hen est ablishes it s ow n dist inct connect ions.
A. COCHLEAR DIVISION The cochlear division (Figure 7-5) of t he cochleovest ibular nerve is t he larger of t he t w o divisions. Nerve f ibers in t he cochlear nerve are cent ral processes of bipolar neurons in t he spiral ganglion locat ed in t he modiolus of t he inner ear. The peripheral processes of t hese bipolar neurons are linked t o t he hair cells of t he audit ory end organ in t he organ of Cort i. As f ibers of t he cochlear nerve reach t he caudal part of t he pons, t hey ent er it s lat eral surf ace caudal and lat eral t o t he vest ibular division and project on t he dorsal and vent ral cochlear nuclei. The dorsal cochlear nucleus, sit uat ed on t he dorsolat eral surf ace of t he rest if orm body, receives f ibers originat ing in t he basal t urns of t he cochlea (mediat ing high-f requency sound). The vent ral cochlear nucleus, sit uat ed on t he vent rolat eral aspect of t he rest if orm body, receives f ibers f rom apical t urns of t he cochlea (mediat ing low -f requency sound). The t ot al number of neurons in t he cochlear nuclei f ar exceeds t he t ot al number of cochlear nerve f ibers, and so each f iber is believed t o project on several neurons.
Fi gure 7-4. Aff erent and eff erent connect ions of t he pedunculopont ine nucleus. PPN, pedunculopont ine nucleus; G Pi, int ernal segment of globus pallidus; SNr, subst ant ia nigra pars ret iculat a; STN, subt halamic nucleus; SNc, subst ant ia nigra pars compact a; G Pe, ext ernal segment of globus pallidus.
Second-order neurons f rom t he cochlear nuclei course t hrough t he t egment um of t he pons t o f orm t he t hree acoust ic st riae: dorsal, vent ral, and int ermediat e. The dorsal acoust ic st ria is f ormed by axons of neurons in t he dorsal cochlear
nucleus, t he vent ral acoust ic st ria (t rapezoid body) is f ormed by axons f rom t he inf erior cochlear nucleus, and t he int ermediat e acoust ic st ria originat es in t he inf erior and superior cochlear nuclei. The vent ral acoust ic st ria (t he t rapezoid body) is t he largest of t he t hree st riae. Fibers in t his st ria project on neurons in t he superior olivary complex and t he nucleus of t he t rapezoid body. The superior olivary nuclear complex is embedded in t he t rapezoid body. I t includes t he lat eral and medial superior olivary nuclei. The olivary nuclei are elongat ed cell masses of w hich t he medial superior olivary nucleus is much bet t er developed in humans, w hereas t he lat eral superior olivary nucleus and t he nucleus of t he t rapezoid body are poorly developed. The nucleus of t he t rapezoid body consist s of small cells sit uat ed at t he caudal half of t he superior olivary nucleus. The t w o superior olivary nuclei and t he nucleus of t he t rapezoid body are surrounded by a zone of cells of varying sizes and shapes know n collect ively as t he periolivary nuclei. I t w as originally believed t hat t he periolivary nuclei are exclusively involved in descending audit ory pat hw ays, but it has been est ablished t hat t hese cells are involved in descending as w ell as ascending audit ory project ions. Funct ions of t he superior olivary complex include: (1) processing of cochlear signals via t he ascending audit ory pat hw ay, (2) det ect ion of int eraural sound int ensit y, and (3) providing f eedback cont rol of cochlear mechanism t hrough t he olivocochlear bundle.
Fi gure 7-5. Schemat ic diagram of t he audit ory pat hw ays.
Aff erent s t o t he superior olivary complex f rom nonaudit ory areas have been described f rom serot oninergic and noradrenergic brain st em nuclei. Compared t o t he audit ory aff erent s, t he serot oninergic and noradrenergic aff erent s are sparse. An input f rom t he t rigeminal ganglion t o t he superior olivary nuclear complex has also been described. Third-order neurons f rom t he superior olivary complex, t he nucleus of t he t rapezoid body, and t he periolivary nuclei cont ribut e mainly t o t he cont ralat eral lat eral lemniscus, w it h some project ion t o t he homolat eral lat eral lemniscus. The lat eral lemniscus also receives f ibers f rom t he dorsal and int ermediat e acoust ic st riae. Fibers in t he lat eral lemniscus project on t he nucleus of t he lat eral lemniscus. The nucleus of t he lat eral lemniscus is an elongat ed st rand of cells embedded w it hin t he lat eral lemniscus at t he ist hmus level. Tw o subnuclei are recognized: dorsal and vent ral. Subsequent st at ions in t he audit ory syst em include synapses in t he inf erior colliculus and t he medial geniculat e body. The inf erior colliculus is t he most import ant relay st at ion in t he ascending and descending audit ory project ions. I t consist s of a large compact cent ral nucleus and a more diff use lat erally sit uat ed zone. The majorit y of ascending audit ory f ibers t o t he inf erior colliculus t erminat e in t he cent ral nucleus. The lat eral zone
of t he inf erior colliculus receives aff erent s f rom t he cent ral nucleus as w ell as f rom t he nucleus of t he lat eral lemniscus. There is evidence t hat t he ipsilat eral medial superior olivary nucleus and t he cont ralat eral lat eral superior olivary nucleus send excit at ory project ions t o t he cent ral nucleus of t he inf erior colliculus, w hereas t he ipsilat eral lat eral superior olivary nucleus sends inhibit ory project ions t o t he cent ral nucleus. O nly a limit ed number of f ibers belonging t o t he ascending audit ory project ion bypass t he inf erior colliculus t o reach t he medial geniculat e body direct ly. These f ibers usually arise f rom t he cochlear nuclei and t he nucleus of t he lat eral lemniscus. The t w o inf erior colliculi are connect ed t o each ot her by t he commissure of t he inf erior colliculus and t o t he medial geniculat e nucleus by t he brachium of t he inf erior colliculus (inf erior quadrigeminal brachium). The f inal st at ion is t he primary audit ory cort ex (t ransverse Heschl's gyri) in t he t emporal lobe. The audit ory project ion (audit ory radiat ion) f rom t he medial geniculat e body t o t he primary audit ory cort ex t raverses t he sublent icular port ion of t he int ernal capsule. From t he level of t he inf erior colliculus onw ard t o t he primary audit ory cort ex, t he audit ory project ion is subdivided int o c ore and b elt project ions. The core project ion t erminat es in t he primary audit ory cort ex; t he belt project ion t erminat es in cort ical areas surrounding t he primary audit ory cort ex. The core and belt project ions also have dist inct zones of origin w it hin t he inf erior colliculus, w here t he cent ral nucleus is relat ed t o t he core project ion, w hereas t he lat eral zone is relat ed t o t he belt project ion. Tonot opic localizat ion exist s t hroughout t he audit ory syst em. I n addit ion t o t his c lassic audit ory pat hw ay, evidence suggest s t he exist ence of anot her mult isynapt ic audit ory pat hw ay t hrough t he ret icular f ormat ion. The evidence f or a ret icular pat hw ay is based on several experiment al observat ions. 1. Ret icular t halamic neurons project t o t he medial geniculat e nucleus. 2. The nucleus of t he lat eral lemniscus and t he inf erior colliculus are connect ed w it h t he mesencephalic ret icular f ormat ion. 3. Audit ory-responding cells have been ident if ied in t he mesencephalic ret icular f ormat ion and t he pret ect um. 4. An increase in 2-deoxy-D-glucose met abolism t hroughout t he audit ory pat hw ays has been obt ained by means of elect ric st imulat ion of t he mesencephalic ret icular f ormat ion. Several f iber bundles of t he audit ory syst em decussat e at various levels: 1. I n t he pont ine t egment um, t he superior, middle, and inf erior acoust ic st riae decussat e and link t he right and lef t cochlear nuclear complexes.
2. The olivocochlear bundle (eff erent bundle of Rasmussen), w hich w ill be discussed below, also decussat es in t he pont ine t egment um. 3. The nuclei of t he lat eral lemniscus are connect ed via Probst 's commissure, w hich passes t hrough t he brachium conjunct ivum and t he most rost ral part of t he pont ine t egment um. Probst 's commissure also carries f ibers f rom t he nuclei of t he lat eral lemniscus t o t he cont ralat eral inf erior colliculus. 4. At t he midbrain level, t he t w o inf erior colliculi communicat e via t he commissure of t he inf erior colliculus. This commissure also carries f ibers passing f rom t he inf erior colliculus t o t he medial geniculat e body. The audit ory syst em is charact erized by t he presence of several inhibit ory f eedback mechanisms t hat consist of descending pat hw ays linking t he diff erent cort ical and subcort ical audit ory nuclei. Thus, a syst em of descending f ibers links t he primary audit ory cort ex, t he medial geniculat e body, t he inf erior colliculus, t he nucleus of t he lat eral lemniscus, t he superior olivary nuclear complex, and t he cochlear nuclei. How ever, t he most import ant f eedback mechanism is served by t he olivocochlear bundle, also know n as t he eff erent bundle of Rasmussen (Figure 7-6). This bundle of f ibers arises f rom cholinergic neurons of t he periolivary nuclei and project s on hair cells in t he organ of Cort i. I t has bot h crossed and uncrossed component s w hich diff erent ially innervat e t he t w o t ypes of hair cells. The crossed bundle originat es f rom large cells in t he vent romedial part of t he periolivary area, courses dorsally in t he pont ine t egment um, bypasses t he nucleus of t he abducens nerve, and crosses t o t he cont ralat eral side t o t erminat e by large synapt ic t erminals abut t ing t he basal part s of t he out er hair cells. The uncrossed component is smaller and originat es f rom small neurons in t he vicinit y of t he lat eral superior olivary nucleus. I t t erminat es by en passant synapses on primary aff erent cochlear f ibers just beneat h t he inner hair cells. Bot h component s init ially join t he vest ibular division of t he cochleovest ibular nerve (cranial nerve VI I I ), but at t he vest ibulocochlear anast omosis, t hey leave it and t ravel w it h t he cochlear division as f ar as t he hair cells of t he organ of Cort i. St imulat ion of t he olivocochlear bundle suppresses t he recept ivit y of t he organ of Cort i, and t hus act ivit y in t he audit ory nerve. A variet y of f unct ions have been proposed f or t he olivocochlear bundle. These include: (1) a prot ect ive eff ect on t he cochlea against loud sound, (2) f requency select ivit y, (3) select ive audit ory at t ent ion t hat permit s det ect ion of new signals and underst anding of speech in a noisy background.
Fi gure 7-6. Schemat ic diagram show ing t he origins and course of t he olivocochlear bundle.
The hair cells of t he organ of Cort i t ransduce mechanical energy int o nerve impulses and exhibit a graded generat or pot ent ial. Spike pot ent ials appear in t he cochlear nerve. Cochlear nerve f ibers respond t o bot h displacement and velocit y of t he basilar membrane of t he organ of Cort i. Displacement of t he basilar membrane t ow ard t he scala vest ibuli produces inhibit ion, w hereas displacement t ow ard t he scala t ympani produces excit at ion. A single f iber in t he cochlear nerve may respond t o bot h displacement and velocit y. Ref lex movement s of t he eyes and neck t ow ard a sound source are mediat ed via t w o ref lex pat hw ays. The f irst runs f rom t he inf erior colliculus t o t he superior colliculus and f rom t here via t ect obulbar and t ect ospinal pat hw ays t o t he nuclei of eye muscles and t he cervical musculat ure. The ot her pat hw ay runs f rom t he superior olive t o t he abducens nerve (cranial nerve VI ) nucleus and t hen via t he medial longit udinal f asciculus t o t he nuclei of cranial nerves of ext raocular muscles. O t her ref lex pat hw ays include t hose bet w een cochlear nuclei and t he ascending ret icular act ivat ing syst em, w hich give rise t o t he audit ory-evoked st art le response, and t hose bet w een t he vent ral cochlear nuclei and t he mot or nuclei of t he t rigeminal and f acial nerves. The lat t er pat hw ays const it ut e ref lex arcs t hat link t he organ of Cort i w it h t he t ensor t ympani and st apedius muscles. Thus, in response t o sounds of high int ensit y, t hese muscles ref lexly cont ract and dampen t he vibrat ion of t he ear ossicles.
B. VESTIBULAR DIVISION
Vest ibular nerve f ibers are cent ral processes of bipolar cells in Scarpa's ganglion. Peripheral processes of t hese bipolar cells are dist ribut ed t o t he vest ibular end organ in t he t hree semicircular canals, t he ut ricle, and saccule. The semicircular canals are concerned w it h angular accelerat ion (det ect ing a simult aneous increase in velocit y and direct ion w hen one is rot at ing or t urning); t he ut ricle and saccule are concerned w it h linear accelerat ion (det ect ing a change in velocit y w it hout a change in direct ion, t he gravit at ional eff ect ). The superior port ion of Scarpa's ganglion receives f ibers f rom t he ant erior and horizont al semicircular canals, t he ut ricle and saccule. The inf erior port ion of t he ganglion receives f ibers f rom t he post erior semicircular canal and t he saccule (Figure 7-7). The vest ibular nerve accompanies t he cochlear nerve f rom t he int ernal audit ory meat us t o t he pons, w here it ent ers t he lat eral surf ace at t he pont omedullary junct ion medial t o t he cochlear nerve. Wit hin t he pons, vest ibular nerve f ibers course in t he t egment um bet w een t he rest if orm body and t he spinal t rigeminal complex. The major port ion of t hese f ibers project s on t he f our vest ibular nuclei; a smaller port ion goes direct ly t o t he cerebellum via t he juxt arest if orm body. I n t he cerebellum, t hese f ibers t erminat e as mossy f ibers on neurons in t he f locculonodular lobe and t he uvula. There are f our vest ibular nuclei: medial, inf erior, lat eral, and superior. The medial nucleus (principal nucleus [ Schw albe's nucleus] ) appears in t he medulla oblongat a at t he rost ral end of t he inf erior olive and ext ends t o t he caudal part of t he pons. The inf erior nucleus (spinal nucleus) lies bet w een t he medial nucleus and t he rest if orm body. The inf erior nucleus, w hich is charact erized in hist ologic sect ions by myelinat ed f ibers t hat t raverse it f rom t he vest ibular nerve, ext ends f rom t he rost ral ext remit y of t he gracile nucleus t o t he pont omedullary junct ion. The lat eral nucleus (Deit ers' nucleus), w hich is charact erized in hist ologic sect ions by t he presence of large mult ipolar neurons, ext ends f rom t he pont omedullary junct ion t o t he level of t he abducens nerve (cranial nerve VI ) nucleus. The superior nucleus (Becht erew 's nucleus) is smaller t han t he ot her nuclei and lies dorsal and medial t o t he medial and lat eral nuclei. The number of neurons in t he vest ibular nuclei f ar exceeds t he number of vest ibular nerve f ibers. Vest ibular nerve f ibers project only t o limit ed regions w it hin each vest ibular nucleus. I n addit ion t o input f rom t he vest ibular nerve, t he vest ibular nuclei receive f ibers f rom: (1) t he spinal cord, (2) t he cerebellum, and (3) t he vest ibular cort ex (Figure 7-8). The out put f rom t he vest ibular nuclei is t o: (1) t he spinal cord, (2) t he cerebellum, (3) t he t halamus, (4) t he nuclei of t he ext raocular muscles, (5) t he vest ibular cort ex, and (6) t he vest ibular end organ.
Fi gure 7-7. Schemat ic diagram show ing t he origin and t erminat ion of t he vest ibular nerve.
The vest ibular project ion t o t he spinal cord (Figure 7-9) is t hrough t he lat eral vest ibulospinal t ract (f rom t he lat eral vest ibular nucleus) and t he medial vest ibulospinal t ract (f rom t he medial vest ibular nucleus) via t he descending component of t he medial longit udinal f asciculus. The lat eral vest ibulospinal t ract f acilit at es ext ensor mot or neurons, w hereas t he medial t ract f acilit at es f lexor mot or neurons. The medial vest ibulospinal t ract sends f ibers t o t he dorsal mot or nucleus of t he vagus. This explains t he nausea, sw eat ing, and vomit ing t hat occur af t er st imulat ion of t he vest ibular end organ. Project ions f rom t he vest ibular nuclei t o t he cerebellum (Figure 7-9) t ravel via t he juxt arest if orm body along w it h t he primary vest ibulocerebellar f ibers. These project ions arise f rom t he superior, inf erior, and medial vest ibular nuclei and t erminat e mainly ipsilat erally (but also bilat erally) on neurons in t he f locculonodular lobe, t he uvula, and t he nucleus f ast igii. Cerebellovest ibular connect ions are much more abundant t han are vest ibulocerebellar connect ions. Vest ibulot halamic project ions arise f rom t he medial, lat eral, and superior vest ibular nuclei and project bilat erally on several t halamic nuclei (vent ral post erolat eral, cent rolat eral, lat eral geniculat e, and post erior group). They reach t heir dest inat ions via several pat hw ays (lat eral lemniscus, brachium conjunct ivum, ret icular f ormat ion), w it h a f ew t raveling via t he medial longit udinal f asciculus. Vest ibular project ions t o t he nuclei of ext raocular muscles t ravel via t he ascending component of t he medial longit udinal f asciculus. They arise f rom all
f our vest ibular nuclei and project on nuclei of t he oculomot or (cranial nerve I I I ), t rochlear (cranial nerve I V), and abducens (cranial nerve VI ) nerves. The crossed component of t his syst em exert s an excit at ory eff ect , w hereas t he uncrossed component exert s an inhibit ory eff ect , on nuclei of ext raocular movement . A project ion f rom t he vest ibular nuclei t o t he primary vest ibular cort ex in t he t emporal lobe probably reaches t he vest ibular cort ex via relays in t he t halamus. A project ion t o t he vest ibular end organ has been described. Axons t ravel w it h t he vest ibular nerve and t erminat e in a bilat eral f ashion on hair cells in crist ae of t he semicircular canal and t he maculae of t he ut ricle and saccule. I n cont rast t o t he olivocochlear bundle, w hich exert s an inhibit ory eff ect on t he cochlear end organ, t his bundle is excit at ory t o t he vest ibular end organ.
Fi gure 7-8. Schemat ic diagram show ing t he major input s t o t he vest ibular nuclei.
The vest ibular out put t o t he nuclei of ext raocular muscles plays an import ant role in t he cont rol of conjugat e eye movement s (Figure 7-9). This cont rol is mediat ed via t w o pat hw ays: t he ascending component of t he medial longit udinal f asciculus and t he ret icular f ormat ion. Ref lex conjugat e deviat ion of t he eyes in a specif ic direct ion, w hich is know n as nyst agmus, has t w o component s: a slow component aw ay f rom t he st imulat ed vest ibular syst em and a f ast component t ow ard t he st imulat ed side. I n clinical medicine, t he t erm nyst agmus ref ers t o t he f ast component . Alt hough t he mechanism of t he slow component is f airly w ell underst ood in t erms of neuronal connect ions, t he same cannot be said of t he f ast component , w hich is believed t o represent a correct ive at t empt t o ret urn t he eyes t o a neut ral posit ion. St imulat ion of t he right horizont al semicircular canal (t urning t o t he right in a Bárány chair or pouring w arm w at er in t he right ear) or t he right medial, lat eral, or inf erior vest ibular nucleus result s in a ref lex conjugat e horizont al deviat ion of t he eyes (horizont al nyst agmus) w it h a slow component t o t he lef t and a f ast component t o t he right . Bilat eral st imulat ion of t he ant erior semicircular canal result s in upw ard movement of t he eyes, w hile st imulat ion of t he post erior canal produces dow nw ard movement . Sect ioning of t he medial longit udinal f asciculus rost ral t o t he abducens nuclei abolishes t hese primary oculomot or responses. Nyst agmus, how ever, can st ill result f rom labyrint hine st imulat ion, conf irming t hat pat hw ays essent ial f or nyst agmus probably pass via t he ret icular f ormat ion. St imulat ion of t he superior vest ibular nucleus produces vert ical nyst agmus. Lesions of t he medial longit udinal f asciculus (MLF) rost ral t o t he abducens nucleus int erf ere w it h normal conjugat e eye movement s. I n t his condit ion, w hich is know n as int ernuclear opht halmoplegia or t he MLF syndrome, t here is paralysis of adduct ion ipsilat eral t o t he MLF lesion and horizont al monocular nyst agmus of t he abduct ing eye (Figure 7-10). This condit ion is know n t o occur in mult iple sclerosis and vascular disorders of t he pons. Experiment al evidence has show n t hat t his t ype of lesion int errupt s MLF f ibers dest ined f or t he part of t he oculomot or nuclear complex t hat innervat es t he medial rect us; t his explains t he loss of adduct ion. There is no sat isf act ory explanat ion f or t he monocular horizont al nyst agmus of t he abduct ing eye. Tw o t heories have been proposed t o explain t his phenomenon. The f irst suggest s t hat nyst agmus is due t o t he ut ilizat ion of convergence mechanisms t o adduct t he ipsilat eral eye. This induces adduct ion of t he cont ralat eral eye, w hich t hen jerks back t o t he posit ion of f ixat ion. The second t heory suggest s t hat t he medial longit udinal f asciculus carries f acilit at ory f ibers t o t he ipsilat eral medial rect us neurons and inhibit ory f ibers t o t he cont ralat eral medial rect us neurons. I n lesions of t he medial longit udinal f asciculus, f ailure of inhibit ion of adduct ion in t he cont ralat eral eye t hus causes an abduct ing (correct ive) nyst agmus in t hat eye. The t erm i nt ernuclear opht halmoplegia (at axic nyst agmus, Lhermit t e syndrome, Bielschow sky-Lut zCogan syndrome) w as coined by Lhermit t e, a French neurologist . Lut z, a Cuban
opht halmologist , def ined t w o variet ies of t his syndrome: (1) ant erior, in w hich t he lat eral rect us f unct ions normally but t he medial rect us is paralyzed on t he side of t he MLF lesion and (2) post erior, in w hich t he lat eral rect us is paralyzed but t he medial rect us f unct ions normally. The validit y of t his division of t he syndrome is not cert ain.
Fi gure 7-9. Schemat ic diagram show ing t he eff erent connect ions of t he vest ibular nuclei. MLF, medial longit udinal f asciculus.
Fi gure 7-10. Schemat ic diagram show ing t he eff ect s of lesions in t he medial longit udinal f asciculus (MLF) on conjugat e eye movement s. Zigzag arrow s indicat e nyst agmus.
Facial Nerve (Cranial Nerve VII) The f acial nerve (Figure 7-11) is a mixed nerve w it h bot h sensory and mot or component s. This nerve is responsible f or our individualit y, t he f acial expressions t hat charact erize each of us.
A. SENSORY COM PONENTS The f acial nerve carries t w o t ypes of sensory aff erent s: ext erocept ive f ibers f rom t he ext ernal ear and t ast e f ibers f rom t he ant erior t w o-t hirds of t he t ongue.
Fi gure 7-11. Schemat ic diagram show ing t he nuclei of origin, course, and areas of supply of t he f acial nerve (cranial nerve VI I ).
The ext erocept ive f ibers f rom t he ext ernal ear are peripheral processes of neurons in t he geniculat e ganglion. Cent ral processes project on neurons in t he spinal t rigeminal nucleus (similar t o f ibers f rom t he same area carried by t he glossopharyngeal [ cranial nerve I X] and vagus [ cranial nerve X] nerves).
The t ast e f ibers have t heir neurons of origin in t he geniculat e ganglion. Peripheral processes of t hese neurons reach t he t ast e buds in t he ant erior t w ot hirds of t he t ongue; cent ral processes ent er t he brain st em w it h t he nervus int ermedius and project on neurons in t he gust at ory part of t he nucleus solit arius, along w it h f ibers carried by t he glossopharyngeal (f rom t he post erior t hird of t he t ongue) and vagus (f rom t he epiglot t ic region) nerves. The sensory and gust at ory f ibers, along w it h t he visceral mot or component , f orm a separat e lat eral root of t he f acial nerve, t he nervus int ermedius (Wrisberg's nerve).
B. M OTOR COM PONENTS The f acial nerve carries t w o t ypes of mot or f ibers: somat ic and secret omot or.
1. Somatic Motor Fibers Somat ic mot or f ibers supply t he muscles of f acial expression and t he st apedius, t he st ylohyoid, and t he post erior belly of t he digast ric. These f ibers arise f rom t he f acial mot or nucleus in t he pont ine t egment um. From t heir neurons of origin, f ibers course dorsomedially and t hen rost rally in t he t egment um and f orm a compact bundle near t he abducens (cranial nerve VI ) nucleus in t he f loor of t he f ourt h vent ricle (t he f acial colliculus). They bend (genu) lat erally over t he abducens nucleus and t urn vent rolat erally t o emerge at t he lat eral border of t he pons. This peculiar course of t he somat ic mot or component of t he f acial nerve f ibers in t he t egment um result s f rom t he migrat ion of f acial mot or neurons f rom a dorsal posit ion in t he f loor of t he f ourt h vent ricle caudally and vent rally, pulling t heir axons w it h t hem. The migrat ion of t he f acial mot or nucleus is explained by neurobiot axis, in w hich neurons t end t o migrat e t ow ard major sources of st imuli. I n t he case of t he f acial mot or nucleus, t his migrat ion brings it closer t o t he t rigeminal spinal nucleus and it s t ract . Visceral mot or and sensory component s of t he f acial nerve do not make a loop around t he abducens nucleus. I nst ead, t hey f orm a separat e lat eral root of t he f acial nerve, t he nervus int ermedius. The mot or nucleus of t he f acial nerve is organized int o longit udinally orient ed mot or columns (subnuclei) concerned w it h specif ic f acial muscles: t he medial, dorsal, int ermediat e, and lat eral subnuclei. Mot or neurons t hat supply upper f acial muscles are locat ed in t he dorsal part of t he nucleus, t hose innervat ing low er f acial muscles are primarily locat ed in t he lat eral part of t he nucleus, and t hose supplying t he plat ysma and t he post erior auricular muscles are in t he medial part of t he nucleus. The f acial mot or nucleus receives f ibers f rom t he f ollow ing sources:
a. Cerebral cortex
Cort icof acial f ibers originat e f rom areas of f ace represent at ions in t he primary mot or, supplement ary mot or, premot or, rost ral, and caudal cingulat e cort ices. These f ibers t ravel as direct cort icobulbar or indirect cort icoret iculobulbar f ibers. The cort ical input t o t he f acial nucleus is bilat eral t o t he part of t he nucleus t hat supplies t he upper f acial muscles and only cont ralat eral t o t he part t hat innervat es t he perioral musculat ure. I n lesions aff ect ing one hemisphere, only t he low er f acial muscles cont ralat eral t o t he lesion are aff ect ed (Figure 7-12). This is ref erred t o as cent ral (supranuclear) f acial paresis, in cont radist inct ion t o peripheral f acial paralysis or paresis (result ing f rom lesions of t he f acial mot or nucleus or t he f acial nerve), in w hich all t he muscles of f acial expression ipsilat eral t o t he lesion are aff ect ed. Tw o t ypes of cent ral f acial paresis (palsy) have been described: volunt ary and involunt ary (mimet ic). Volunt ary cent ral f acial palsy result s f rom lesions involving t he cont ralat eral cort icobulbar or cort icoret iculobulbar f ibers. Mimet ic or emot ional innervat ion of t he muscles of f acial expression is involunt ary and of uncert ain origin. I t allow s cont ract ion of t he low er f acial muscles in response t o genuine emot ional st imuli. Cert ain neural lesions can produce mimet ic cent ral f acial paralysis w it hout volunt ary cent ral f acial paralysis. More ext ensive lesions produce combined volunt ary and mimet ic cent ral f acial paralysis.
Fi gure 7-12. Schemat ic diagram illust rat ing t he concept of cent ral f acial paresis.
Recent experiment al evidence provides an alt ernat ive explanat ion f or t he sparing of t he upper f acial musculat ure in pat ient s w it h cent ral (hemispheral) lesions. Sparse dat a f rom human st udies coupled w it h t he result s of experiment al st udies in a variet y of mammals, including monkeys, have show n t hat (1) t he bilat eral cort ical input t o f acial mot or neurons t hat innervat e upper f acial muscles is sparse, (2) mot or neurons of t he f acial nucleus t hat innervat e t he low er f acial muscles receive signif icant and bilat eral cort ical input w hich is t hreef old heavier on t he cont ralat eral side, and (3) cort ical innervat ion of t he ipsilat eral low er f acial mot or subnucleus is considerably heavier t han t hat of t he ipsilat eral upper f acial mot or subnucleus. O n t he basis of t hese f indings, it has been proposed t hat t he def icit of f acial muscles seen af t er unilat eral hemispheral lesions ref lect s t he ext ent t o w hich direct cort ical innervat ion of f acial mot or neuron is lost . Thus, mot or neurons innervat ing t he upper f ace w ould be lit t le aff ect ed because t hey do not receive much direct cort ical input . Also, low er f acial mot or neurons cont ralat eral t o t he lesion w ould suff er loss of f unct ion because t hey are most dependent on direct cont ralat eral cort ical innervat ion and because t he remaining ipsilat eral cort ical project ion apparent ly is insuff icient t o drive t hem. The small loss of cort ical input t o low er f acial mot or neurons ipsilat eral t o t he lesion is compensat ed by t he remaining, much more int ense, input f rom t he int act hemisphere. Alt ernat ely, it is possible t hat t he low er f acial muscles ipsilat eral t o t he lesion display some mild w eakness, but t his is obscured by t he much more prof ound cont ralat eral w eakness. The course of cort icobulbar f ibers t o t he f acial nucleus in humans remains uncert ain. Hist ologic st udies in human aut opsy mat erial at t he t urn of t he 20t h cent ury described an a berrant bundle separat ing f rom t he cort icospinal t ract at t he midbrain and upper pons and coursing along t he t egment al border adjacent t o t he lemniscal f ibers. These observat ions w ere subsequent ly conf irmed using more reliable st aining met hods. Recent st udies have described t hree possible t raject ories f or t he cort icof acial f ibers: (1) via t he a berrant bundle, (2) separat ing f rom t he cort icospinal t ract in t he caudal basis pont is and coursing dorsally t o t he f acial nucleus in t he pont ine t egment um, and (3) f orming a loop int o t he medulla oblongat a bef ore reaching t he f acial nucleus. These t raject ories w ould explain t he occurrence of cent ral f acial palsy in lesions aff ect ing t he pont ine t egment um and basis pont is and t hose associat ed w it h t he lat eral medullary syndrome.
b. Basal gan glia This input t o t he f acial mot or nucleus explains t he movement of paret ic f acial muscles in response t o emot ional st imulat ion. Pat ient s w it h cent ral f acial paralysis w ho are unable t o move t he low er f acial muscles volunt arily may be able t o do so ref lexly in response t o emot ional st imulat ion.
c. Su perior olive This input is part of a ref lex involving t he f acial and audit ory nerves. I t explains t he grimacing of f acial muscles t hat occurs in response t o a loud noise.
d. Trigemin al system This input is also ref lex in nat ure, linking t he t rigeminal and f acial nerves. I t underlies t he blinking of t he eyelids in response t o corneal st imulat ion.
e. Su perior collicu lu s This input via t ect obulbar f ibers is ref lex in nat ure and provides f or closure of t he eyelids in response t o int ense light or a rapidly approaching object .
2. Secretomotor (Visceral Motor) Fibers. These f ibers arise f rom t he superior salivat ory nucleus in t he t egment um of t he pons. They are preganglionic f ibers t hat leave t he brain st em w it h t he nevus int ermedius (Wrisberg's nerve) and synapse in collat eral ganglia. Fibers dest ined f or t he lacrimal gland leave t he nervus int ermedius and t ravel in t he great er superf icial pet rosal and t he nerve of t he pt erygoid canal (vidian nerve) bef ore synapse in t he pt erygopalat ine ganglion, f rom w hich post ganglionic parasympat het ic f ibers t ravel in t he maxillary, zygomat ic, zygomat icot emporal, and lacrimal nerves t o reach t he lacrimal gland. Fibers dest ined f or t he submandibular and sublingual glands join t he chorda t ympani and t he lingual nerves and synapse in t he submandibular ganglion, f rom w hich post ganglionic parasympat het ic f ibers arise. Because f ibers f or t he lacrimal, submandibular, and sublingual glands leave t he brain st em t oget her, lesions of t he f acial nerve proximal t o t he geniculat e ganglion may result in aberrant grow t h of regenerat ing f ibers so t hat f ibers dest ined t o innervat e t he lacrimal glands reach t he submandibular and sublingual salivary glands. This aberrant grow t h is responsible f or t he phenomenon of c rocodile t ears, in w hich t he presence of f ood in t he mout h is f ollow ed by lacrimat ion rat her t han salivat ion.
C. FACIAL NERVE LESIONS Signs of f acial nerve paralysis (Bell's palsy) vary w it h t he locat ion of t he lesion (Figure 7-13). Bell's palsy is named af t er Sir Charles Bell (1774 1 842), a Brit ish anat omist , physiologist , surgeon, and neurologist w ho w as also a pioneer in t he st udy of f acial expression.
Fi gure 7-13. Schemat ic diagram show ing lesions in t he f acial nerve at diff erent sit es and t he result ing clinical manif est at ions of each.
1. Proximal to Geniculate Ganglion Lesions of t he f acial nerve proximal t o t he geniculat e ganglion result in t he f ollow ing signs: 1. Paralysis of all t he muscles of f acial expression 2.
Loss of t ast e in t he ant erior t w o-t hirds of t he ipsilat eral half of t he t ongue
3. I mpaired salivary secret ion 4. I mpaired lacrimat ion 5. Hyperacusis (hypersensit ivit y t o sound as a result of paralysis of t he st apedius muscle) 6. Crocodile t ears in some pat ient s w it h aberrant grow t h of regenerat ing f ibers
2. Distal to Geniculate Ganglion Lesions of t he f acial nerve dist al t o t he geniculat e ganglion but proximal t o t he chorda t ympani result in t he f ollow ing ipsilat eral signs: 1. Paralysis of all t he muscles of f acial expression 2. Loss of t ast e in t he ant erior t w o-t hirds of t he t ongue 3. I mpaired salivary secret ion 4. Hyperacusis Lacrimat ion is not aff ect ed by t his t ype of lesion, since t he f ibers dest ined f or t he lacrimal gland leave t he nerve proximal t o t he level of t he lesion.
3. Stylomastoid Foramen Lesions of t he f acial nerve at t he st y-lomast oid f oramen (w here t he mot or f ibers dest ined f or t he muscles of f acial expression leave t he cranium) result only in paralysis of t he muscles of f acial expression t hat are ipsilat eral t o t he lesion.
Abducens Nerve (Cranial Nerve VI) The abducens nerve (Figure 7-14) is a purely mot or nerve t hat innervat es t he lat eral rect us muscle. The abducens nucleus is locat ed in a paramedian sit e in t he t egment um of t he pons, in t he f loor of t he f ourt h vent ricle. I t ext ends f rom t he rost ral limit of t he lat eral vest ibular nucleus t o t he rost ral port ion of t he descending vest ibular nucleus. The abducens nucleus has t w o populat ions of neurons: large (mot or neurons) and small (int erneurons). Axons of t he large neurons (mot or neurons) f orm t he abducens nerve and supply t he lat eral rect us muscles. Axons of t he small neurons (int erneurons) join t he cont ralat eral medial longit udinal f asciculus and t erminat e on neurons in t he oculomot or nucleus t hat supply t he medial rect us muscle (medial rect us subnucleus). Axons of t he abducens nerve course t hrough t he t egment um and basis pont is and exit on t he vent ral surf ace of t he pons in t he groove bet w een t he pons and t he medulla oblongat a (Figure 7-14). The abducens nucleus (Figure 7-14) receives f ibers f rom (1) t he cerebral cort ex (cort icoret iculobulbar f ibers), (2) t he medial vest ibular nucleus via t he medial longit udinal f asciculus, (3) t he paramedian pont ine ret icular f ormat ion (PPRF), and (4) t he nucleus preposit us hypoglossi. The cort icobulbar input is bilat eral, t he input s f rom t he PPRF and t he nucleus preposit us are uncrossed, and t he input f rom t he medial vest ibular nucleus is predominant ly uncrossed. Direct aff erent f ibers f rom Scarpa's ganglion t o t he abducens nucleus have been described.
Fi gure 7-14. Schemat ic diagram show ing sources of modulat ing input s int o t he abducens (cranial nerve VI ) nucleus and int rapont ine course of t he abducens nerve.
Fi gure 7-15. Schemat ic diagram show ing t he clinical manif est at ions result ing f rom lesions in t he abducens nucleus (B) and nerve (A).
Lesions of t he abducens nerve result in paralysis of t he ipsilat eral lat eral rect us muscle and diplopia (double vision) on at t empt ed horizont al gaze
t ow ard t he side of t he paralyzed muscle (Figure 7-15A); t he t w o images are horizont al, and t he dist ance bet w een t hem increases as t he eyes move in t he direct ion of act ion of t he paralyzed muscle. The abducens nerve has a long int racranial course and t heref ore is commonly aff ect ed in int racranial diseases of varying et iologies and sit es. I n cont rast t o lesions of t he abducens nerve, lesions of t he abducens nucleus do not result in paralysis of abduct ion but inst ead in paralysis of horizont al gaze ipsilat eral t o t he lesion; t his is manif est ed by t he f ailure of bot h eyes t o move on at t empt ed ipsilat eral horizont al gaze (Figure 715). Paralysis of lat eral gaze af t er abducens nucleus lesions is explained by involvement of t he large neurons t hat supply t he ipsilat eral lat eral rect us muscle and t he small neurons (int erneurons) t hat supply t he cont ralat eral medial rect us neurons (medial rect us subnucleus) w it hin t he oculomot or nucleus (Figure 7-16). The not ion t hat pont ine ret icular neurons are responsible f or paralysis of adduct ion no longer appears t enable. Trit iat ed amino acids inject ed int o t he paramedian pont ine ret icular f ormat ion do not reveal t erminat ions in t he oculomot or nucleus but inst ead in t he abducens nucleus and t he int erst it ial nucleus of t he medial longit udinal f asciculus, w hich is believed t o be involved in vert ical (dow nw ard) gaze. The pont ine cent er f or lat eral gaze and t he abducens nucleus probably const it ut e a single ent it y. The PPRF (pont ine cent er f or lat eral gaze) is a physiologically def ined neuronal pool t hat is rost ral t o t he abducens nucleus. I t is composed of caudal and rost ral part s. The caudal part is connect ed t o t he ipsilat eral abducens nucleus. St imulat ion of t he caudal part result s in conjugat e horizont al deviat ion of t he eyes. The rost ral part is connect ed t o t he rost ral int erst it ial nucleus of t he MLF (RiMLF), w hich in t urn project s t o t he ipsilat eral oculomot or nucleus by pat hw ays ot her t han t he MLF. St imulat ion of t he rost ral PPRF result s in vert ical gaze. Lesions in t he caudal PPRF abolish conjugat e lat eral gaze, w hereas lesions in t he rost ral PPRF abolish vert ical gaze. Ext ensive lesions in PPRF result in paralysis of bot h horizont al and vert ical gaze.
Fi gure 7-16. Schemat ic diagram illust rat ing t he basis of lat eral gaze paralysis in abducens nucleus lesions.
Abducens nerve root let s along t heir course w it hin t he pons may be involved in a variet y of int raaxial vascular lesions. 1. Lesions in t he basis pont is involving t he cort icospinal f ibers and t he root let s of t he abducens nerve result in alt ernat ing hemiplegia manif est ed by ipsilat eral lat eral rect us paralysis (and diplopia) as w ell as an upper mot or neuron paralysis of t he cont ralat eral half of t he body (Figure 7-17A). 2. Lesions in t he pont ine t egment um involving t he abducens root let s and t he medial lemniscus result in ipsilat eral lat eral rect us paralysis (and diplopia) and cont ralat eral loss of kinest hesia and discriminat ive t ouch (Figure 7-17B). 3. More dorsal lesions involving t he abducens nucleus, t he medial longit udinal f asciculus, and t he curving root let s of t he f acial nerve produce paralysis of horizont al gaze and peripheral-t ype f acial paralysis, bot h ipsilat eral t o t he lesion (Figure 7-17C). 4. Small lacunar inf arct involving sixt h nerve f ascicles w it hin t he pons produce isolat ed abducens nerve palsy.
Fi gure 7-17. Schemat ic diagram of lesions of t he abducens nerve (cranial nerve VI ) and nucleus and t he result ing clinical manif est at ions.
Unilat eral and bilat eral duplicat ions of t he abducens nerve have been report ed.
I n some cases, t he nerve emerged f rom t he brain st em as a single t runk and split int o t w o branches in t he subarachnoid space bef ore reaching t he cavernous sinus. I n ot her cases, t he nerve exit ed t he brain st em as t w o separat e branches. I n bot h sit uat ions, t he t w o branches usually merge w it hin t he cavernous sinus.
Trigeminal Nerve (Cranial Nerve V) The t rigeminal nerve is t he largest of t he t w elve cranial nerves. I t t ransmit s sensory inf ormat ion f rom t he head and neck and provides innervat ion t o t he muscles of mast icat ion, t he t ensor t ympani, t ensor palat i, myelohyoid, and ant erior belly of t he digast ric. The t rigeminal nerve has t w o root s: a smaller (port io minor) eff erent root and a larger (port io major) aff erent root . The mot or root is composed of as many as 14 separat ely originat ing root let s t hat are joined about 1 cm f rom t he pons. At t he pons, t he f irst division of t he t rigeminal sensory root (V1) usually is locat ed in a dorsomedial posit ion adjacent t o t he mot or root and t he t hird division (V3) is in a caudolat eral posit ion. V3, how ever, may vary f rom being direct ly lat eral t o direct ly caudal t o V1. Aberrant sensory root s exist in about 50 percent of individuals and may explain t he persist ence of f acial pain (t rigeminal neuralgia) af t er surgical sect ioning of t he sensory root . Aberrant sensory root let s ent er t he sensory root w it hin 1 cm of t he pons and cont ribut e mainly t o V1. Some root let s bet w een t he mot or and sensory root s may join eit her root f art her aw ay f rom t he pons. Anast omosis bet w een t he mot or and sensory root s has been described and may explain t he f ailure of sensory root sect ioning t o relieve f acial pain.
A. EFFERENT ROOT The eff erent root of t he t rigeminal nerve arises f rom t he mot or nucleus of t he t rigeminal nerve in t he t egment um of t he pons. The eff erent root supplies t he muscles of mast icat ion and t he t ensor t ympani, t he t ensor palat i, t he mylohyoid, and t he ant erior belly of t he digast ric. The mot or nucleus receives f ibers f rom t he cerebral cort ex (cort icobulbar) and t he sensory nuclei of t he t rigeminal nerve. The cort ical project ions t o t rigeminal mot or neurons are bilat eral and symmet ric via direct cort icobulbar and indirect cort icoret iculobulbar f ibers. Lesions aff ect ing t he mot or nucleus or eff erent root result in paralysis of t he low er mot or neuron t ype of t he muscles supplied by t his root .
B. AFFERENT ROOT The aff erent root (Figure 7-18) of t he t rigeminal nerve cont ains t w o t ypes of aff erent f ibers.
1. Proprioceptive Fibers.
Propriocept ive f ibers f rom deep st ruct ures of t he f ace t ravel via t he eff erent and aff erent root s. They are peripheral processes of unipolar neurons in t he mesencephalic nucleus of t he t rigeminal nerve locat ed at t he rost ral pont ine and caudal mesencephalic levels. This nucleus is unique in t hat it is homologous t o t he dorsal root ganglion yet is cent rally placed. Propriocept ive f ibers t o t he mesencephalic nucleus convey pressure and kinest hesia f rom t he t eet h, periodont ium, hard palat e, and joint capsules as w ell as impulses f rom st ret ch recept ors in t he muscles of mast icat ion. The out put f rom t he mesencephalic nucleus is dest ined f or t he cerebellum, t he t halamus, t he mot or nuclei of t he brain st em, and t he ret icular f ormat ion. The mesencephalic nucleus is concerned w it h mechanisms t hat cont rol t he f orce of t he bit e.
2. Exteroceptive Fibers Ext erocept ive f ibers are general somat ic sensory f ibers t hat convey pain, t emperat ure, and t ouch sensat ions f rom t he f ace and t he ant erior aspect of t he head. The neurons of origin of t hese f ibers are sit uat ed in t he semilunar (gasserian) ganglion. The peripheral processes of neurons in t he ganglion are dist ribut ed in t he t hree divisions of t he t rigeminal nerve: opht halmic, maxillary, and mandibular. The cent ral processes of t hese unipolar neurons ent er t he lat eral aspect of t he pons and dist ribut e t hemselves as f ollow s.
Fi gure 7-18. Schemat ic diagram show ing t he cells of origin and course of t he sensory root of t he t rigeminal nerve (cranial nerve V).
Some of t hese f ibers descend in t he pons and medulla and run dow n t o t he level of t he second or t hird cervical spinal segment as t he descending (spinal) t ract of t he t rigeminal nerve. They convey pain and t emperat ure sensat ions. Throughout t heir caudal course t hese f ibers project on neurons in t he adjacent nucleus of t he descending t ract of t he t rigeminal nerve (spinal t rigeminal nucleus). The spinal t rigeminal nucleus is divided int o t hree part s on t he basis of it s cyt oarchit ect ure: (1) an oral part , w hich ext ends f rom t he ent ry zone of t he t rigeminal nerve in t he pons t o t he level of t he rost ral t hird of t he inf erior olivary nucleus in t he medulla oblongat a and receives t act ile sensibilit y f rom oral mucosa, (2) an int erpolar part , w hich ext ends f rom t he caudal ext ent of t he oral part t o just rost ral t o t he pyramidal decussat ion in t he medulla oblongat a and receives dent al pain, and (3) a caudal part , w hich ext ends f rom t he pyramidal decussat ion dow n t o t he second or t hird cervical spinal segment s and receives pain and t emperat ure sensat ions f rom t he f ace. Axons of neurons in t he spinal t rigeminal nucleus cross t he midline and f orm t he vent ral secondary ascending t rigeminal t ract , w hich courses rost rally t o t erminat e in t he t halamus. During t heir rost ral course t hese second-order f ibers send collat eral branches t o several mot or nuclei of t he brain st em (hypoglossal [ cranial nerve XI I ] , vagus [ cranial nerve X] , glossopharyngeal [ cranial nerve I X] , f acial [ cranial nerve VI I ] , and t rigeminal [ cranial nerve V] ) t o est ablish ref lexes. The spinal t ract of t he t rigeminal nerve is concerned mainly w it h t he t ransmission of pain and t emperat ure sensat ions. I t somet imes is cut surgically at a low level (t rigeminal t ract ot omy) t o relieve int ract able pain. These operat ions may relieve pain but leave t ouch sensat ion int act . The spinal t ract of t he t rigeminal nerve also carries somat ic aff erent f ibers t raveling w it h ot her cranial nerves (f acial [ cranial nerve VI I ] , glossopharyngeal [ cranial nerve I X] , and vagus [ cranial nerve X] ), as w as out lined previously. O t her incoming f ibers of t he t rigeminal nerve bif urcat e on ent ry int o t he pons int o ascending and descending branches. These f ibers convey t ouch sensat ion. The descending branches join t he spinal t ract of t he t rigeminal nerve and f ollow t he course t hat w as out lined above. The short er ascending branches project on t he main sensory nucleus of t he t rigeminal nerve. From t he main sensory nucleus, second-order f ibers ascend ipsilat erally and cont ralat erally as t he dorsal ascending t rigeminal t ract t o t he t halamus. Some crossed f ibers also t ravel in t he vent ral ascending t rigeminal t ract . O nce t hey are f ormed, bot h secondary t rigeminal t ract s (dorsal and vent ral) lie lat eral t o t he medial lemniscus bet w een it and t he spinot halamic t ract . Since f ibers t hat convey t ouch sensat ion bif urcat e on ent ry t o t he pons and t erminat e on bot h t he spinal and t he main sensory t rigeminal nuclei, t ouch sensat ions are not abolished w hen t he spinal t rigeminal t ract is cut (t rigeminal t ract ot omy). A schemat ic summary of t he aff erent and eff erent t rigeminal root s and t heir nuclei is show n in Figure 7-19. St udies of t rigeminot halamic f ibers have revealed t hat t he bulk of t hese f ibers arise f rom t he main sensory nucleus and t he int erpolaris segment of t he spinal
nucleus. Most of t hese f ibers t erminat e in t he cont ralat eral t halamus (vent ral post erior medial [ VPM] nucleus) w it h f ew t erminat ions ipsilat erally. O t her eff erent s of t he t rigeminal nuclei include project ions t o t he ipsilat eral cerebellum via t he inf erior cerebellar peduncle (f rom t he spinal and main sensory nuclei), t he spinal cord dorsal horn (bilat erally) f rom t he spinal nucleus, and t he cerebellum (f rom t he mesencephalic nucleus). Trigeminal neuralgia (t ic douloureux) is a disabling painf ul sensat ion in t he dist ribut ion of t he branches of t he t rigeminal nerve. The pain is paroxysmal, st abbing, or like light ning in nat ure and usually is t riggered by eat ing, t alking, or brushing t he t eet h. Several met hods of t reat ment , including drugs, alcohol inject ion of t he nerve, elect rocoagulat ion of t he ganglion, and surgical int errupt ion of t he nerve or spinal t ract in t he medulla oblongat a (t rigeminal t ract ot omy), have been t ried w it h varying degrees of success.
C. TRIGEM INAL REFLEXES Collat erals f rom t he secondary ascending t rigeminal t ract s est ablish synapses w it h t he f ollow ing cranial nerve nuclei t o est ablish ref lex responses: 1. The mot or nucleus of t he t rigeminal t o elicit t he jaw ref lex 2. The f acial mot or nuclei on bot h sides, result ing in a bilat eral blink ref lex, t he corneal ref lex (direct and consensual), in response t o unilat eral corneal st imulat ion. The ref lex is elicit ed by gent ly t ouching t he cornea (usually w it h a cot t on w isp). The aff erent limb of t he ref lex is t he t rigeminal nerve and t he descending (spinal) t ract of t he t rigeminal nerve. Collat eral branches of t he spinal t ract synapse in t he oral or int erpolar part s of t he spinal nucleus of t he t rigeminal nerve. Connect ions are t hen made via t he ret icular f ormat ion w it h t he f acial nuclei bilat erally. Trigeminal f ibers est ablish t hree t ypes of synapses w it h f acial nuclei: (1) disynapt ic w it h t he ipsilat eral f acial nerve nucleus, (2) polysynapt ic w it h t he ipsilat eral f acial nucleus, and (3) indirect and polysynapt ic w it h t he cont ralat eral f acial nerve nucleus. 3. The nucleus ambiguus, t he respirat ory cent er of t he ret icular f ormat ion, and t he spinal cord (phrenic nerve nuclei and ant erior horn cells t o int ercost al muscles), result ing in t he sneezing ref lex in response t o st imulat ion of t he nasal mucous membrane 4. The dorsal mot or nucleus of t he vagus as part of t he vomit ing ref lex 5. The inf erior salivat ory nucleus f or t he salivat ory ref lex 6. The hypoglossal nucleus f or ref lex movement s of t he t ongue in response t o t ongue st imulat ion 7. The superior salivat ory nucleus, result ing in t ears in response t o corneal irrit at ion, t he t earing ref lex
Fi gure 7-19. Composit e schemat ic diagram of t he aff erent and eff erent root s of t he t rigeminal nerve (cranial nerve V) and t heir nuclei.
D. BLOOD SUPPLY The blood supply of t he pons (Figures 7-20 and 7-21) is derived f rom t he basilar art ery. Three groups of vessels provide blood t o specif ic regions of t he pons: t he paramedian and t he short and long circumf erent ial. The paramedian vessels (f our t o six in number) arise f rom t he basilar art ery and ent er t he pons vent rally, supplying t he medial basis pont is and t he t egment um. Pont ine nuclei, cort icospinal t ract bundles w it hin t he basis pont is, and t he medial lemniscus are among t he st ruct ures supplied by t hese vessels. Short circumf erent ial art eries arise f rom t he basilar art ery, ent er t he brachium pont is, and supply t he vent rolat eral region of t he basis pont is. Long circumf erent ial art eries include t he ant erior inf erior cerebellar art ery (AI CA), t he int ernal audit ory art ery, and t he superior cerebellar art ery. The AI CA supplies t he lat eral t egment um of t he low er t w o-t hirds of t he pons as w ell as t he vent rolat eral cerebellum. The int ernal audit ory art ery, w hich may arise f rom t he AI CA or t he basilar art ery, supplies t he audit ory, vest ibular,
and f acial cranial nerves. The superior cerebellar art ery supplies t he dorsolat eral pons, brachium pont is, brachium conjunct ivum, and dorsal ret icular f ormat ion. O ccasionally t he vent rolat eral pont ine t egment um is also supplied by t his vessel.
Fi gure 7-20. Schemat ic diagram of vascular t errit ories in t he rost ral pons.
Fi gure 7-21. Schemat ic diagram of vascular t errit ories in t he caudal pons.
TERM INOLOGY Abducens nerve (Latin, d rawing away ) . The sixt h cranial nerve, discovered by Eust achius in 1564, is so named because it supplies t he lat eral rect us muscle, w hose f unct ion is t o direct t he eye t o t he lat eral side aw ay f rom t he midline. Acoustic neuroma. A t umor of t he eight h cranial nerve charact erized by deaf ness and vert igo. May involve adjacent st ruct ures in t he brain st em. Described by Harvey Cushing, an American neurosurgeon, in 1917. Alternating hemiplegia. Paresis of t he cranial nerves ipsilat eral t o a brain st em lesion and of t he t runk and limbs cont ralat eral t o t he lesion. Alzheimer's disease. A degenerat ive disease of t he brain f ormerly know n as senile dement ia. Charact erized by memory loss, cort ical at rophy, senile plaques, and neurof ibrillary t angles. Described by Alois Alzheimer, a G erman neuropsychiat rist , in 1907. Bárány chair test. A t est of labyrint hine f unct ion in w hich t he subject , w earing opaque lenses, is rot at ed w hile seat ed on a chair w it h t he head t ilt ed 30 degrees f orw ard t o bring t he horizont al semicircular canal int o t he t rue horizont al plane. Rot at ion normally elicit s horizont al nyst agmus opposit e t o t he direct ion of rot at ion. Bechterew's nucleus. The superior nucleus of t he vest ibular nerve. Described by Vladimir Becht erew, a Russian neurologist , in 1908. Bell's palsy. Facial paralysis ipsilat eral t o a f acial nerve lesion. Described by Sir Charles Bell, a Scot t ish anat omist and surgeon, in 1821. Brachium conjunctivum (Latin, G reek brachi on, a rm ; conj uncti va, c onnecting ) . An armlike bundle of f ibers t hat connect t he cerebellum and midbrain. Brachium pontis (Latin, G reek, brachi on, a rm ; ponti s, b ridge ) . An armlike bundle of f ibers t hat connect t he pons and cerebellum. Central facial palsy. Weakness of t he low er f acial muscles cont ralat eral t o a lesion in t he cerebral
cort ex or cort icobulbar f ibers. Cerebellopontine angle. The angle bet w een t he medulla oblongat a, pons, and cerebellum. Cont ains t he sevent h (f acial) and eight h (cochleovest ibular) cranial nerves. Cochlea (Latin, s nail shell ) . So named because it has a spiral f orm resembling a snail shell. Conjugate eye movement (Latin conj ugatus, y oked together ) . The lat eral deviat ion of t he t w o eyes in parallel. Corneal reflex. Blinking in response t o corneal st imulat ion. The aff erent limb of t he ref lex is via t he t rigeminal nerve, and t he eff erent limb is via t he f acial nerve. Crocodile tears (Bogorad syndrome). Shedding of t ears w hile eat ing as a result of aberrant innervat ion of f acial nerve f ibers so t hat f ibers dest ined t o innervat e t he lacrimal glands reach t he submandibular and sublingual glands. Named af t er F. A. Bogorad, a Russian physiologist w ho suggest ed t he name and t he physiologic mechanism in 1928. The phenomenon had been described by Hermann O ppenheim, a G erman neurologist , in 1913. Deiters' nucleus. The lat eral vest ibular nucleus. Described by O t t o Friedrich Karl Deit ers, a G erman anat omist , in 1865. Diplopia (G reek di pl os, d ouble ; ops, e ye ) . The percept ion of t w o images of a single object . Double vision result ing f rom ext raocular muscle w eakness. Down syndrome. A genet ic syndrome caused by t risomy of chromosome 21 or t ranslocat ion of chromosomal mat erial. Charact erized by unique f acial f eat ures, ment al ret ardat ion, skelet al abnormalit ies, congenit al cardiac lesions, and a single t ransverse palmar crease. Described by James Langdon Haydon Dow n, an English physician, in 1866. Efferent bundle of Rasmussen. The olivocochlear eff erent bundle in t he pons ext ends f rom t he periolivary nuclei t o t he hair cells of t he organ of Cort i. Suppresses t he recept ivit y of t he cochlear end organ. Described by Theodor Rasmussen, a Canadian neurosurgeon, in 1946. Facial colliculus (Latin col l i cul us, s mall elevation ) . An elevat ion in t he f loor of t he f ourt h vent ricle overlying t he genu of t he f acial nerve and t he abducens nucleus. Facial nerve.
The sevent h cranial nerve. Willis divided t he sevent h nerve int o a port io dura (f acial) and a port io mollis (audit ory). Soemmering separat ed t he t w o and numbered t hem separat ely. G asserian ganglion. The sensory t rigeminal (semilunar) ganglion w as named af t er Johann G asser, an Aust rian anat omist , by one of his st udent s in 1765. G asser had described t he ganglion in his t hesis. Heschl's gyri (G reek gyros, c ircle ) . The t ransverse gyri in t he t emporal lobe are t he sit es of t he primary audit ory cort ex. Named af t er Richard Heschl, an Aust rian anat omist w ho described t hem in 1855. Horner's syndrome. Drooping of t he eyelids (pt osis), const rict ion of t he pupil (miosis), ret ract ion of t he eyeball (enopht halmos), and loss of sw eat ing on t he f ace (anhidrosis) const it ut e t his syndrome described by Johann Friedrich Horner, a Sw iss opht halmologist , in 1869. The syndrome is due t o int errupt ion of descending sympat het ic f ibers. Also know n as Bernard-Horner syndrome and oculosympat het ic palsy. Described in animals by Francois du Pet it in 1727. Claude Bernard in France in 1862 and E. S. Hare in G reat Brit ain in 1838 gave precise account s of t he syndrome bef ore Horner did. Hyperacusis (G reek hyper, a bove ; akousi s, h earing ) . Abnormal sensit ivit y t o loud sounds. Commonly seen in persons w it h f acial nerve lesions and subsequent paralysis of t he st apedius muscle. Internuclear ophthalmoplegia (MLF syndrome). A condit ion charact erized by paralysis of ocular adduct ion ipsilat eral t o t he medial longit udinal f asciculus lesion and monocular nyst agmus in t he cont ralat eral abduct ing eye. Isthmus (G reek i sthmos, a narrow connection between two large bodies or spaces ) . The narrow est port ion of t he hindbrain. I t is sit uat ed bet w een t he pons and t he midbrain. Jaw reflex. Cont ract ion of t he masset er and t he t emporalis muscle in response t o a t ap just below t he low er lip. The aff erent s and eff erent limbs of t he ref lex are via t he t rigeminal nerve. The ref lex is evident in upper mot or neuron lesions. Juxtarestiform body (Latin j uxta, n ear, close by ; resti s, r ope ; forma, s hape ) . A bundle of nerve f ibers in close proximit y t o t he rest if orm body (inf erior cerebellar peduncle). Carries vest ibular and ret icular f ibers f rom and t o t he cerebellum.
Lateral lemniscus (Latin from G reek l emni skos, r ibbon ) . A f iber bundle carrying second- and t hird-order audit ory f ibers in t he brain st em. Locus ceruleus (Latin, p lace, dark blue ) . A pigment ed noradrenergic nucleus in t he rost ral pons t hat is dark blue in sect ions. Modiolus (Latin, n ave, hub ) . The cent ral pillar (axis) of t he cochlea. Described and named by Eust achius in 1563. I t s st ruct ure suggest s t he hub of t he w heel w it h radiat ing spokes (lamina spiralis) at t ached t o it . Nervus intermedius (Wrisberg's nerve). Lat eral root of t he f acial nerve cont aining visceral mot or and sensory component s. Named by Heinrich August Wrisberg, a G erman anat omist . Nucleus prepositus. O ne of t he perihypoglossal ret icular nuclei in t he medulla oblongat a. Relat ed t o ocular movement . Nystagmus (G reek nystagmos, d rowsiness, nodding ) . Nodding or closing of t he eyes in a sleepy person. The t erm now ref ers t o involunt ary rhyt hmic oscillat ion of t he eyes. O rgan of Corti. The cochlear recept or organ in t he inner ear. Described by Marchese Alf onso Cort i, an I t alian hist ologist , in 1851. Parkinson's disease. A degenerat ive disease of t he brain charact erized by post ural t remor and rigidit y f rom loss of dopaminergic neurons in t he subst ant ia nigra. Described by James Parkinson, an English physician, in 1817 under t he name of shaki ng pal sy. Pons (Latin, b ridge ) . A bridge bet w een t he medulla oblongat a, midbrain, and cerebellum. Described by Eust achius and Varolius. The illust rat ions of Eust achius w ere superior t o t hose of Varolius but w ere not published unt il 1714, w hereas t hose of Varolius w ere published in 1573; hence t he name pons varol i i. Probst's commissure. A bundle of f ibers connect ing t he nuclei of t he lat eral lemniscus w it h each ot her and w it h t he inf erior colliculus. Restiform body (Latin resti s, r ope ; forma, f orm ) . A body (inf erior cerebellar peduncle) shaped like a rope. Described by Humphrey Ridley, an English anat omist , in 1695. Saccule (Latin saccul us, l ittle bag or sac ) . O ne of t he vest ibular end organs in t he inner ear. Det ect s linear displacement of t he body.
Salivatory reflex. Salivat ion in response t o t rigeminal st imulat ion. The aff erent limb of t he ref lex is via t he t rigeminal nerve; t he eff erent limb is via t he glossopharyngeal nerve. Scarpa's ganglion (G reek gangl i on, k not ) . A st ruct ure cont aining bipolar cells t hat give rise t o t he vest ibular nerve. Locat ed in t he int ernal audit ory meat us. Described by Ant onius Scarpa, an I t alian surgeon and anat omist , in 1779. Schwalbe's nucleus. The medial vest ibular nucleus. Described by G ust av Schw albe (1844 1 916), a G erman anat omist . Semilunar ganglion (Latin semi , h alf ; l una, m oon ) . Resembling a crescent or half moon. The semilunar (gasserian) ganglion of t he t rigeminal nerve lies on t he medial end of t he pet rous bone. Sneezing (nasal) reflex. Sneezing in response t o a nasal t ickle. The aff erent limb of t he ref lex is via t he t rigeminal nerve; t he eff erent limbs are via t he vagus, phrenic, and int ercost al nerves. Spiral ganglion. The sensory ganglion of t he cochlear nerve. Cont ains bipolar cells. Tearing reflex. Product ion of t ears in response t o corneal st imulat ion. The aff erent limb of t he ref lex is via t he t rigeminal nerve; t he eff erent limb is via t he f acial nerve. Tegmentum (Latin, a c overing ) . The dorsal part s of t he pons and midbrain. Trapezoid body (Latin trapezoi des, t able-shaped ) . The vent ral acoust ic st ria in t he t egment um of t he pons const it ut es t he t rapezoid body. Trigeminal nerve (Latin tres, t hree ; gemi nus, t win ) . The f if t h cranial nerve w as described by Fallopius. So named because it has t hree divisions: opht halmic, maxillary, and mandibular. Trigeminal neuralgia (tic douloureux, Fothergill's syndrome). Paroxysmal at t acks of severe f acial pain in t he t rigeminal sensory dist ribut ion. Described by John Fot hergill, an English physician, in 1773. Trigeminal tractotomy. Cut t ing of t he spinal t rigeminal t ract in t he brain st em t o relieve severe int ract able f acial pain. Utricle (Latin utri cul us, s mall sac ) . A sensory vest ibular end organ t hat det ect s linear displacement of t he body.
Vomiting reflex. Vomit ing in response t o st imulat ion of t he pharyngeal w all. The aff erent limb of t he ref lex is via t he t rigeminal nerve; t he eff erent limb is via t he vagus nerve.
SUGGESTED READINGS Ash PR, Kelt ner JL: Neuro-opht halmic signs in pont ine lesions. Medi ci ne (Bal ti more) 1979; 58: 304 3 20. At illa H et al: I solat ed sixt h nerve palsy f rom pont ine inf arct . Acta Neurol Bel gi ca 2000; 100: 246 2 47. Brodal P: The pont ocerebellar project ion in t he Rhesus monkey: An experiment al st udy w it h ret rograde axonal t ransport of horseradish peroxidase. Neurosci ence 1979; 4: 193 2 08. Burt on H, Craig AD: Dist ribut ion of t rigeminot halamic project ion cells in cat and monkey. Brai n Res 1979; 161: 515 5 21. Carpent er MB, Bat t on RR: Abducens int ernuclear neurons and t heir role in conjugat e horizont al gaze. J Comp Neurol 1980; 189: 191 2 09. Fisher CM: At axic hemiparesis: A pat hologic st udy. Arch Neurol 1978; 35: 126 1 28. G acek RR: Locat ion of abducens aff erent neurons in t he cat . Exp Neurol 1979; 64: 342 3 53. G udmundsson K et al: Det ailed anat omy of t he int racranial port ion of t he t rigeminal nerve. J Neurosurg 1971; 35: 592 6 00. Haymaker W: The Founders of Neurol ogy. Springf ield, I L, Charles C. Thomas, 1953. Hu JW, Sessle BJ: Trigeminal nocicept ive and non-nocicept ive neurons: Brain st em int ranuclear project ions and modulat ion by orof acial, periaqueduct al gray and nucleus raphe magnus st imuli. Brai n Res 1979; 170: 547 5 52. Jenny AB, Saper CB: O rganizat ion of t he f acial nucleus and cort icof acial project ion in t he monkey: A reconsiderat ion of t he upper mot or neuron f acial palsy. Neurol ogy 1987; 37: 930 9 39.
Jones BE: Eliminat ion of paradoxical sleep by lesions of t he pont ine gigant ocellular t egment al f ield in t he cat . Neurosci Lett 1979; 13: 285 2 93. Kort e G E, Mugnaini E: The cerebellar project ion of t he vest ibular nerve in t he cat . J Comp Neurol 1979; 184: 265 2 78. Kot chabhakdi N et al: The vest ibulot halamic project ions in t he cat st udied by ret rograde axonal t ransport of horseradish peroxidase. Exp Brai n Res 1980; 40: 405 4 18. Kushida CA et al: Cort ical asymmet ry of REM sleep EEG f ollow ing unilat eral pont ine hemorrhage. Neurol ogy 1991; 41: 598 6 01. Lang W et al: Vest ibular project ions t o t he monkey t halamus: An aut oradiographic st udy. Brai n Res 1979; 177: 3 1 7. Loew y AD et al: Descending project ion f rom t he pont ine mict urit ion cent er. Brai n Res 1979; 172: 533 5 38. Mat sumura M et al: O rganizat ion of somat ic mot or input s f rom t he f ront al lobe t o t he pedunculopont ine t egment al nucleus in t he macaque monkey. Neurosci ence 2000; 98: 97 110. Moore JK: O rganizat ion of t he human superior olivary complex. Mi crosc Res Techn 2000; 51: 403 4 12.
Morecraf t RJ et al: Cort ical innervat ion of t he f acial nucleus in t he nonhuman primat e. A new int erpret at ion of t he eff ect s of st roke and relat ed subt ot al brain t rauma on t he muscles of f acial expression. Brai n 2001; 124: 176 2 08. Nakao S, Sasaki S: Excit at ory input f rom int erneurons in t he abducens nucleus t o medial rect us mot oneurons mediat ing conjugat e horizont al nyst agmus in t he cat . Exp Brai n Res 1980; 39: 23 3 2. Nieuw enhuys R: Anat omy of t he audit ory pat hw ays, w it h emphasis on t he brain st em. Adv O torhi nol aryngol 1984; 34: 25 3 8. O liver DL: Ascending eff erent project ions of t he superior olivary complex. Mi crosc Res Techn 2000; 51: 353 3 63.
O zveren FM et al: Duplicat ion of t he abducens nerve at t he pet roclival region: An anat omic st udy. Neurosurgery 2003; 52: 465 6 52. Phillips CD, Bubash LA: The f acial nerve: Anat omy and common pat hology. Semi n Ul trasound 2000; 23: 202 2 17. Pryse-Phillips W: Compani on to Cl i ni cal Neurol ogy. Bost on, Lit t le, Brow n, 1995. Reuss S: I nt roduct ion t o t he superior olivary complex. Mi crosc Res Techn 2000; 51: 303 3 06. Scarnat i E, Florio T: The pedunculopont ine nucleus and relat ed st ruct ures: Funct ional organizat ion. Adv Neurol 1997; 47: 97 110. Schmahmann JD, Pandya DN: Anat omic organizat ion of t he basilar pont ine project ions f rom pref ront al cort ices in rhesus monkey. J Neurosci 1997; 17: 438 4 58. St iller J et al: Brainst em lesion w it h pure mot or hemiparesis: Comput ed t omographic demonst rat ion. Arch Neurol 1982; 39: 660 6 61. Thompson AM, Schof ield BR: Aff erent project ions of t he superior olivary complex. Mi crosc Res Techn 2000; 51: 330 3 54. Uesaka Y et al: The pat hw ay of gust at ory f ibers of t he human ascends ipsilat erally in t he pons. Neurol ogy 1998; 50: 827 8 28. Urban PP et al: The course of cort icof acial project ions in t he human brainst em. Brai n 2001; 124: 1866 1 876. Venna N, Sabin TD: Universal dissociat ed anest hesia, due t o bilat eral brainst em inf arct s. Arch Neurol 1985; 42: 918 9 22. Vilensky JA, Van Hoesen G W: Cort icopont ine project ions f rom t he cingulat e cort ex in t he Rhesus monkey. Brai n Res 1981; 205: 391 3 95. Wiesendanger R et al: An anat omical invest igat ion of t he cort icopont ine project ion in t he primat e (Macaca f asci cul ari s and Sai mi ri sci ureus): I I . The project ion f rom f ront al and pariet al associat ion areas. Neurosci ence 1979; 4: 747 7 65.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 8 - P ons : C linic al C or r elates
8 Pons: Clinical Correlates
Basal Pontine Syndrom es Caudal Basal Pontine Syndromes Rostral Basal Pontine Syndrome Pure Motor and Ataxic Hemiparesis Dysarthria C lumsy Hand Syndrome The Locked-in Syndrome Crying and Laughter Tegm ental Pontine Syndrom es The Medial Tegmental Syndrome The One-and-a-Half Syndrome Dorsolateral Tegmental Pontine Syndrome Caudal Tegmental Pontine Syndromes Mid-Tegmental Pontine Syndrome (Grenet Syndrome) Rostral Tegmental Pontine Syndrome (RaymondCestan-Chenais Syndrome) Extreme Lateral Tegmental Pontine Syndrome (Marie-Foix Syndrome) Ocular Bobbing and Dipping REM Sleep Central Neurogenic Hyperventilation The Pons and Respiration
KEY CONCEPTS Manifestations of the Millard-Gubler syndrome consist of ipsilateral facial nerve palsy and contralateral hemiplegia. In some patients the abducens nerve may be involved ipsilateral to the lesion. Manifestations of the Gellé syndrome consist of ipsilateral deafness and vertigo, with or without facial palsy, and contralateral hemiparesis. Manifestations of the Brissaud-Sicard syndrome consist of ipsilateral facial hemispasm and contralateral hemiparesis. Manifestations of the rostral basal pontine syndrome consist of ipsilateral trigeminal nerve palsy (motor and sensory) and contralateral hemiplegia. The medial tegmental syndrome is manifested by ipsilateral abducens and facial nerve palsies and contralateral loss of kinesthesia and discriminative touch. The one-and-a-half syndrome is manifested by ipsilateral horizontal gaze paralysis and internuclear ophthalmoplegia. The dorsolateral pontine tegmental syndrome is manifested by dissociated sensory loss (loss of pain and temperature sense with preservation of kinesthesia and discriminative touch) over the ipsilateral face and contralateral trunk and extremities. Foville syndrome is manifested by ipsilateral facial nerve palsy, ipsilateral horizontal gaze paralysis, and contralateral hemiparesis.
Manifestations of the Grenet syndrome consist of bilateral facial and contralateral trunk thermoanalgesia, ipsilateral paralysis of muscles of mastication, ataxia and tremor, and contralateral hemiparesis. The Raymond-Cestan-Chenais syndrome is manifested by ipsilateral internuclear ophthalmoplegia and ataxia and contralateral hemiparesis and hemisensory loss. The Marie-Foix syndrome is manifested by ipsilateral ataxia and contralateral hemiparesis with or without hemisensory loss.
Fi gure 8-1. Schemat ic diagram of t he st ruct ures involved in t he caudal pont ine syndrome (Millard-G ubler) and t he result ing clinical manif est at ions.
Vascular lesions of t he pons are best suit ed t o anat omicoclinical correlat ions. The f ollow ing syndromes are part icularly illust rat ive.
BASAL PONTINE SYNDROM ES Basal pont ine syndromes are caused by lesions in t he basal part of t he pons, aff ect ing t he root let s of cranial nerves and cort icospinal t ract bundles in t he basis pont is.
Caudal Basal Pontine Syndromes A. M ILLARD-GUBLER SYNDROM E The manif est at ions of t his syndrome, as originally described by Millard and G ubler in 1856, include ipsilat eral f acial paralysis of t he peripheral t ype and cont ralat eral hemiplegia of t he upper mot or neuron t ype (Figure 8-1). Frequent ly, t he lesion may ext end medially and rost rally t o include t he root let s of t he sixt h nerve (Figure 8-2). I n t his sit uat ion, t he pat ient also manif est s signs of ipsilat eral sixt h nerve paralysis. Current t ext book def init ions of t he MillardG ubler syndrome concur on t he presence of cont ralat eral hemiplegia of t he upper mot or neuron t ype in associat ion w it h ipsilat eral f acial nerve or abducens nerve paresis or bot h and w it h occasional involvement of t he medial lemniscus.
B. GELLÉ SYNDROM E Described in 1901, t he G ellé syndrome consist s of ipsilat eral deaf ness, vert igo, variable f acial nerve palsy, and cont ralat eral hemiparesis. The lesion is in t he caudal vent rolat eral pons involving t he cochleovest ibular (cranial nerve VI I I ) nerve and cort icospinal t ract f ibers w it h variable involvement of t he f acial nerve.
C. BRISSAUD-SICARD SYNDROM E Described in 1906, t he Brissaud-Sicard syndrome consist s of ipsilat eral f acial hemispasm and cont ralat eral hemiparesis. The lesion is in t he caudal vent ral pons involving f acial nerve (cranial nerve VI I ) root let s and cort icospinal t ract f ibers.
Rostral Basal Pontine Syndrome I f t he basal pont ine lesion occurs more rost rally, at t he level of t he t rigeminal nerve (Figure 8-3), t he manif est at ions include ipsilat eral t rigeminal signs (sensory and mot or) and a cont ralat eral hemiplegia of t he upper mot or neuron variet y.
Pure Motor and Ataxic Hemiparesis Discret e lesions in t he basis pont is have been report ed t o result in pure mot or hemiparesis or at axic hemiparesis. Pure mot or hemiparesis is secondary t o involvement of cort icospinal t ract f ascicles w it hin t he basis pont is. At axic hemiparesis is due t o involvement of cort icospinal t ract f ascicles along w it h pont ocerebellar f ascicles in t he basis pont is.
Dysarthria C lumsy Hand Syndrome Vascular lesions of t he basis pont is at t he junct ion of t he upper t hird and low er t w o-t hirds of t he pons have been associat ed w it h t he dysart hria c lumsy hand syndrome. This syndrome is charact erized by cent ral (supranuclear) f acial w eakness, severe dysart hria and dysphagia, hand paresis, and clumsiness.
Fi gure 8-2. Schemat ic diagram of t he st ruct ures involved in medial and rost ral ext ensions of t he caudal basal pont ine syndrome and t he result ing clinical manif est at ions.
Fi gure 8-3. Schemat ic diagram show ing st ruct ures involved in t he rost ral basal pont ine syndrome and t he result ing clinical manif est at ions.
The Locked-in Syndrome The locked-in syndrome is a severely disabling basal pont ine syndrome t hat is due t o an inf arct in t he vent ral half of t he pons. I n t his syndrome t here is paralysis of all mot or act ivit y as a result of involvement of cort icospinal t ract s in t he basis pont is and aphonia (loss of voice) caused by t he involvement of cort icobulbar f ibers coursing in t he basis pont is. Vert ical gaze and blinking are spared and are t he only means by w hich such pat ient s communicat e. Such pat ient s have been described as c orpses w it h living eyes.
Crying and Laughter Discret e unilat eral or bilat eral vascular lesions in t he basis pont is have been associat ed w it h pat hologic crying and, rarely, laught er. These episodes consist of a sudden onset of involunt ary crying (rarely laught er) last ing about 15 t o 30 seconds. Such emot ional i ncont inence may herald a brain st em st roke, be part of it , or f ollow t he onset of a st roke by a f ew days. The anat omic basis f or t he emot ional incont inence in pont ine lesions has not been est ablished. Most cases of pat hologic crying or laught er are associat ed w it h bilat eral f ront al or pariet al lesions w it h pseudobulbar palsy. Some invest igat ors have post ulat ed t hat lesions
in t he basis pont is int errupt an inhibit ory cort icobulbar pat hw ay t o t he pont ine t egment al cent er f or laughing and crying, essent ially releasing t hat cent er f rom cort ical inhibit ion.
TEGM ENTAL PONTINE SYNDROM ES Tegment al pont ine syndromes are caused by lesions in t he t egment um of t he pons t hat aff ect cranial nerve nuclei or root let s and long t ract s in t he t egment um.
The Medial Tegmental Syndrome St ruct ures aff ect ed in t he medial t egment al syndrome include t he nucleus and root let s of t he abducens nerve (cranial nerve VI ), t he genu of t he f acial nerve, and t he medial lemniscus (Figure 8-4). The manif est at ions of t he lesion t heref ore include ipsilat eral sixt h nerve paralysis and a lat eral gaze paralysis, ipsilat eral f acial paralysis of t he peripheral variet y, and cont ralat eral loss of kinest hesia and discriminat ive t ouch.
The One-and-a-Half Syndrome The one-and-a-half syndrome is charact erized by ipsilat eral lat eral gaze paralysis result ing f rom involvement of t he abducens nucleus and int ernuclear opht halmoplegia (paralysis of adduct ion of t he eye ipsilat eral t o t he lesion and nyst agmus of t he abduct ing eye) as a result of involvement of t he medial longit udinal f asciculus. The vascular lesion is discret e in t he dorsal paramedian t egment um, involving t he abducens nucleus and t he medial longit udinal f asciculus (t ype I one-and-a-half syndrome, Figure 8-5). Type I I one-and-a-half syndrome is associat ed w it h cavernous sinus t hrombosis t hat aff ect s t w o of it s cont ent s: abducens nerve and int ernal carot id art ery. The clinical pict ure is t hat of abducens nerve palsy and cerebral hemisphere (gaze cent er) inf arct ion (Figure 8-6)
Fi gure 8-4. Schemat ic diagram show ing st ruct ures involved in t he t egment al pont ine syndrome and t he result ing clinical manif est at ions.
Fi gure 8-5. O ne-and-a-half syndrome, t ype I . MLF, medial longit udinal f asciculus.
Dorsolateral Tegmental Pontine Syndrome Vascular lesions in t he dorsolat eral pont ine t egment um t hat aff ect st ruct ures supplied by t he ant erior inf erior cerebellar art ery (AI CA) on one side coupled w it h a vascular lesion in t he dorsolat eral medulla t hat aff ect s st ruct ures supplied by t he post erior inf erior cerebellar art ery (PI CA) on t he ot her side have been report ed t o produce dissociat ed sensory loss (loss of pain and t emperat ure sense w it h preservat ion of vibrat ion and posit ion sense) enveloping t he ent ire body, accompanied by t runcal and limb at axia w it hout w eakness. The dissociat ed sensory loss is due t o simult aneous and bilat eral involvement of t he spinot halamic t ract s and t he t rigeminal syst em w it h sparing of t he lemniscal syst em. The at axia is due t o involvement of cerebellar-dest ined f ibers coursing in t he t egment um or, alt ernat ively, t he cerebellum it self .
Caudal Tegmental Pontine Syndromes A. FOVILLE'S SYNDROM E (RAYM OND-FOVILLE SYNDROM E)
Foville's syndrome is charact erized by an ipsilat eral peripheral t ype of f acial nerve palsy and horizont al gaze palsy and cont ralat eral hemiparesis. The lesion usually is in t he caudal pons and involves t he cort icospinal t ract (cont ralat eral hemiparesis), t he paramedian pont ine ret icular f ormat ion (PPRF), and/ or t he abducens nucleus (conjugat e gaze palsy), as w ell as t he nucleus or f ascicles of t he f acial nerve (f acial muscle w eakness).
B. M USICAL HALLUCINOSIS Lat eral or paramedian lesions in t he t egment um of t he caudal pons have been associat ed w it h musical hallucinosis. The musical melodies or sounds are usually f amiliar. The lesion usually involves one or more of t he f ollow ing audit ory st ruct ures: acoust ic st riae (including t he t rapezoid body), superior olivary nucleus, lat eral lemniscus. I n addit ion, t he lesion involves t rigeminal nerve f ibers dest ined t o t he t ensor t ympani muscle and f acial nerve f ibers t o t he st apedius muscle, bot h of w hich t ravel in caudal pons. The hallucinat ions are at t ribut ed t o release of audit ory memories by disinhibit ion of ret icular pat hw ays f rom nucleus raphe pont is t o sensory cent ers in t he t halamus and cerebral cort ex.
Mid-Tegmental Pontine Syndrome (Grenet Syndrome) Described by G renet in 1856, t his syndrome consist s of t hermoanalgesia in bot h sides of t he f ace and t he cont ralat eral t runk, ipsilat eral t rigeminal (cranial nerve V) nerve mot or involvement (paralysis of muscles of mast icat ion), at axia and t remor, and cont ralat eral hemiparesis. The lesion is in mid-pons t egment um and involves t he t rigeminal nucleus and t rigeminot halamic f ibers, superior cerebellar peduncle, and spinot halamic t ract , and it ext ends vent rally t o involve cort icospinal f ibers.
Rostral Tegmental Pontine Syndrome (RaymondCestan-Chenais Syndrome) I n t he Raymond-Cest an-Chenais syndrome t he lesion is in t he rost ral pons and involves t he medial lemniscus, medial longit udinal f asciculus, spinot halamic t ract , and cerebellar f ibers. The manif est at ions are int ernuclear opht halmoplegia (medial longit udinal f asciculus), ipsilat eral at axia (cerebellar f ibers), and hemisensory loss (medial lemniscus and spinot ha-lamic t ract ). Wit h vent ral ext ension, t here may be cont ralat eral hemiparesis due t o cort icospinal t ract involvement .
Fi gure 8-6. O ne-and-a-half syndrome, t ype I I .
Extreme Lateral Tegmental Pontine Syndrome (MarieFoix Syndrome) I n t he Marie-Foix syndrome t here is ipsilat eral cerebellar at axia and cont ralat eral hemiparesis w it h or w it hout hemisensory loss. The lesion in t he rost ral ext reme lat eral pons involves t he brachium pont is (at axia), t he spinot halamic t ract (hemisensory loss), and t he cort icospinal t ract (hemiparesis). The f ull clinical pict ure of t he Marie-Foix syndrome has rarely been report ed and includes ipsilat eral cranial nerve palsies, Horner's syndrome, hemiat axia, palat al myoclonus, and cont ralat eral spinot halamic sensory loss.
Ocular Bobbing and Dipping A variet y of oscillat ory eye movement abnormalit ies have been described in pat ient s w it h pont ine vascular lesions. These abnormalit ies have been ref erred t o as ocular bobbing, inverse ocular bobbing, ocular dipping, and inverse ocular dipping on t he basis of t he predominant oscillat ory abnormalit y.
REM Sleep The pons is also necessary and suff icient t o generat e rapid eye movement (REM) sleep. I n humans, bilat eral pont ine damage may prevent REM sleep.
Central Neurogenic Hyperventilation
Report s in humans suggest t hat medial t egment al pont ine lesions, possibly aff ect ing t he PPRF bilat erally, are associat ed w it h t he syndrome of cent ral neurogenic hypervent ilat ion. This syndrome is charact erized by sust ained t achypnea t hat persist s despit e an elevat ed art erial PO2 and pH and a low art erial PCO2 . I t has been hypot hesized t hat a pont ine lesion of t his t ype disinhibit s inhibit ory pont ine inf luences on medullary respirat ory neurons.
The Pons and Respiration Respirat ion is of t w o t ypes: volunt ary and aut omat ic. Select ive loss of volunt ary respirat ion occurs in pat ient s w it h lesions of t he basis pont is. Select ive loss of volunt ary or aut omat ic respirat ion also has been described as part of t he lockedin syndrome. Aut omat ic respirat ory pat hw ays are presumed t o be init iat ed in limbic cort ex and involve diencephalic st ruct ures, t he ret icular syst em of t he brain st em, t he lat eral or dorsal pons, t he medullary nuclei mediat ing aut omat ic respirat ions, and respirat ory neurons of t he spinal cord. Select ive loss of aut omat ic respirat ion occurs in pat ient s w it h O ndine's curse, lesions of t he medulla oblongat a, or bilat eral high cervical cord lesions.
TERM INOLOGY Ataxia (G reek an, n egative ; taxi s, o rder ) . Wit hout order, disorganized. I ncoordinat ion of movement seen in cerebellar disease. The t erm w as used by Hippocrat es and G alen f or disordered act ion of any t ype, such as irregularit y of pulse. Brissaud, Edward (1852 1 909). French neuropsychiat rist w ho t rained under Charcot and lat er deput ized f or him at t he Salpęt ričre hospit al in Paris. He described t he Brissaud-Sicard pont ine syndrome and many ot her syndromes. Died of brain t umor. Dysarthria (G reek dys, d ifficult ; arthroun, t o utter distinctly ) . I mperf ect art iculat ion of speech caused by a dist urbance of muscular cont rol. Dysphagia (G reek dys, d ifficult ; phagi en, t o eat ) . Diff icult y sw allow ing. Foville syndrome (Raymond-Foville syndrome). A syndrome of alt ernat ing hemiplegia caused by vascular lesions in t he t egment um of t he caudal pons. Charact erized by ipsilat eral f acial nerve palsy and conjugat e gaze paralysis and cont ralat eral hemiparesis. Described by Achille-Louis-François Foville in 1858. Internuclear ophthalmoplegia (MLF syndrome).
A condit ion charact erized by paralysis of ocular adduct ion ipsilat eral t o a medial longit udinal f asciculus (MLF) lesion and monocular nyst agmus in t he cont ralat eral abduct ing eye. Marie-Foix syndrome. A vascular pont ine syndrome charact erized by ipsilat eral cerebellar at axia and cont ralat eral hemiparesis w it h or w it hout hemisensory loss. Described in 1913 by Pierre Marie, a French neurologist , and his st udent , Charles Foix. Millard-G ubler syndrome (caudal basal pontine syndrome). A vascular syndrome of t he caudal basis pont is charact erized by ipsilat eral f acial nerve palsy and cont ralat eral hemiplegia. The syndrome may include abducens nerve palsy. Described by August e Millard and Adolphe-Marie G ubler, French physicians, in 1856. O cular bobbing. Saccadic repet it ive f ast movement of t he eyes dow nw ard w it h a slow ret urn t o t he primary posit ion. Seen in pat ient s w it h severe pont ine dysf unct ion, w ho are usually unresponsive. Described by C. M. Fisher in 1964. O cular dipping (inverse ocular bobbing). Spont aneous eye movement in comat ose pat ient s w it h slow dow nw ard movement and a f ast ret urn t o t he primary posit ion. The reverse of ocular bobbing. Seen in pat ient s w it h disorders of t he pons, basal ganglia, or cerebral cort ex. O ndine's curse. A syndrome charact erized by cessat ion of breat hing in sleep because of f ailure of t he medullary aut omat ic cent er. Named af t er t he st ory of O ndine, a w at er nymph w ho punished her unf ait hf ul husband by depriving him of t he abilit y t o breat he w hile asleep. Raymond-Cestan-Chenais syndrome. A vascular syndrome of t he rost ral t egment um of t he pons charact erized by int ernuclear opht halmoplegia, ipsilat eral at axia, and cont ralat eral mild hemiparesis and hemisensory loss. Described by Fulgence Raymond, Et ienne Jacques-Marie-Raymond Cest an, and L. G . Chenais, French physicians, in 1903. Sicard, Jean-Athenase (1872 1 929). French neurologist w ho, w it h his ment or Brissaud, described t he pont ine Brissaud-Sicard syndrome. He also cont ribut ed t o t he descript ion of t he medullary Collet -Sicard syndrome and t he Sicard-Hagueman syndrome (Meige syndrome, Breughel syndrome, orof acial dyst onia). Tachypnea (G reek tachys, s wift ; pnoi a, b reath ) . Excessive rapidit y of respirat ion.
SUGGESTED READINGS Asf ora WT et al: I s t he syndrome of pat hological laughing and crying a
manif est at ion of pseudobulbar palsy? J Neurol Neurosurg Psychi atry 1989; 52: 523 5 25. Ash PR, Kelt ner JL: Neuro-opht halmic signs in pont ine lesions. Medi ci ne (Bal ti more) 1979; 58: 304 3 20. Basset t i C et al: I solat ed inf arct s of t he pons. Neurol ogy 1996; 46: 165 1 75. Brazis PW: The localizat ion of lesions aff ect ing t he brainst em. I n Brazis PW et al (eds): Local i zati on i n Cl i ni cal Neurol ogy. Bost on, Lit t le, Brow n, 1985: 225 2 38. Cart er JE, Rauch RA: O ne-and-a-half syndrome, t ype I I . Arch Neurol 1994; 51: 87 8 9. Deleu D et al: Dissociat ed ipsilat eral horizont al gaze palsy in one-and-a-half syndrome: A clinicopat hologic st udy. Neurol ogy 1988; 38: 1278 1 280. Fisher CM: O cular bobbing. Arch Neurol 1964; 11: 543 5 46. Fisher CM: Some neuro-opht halmologic observat ions. J Neurol Neurosurg Psychi atry 1967; 30: 383 3 92. Fisher CM: At axic hemiparesis: A pat hologic st udy. Arch Neurol 1978; 35: 126 1 28. G oebel HH et al: Lesions of t he pont ine t egment um and conjugat e gaze paralysis. Arch Neurol 1971; 24: 431 4 40. Jaeckle KA et al: Cent ral neurogenic hypervent ilat ion: Pharmacologic int ervent ion w it h morphine sulf at e and correlat ive analysis of respirat ory, sleep, and ocular mot or dysf unct ion. Neurol ogy 1990; 40: 1715 1 720. Kushida CA et al: Cort ical asymmet ry of REM sleep EEG f ollow ing unilat eral pont ine hemorrhage. Neurol ogy 1991; 41: 598 6 01. Mat lis A et al: Radiologic-clinical correlat ion, Millard-G ubler syndrome. AJNR 1994; 15: 179 1 81. Munschauer FE et al: Select ive paralysis of volunt ary but not limbically inf luenced aut omat ic respirat ion. Arch Neurol 1991; 48: 1190 1192.
Pryse-Phillips W: Compani on to Cl i ni cal Neurol ogy. Bost on, Lit t le, Brow n, 1995. Rot hst ein TL, Alvord EC: Post erior int ernuclear opht halmoplegia: A clinicopat hologic st udy. Arch Neurol 1971; 24: 191 2 02. Schielke E et al: Musical hallucinat ions w it h dorsal pont ine lesions. Neurol ogy 2000; 55: 454 4 55. Silverman I E et al: The crossed paralyses. The original brain-st em syndromes of Millard-G ubler, Foville, Weber, and Raymond Cest an. Arch Neurol 1995; 52: 635 6 38. St iller J et al: Brainst em lesions w it h pure mot or hemiparesis. Comput ed t omographic demonst rat ion. Arch Neurol 1982; 39: 660 6 61. Tat emichi TK et al. Pat hological crying: A pont ine pseudobulbar syndrome. Ann Neurol 1987; 22: 133. Troost BT: Signs and sympt oms of st roke syndromes of t he brain st em. I n Hoff erbert h B et al (eds): Vascul ar Brai n Stem Di seases. Basel, Karger, 1990: 112. Venna N, Sabin TD: Universal dissociat ed anest hesia due t o bilat eral brainst em inf arct s. Arch Neurol 1985; 42: 918 9 22. Wall M, Wray SH: The one-and-a-half syndrome: A unilat eral disorder of t he pont ine t egment um: A st udy of 20 cases and review of t he lit erat ure. Neurol ogy 1983; 33: 971 9 80. Yarnell PR: Pat hological crying localizat ion. Ann Neurol 1987; 22: 133 1 34.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 9 - Mes enc ephalon ( Midbr ain)
9 Mesencephalon (Midbrain)
Gross Topography Ventral View Dorsal View Microscopic Structure General Organization Inferior Colliculus Level Superior Colliculus Level Light Reflex Afferent Pathway Efferent Pathway Accom m odation-Convergence Reflex Mesencephalic Reticular Form ation Vertical Gaze Control of Saccadic Eye Movem ent Sm ooth Pursuit Eye Movem ents Blood Supply Inferior Colliculus Level Superior Colliculus Level Pretectal Level KEY CONCEPTS In cross section the mesencephalon is divided into three regions: the tectum, the tegmentum, and the
basal portion. The inferior colliculus receives inputs from the lateral lemniscus, medial geniculate body, primary auditory cortex, and cerebellar cortex. The output of the inferior colliculus is to the medial geniculate body, nucleus of the lateral lemniscus, superior colliculus, and cerebellum. Axons of trochlear neurons form the trochlear nerve, the smallest cranial nerve and the only one that decussates before exiting the neuraxis from the dorsal surface of the midbrain. In the cerebral peduncle, corticospinal fibers occupy the middle three-fifths, flanked on each side by corticopontine fibers. The substantia nigra receives inputs from the neostriatum, cerebral cortex, globus pallidus, subthalamic nucleus, and midbrain reticular formation. The output of the substantia nigra is to the neostriatum, limbic cortex, globus pallidus, red nucleus, subthalamic nucleus, thalamus, superior colliculus, midbrain reticular formation, and amygdala. On the basis of its projection sites, the mesencephalic dopaminergic system is subdivided into mesostriatal, mesoallocortical, and mesoneocortical subdivisions. The superior colliculus receives inputs from the cerebral cortex, retina, spinal cord, and inferior colliculus. The output of the superior colliculus is to the spinal cord, pontine nuclei, reticular formation of the
midbrain, and thalamus. The pretectal area is involved in the pupillary light reflex and vertical gaze. Input to the red nucleus comes mainly from the deep cerebellar nuclei and the cerebral cortex. The output of the red nucleus is mainly to the spinal cord, cerebellum, reticular formation, and inferior olive. Somatic motor neurons of the oculomotor nucleus are organized into subnuclei that correspond to the eye muscles supplied by the oculomotor nerve. All these subnuclei supply ipsilateral muscles except the superior rectus subnucleus, which supplies the contralateral superior rectus muscle, and the levator palpebrae subnucleus, which supplies both levator palpebrae muscles. Lesions of the oculomotor nerve within the midbrain result in oculomotor nerve palsy and either contralateral tremor (if the red nucleus is concomitantly involved) or contralateral upper motor neuron paralysis (if the cerebral peduncle is involved). Accessory oculomotor nuclei include Cajal's interstitial nucleus, rostral interstitial nucleus of the medial longitudinal fasciculus (RiMLF), Darkschewitsch's nucleus, and nucleus of the posterior commissure. The periaqueductal (central) gray region is concerned with modulation of pain, vocalization, control of reproductive behavior, modulation of medullary respiratory centers, aggressive behavior, and vertical gaze.
Constriction of the pupil ipsilateral to light stimulation constitutes the direct light reflex; constriction of the pupil contralateral to light stimulation constitutes the consensual light reflex. In an Argyll Robertson pupil, light reflex is lost while accommodation convergence is preserved. The midbrain reticular formation is involved in wakefulness and sleep. The neural substrates for vertical gaze consist of the ocular motor neurons of cranial nerves III and IV, the rostral interstitial nucleus of the medial longitudinal fasciculus, interstitial nucleus of Cajal, nucleus of the posterior commissure, the posterior commissure, the mesencephalic reticular formation, and the medial longitudinal fasciculus. Saccadic eye movements are controlled by cortical inputs to the brain stem pulse generators either directly or indirectly via the superior colliculus. Brain stem pulse generators for horizontal saccades are in the paramedian pontine reticular formation, and for vertical saccades they are in the midbrain (RiMLF). Smooth pursuit eye movements are controlled by input from cortical areas 8, 19, 37, and 39 to the dorsolateral pontine nucleus and the nucleus reticularis tegmenti pontis and cerebellum. The midbrain receives the bulk of its blood supply from the basilar artery via the paramedian, superior cerebellar, and posterior cerebral branches.
GROSS TOPOGRAPHY
Ventral View The inf erior surf ace of t he mesencephalon (midbrain) is marked by t he divergence of t w o massive bundles of f ibers t he cerebral peduncles w hich carry cort icof ugal f ibers t o low er levels (Figure 9-1). Caudally, t he cerebral peduncles pass int o t he basis pont is; rost rally, t hey cont inue int o t he int ernal capsule. Bet w een t he cerebral peduncles lies t he int erpeduncular f ossa, f rom w hich exit s t he oculomot or nerve (cranial nerve I I I ). The t rochlear nerve (cranial nerve I V) emerges f rom t he dorsal aspect of t he mesencephalon, curves around, and appears at t he lat eral borders of t he cerebral peduncles. The opt ic t ract passes under t he cerebral peduncles bef ore t he peduncles disappear int o t he subst ance of t he cerebral hemispheres.
Dorsal View The dorsal surf ace of t he mesencephalon f eat ures f our elevat ions (corpora quadrigemina) (see Figure 5-2). The rost ral and larger t w o are t he superior colliculi; t he caudal and smaller t w o are t he inf erior colliculi. The t rochlear nerves emerge just caudal t o t he inf erior colliculi.
M ICROSCOPIC STRUCTURE General Organization Three subdivisions are generally recognized in sect ions of t he mesencephalon ( Figure 9-2). 1. The t ect um is a mixt ure of gray and w hit e mat t er dorsal t o t he cent ral gray mat t er. I t includes t he superior and inf erior colliculi (quadrigeminal plat es). The t erm quadri gemi nal pl ate w as coined by Vesalius t o ref er t o t he t ect um. Anat omist s of t hat t ime w ant ed t o name t he superior and inf erior colliculi af t er t he Lat in equivalent s f or t he t est es and but t ocks. The overlying pineal gland, w hich looked like a pinecone t o t he G reeks, w as mist aken f or a penis. This w as t oo explicit f or Vesalius, w ho renamed t he t ect um t he quadrigeminal plat e.
Fi gure 9-1. Schemat ic diagram of t he vent ral surf ace of t he midbrain and pons show ing major midbrain st ruct ures encount ered on t his surf ace.
2. The t egment um, t he main port ion of t he mesencephalon, lies inf erior t o t he cent ral gray mat t er and cont ains ascending and descending t ract s, ret icular nuclei, and w ell-delineat ed nuclear masses.
Fi gure 9-2. Cross-sect ional diagram of t he midbrain show ing it s major subdivisions.
3. The basal port ion includes t he cerebral peduncles, a massive bundle of cort icof ugal f ibers on t he vent ral aspect of t he mesencephalon, and t he subst ant ia nigra, a pigment ed nuclear mass t hat lies bet w een t he dorsal surf ace of t he cerebral peduncle and t he t egment um. The t erm basi s
peduncul i has been used t o ref er t o t he basal port ion of t he mesencephalon, w hich includes t he cerebral peduncle and subst ant ia nigra. The t erm crus cerebri has been used t o ref er t o t he massive bundle of cort icof ugal f ibers (cerebral peduncle) on t he vent ral aspect of t he mesencephalon. Not f requent ly, t he t erm cerebral peduncl e is erroneously used t o ref er t o t he mesencephalon below t he t ect um (t egment um and basal port ion). The component s of t hese subdivisions are discussed below under t w o charact erist ic levels of t he mesencephalon: t he inf erior colliculus and t he superior colliculus. The inf erior colliculus level is charact erized in hist ologic sect ions by t he decussat ion of t he superior cerebellar peduncle and by t he f ourt h nerve (t rochlear) nucleus. The superior colliculus level is charact erized by t he red nucleus, t he t hird nerve (oculomot or) nucleus, and t he post erior commissure.
Inferior Colliculus Level A. TECTUM The nucleus of t he inf erior colliculus occupies t he t ect um at t he level of t he inf erior colliculus. This nucleus is an oval mass of small and medium-size neurons organized int o t hree part s: (1) main laminat ed mass of neurons, called t he cent ral nucleus, (2) a t hin dorsal cellular layer, t he pericent ral nucleus, and (3) a group of neurons t hat surround t he cent ral nucleus lat erally and vent rally, t he ext ernal nucleus. The cent ral nucleus is t he major relay nucleus in t he audit ory pat hw ay. High-f requency sounds are represent ed in t he vent ral part , and low f requency sounds in t he dorsal part of t he nucleus (similar t o t hat in t he cochlea). The pericent ral nucleus receives only cont ralat eral monaural input and serves t o direct audit ory at t ent ion. The ext ernal nucleus is relat ed primarily t o acoust icomot or ref lexes. The inf erior colliculus has t he f ollow ing aff erent and eff erent connect ions.
1. Afferent Connections (Figure 9-3) Fibers come f rom t he f ollow ing sources. 1.
Lateral l emni scus. These f ibers t erminat e on t he ipsi- and cont ralat eral inf erior colliculi. Some lat eral lemniscus f ibers bypass t he inf erior colliculus t o reach t he medial geniculat e body.
2. Contral ateral i nf eri or col l i cul us. 3. Ipsi l ateral medi al geni cul ate body. This connect ion serves as a f eedback mechanism in t he audit ory pat hw ay. 4. Cerebral cortex ( pri mary audi tory cortex). 5. Cerebel l ar cortex vi a the anteri or medul l ary vel um.
2. Efferent Connections The inf erior colliculus project s t o t he f ollow ing areas (Figure 9-4). 1.
Medi al geni cul ate body vi a the brachi um of the i nf eri or col l i cul us. This pat hw ay is concerned w it h audit ion.
2. Contral ateral i nf eri or col l i cul us. 3. Superi or col l i cul us. This pat hw ay est ablishes ref lexes f or t urning t he neck and eyes in response t o sound. 4. Nucl eus of the l ateral l emni scus and other rel ay nucl ei of the audi tory system f or f eedback. 5. Cerebel l um. The inf erior colliculus is a major cent er f or t he t ransmission of audit ory impulses t o t he cerebellum via t he ant erior medullary velum. The inf erior colliculus t hus is a relay nucleus in t he audit ory pat hw ay t o t he cerebral cort ex and cerebellum. I n addit ion, t he inf erior colliculus plays a role in t he localizat ion of t he source of sound.
Fi gure 9-3. Schemat ic diagram show ing t he major aff erent connect ions of t he inf erior colliculus.
Fi gure 9-4. Schemat ic diagram show ing t he major eff erent connect ions of t he inf erior colliculus.
B. TEGM ENTUM At t he level of t he inf erior colliculus, t he t egment um of t he mesencephalon cont ains f ibers of passage (ascending and descending t ract s) and nuclear groups.
1. Fibers of Passage The f ollow ing f iber t ract s pass t hrough t he mesencephalon (Figure 9-5).
a. Brach iu m con ju n ctivu m (su perior cerebellar pedu n cle)
The brachium conjunct ivum is a massive bundle of f ibers arising in t he deep cerebellar nuclei. These f ibers decussat e in t he t egment um of t he midbrain at t his level. A f ew proceed rost rally t o t erminat e on t he red nucleus; t he ot hers f orm t he capsule of t he red nucleus and cont inue rost rally t o t erminat e on t he vent rolat eral nucleus of t he t halamus.
b. Medial lemn iscu s The medial lemniscus lies lat eral t o t he decussat ing brachium conjunct ivum and above t he subst ant ia nigra. This f iber syst em, w hich conveys kinest hesia and discriminat ive t ouch f rom more caudal levels, cont inues it s course t ow ard t he t halamus. Fibers in t he medial lemniscus are somat ot opically organized, w it h cervical f ibers being most medial and sacral f ibers most lat eral.
c. Trigemin al lemn iscu s The t rigeminal lemniscus is composed of t he vent ral secondary t rigeminal t ract s and t ravels close t o t he medial lemniscus on it s w ay t o t he t halamus.
d. Spin oth alamic tract The spinot halamic t ract conveys pain and t emperat ure sensat ions f rom t he cont ralat eral half of t he body and lies lat eral t o t he medial lemniscus. Mingled w it h t he spinot halamic f ibers are t he spinot ect al f ibers on t heir w ay t o t he t ect um. Fibers in t he spinot halamic t ract are somat ot opically organized, w it h cervical f ibers being most medial and sacral f ibers most lat eral.
e. Lateral lemn iscu s The lat eral lemniscus conveys audit ory f ibers and occupies a posit ion lat eral and dorsal t o t he spinot halamic t ract .
f. Medial lon gitu din al fascicu lu s The medial longit udinal f asciculus maint ains it s posit ion dorsally in t he t egment um in a paramedian posit ion.
g. Cen tral tegmen tal tract The cent ral t egment al t ract conveys f ibers f rom t he basal ganglia and midbrain t o t he inf erior olive and occupies a dorsal posit ion in t he t egment um, vent rolat eral t o t he medial longit udinal f asciculus.
h . Ru brospin al tract The rubrospinal t ract conveys f ibers f rom t he red nucleus t o t he spinal cord and inf erior olive and is locat ed dorsal t o t he subst ant ia nigra.
C. NUCLEAR GROUPS
The f ollow ing nuclei are seen at t he level of t he inf erior colliculus (Figure 9-6).
1. Mesencephalic Nucleus The mesencephalic nucleus of t he t rigeminal nerve is homologous in st ruct ure t o t he dorsal root ganglion but is uniquely placed w it hin t he cent ral nervous syst em. I t cont ains unipolar neurons w it h axons (t he mesencephalic root of t he t rigeminal nerve) w hich convey propriocept ive impulses f rom t he muscles of mast icat ion and t he periodont al membranes. As t hese f ibers approach t he nucleus, t hey gat her in a bundle close t o t he nucleus: t he mesencephalic t ract .
2. Nucleus of the Trochlear Nerve (Cranial Nerve IV) The nucleus of t he t rochlear nerve lies in t he V-shaped vent ral part of t he cent ral gray mat t er. Axons of t his nerve arch around t he cent ral gray mat t er, cross in t he ant erior medullary velum, and emerge f rom t he dorsal aspect of t he mesencephalon (Figure 9-7). These axons supply t he superior oblique eye muscle. The t rochlear nerve is t hus unique in t w o respect s: I t is t he only cranial nerve t hat crosses bef ore emerging f rom t he brain st em, and it is t he only cranial nerve t hat emerges on t he dorsal aspect of t he brain st em. Because of decussat ion, lesions of t he t rochlear nucleus result in paralysis of t he cont ralat eral superior oblique muscle, w hereas lesions of t his nerve af t er it emerges f rom t he brain st em result in paralysis of t he ipsilat eral superior oblique muscle. The superior oblique muscle has t hree act ions: primary of int orsion, secondary of depression, and t ert iary of abduct ion. I t t hus act s by int orsion of t he abduct ed eye and depression of t he adduct ed eye. Pat ient s w it h t rochlear nerve lesions complain of vert ical diplopia (double vision) t hat is especially marked in looking cont ralat erally dow nw ard w hile descending st airs and usually is correct ed by head t ilt (t ow ard t he normal nerve) t o compensat e f or t he act ion of t he paralyzed muscle. Tilt ing t he head t ow ard t he paret ic nerve increases double vision. The t rochlear nucleus receives cont ralat eral and probably some ipsilat eral cort icobulbar f ibers and vest ibular f ibers f rom t he medial longit udinal f asciculus t hat are concerned w it h coordinat ion of eye movement s. Vest ibular f ibers t o t he t rochlear nucleus originat e f rom t he superior and medial vest ibular nuclei. The f ibers f rom t he superior vest ibular nucleus are ipsilat eral and inhibit ory; t hose f rom t he medial vest ibular nucleus are cont ralat eral and excit at ory.
Fi gure 9-5. Schemat ic diagram of t he midbrain at t he inf erior colliculus level, show ing t he major ascending and descending t ract s.
Fi gure 9-6. Schemat ic diagram of t he midbrain at t he inf erior colliculus level show ing major nuclear groups seen at t his level.
Fi gure 9-7. Schemat ic diagram of t he midbrain show ing origin, int ra-axial course of t he t rochlear nerve, and t he ext raocular muscle supplied by t he nerve.
3. Interpeduncular Nucleus The int erpeduncular nucleus, w hich is indist inct in humans, is a poorly underst ood nuclear group in t he base of t he t egment um bet w een t he cerebral peduncles. I t receives f ibers mainly f rom t he habenular nuclei (in t he diencephalon) t hrough t he habenuloint erpeduncular t ract and sends f ibers t o t he dorsal t egment al nucleus t hrough t he pedunculot egment al t ract .
4. Nucleus Parabrachialis Pigmentosus The nucleus parabrachialis pigment osus, w hich lies bet w een t he subst ant ia nigra and t he int erpeduncular nucleus, is a vent ral ext ension of t he vent ral t egment al area of Tsai.
5. Dorsal Tegmental Nucleus The dorsal t egment al nucleus lies dorsal t o t he medial longit udinal f asciculus (MLF) in t he cent ral gray mat t er in close proximit y t o t he dorsal raphe nucleus. I t receives f ibers f rom t he int erpeduncular nucleus and project s on aut onomic nuclei of t he brain st em and t he ret icular f ormat ion.
6. Ventral Tegmental Nucleus The vent ral t egment al nucleus lies vent ral t o t he MLF in t he midbrain t egment um. Cells in t his nucleus are rost ral cont inuat ions of t he superior cent ral nucleus of t he pons. This nucleus receives f ibers f rom t he mamillary bodies in t he
hypot halamus. The dorsal and vent ral t egment al nuclei are part of a circuit concerned w it h emot ion and behavior.
7. Pedunculopontine (Nucleus Tegmenti Pedunculopontis) and Lateral Dorsal Tegmental Nuclei These t w o cholinergic nuclei lie w it hin t he t egment um of t he caudal mesencephalon (inf erior colliculus level) and rost ral pons dorsolat eral t o and overlapping t he lat eral margin of t he rost ral superior cerebellar peduncle, bet w een t hat peduncle and t he lat eral lemniscus. Neurons of t he pedunculopont ine nucleus are aff ect ed in pat ient s w it h progressive supranuclear palsy, a degenerat ive cent ral nervous syst em disease. I t project s t o t he t halamus and t he pars compact a of t he subst ant ia nigra. This nucleus lies in a region f rom w hich w alking movement s can be elicit ed on st imulat ion (locomot or cent er).
8. Nucleus Supratrochlearis (Dorsal Raphe Nucleus) The nucleus suprat rochlearis lies in t he vent ral part of t he periaqueduct al (cent ral) gray mat t er bet w een t he t w o t rochlear nuclei. I t sends serot onergic f ibers t o t he subst ant ia nigra, neost riat um (caudat e and put amen), and neocort ex.
9. Parabigeminal Area The parabigeminal area is an oval collect ion of cholinergic neurons vent rolat eral t o t he nucleus of t he inf erior colliculus and lat eral t o t he lat eral lemniscus. I t receives f ibers f rom superf icial layers of t he superior colliculus and project s bilat erally back int o superf icial layers of t he superior colliculus. Cells in t his area play a role, along w it h t he superior colliculus, in processing visual inf ormat ion. They respond t o visual st imuli and are act ivat ed by bot h moving and st at ionary visual st imuli.
10. Nucleus Pigmentosus (Locus Ceruleus) The nucleus pigment osus is seen in t he rost ral pons and caudal mesencepha-lon. I t cont ains 30, 000 t o 35, 000 neurons. At t he level of t he inf erior colliculus it is sit uat ed at t he edge of t he cent ral gray mat t er. I t is made up of f our subnuclei: cent ral (largest ); ant erior (rost ral end); vent ral (caudal and vent ral), also know n as t he nucleus subceruleus; and post erior dorsal (small). I t s pigment ed cells cont ain melanin granules, w hich are lost in pat ient s w it h Parkinson's disease. The neurons of t he locus ceruleus provide noradrenergic innervat ion t o most cent ral nervous syst em regions. Axons of t he neurons in t he locus ceruleus are elaborat ely branched and ramif y pract ically t hroughout t he brain. These axons reach t heir dest inat ions via t hree major ascending t ract s: t he cent ral t egment al
t ract , t he dorsal longit udinal f asciculus, and t he medial f orebrain bundle. Through t hese t ract s, t he locus ceruleus innervat es t he t halamus, hypot halamus, and basal t elencephalon. I n addit ion, t he locus ceruleus project s t o t he cerebellum (via t he brachium conjunct ivum), t o t he spinal cord and t o sensory nuclei of t he brain st em. This nucleus is believed t o play a role in t he regulat ion of respirat ion as w ell as in t he rapid eye movement (REM) st age of sleep.
D. BASAL PORTION At t he level of t he inf erior colliculus, t he basal port ion of t he mesencephalon includes t he cerebral peduncles and t he subst ant ia nigra.
1. Cerebral Peduncle The cerebral peduncle (Figure 9-8) is a massive f iber bundle t hat occupies t he most vent ral part of t he mesencephalon. I t is cont inuous w it h t he int ernal capsule rost rally and merges caudally int o t he basis pont is. This massive f iber bundle carries cort icof ugal f ibers f rom t he cerebral cort ex t o several subcort ical cent ers. The middle t hree-f if t hs of t he cerebral peduncle is occupied by t he cort icospinal t ract , w hich is cont inuous caudally w it h t he pyramids. Fibers dest ined t o t he arm are medially locat ed, t hose t o t he leg are lat erally placed, and t runk f ibers lie in bet w een. The cort icopont ine f ibers occupy t he areas of t he cerebral peduncle on each side of t he cort icospinal t ract . The medially locat ed cort icopont ine f ibers const it ut e t he f ront opont ine project ion; t he lat erally locat ed f ibers const it ut e t he pariet o-occipit o-t emporo-pont ine project ions. Cort icopont ine f ibers originat e in w ide areas of t he cerebral cort ex, synapse on pont ine nuclei, and ent er t he cont ralat eral cerebellar hemisphere via t he middle cerebellar peduncle (brachium pont is). The cort icobulbar f ibers dest ined f or cranial nerve nuclei occupy a dorsomedial posit ion among t he cort icospinal f ibers. According t o some st udies, t he cerebral peduncle in humans has t w o groups of cort icobulbar t ract s. Those in t he medial port ion of t he peduncle descend t o t he pont ine neurons responsible f or gaze; t hose in t he lat eral port ion descend t o t he mot or nuclei of cranial nerves V, VI I , and XI I and t he nucleus ambiguus.
Fi gure 9-8. Schemat ic diagram of t he midbrain show ing t he major subdivisions of t he cerebral peduncle.
2. Substantia Nigra The subst ant ia nigra w as f irst ident if ied by Felix Vicq d'Azyr, a French physician in 1786. I t w as t hen considered t o be part of t he oculomot or nerve because of it s proximit y t o oculomot or nerve root let s. The subst ant ia nigra is a pigment ed mass of neurons sandw iched bet w een t he cerebral peduncles and t he t egment um. I t is composed of t w o zones: a dorsal zona compact a cont aining melanin pigment and a vent ral zona ret iculat a cont aining iron compounds. Dendrit es of neurons in t he zona compact a arborize in t he zona ret iculat a. The pars lat eralis represent s t he oldest part of t his nucleus. The neuronal populat ion of t he subst ant ia nigra consist s of pigment ed and nonpigment ed neurons. Pigment ed neurons out number nonpigment ed neurons t w o t o one. The neurot ransmit t er in pigment ed neurons is dopamine. Nonpigment ed neurons are eit her cholinergic or G ABAergic. There is a charact erist ic pat t ern of neuronal loss in t he subst ant ia nigra in diff erent disease st at es (Table 9-1). Bot h pigment ed and nonpigment ed neurons are lost in pat ient s w it h Hunt ingt on's chorea. O nly pigment ed (dopaminergic) neurons, especially t hose in t he cent er of t he subst ant ia nigra, are lost in idiopat hic Parkinson's disease. I n t he post encephalit ic t ype of Parkinson's disease, pigment ed (dopaminergic) neurons are lost unif ormly. I n Parkinson's disease d ement ia complex, t here is a unif orm loss of bot h pigment ed and nonpigment ed neurons. Finally, in mult iple syst em at rophy, pigment ed neurons are lost in medial and lat eral nigral zones. Nigral neurons (variable number) show abnormal (reduced) immunost aining f or complex I of t he mit ochondrial elect ron t ransport syst em in pat ient s w it h Parkinson's disease. This reduct ion is believed t o be relat ed t o t he pat hogenesis of t he disease. The neural connect ivit y of t he subst ant ia nigra suggest s an import ant role in t he regulat ion of mot or act ivit y. Lesions of t he subst ant ia nigra are almost
alw ays seen in Parkinson's disease, w hich is charact erized by t remor, rigidit y, and slow ness of mot or act ivit y. The know n aff erent and eff erent connect ions of t he subst ant ia nigra are out lined below.
Tabl e 9-1. Substantia Nigra: Pattern of Cell Loss
Type of cell
Idiopathic Postencepha Huntington's Parkinson's Parkinson disease disease disease
Pigmented neurons
X
Nonpigmented neurons
X
X
X
Distribution Uniform loss
X
Central loss
Medial
Lateral
X
a. Afferen t con n ection s (Figu re 9-9) (1) Neostriatu The neost riat al input t o t he subst ant ia nigra is t he largest and project s primarily t o t he pars ret iculat a w it h a smaller input t o t he pars compact a. I t arises f rom t he associat ive region of t he neost riat um primarily f rom t he caudat e nucleus. The neurot ransmit t er is gamma-aminobut yric acid (G ABA). The st riat onigral f ibers are t opographically organized so t hat t he head of t he caudat e
nucleus project s t o t he rost ral t hird of t he subst ant ia nigra, w hile t he put amen project s t o all t he ot her part s of t he nigra.
(2) Cerebral Cortex The cort iconigral project ion is not as massive as w as previously believed. Most of t hese f ibers are f ibers of passage, and relat ively f ew of t hem t erminat e on nigral neurons.
(3) Globus Pallidus The input t o t he subst ant ia nigra f rom t he globus pallidus arises f rom t he ext ernal (lat eral) segment . I t is composed of G ABAergic f ibers t hat t erminat e mainly on pars ret iculat a, w it h some in t he pars compact a.
Fi gure 9-9. Schemat ic diagram show ing t he major aff erent and eff erent connect ions of t he subst ant ia nigra.
(4) Subthalamic Nucleus The subt halamic nucleus project s in a pat chy manner t o pars ret iculat a. The t ransmit t er is glut amine.
(5) Tegmentonigral Tracts The t egment onigral t ract s arise f rom t he midbrain raphe nuclei, w hich have serot onin and cholecyst okinin, and f rom t he pedunculopont ine nucleus, w hich is cholinergic.
b. Efferen t con n ection s (Figu re 9-9) (1) Nigrostriate Fibers Nigrost riat e f ibers f rom t he pars compact a project t o t he neost riat um (caudat e and put amen) and are dopaminergic. The nigrost riat e project ion is somat ot opically organized so t hat neurons in t he lat eral part of t he pars compact a of t he subst ant ia nigra project t o t he put amen, w hereas t he caudat e nucleus receives it s nigral input mainly f rom t he medial part . The nigrost riat e project ions t erminat e on t he associat ive sensorimot or and limbic st riat um. The sit es of origin of t he project ions t o t he caudat e and put amen are segregat ed in t he pars compact a. Cells in t he pars compact a project t o t he caudat e nucleus or t he put amen but not t o bot h. Dopaminergic nigral project ions t o t he neost riat um t erminat e on dist al dendrit es of medium spiny (project ion) neurons. They f acilit at e neost riat al neurons t hat project t o t he pars ret iculat a of t he subst ant ia nigra and t he int ernal (medial) segment of t he globus pallidus and inhibit neost riat al neurons t hat project t o t he ext ernal (lat eral) segment of t he globus pallidus.
(2) Nigrocortical Tract The nigrocort ical f ibers originat e in t he medial zona compact a and t he adjacent vent ral t egment al area, course t hrough t he medial f orebrain bundle, and t erminat e in t he limbic cort ex. The involvement of t his pat hw ay in parkinsonism may explain t he akinesia seen in t hat disease. Anot her project ion f rom t he subst ant ia nigra and t he vent ral t egment al area t erminat es in t he neocort ex. The f unct ion of t his project ion is not know n but may be relat ed t o cognit ion.
(3) Nigropallidal Tract Nigropallidal project ions are more abundant in t he associat ive pallidal t errit ory compared w it h t he sensorimot or t errit ory.
(4) Nigrorubral Tract A project ion t o t he red nucleus f rom t he subst ant ia nigra has been described in experiment al animals.
(5) Nigrosubthalamic Tract The connect ions bet w een t he subst ant ia nigra and subt halamic nucleus are reciprocal.
(6) Nigrothalamic Tract The nigrot halamic G ABAergic t ract runs f rom t he pars ret iculat a t o t he vent ral ant erior, vent ral lat eral, and dorsomedial nuclei of t he t halamus.
(7) Nigrotegmental Tract and Nigrocollicular Tract The nigrot egment al and nigrocollicular t ract s originat e f rom separat e regions of t he pars ret icularis of t he subst ant ia nigra. They are bot h G ABAergic. The nigrot egment al t ract links t he subst ant ia nigra w it h t he ret icular f ormat ion and w it h t he spinal cord via t he ret iculospinal project ion. The nigrocollicular t ract links t he subst ant ia nigra w it h t he superior colliculus and secondarily w it h t he cont rol of ocular movement as w ell as w it h t he spinal cord (t ect ospinal t ract ). Through it s connect ions w it h t he basal ganglia and t he superior colliculus and ret icular f ormat ion, t he subst ant ia nigra act s as a link t hrough w hich t he basal ganglia exert an eff ect on spinal and ocular movement s.
(8) Nigroamygdaloid Tract The nigroamygdaloid t ract originat es f rom dopaminergic neurons in t he zona compact a and t he pars lat eralis of t he subst ant ia nigra and project s on t he lat eral and cent ral amygdaloid nuclei. The nigral origin of many of t hese eff erent f iber syst ems requires f urt her explorat ion. The G ABAergic out put s f rom t he pars ret iculat a of t he subst ant ia nigra t o t he t halamus, superior colliculus, and ret icular f ormat ion are believed t o play a role in suppressing t he progression of epilept ic discharge. A marked increase in met abolic act ivit y in t he subst ant ia nigra has been report ed t o occur during epilept ic discharge. Nigrot halamic, nigrot ect al, and nigrot egment al pat hw ays originat e f rom separat e regions in t he pars ret iculat a.
E. M ESENCEPHALIC DOPAM INERGIC CELL GROUPS Besides t he pars compact a of t he subst ant ia nigra, t w o ot her cell groups in t he mesencephalic t egment um are dopaminergic: t he vent ral t egment al area of Tsai in close proximit y t o t he medial subst ant ia nigra and t he ret rorubral cell group (subst ant ia nigra, pars dorsalis) in close proximit y t o t he red nucleus. The pars compact a of t he subst ant ia nigra in humans (area A-9 of primat es) is closely associat ed, and merges w it h t he immediat ely adjacent dopamine cell groups of t he vent ral t egment al area, t he most prominent of w hich is t he nucleus parabrachialis pigment osus. The vent ral t egment al area corresponds t o area A10, and t he ret rorubral nucleus corresponds t o area A-8. St udies in primat es and humans have ident if ied t hree subdivisions of t he mesencephalic dopaminergic syst em on t he basis of t heir project ion sit es. O ne subdivision is relat ed t o t he st riat um (mesost riat al subdivision) and
t erminat es on t he caudat e nucleus, put amen, globus pallidus, and nucleus accumbens. The second subdivision is relat ed t o t he allocort ex (mesoallocort ical subdivision) and t erminat es on t he amygdala, olf act ory t ubercle, sept al area, and pirif orm cort ex. The t hird subdivision is relat ed t o t he neocort ex (mesoneocort ical) and t erminat es in all neocort ical areas (f ront al, t emporal, pariet al, and occipit al cort ices). Recent ly, a dopaminergic project ion t o t he cerebellar cort ex f rom t he vent ral t egment al area of Tsai w as described, possibly as part of t he hypot halamo-t egment al-cerebellar hypot halamic loop. The t erm mesostri atal is used t o describe t he f irst subdivision in pref erence t o t he t erm ni grostri atal system, since evidence suggest s t hat bot h t he vent ral t egment al area and t he subst ant ia nigra cont ribut e t o t his project ion. A reduct ion in dopaminergic neurot ransmission in t his syst em is associat ed w it h parkinsonism. Hyperact ivit y of t his syst em has been implicat ed in Hunt ingt on's chorea. Hyperact ivit y in t he mesoallocort ical subdivision is believed t o play a role in t he sympt omat ology of psychot ic disorders, w hereas a reduct ion in f unct ion may cont ribut e t o t he cognit ive abnormalit ies f ound in pat ient s w it h Parkinson's disease. Very lit t le is know n about t he f unct ional role of t he mesoneocort ical syst em. Some researchers have suggest ed a role in human cognit ion. A decrease in dopamine in t his syst em may explain cognit ive impairment s in pat ient s w it h Parkinson's disease. A decrease in dopamine in t he visual cort ex has been implicat ed in phot osensit ive epilepsy (Table 9-2). Tw o t ypes of response mode have been demonst rat ed in mesencephalic dopamine neurons: (1) a phasic mode response t o rew ard and rew ard-predict ing st imuli t hat have t o be processed by t he subject w it h high priorit y and (2) a t onic mode response involved in maint aining st at es of behavioral alert ness. Thus, t he dopamine syst em is involved in bot h t he set t ing and t he maint enance of levels of alert ness t hrough t he phasic and t onic mode responses.
Superior Colliculus Level A. TECTUM The nucleus of t he superior colliculus occupies t he t ect um at t he level of t he superior colliculus. The superior colliculus is a laminat ed mass of gray mat t er t hat plays a role in visual ref lexes and cont rol of eye movement . The laminat ed appearance result s f rom alt ernat ing st rat a of w hit e and gray mat t er. Superf icial layers of t he superior colliculus cont ain cells aligned in an orderly f ashion w it h w ell-def ined visual recept ive f ields and apparent ly represent a map of visual space. I n cont rast , t he deep layers cont ain cells w hose act ivit y is relat ed t o t he goal point s of saccadic eye movement s. I t t hus appears t hat a sensory map of t he visual space in t he superf icial layers is t ransf ormed in t he deeper layers int o a mot or map on w hich a vect or f rom an init ial eye posit ion t o a goal eye posit ion is represent ed. The vect or is t hen t ranslat ed int o command signals f or saccade
generat ors such as t he paramedian pont ine ret icular f ormat ion (PPRF).
1. Afferent Connections Aff erent connect ions t o t he superior colliculus (Figure 9-10) come f rom t he f ollow ing sources.
a. Cerebral Cortex Cort icocollicular f ibers arise f rom all over t he cerebral cort ex, but most abundant ly f rom t he occipit al (visual) cort ex. Fibers originat ing f rom t he f ront al lobe are concerned w it h conjugat e eye movement s and reach t he superior colliculus by a t ranst egment al rout e. O ccipit ot ect al f ibers are concerned w it h ref lex scanning eye movement s in pursuit of a passing object and reach t he colliculus via t he brachium of t he superior colliculus. Cort icot ect al f ibers are ipsilat eral. O ccipit ot ect al and f ront ot ect al f ibers t erminat e in t he superf icial and middle layers of t he superior colliculus. Temporot ect al f ibers (f rom t he audit ory cort ex), in cont rast , project int o deep collicular layers.
b. Retin a Ret inal f ibers project on t he same layer of t he superior colliculus as do t hose of t he cerebral cort ex. I n cont rast t o cort ical f ibers, f ibers f rom t he ret ina are bilat eral, w it h a preponderance of cont ralat eral input . Ret inal f ibers reach t he superior colliculus by w ay of t he brachium of t he superior colliculus; t hey leave t he opt ic t ract proximal t o t he lat eral geniculat e body. Ret inot ect al f ibers arise f rom homonymous port ions of t he ret ina of each eye, but crossed f ibers are t he most numerous. The cont ralat eral homonymous halves of t he visual f ield are t hus represent ed in each superior colliculus. The ret inot ect al f ibers are ret inot opically organized so t hat upper ret inal quadrant s of t he cont ralat eral visual f ields are in t he medial part s of t he superior colliculus and low er ret inal quadrant s are in t he lat eral part s of t he colliculus. Peripheral visual f ields are represent ed in t he caudal superior colliculus, and cent ral visual f ields are rost rally placed in t he colliculus. Tabl e 9-2. Disorders of the Mesencephalic Dopaminergic System
Subdivision Mesostriatal
Hypoactivity Parkinson's disease
Hyperactivity Huntington's chorea
Mesoallocortical
Cognitive impairment (Parkinson's disease)
Mesoneocortical
Cognitive impairment (Parkinson's disease) Photosensitive epilepsy (visual cortex)
Psychotic disorders
Undetermined
Fi gure 9-10. Schemat ic diagram show ing t he major aff erent connect ions of t he superior colliculus.
c. Spin al cord
Spinot ect al f ibers ascend in t he ant erolat eral part of t he cord (w it h t he spinot halamic t ract ) t o reach t he superior colliculus. They belong t o a mult isynapt ic syst em t hat conveys pain sensat ion.
d. In ferior collicu lu s The input f rom t he inf erior colliculus and a number of ot her audit ory relay nuclei is part of a ref lex arc t hat t urns t he neck and eyes t ow ard t he source of a sound. O t her input s t o t he superior colliculus have been report ed t o arise f rom t he midbrain t egment um, cent ral (periaqueduct al) gray mat t er, subst ant ia nigra (pars ret iculat a), and spinal t rigeminal nucleus.
2. Efferent Connections Eff erent connect ions (Figure 9-11) leave t he superior colliculus via t he f ollow ing t ract s.
Fi gure 9-11. Schemat ic diagram show ing t he major eff erent connect ions of t he superior colliculus.
a. Tectospin al tract From t heir neurons of origin in t he superior colliculus, f ibers of t he t ect ospinal t ract syst em cross in t he dorsal t egment al decussat ion in t he midbrain t egment um and descend as part of or in close proximit y t o t he medial longit udinal f asciculus t o reach t he cervical spinal cord and t erminat e on Rexed's laminae VI I and VI I I . They are concerned w it h ref lex neck movement in response t o visual st imuli.
b. Tectopon tocerebellar tract The t ect opont ocerebellar t ract descends t o t he ipsilat eral pont ine nuclei, w hich also receive f ibers f rom visual and audit ory cort ex. This t ract is believed t o convey visual impulses f rom t he superior colliculus t o t he cerebellum via t he pont ine nuclei.
c. Tectoreticu lar tract The t ect oret icular t ract project s prof usely and bilat erally on ret icular nuclei in t he midbrain as w ell as on t he accessory oculomot or nuclei.
d. Tectoth alamic tract The t ect ot halamic t ract project s t o t he lat eral post erior nucleus of t he t halamus, t he lat eral geniculat e, and t he pulvinar. The pulvinar receives ext ensive project ions f rom superf icial layers of t he superior colliculus and relays t hem t o ext rast riat e cort ical areas 18 and 19. I nput t o t he lat eral geniculat e nucleus arises f rom superf icial layers of t he superior colliculus and is relayed t o t he st riat e cort ex. As w it h t he aff erent connect ions of t he superior colliculus, t he eff erent connect ions originat e f rom diff erent laminae of t he superior colliculus. I n general, t he ascending t ect ot halamic project ions originat e f rom superf icial laminae, w hereas t he descending t ect ospinal, t ect opont ine, and t ect oret icular project ions originat e in deeper laminae. Unilat eral lesions of t he superior colliculus in animals have been associat ed w it h t he f ollow ing f unct ional def icit s: relat ive neglect of visual st imuli in t he cont ralat eral visual f ield, height ened responses t o st imuli in t he ipsilat eral visual f ield, and def icit s in percept ion involving spat ial discriminat ion and t he t racking of moving object s. St imulat ion of t he superior colliculus result s in cont ralat eral conjugat e deviat ion of t he eyes. Since t here are no demonst rable direct connect ions of t he superior colliculus t o t he nuclei of ext raocular movement , t his eff ect may be mediat ed via connect ions t o t he rost ral int erst it ial nucleus of t he medial longit udinal f asciculus (RiMLF) and t he PPRF. Most collicular neurons respond only t o moving st imuli, and most also show direct ional select ivit y.
B. PRETECTAL AREA Rost ral t o t he superior colliculus at t he mesencephalic-diencephalic junct ion is t he pret ect al area (pret ect al nucleus). This area is an import ant st at ion in t he ref lex pat hw ay f or t he pupillary light ref lex and vert ical gaze. I t receives f ibers f rom t he ret inas and project s f ibers bilat erally t o bot h oculomot or nuclei. Several nuclei in t he pret ect al region have been ident if ied, including t he nucleus
of t he opt ic t ract , along t he dorsolat eral border of t he pret ect um at it s junct ion w it h t he pulvinar, and t he pret ect al olivary nucleus, w hich is seen best at t he level of t he caudal post erior commissure. Experiment s in w hich t he pret ect al area and/ or t he post erior commissure w ere ablat ed suggest st rongly t hat t hese st ruct ures are essent ial f or vert ical gaze. This may explain t he paralysis of vert ical gaze in pat ient s w it h pineal t umors, w hich compress t hese st ruct ures. I n humans, a group of signs and sympt oms result ing f rom a lesion in t he pret ect al area are ref erred t o as t he pret ect al syndrome. Synonyms include t he sylvian aqueduct syndrome, t he dorsal midbrain syndrome, Koerber-Salus-Elschnig syndrome, t he pineal syndrome, and Parinaud's syndrome. The conglomerat e signs and sympt oms t hat const it ut e t his syndrome include vert ical gaze palsies, pupillary abnormalit ies (anisocoria, light near dissociat ion), conversion ret ract ion nyst agmus, lid ret ract ion (Collier's sign), inappropriat e conversion (pseudoabducens palsy), impaired convergence, skew ed eye deviat ion in t he neut ral posit ion, papilledema, and lid f lut t er. This syndrome has been report ed in a variet y of clinical st at es, including brain t umors (pineal, t halamic, midbrain, t hird vent ricle), hydrocephalus, st roke, inf ect ion, t rauma, and t ent orial herniat ion.
C. TEGM ENTUM At t he level of t he superior colliculus, t he t egment um cont ains f ibers of passage and nuclear groups.
1. Fibers of Passage The f ibers of passage include all t he f iber t ract s encount ered at t he level of t he inf erior colliculus except t he lat eral lemniscus, w hich t erminat es on inf erior colliculus neurons and is not seen at superior colliculus levels. The brachium conjunct ivum f ibers, w hich decussat e at inf erior colliculus levels, t erminat e in t he red nucleus at t his level or f orm t he capsule of t he red nucleus on t heir w ay t o t he t halamus. The ot her t ract s discussed under I nf erior Colliculus Level above maint ain approximat ely t he same posit ions at t his level.
2. Nuclear Groups The nuclear groups include t he red nucleus, t he oculomot or nucleus, and accessory oculomot or nuclei (Figure 9-12).
a. Red n u cleu s The red nucleus, so named because in f resh preparat ions it s rich vascularit y gives it a pinkish hue, is a prominent f eat ure of t he t egment um at t his level. I t is composed of a rost ral, phylogenet ically recent small cell part (parvicellular) and a caudal, phylogenet ically older large cell part (magnicellular). The rost ral part is w ell developed in humans. The nucleus is t raversed by t he f ollow ing f iber
syst ems: (1) t he superior cerebellar peduncle (brachium conjunct ivum), (2) t he oculomot or nerve (cranial nerve I I I ) root let s, and (3) t he habenuloint erpeduncular t ract . O f t he t hree syst ems, only t he brachium conjunct ivum project s on t his nucleus; t he ot her t w o are relat ed t o t he red nucleus only by proximit y. The red nucleus has t he f ollow ing aff erent and eff erent connect ions.
(1) Afferent Connections Aff erent connect ions t hat are most document ed come f rom t w o sources (Figure 9-13).
(a) Deep Cerebellar Nu clei The cerebellorubral f ibers arise f rom t he dent at e, globose, and embolif orm nuclei of t he cerebellum. They t ravel via t he brachium conjunct ivum, decussat e in t he t egment um of t he inf erior colliculus, and project part ly t o t he cont ralat eral red nucleus. Fibers f rom t he dent at e nucleus t erminat e on t he rost ral (parvicellular) part of t he red nucleus w hich project s t o t he inf erior olive, w hile f ibers f rom t he globose and embolif orm nuclei project on t he caudal part (magnicellular) of t he nucleus, w hich project s t o t he spinal cord. I nt errupt ion of t he cerebellorubral f iber syst em result s in a volit ional t ype of t remor t hat is manif est ed w hen t he ext remit y is in mot ion (e. g. , at t empt ing t o reach f or an object ). The t riangular area bounded by t he red nucleus, t he inf erior olive (in t he medulla oblongat a), and t he dent at e nucleus of t he cerebellum is know n as Mollaret 's t riangle. Lesions t hat int errupt connect ivit y among t hese t hree st ruct ures result in spont aneous rhyt hmic movement of t he palat e (palat al myoclonus).
(b) Cerebral Cortex Cort icorubral f ibers arise mainly f rom t he mot or and premot or cort ices and project mainly t o t he ipsilat eral red nucleus. This project ion is somat ot opically organized. Project ions f rom t he medial part of area 6 (supplement ary mot or area MI I ) are crossed and end in t he magnicellular region of t he nucleus. Project ions f rom t he precent ral (mot or) cort ex are ipsilat eral t o t he magnicellular part of t he nucleus and correspond t o t he somat ot opic origin of t he rubrospinal f ibers. The cort icorubral and rubrospinal t ract s are considered an indirect cort icospinal f iber syst em. The cort icorubral input t o t he red nucleus est ablishes primarily axodendrit ic synapses. Deaff erent at ion experiment s have show n t hat af t er cerebellar ablat ion t he cerebral input t o t he red nucleus est ablishes axosomat ic synapses t o replace t he deaff erent ed cerebellar input .
Fi gure 9-12. Schemat ic diagram of t he midbrain at t he superior colliculus level, show ing it s major nuclear groups.
Fi gure 9-13. Schemat ic diagram show ing t he major aff erent connect ions of
t he red nucleus.
The t w o aff erent connect ions ment ioned above are t he best est ablished. O t her possible aff erent t ract s include t ect orubral f rom t he superior colliculus and t he pallidorubral f rom t he globus pallidus.
(2) Efferent Connections Eff erent connect ions project t o t he f ollow ing areas (Figure 9-14).
(a) Spin al Cord Rubrospinal f ibers arise f rom t he caudal part (magnicellular) of t he nucleus, cross in t he vent ral t egment al decussat ion, and descend t o t he spinal cord. They project on t he same spinal cord laminae as does t he cort icospinal t ract . Like t he cort icospinal t ract , t he rubro-spinal t ract f acilit at es f lexor mot or neurons and inhibit s ext ensor mot or neurons. Because of t heir common t erminat ion and t he f act t hat t he red nucleus receives cort ical input , t he rubrospinal t ract has been considered an indirect cort icospinal t ract . I n most mammals, t he red nucleus sends it s major out put t o t he spinal cord and clearly subserves a mot or f unct ion. The project ion t o t he spinal cord has diminished w it h evolut ion, and in humans t he red nucleus sends it s major out put t o t he inf erior olive. I n t urn, t he inf erior olive is connect ed t o t he cerebellum.
Fi gure 9-14. Schemat ic diagram show ing t he major eff erent connect ions of t he red nucleus.
(b) Cerebellu m I n most mammals t he rubrocerebellar f ibers are collat erals f rom t he rubrospinal t ract . I n t he upper pons some rubrospinal f ibers leave t he descending t ract and accompany t he superior cerebellar peduncle t o t he cerebellum. I n t he cerebellum t hese f ibers t erminat e on cells of t he int erposed nuclei (embolif orm and globose).
(c) Reticu lar Formation Rubroret icular f ibers are also off shoot s f rom t he rubrospinal t ract . They separat e f rom t he descending t ract in t he medulla oblongat a and t erminat e in t he ipsilat eral lat eral ret icular nucleus. The lat eral ret icular nucleus in t urn project s t o t he cerebellum. Thus, a f eedback circuit is est ablished bet w een t he cerebellum, t he red nucleus, t he lat eral ret icular nucleus, and back t o t he cerebellum.
(d) In ferior Olive The rubro-olivary t ract arises in t he rost ral small cell part (parvicellular) of t he nucleus and project s t o t he ipsilat eral inf erior olive via t he cent ral t egment al
t ract . The inf erior olive in t urn project s t o t he cerebellum, t hus est ablishing anot her f eedback circuit bet w een t he cerebellum, t he red nucleus, t he inf erior olive, and back t o t he cerebellum. The rubro-olivary t ract in humans is more import ant t han is t he rubrospinal t ract .
(e) Oth er Projection s O t her eff erent project ions include f ibers t o Darkschew it sch's nucleus, t he Edinger-West phal nucleus, t he mesencephalic ret icular f ormat ion, t he t ect um, t he pret ect um, principal sensory and spinal t rigeminal nuclei, and t he f acial mot or nucleus. Thus, t he red nucleus is a synapt ic st at ion in neural syst ems concerned w it h movement , linking t he cerebral cort ex, cerebellum, and spinal cord. Lesions of t he red nucleus result in cont ralat eral t remor.
b. Ocu lomotor n u cleu s The oculomot or nucleus lies dorsal t o t he medial longit udinal f asciculus (MLF) at t he level of t he superior colliculus. I t is composed of a lat eral somat ic mot or cell column and a medial visceral cell column. I t is approximat ely 10 mm in lengt h. This nucleus receives f ibers f rom t he f ollow ing sources.
(1) Cerebral Cortex Cort icoret iculobulbar f ibers are bilat eral but come mainly f rom t he cont ralat eral hemisphere.
(2) Mesencephalon Mesencephalic project ions t o t he oculomot or nucleus originat e f rom Cajal's int erst it ial nucleus, t he rost ral int erst it ial nucleus of t he medial longit udinal f asciculus (RiMLF), and t he pret ect al olivary nucleus. Fibers f rom Cajal's int erst it ial nucleus course in t he post erior commissure and project mainly on t he cont ralat eral oculomot or nucleus. I nt errupt ion of t hese f ibers result s in paralysis of upw ard gaze. The RiMLF is just rost ral t o Cajal's int erst it ial nucleus. The project ion f rom t he RiMLF t o t he oculomot or nucleus is mainly ipsilat eral. Lesions of t he RiMLF lead t o paralysis of dow nard gaze. Physiologic st udies have show n t hat neurons in Cajal's int erst it ial nucleus and t he RiMLF are act ive just bef ore vert ical eye movement s. Cajal's int erst it ial nucleus and t he RiMLF project f ibers t o t he somat ic mot or cell column of t he oculomot or nucleus, w hereas t he pret ect al area project s mainly t o t he Edinger-West phal nucleus of t he visceral cell column. The pret ect al area receives f ibers f rom bot h ret inas and project s t o bot h oculomot or nuclei. This connect ion plays a role in t he pupillary light ref lex.
(3) Pons and Medulla
Pont ine and medullary project ions t o t he oculomot or nucleus arise f rom t he vest ibular nuclei, t he nucleus preposit us, and t he abducens nucleus. The vest ibular project ions originat e in t he superior and medial vest ibular nuclei. Project ions f rom t he medial vest ibular nuclei via t he MLF are bilat eral, w hile t hose f rom t he superior vest ibular nucleus, via t he MLF, are ipsilat eral. O t her f ibers f rom t he superior vest ibular nucleus t hat are not cont ained in t he MLF cross in t he caudal midbrain and project t o t he superior rect us and t he inf erior oblique subnuclei of t he oculomot or complex. The project ion f rom t he abducens nucleus arises f rom int erneurons, is crossed, and reaches t he oculomot or nucleus via t he MLF along w it h vest ibular f ibers. The connect ion bet w een t he abducens and oculomot or nuclei provides t he anat omic subst rat e f or t he coordinat ion bet w een t he lat eral rect us and medial rect us muscles in conjugat e horizont al gaze. The nucleus preposit us project s ipsilat erally t o t he oculomot or complex and may be involved in vert ical eye movement .
(4) Cerebellum Cerebello-oculomot or f ibers t o t he somat ic mot or cell column arise f rom t he cont ralat eral dent at e nucleus and are concerned w it h t he regulat ion of eye movement s. I n addit ion, t he cerebellum exert s an inf luence on aut onomic neurons of t he oculomot or nucleus. Short -lat ency (direct ) as w ell as long-lat ency (indirect ) responses have been elicit ed in t he Edinger-West phal nucleus af t er st imulat ion of t he int erposed and f ast igial cerebellar nuclei. This connect ion is believed t o course in t he brachium conjunct ivum and plays a role in pupillary const rict ion and accommodat ion. The short -lat ency connect ion is f acilit at ory, w hereas t he long-lat ency connect ion is inhibit ory. The somat ic mot or cell column is organized int o subgroups (Figure 9-15) f or each of t he eye muscles supplied by t he oculomot or nerve. From t he most rost ral ext ension of t he oculomot or nucleus t o it s middle t hird are t he EdingerWest phal nuclei and t he inf erior rect us subnuclei. I nf erior rect us subnuclei ext end rost rally like a peninsula and are t he only subnuclei seen in t he most rost ral part of t he nucleus. A discret e lesion of t he oculomot or nucleus at it s most rost ral level may result in an isolat ed inf erior rect us paresis w it h or w it hout pupillary abnormalit ies. The inf erior oblique subnuclei are t he most lat erally placed subnuclei in t he middle and caudal t hirds of t he nuclear complex. Superior rect us subnuclei are medially locat ed in t he middle and caudal t hirds of t he nucleus and are t he only subnuclei in t he t hird nuclear complex t hat supply cont ralat eral eye muscles (superior rect us muscle). All ot her subnuclei supply corresponding ipsilat eral eye muscles. The superior rect us subnucleus is adjacent t o and caudal t o t he inf erior rect us subnucleus. A lesion slight ly caudal t o a lesion t hat produces an isolat ed inf erior rect us palsy can aff ect t he inf erior and superior rect us subnuclei, producing an ipsilat eral inf erior rect us and cont ralat eral superior rect us paresis. The medial rect us subnuclei are locat ed
primarily in t he vent ral oculomot or nuclear complex in close proximit y t o t he MLF. The levat or palpebrae subnucleus is a single cent ral nucleus in t he caudal t hird of t he nucleus. Axons f rom t he neurons of t his single nucleus divide int o right and lef t bundles t o supply t he t w o levat or palpebrae muscles. Discret e lesions in individual subnuclei of t he oculomot or nuclear complex have been report ed (using magnet ic resonance imaging) w it h isolat ed unilat eral inf erior rect us paresis, bilat eral inf erior rect us paresis and unilat eral superior rect us w eakness, and isolat ed unilat eral inf erior rect us and cont ralat eral superior rect us w eakness.
Fi gure 9-15. Simplif ied schemat ic diagram of t he rost rocaudal arrangement of oculomot or subnuclei. EW, Edinger-West phal; I R, inf erior rect us; SR, superior rect us; L, levat or; I O , inf erior oblique; MR, medial rect us; MLF, medial longit udinal f asciculus.
Axons of neurons in t he somat ic mot or column course t hrough t he t egment um of t he midbrain, pass near or t hrough t he red nucleus, and emerge f rom t he int erpeduncular f ossa medial t o t he cerebral peduncle. I n t heir course in t he midbrain t egment um, oculomot or nerve f ascicles are organized so t hat f ascicles t o t he inf erior oblique are most lat erally placed, f ollow ed f rom lat eral t o medial by superior rect us, medial rect us, inf erior rect us, and pupillary f ascicles. The levat or palpebrae f ascicles lie dorsally close t o t hose of t he medial rect us. Discret e lesions involving one or more of t hese f ascicles may result in part ial oculomot or nerve paresis. The oculomot or nerve leaves t he brain st em bet w een t he superior cerebellar art ery and t he post erior cerebral art ery. O nce it leaves t he brain st em, t his nerve courses ant eriorly in t he subarachnoid space unt il it pierces t he dura covering t he roof of t he cavernous sinus. I n t he ant erior part of t he cavernous sinus, t he oculomot or nerve divides int o superior and inf erior divisions. The superior division innervat es t he levat or palpebrae superioris and superior rect us
muscles. The inf erior division innervat es t he inf erior rect us, medial rect us, and inf erior oblique muscles and t he iris sphinct er. The inf erior oblique muscle low ers t he eye w hen one is looking medially, and t he superior and inf erior rect us muscles elevat e and low er t he eye, respect ively, w hen one is looking lat erally. The medial rect us adduct s t he eye. The levat or palpebrae elevat e t he lid. The visceral cell column includes t he Edinger-West phal nucleus and Perlia's nucleus. The Edinger-West phal nucleus is concerned w it h t he light ref lex. Perlia's nucleus is probably concerned w it h accommodat ion but has not been ident if ied in humans. The axons of neurons in t he visceral cell column accompany t hose of t he somat ic mot or column as f ar as t he orbit . I n t he orbit t hey part company, and t he visceral axons project t o t he ciliary ganglion. Post ganglionic f ibers f rom t he ciliary ganglion innervat e t he sphinct er pupillae and ciliaris muscles. Lesions in t his component of t he oculomot or nerve result in a dilat ed pupil t hat is unresponsive t o light or accommodat ion. Lesions of t he oculomot or nerve out side t he brain st em (Figure 9-16A) result in (1) paralysis of t he muscles supplied by t he nerve, manif est ed by drooping of t he ipsilat eral eyelid (pt osis) and deviat ion of t he ipsilat eral eye dow nw ard and out w ard by t he act ion of t he int act lat eral rect us and superior oblique muscles (supplied by t he abducens and t rochlear nerves, respect ively), (2) double vision (diplopia), and (3) paralysis of t he sphinct er pupillae and ciliaris muscles, manif est ed by an ipsilat eral dilat ed pupil t hat is unresponsive t o light and accommodat ion. Lesions at t he int erpeduncular f ossa (Figure 9-16B) involving t he cerebral peduncle and t he root let s of t he oculomot or nerve result in (1) deviat ion of t he ipsilat eral eye dow nw ard and out w ard, w it h drooping of t he eyelid, (2) diplopia, (3) ipsilat eral loss of light and accommodat ion ref lexes, (4) dilat at ion of t he ipsilat eral pupil, and (5) cont ralat eral upper mot or neuron paralysis. Lesions in t he mesencephalon involving t he red nucleus and t he root let s of t he oculomot or nerve (Figure 9 1 6C) are manif est ed by (1) deviat ion of t he ipsilat eral eye dow nw ard and out w ard, w it h drooping of t he eyelid, (2) diplopia, (3) ipsilat eral loss of light and accommodat ion ref lexes, (4) dilat at ion of t he ipsilat eral pupil, and (5) cont ralat eral t remor.
Fi gure 9-16. Schemat ic diagram show ing lesions of t he oculomot or nerve in it s int ra- and ext ra-axial course and t heir respect ive clinical manif est at ions.
Follow ing lesions in t he oculomot or nerve, at ypical movement s of t he pupil, lid, or eye can occur due t o aberrant nerve degenerat ion. This phenomenon is ref erred t o as oculomot or synkinesis. I n most of t hese cases, t he oculomot or nerve lesion is ext ra-axial. O ccasional oculomot or synkinesis has been report ed in ischemic int ra-axial lesions. The relat ionship of t he oculomot or nerve t o t he post erior cerebral and superior cerebellar art eries makes t his nerve vulnerable t o aneurysms in t hose vessels. Rupt ure of t hese aneurysms is usually manif est ed by t he sudden onset of headache and signs of oculomot or nerve lesion. I t is w ort h not ing t hat t he parasympat het ic f ibers concerned w it h t he pupillary light ref lex t ravel on t he superf icial aspect of t he oculomot or nerve in it s cist ernal port ion and t hus are t he most suscept ible t o ext rinsic compression by ext raneural masses such as post erior communicat ing art ery aneurysms. Conversely, in t he majorit y of cases of vascular ischemic disease of t he nerve, such as diabet es mellit us, w hich aff ect cent rally locat ed f ibers, t he pupillary f ibers are spared. The blood supply of t he oculomot or nerve dips deep int o t he nerve, and t hus int errupt ion of t he blood supply adversely aff ect s deeper f ibers and spares t he more superf icial ones concerned w it h t he pupillary light ref lex. The pupillary f ibers are also of t he small unmyelinat ed t ype and are relat ively resist ant t o ischemia. The sparing of parasympat het ic pupillary f ibers in ischemic disease and t heir
dysf unct ion in compressive disease are not , how ever, absolut e. I n 3 t o 5 percent of aneurysms, t he pupil may be spared. Pupil-sparing oculomot or nerve palsy is not , how ever, unique t o nerve involvement out side t he brain st em (in t he subarachnoid space or cavernous sinus). These palsies also have been report ed w it h int ra-axial (w it hin t he midbrain) lesions. Many, how ever, are associat ed w it h ot her neurologic signs (e. g. , t remor), suggest ing t he involvement of adjacent st ruct ures such as t he red nucleus. Few cases of pupil-sparing oculomot or nerve palsy f rom int ra-axial lesions have been report ed w it hout anot her associat ed neurologic sign. Such cases are explained by isolat ed involvement of t he appropriat e nerve f ascicles by t he ischemic process.
c. Accessory ocu lomotor n u clei The accessory oculomot or nuclei include t he f ollow ing nuclei (see Figure 9-12).
(1) Interstitial Nucleus of Cajal The int erst it ial nucleus of Cajal is locat ed rost ral t o t he Edinger-West phal nucleus and caudal t o t he rost ral int erst it ial nucleus of t he medial longit udinal f asciculus. I t cont ains t w o subpopulat ions of neurons. O ne subpopulat ion is relat ed t o int egrat ion of vert ical gaze, and t he ot her is concerned w it h eye-head coordinat ion. The nucleus receives input s f rom burst neurons in t he rost ral int erst it ial nucleus of t he medial longit udinal f asciculus and f rom t he vest ibular nuclei. I t project s f ibers (via t he post erior commissure) t o t he ocular mot or nuclei (cranial nerves I I I and I V) and t he cont ralat eral int erst it ial nucleus of Cajal. I t also sends f ibers t o t he ret icular f ormat ion and bot h RiMLF.
(2) Rostral Interstitial Nucleus of the Medial Longitudinal Fasciculus The RiMLF is locat ed dorsomedial t o t he red nucleus, rost ral t o t he oculomot or nucleus, and vent ral t o t he periaqueduct al gray mat t er. Synonyms include t he nucleus of t he prerubral f ield and t he nucleus of t he f ield of Forel. The nucleus cont ains burst neurons t hat f ire w it h bot h upw ard and dow nw ard eye movement s. The nucleus receives input s f rom t he f ront al eye f ields; raphe nucleus int erposit us, w hich gat es act ivit y of burst neurons; nucleus of t he post erior commissure; superior colliculus; and t he nucleus f ast igii of t he cerebellum. The t w o RiMLF nuclei are int erconnect ed. The nucleus project s t o ocular mot or neurons (cranial nerves I I I and I V). Each RiMLF project s simult aneously t o mot or neurons t hat move each eye in t he same direct ion (e. g. , inf erior rect us muscle of one eye and t he superior oblique muscle of t he ot her eye). Project ions t o mot or neurons t hat innervat e elevat or (upgaze) muscles are bilat eral, w it h crossing occurring w it hin t he cranial nerve nucleus (cranial nerve I I I ). Project ions t o mot or neurons t hat innervat e depressor (dow ngaze) muscles are ipsilat eral. The RiMLF also project s t o t he int erst it ial nucleus of Cajal.
(3) Darkschewitsch's Nucleus Darkschew it sch's nucleus lies dorsal and lat eral t o t he somat ic mot or cell column of t he oculomot or nerve. I t project s t o t he nuclei of t he post erior commissure but does not project t o t he oculomot or nuclear complex.
(4) Nucleus of the Posterior Commissure This nucleus is locat ed w it hin t he post erior commissure. I t has connect ions w it h pret ect al and post erior t halamic nuclei. Lesions involving nuclei of t he post erior commissure and crossing f ibers f rom Cajal's int erst it ial nuclei produce bilat eral eyelid ret ract ion and impairment of vert ical eye movement . The accessory oculomot or nuclei are direct ly or indirect ly connect ed w it h t he oculomot or complex. Cajal's int erst it ial nucleus also sends f ibers t o t he spinal cord via t he MLF.
D. CENTRAL (PERIAQUEDUCTAL) GRAY The cent ral gray region of t he mesencephalon surrounds t he aqueduct of Sylvius and cont ains scat t ered neurons, several nuclei, and some f ine myelinat ed and unmyelinat ed f ibers. The oculomot or, accessory oculomot or, and t rochlear nuclei, as w ell as t he mesencephalic nucleus of t he t rigeminal nerve, lie at t he edge of t his region. The dorsal longit udinal f asciculus (f asciculus of Schüt z) is a perivent ricular ascending and descending f iber syst em t hat courses in t he cent ral gray mat t er. I t arises in part f rom t he hypot halamus and cont ains aut onomic f ibers. I t generally connect s t he hypot halamus w it h t he periaqueduct al gray and w it h aut onomic nuclei in t he pons and medulla. The neuropept ide enkephalin has been ident if ied in t he cent ral gray mat t er. St imulat ion of cert ain sit es w it hin t he cent ral gray mat t er release enkephalins, w hich act on serot onergic neurons in t he medulla oblongat a, w hich in t urn project on primary aff erent axons (concerned w it h pain conduct ion) in t he dorsal horn of t he spinal cord t o produce analgesia. St imulus-produced analgesia has been achieved by st imulat ion of vent rolat eral regions of t he cent ral gray mat t er. I n cont rast , st imulat ion of t he rost ral and lat eral cent ral gray mat t er f acilit at es pain sensat ions. I n addit ion t o it s role in cent ral analgesic mechanisms, t he cent ral (periaqueduct al) gray region has been implicat ed in vocalizat ion, cont rol of reproduct ive behavior, modulat ion of medullary respirat ory cent ers, aggressive behavior, and vert ical gaze. The peri-aqueduct al gray, along w it h deep layers of t he superior colliculus, have been show n t o be involved in diff erent component s of aversive st at es. Escape behavior and def ensive or f ear-like behavior are elicit ed by st imulat ion of t hese areas. The periaqueduct al gray receives inf ormat ion about urinary bladder f illing and t hus is involved in t he cent ral process of mict urit ion. Through connect ions t o t he hypot halamus and rost ral medulla, t he periaqueduct al gray has been implicat ed in t he process of penile
erect ion. Aff erent s t o t his region arise f rom t he hypot halamus, t he amygdala, t he brain st em ret icular f ormat ion, t he locus ceruleus, and t he spinal cord. I mmunoreact ivit y t o a variet y of neuropept ides has been demonst rat ed in periaqueduct al neurons; t hese neuropept ides include enkephalin, subst ance P, cholecyst okinin, neurot ensin, serot onin, dynorphin, and somat ost at in.
LIGHT REFLEX St imulat ion of t he ret ina by light set s off a ref lex w it h t he f ollow ing aff erent and eff erent pat hw ays (Figure 9-17).
Afferent Pathway From t he ret ina t he impulse t ravels via t he opt ic nerve and opt ic t ract t o t he pret ect al area. Af t er synapsing on neurons of t he pret ect al area, t he impulse t ravels via t he post erior commissure t o bot h Edinger-West phal nuclei in t he oculomot or complex.
Efferent Pathway From t he Edinger-West phal nucleus, parasympat het ic preganglionic f ibers t ravel w it h t he somat ic mot or component of t he oculomot or nerve as f ar as t he orbit . I n t he orbit , t he parasympat het ic f ibers project on neurons in t he ciliary ganglion. Post ganglionic f ibers arise f rom t he ciliary ganglion (short ciliary nerves) and innervat e t he sphinct er pupillae and ciliaris muscles. Thus, w hen light is t hrow n on one ret ina, bot h pupils respond by const rict ing. The response of t he ipsilat eral pupil is t he direct light ref lex, w hereas t hat of t he cont ralat eral pupil is t he consensual light ref lex. A consensual light ref lex is possible because of t he project ion of t he pret ect al area t o bot h oculomot or nuclei. Lesions of t he opt ic nerve (Figure 9-18) abolish bot h direct and consensual light ref lexes in response t o light st imulat ion of t he ipsilat eral ret ina. Lesions of t he oculomot or nerve (Figure 9-19) abolish t he direct light ref lex but not t he consensual light ref lex in response t o light st imulat ion of t he ipsilat eral ret ina.
Fi gure 9-17. Schemat ic diagram show ing t he aff erent and eff erent pat hw ays of t he pupillary light ref lex.
Fi gure 9-18. Schemat ic diagram show ing t he eff ect s of opt ic nerve lesions
on t he direct and consensual pupillary light ref lexes.
The Marcus G unn phenomenon is a paradoxical dilat at ion of bot h pupils t hat occurs w hen light is shone in t he sympt omat ic eye (opt ic nerve lesion) af t er having been shone in t he normal eye. When light is shone in t he normal eye, bot h pupils const rict (direct and consensual light ref lexes). When light is t hen sw ung t o t he sympt omat ic eye, less light reaches t he oculomot or nucleus because of t he opt ic nerve lesion (opt ic neuropat hy). The oculomot or nucleus senses t he less int ense light and shut s off t he parasympat het ic response, result ing in paradoxical pupillary dilat at ion (Figure 9-20). Adie's pupil, or t onic pupil, is charact erized by a w idely dilat ed pupil and a sluggish, prolonged pupillary cont ract ion in react ion t o light . When it is const rict ed, t he pupil t akes a long t ime t o dilat e. The aff ect ed pupil is larger t han t he normal pupil, but in darkness it may be smaller, since t he normal pupil is f ree t o dilat e w idely. Adie's pupil show s a more def init e response t o accommodat ion. I t result s f rom pat hology in t he ciliary ganglion w it hin t he orbit . The et iology of Adie's pupil is unknow n, but believed t o be due, in part , t o redirect ion of regenerat ing parasympat het ic f ibers. Normally, 90 percent of parasympat het ic nerves in t he ciliary ganglion innervat e t he ciliary body and t he remaining 10 percent innervat e t he iris sphinct er. When t he ciliary ganglion is damaged, t he pupil becomes dilat ed and unresponsive t o light or accommodat ion. During recovery reinnervat ion t akes place in a random f ashion. As a result , 90 percent of t he parasympat het ic f ibers t hat previously innervat ed t he pupil now innervat e t he ciliary body. When light is shone in t he eye, 90 percent of t he parasympat het ic inst ruct ion t o const rict t he pupil is dissipat ed in t he ciliary body, leaving only 10 percent f or pupillary const rict ion.
Fi gure 9-19. Schemat ic diagram show ing t he eff ect s of oculomot or nerve lesions on t he direct and consensual pupillary light ref lexes.
Fi gure 9-20. Schemat ic diagram show ing response t o light st imulat ion of t he Marcus G unn pupil.
ACCOM M ODATION-CONVERGENCE REFLEX The accommodat ion-convergence ref lex involves t he f ollow ing processes: 1. The assumpt ion of a convex shape by t he lens is secondary t o cont ract ion of t he ciliary muscle, w hich causes relaxat ion of t he suspensory ligament . This
is a process of accommodat ion of t he lens, w hich t hickens t o keep t he image in sharp f ocus. 2. Cont ract ion of bot h medial rect i muscles f or convergence brings t he eyes int o alignment . 3. Pupillary const rict ion occurs as an aid in regulat ing t he dept h of f ocus f or sharper images. The accommodat ion-convergence ref lex occurs w hen t he eyes converge volunt arily t o look at a nearby object or make a ref lex response t o an approaching object . The pat hw ay of t he accommodat ion-convergence ref lex has not been w ell delineat ed. I t is believed, how ever, t hat aff erent impulses f rom t he ret ina reach t he occipit al cort ex and t hat t he eff erent pat hw ay f rom t he occipit al cort ex reaches t he oculomot or complex af t er synapsing in t he pret ect al nucleus and/ or superior colliculus. I n t he oculomot or complex, Perlia's nucleus has been assumed t o play a role in convergence (Figure 9-21). The pat hw ay f or t he accommodat ion-convergence ref lex is t hus diff erent f rom t hat of t he light ref lex. This is support ed clinically by a condit ion know n as t he Argyll Robert son pupil, in w hich t he light ref lex is lost w hile t he accommodat ion-convergence ref lex persist s. The sit e of t he lesion in t his condit ion has not been est ablished w it h cert aint y, but it s et iology is know n t o be syphilis of t he nervous syst em.
M ESENCEPHALIC RETICULAR FORM ATION The mesencephalic ret icular f ormat ion is a cont inuat ion of t he pont ine ret icular nuclei and merges rost rally w it h t he zona incert a. The major out put f rom t he mesencephalic ret icular f ormat ion ascends t o t he diencephalon and cerebral cort ex and is involved in w akef ulness and sleep. The ret icular nuclei of t he mesencephalon and ot her brain st em areas are discussed in t he chapt er on ret icular f ormat ion, w akef ulness, and sleep.
VERTICAL GAZE Whereas cont rol of lat eral gaze is a f unct ion of t he pons, t he rost ral midbrain at t he mesencephalic-diencephalic junct ion is crit ical in t he mediat ion of vert ical gaze. The f ollow ing st ruct ures are import ant f or vert ical eye movement s: 1. Mot or neurons in t he oculomot or (cranial nerve I I I ) and t rochlear (cranial nerve I V) nuclei t hat supply ocular muscles involved in vert ical eye movement s: superior rect us, inf erior rect us, inf erior oblique (cranial nerve I I I ), and superior oblique (cranial nerve I V).
Fi gure 9-21. Schemat ic diagram show ing t he aff erent and eff erent pat hw ays of t he accommodat ion-convergence ref lex.
2.
RiMLF. This nucleus const it ut es t he neural subst rat e f or vert ical eye movement s. I t cont ains burst neurons t hat f ire on upw ard and dow nw ard gaze. Alt hough t he RiMLF is t he key subst rat e f or vert ical eye movement s, vert ical burst neurons also reside in t he mesencephalic ret icular f ormat ion. Bilat eral lesions in t he RiMLF abolish all vert ical (up and dow n) eye movement s. Unilat eral lesions result in def ect in dow nw ard gaze. The diff erence in out come bet w een bilat eral and unilat eral lesions is consist ent w it h bilat eral project ions of t he nucleus t o elevat or mot or neurons and ipsilat eral project ions t o t he depressor mot or neurons.
3. I nt erst it ial nucleus of Cajal (I NC). The I NC is t he neural int egrat or f or vert ical gaze. Bilat eral lesions in t he nucleus result in limit at ions in t he range of vert ical gaze and in gaze holding. Because of t he project ions of t he I NC t o ocular mot or neurons (cranial nerves I I I and I V) and t o t he opposit e I NC via t he post erior commissure, a lesion in one I NC becomes in eff ect a bilat eral lesion. Ref lex eye movement s in response t o head t urning (oculocephalic response) are mediat ed by vest ibular originat ing f ibers dest ined t o t he oculomot or and t rochlear nuclear complexes via t he medial longit udinal f asciculus w it h relays in t he int erst it ial nucleus of Cajal. Lesions in t he int erst it ial nucleus of Cajal are t hus associat ed w it h abolit ion of t he oculocephalic response. 4. Post erior commissure. The post erior commissure cont ains crossing nerve f ibers int ermixed w it h t he nucleus of t he post erior commissure (NPC). The f ibers in t he post erior commissure are: (a) project ions f rom t he I NC t o t he cont ralat eral ocular mot or nuclear complex (cranial nerves I I I and I V) and t he cont ralat eral int erst it ial nucleus of Cajal, (b) project ions f rom t he NPC t o t he
cont ralat eral I NC and t he RiMLF. Lesions of t he post erior commissure result in impairment of vert ical gaze holding and rest rict all vert ical eye movement s, but especially upw ard movement s. The impairment of vert ical gaze holding is explained by involvement of axons of I NC. The rest rict ion of vert ical eye movement s is at t ribut ed t o involvement of t he nucleus of t he post erior commissure. Paralysis of bot h upw ard and dow nw ard gaze by bot h saccadic and vest ibular means usually implies involvement of t he int erst it ial nucleus of Cajal or t he post erior commissure singly or t oget her. 5. Nucleus of t he post erior commissure. The nucleus of t he post erior commissure has an import ant role (not f ully explored yet ) in vert ical eye movement s as w ell as in lid movement . 6. The medial longit udinal f asciculus. The medial longit udinal f asciculus carries input s f rom vest ibular nuclei t o oculomot or nuclear complex, t rochlear nuclear complex, and t he int erst it ial nucleus of Cajal. These f ibers carry signals import ant f or vert ical vest ibular eye movement s and, t o a lesser ext ent , vert ical gaze-holding commands.
CONTROL OF SACCADIC EYE M OVEM ENT Commands f or saccadic eye movement s are init iat ed f rom t he cerebral cort ex (Figure 9-22). The f ront al eye f ield (area 8 in t he f ront al lobe), t he angular gyrus (area 39), and t he adjacent area 19 of t he pariet o-occipit al cort ices project t o t he superior colliculus. The cort ical areas of ocular mot ilit y are int erconnect ed. The superior colliculus in t urn project s t o t he brain st em pulse generat ors in t he pons and midbrain. The pulse generat ors also receive cort ical input direct ly f rom t he f ront al eye f ields. The pulse generat or f or horizont al saccades is in t he PPRF. The pulse generat or f or vert ical saccades is in t he mesencephalic RiMLF. Thus, t here are t w o pat hw ays concerned w it h saccadic movement s: (1) an ant erior pat hw ay f rom t he f ront al eye f ields direct ly and indirect ly (via t he superior colliculus) t o t he brain st em cent ers f or saccadic movement s (PPRF f or horizont al saccades and t he mesencephalic RiMLF f or vert ical saccades), and (2) a post erior pat hw ay f rom t he pariet o-occipit al cort ex t o t he superior colliculus and t hen t o t he brain st em cent ers f or saccadic movement s. The ant erior pat hw ay generat es int ent ional saccades; t he post erior pat hw ay generat es ref lexive saccades. Each pat hw ay can compensat e part ially f or t he ot her.
Fi gure 9-22. Schemat ic diagram show ing cort ical and subcort ical cont rol of saccadic eye movement s. MLF, medial longit udinal f asciculus; PPRF, paramedian pont ine ret icular f ormat ion.
SM OOTH PURSUIT EYE M OVEM ENTS Each hemisphere has been show n t o mediat e smoot h pursuit eye movement s t o t he ipsilat eral side. The cort ical areas involved in smoot h pursuit are not as w ell delineat ed as are t hose involved in saccadic eye movement s but probably include t he post erior pariet al cort ex or t he t emporo-occipit o-pariet al region. The pat hogenesis of t he pursuit def icit s and pat hw ays involved in smoot h pursuit eye movement s are not complet ely underst ood. Specif ic lesions in t he t emporooccipit o-pariet al cort ex t hat are associat ed w it h smoot h pursuit def icit s in humans correspond t o Brodmann areas 19, 37, and 39. Lesions in t he f ront al eye f ield also have been associat ed w it h def icit s in smoot h pursuit . The cort icof ugal pat hw ay f or smoot h pursuit movement s remains cont roversial. Tw o pat hw ays have been described. The f irst courses f rom t he t emporooccipit o-pariet al cort ex t hrough t he post erior limb of t he int ernal capsule t o t he dorsolat eral pont ine nucleus. The second courses f rom t he f ront al eye f ield t o t he dorsolat eral pont ine nucleus and t he nucleus ret icularis t egment i pont is. Pursuit pat hw ays in t he brain st em and cerebellum are less w ell def ined, alt hough t he dorsolat eral pont ine nucleus and t he cerebellar f locculus are import ant in t he
monkey. Cerebral hemisphere lesions impair ocular pursuit ipsilat erally or bilat erally, w hereas post erior f ossa lesions impair ocular pursuit cont ralat erally or ipsilat erally. This variabilit y probably ref lect s t he involvement of a presumed pursuit pat hw ay t hat crosses f rom t he pont ine nuclei t o t he cerebellum and t hen consist s of a unilat eral project ion f rom t he cerebellum t o t he vest ibular nuclei.
Fi gure 9-23. Schemat ic diagram show ing vascular t errit ories of t he midbrain
at t hree caudal-rost ral levels.
BLOOD SUPPLY Compared w it h t he vascular supply of t he pons, t he midbrain vasculat ure is complex (Figure 9-23). The mesencephalon (midbrain) receives it s blood supply f rom t he basilar art ery via paramedian as w ell as superior cerebellar and post erior cerebral branches.
Inferior Colliculus Level (Figure 9-23A) At t he level of t he inf erior colliculus (low er midbrain), t he paramedian branches supply t he medial region of t he mesencephalon, including t he MLF, t he paramedian ret icular nuclei, and t he brachium conjunct ivum. The superior cerebellar art ery supplies t he lat eral region of t he midbrain, including t he inf erior colliculus, t he root let s of t he t rochlear nerve, t he spinal and medial lemniscus, and t he lat eral part of t he cerebral peduncle. A w edge bet w een t hese t w o regions, w hich includes t he t rochlear nucleus, t he cerebral peduncle, and t he medial part of t he medial lemniscus, has a variable and inconst ant blood supply.
Superior Colliculus Level (Figure 9-23B) At t he level of t he superior colliculus (middle midbrain), t he mesencephalon is divided int o t hree zones of blood supply. The medial zone, w hich includes t he t hird cranial nerve nuclear complex, receives blood f rom t he t ip of t he basilar art ery. The t ect um (dorsal zone) is supplied by t he superior cerebellar art ery. The rest of t he midbrain is supplied by t he post erior cerebral art ery. This zone includes t he spinal and medial lemnisci, t he subst ant ia nigra, t he cerebral peduncle, t he red nucleus, and t he t hird cranial nerve root let s.
Pretectal Level (Figure 9-23C) At t he level of t he upper midbrain (t he pret ect al level), t he medial zone, including t he medial part of t he red nucleus, and root let s of t he oculomot or nerve receive blood f rom paramedian branches of t he basilar art ery. The rest of t he midbrain receives blood f rom t he post erior cerebral art ery.
TERM INOLOGY Adduction (Latin adducere, t o draw toward ) . The process of draw ing t ow ard t he median plane. Adie's pupil (tonic pupil, Holmes-Adie syndrome). A condit ion in w hich t he pupil exhibit s sluggish prolonged const rict ion t o light
and, w hen it is const rict ed, t akes a long t ime t o dilat e. The phenomenon result s f rom pat hology in t he ciliary ganglion. Described by James Ware in 1812, by Pilt z in 1899, and by ot hers bef ore William John Adie, an Aust ralian neurologist , described it in 1931. Akinesia (G reek a, n egative ; ki nesi s, m otion ) . Povert y or absence of movement . Anisocoria (G reek ani sos, u nequal, uneven ; kore, p upil ) . I nequalit y in t he diamet ers of t he pupils. Aqueduct of Sylvius (cerebral aqueduct) (Latin aqua, w ater ; ductus, c anal ) . The narrow passage in t he midbrain linking t he t hird and f ourt h vent ricles. Described by Jacques Dubois (Sylvius) in 1555. Argyll-Robertson pupil. A pupil t hat react s t o accommodat ion but not t o light . Described by Argyll Robert son, a Scot t ish opht halmologist , in 1869. Syphilis is t he classical et iology, but diabet es and lesions in t he midbrain can cause t his phenomenon. Brachium conjunctivum (Latin, G reek brachi on, a rm ; conj uncti va, c onnecting ) . An armlike bundle of f ibers t hat connect s t he cerebellum and midbrain. Colliculus (Latin, a s mall elevation ) . The inf erior and superior colliculi are small elevat ions in t he dorsal surf ace of t he midbrain. Collier's sign. Bilat eral lid ret ract ion seen in t he pret ect al syndrome. Corpora quadrigemina (Latin corpus, b ody ; quadri gemi nus, f ourfold ) . Four bodies in t he dorsal aspect of t he midbrain, consist ing of t w o inf erior colliculi and t w o superior colliculi. Darkschewitsch's nucleus. O ne of t he accessory oculomot or nuclei. Named af t er Liverij O sipovich Darkschew it sch, a Russian anat omist . Dentate nucleus (Latin dentatus, t oothlike ) . A nucleus in t he cerebellum t hat is serrat ed like a t oot h. Diplopia (G reek di pl oos, d ouble ; ops, e ye ) . Double vision. Dorsal longitudinal fasciculus (fasciculus of Schütz). A perivent ricular ascending and descending f iber syst em t hat connect s t he hypot halamus w it h t he periaqueduct al gray mat t er and w it h aut onomic nuclei in t he pons and medulla oblongat a. Edinger-Westphal nucleus.
The parasympat het ic component of t he oculomot or nuclear complex. Described by Ludw ig Edinger, a G erman anat omist and neurologist , in 1885 and by Carl Friedreich O t t o West phal, a G erman psychiat rist , neurologist , and anat omist , 2 years lat er. Emboliform (G reek embol os, p lug ) . The embolif orm nucleus in t he cerebellum p lugs t he dent at e nucleus. G lobose (Latin gl obus, a ball, sphere-shaped ) . The globose nucleus in t he cerebellum is spherical in shape. Habenula (Latin habena, s mall strap or bridle rein ) . The habenular nuclei in t he caudal diencephalon near t he pineal gland f orm part of t he epit halamus. Early anat omist s considered t he pineal gland t he abode of t he soul; it w as likened t o a driver w ho direct s t he operat ions of t he mind via t he habenula, or reins. Huntington's chorea (G reek chorei a, d ance ) . A progressive neurodegenerat ive disorder inherit ed as an aut osomal dominant t rait . The disease w as import ed t o America f rom Suff olk in t he Unit ed Kingdom by t he emigrant w if e of an Englishman in 1630. Her f at her w as choreic, and t he groom's f at her disapproved of t he mat ch because of t he bride's f at her's illness. The disorder is named af t er G eorge Sumner Hunt ingt on, a general pract it ioner w ho described it in 1872. Charact erized by t he ceaseless occurrence of a w ide variet y of rapid, complex, jerky movement s perf ormed involunt arily and resembling a dance. Intorsion (Latin i n, t oward ; torsi o, t wisting ) . I nw ard rot at ion of eye. Koerber-Salus-Elschnig syndrome. A syndrome of vert ical gaze palsy, anisocoria, light -near dissociat ion, conversion ret ract ion nyst agmus, lid ret ract ion, impaired convergence, skew ed eye deviat ion, papilledema, and lid f lut t er associat ed most commonly w it h pineal t umors or disorders of t he pret ect al region. Also know n as Parinaud's syndrome, t he pret ect al syndrome, t he sylvian aqueduct syndrome, and t he syndrome of t he post erior commissure. Locus ceruleus (Latin, p lace, dark blue ) . The pigment ed noradrenergic nucleus in t he rost ral pons is dark blue in sect ions. Marcus G unn pupil. Paradoxical dilat at ion of bot h pupils w hen light is shone in a sympt omat ic eye w it h an opt ic nerve lesion af t er having been shone in t he normal eye (sw inging f lashlight t est ). When light is shone in t he normal eye, bot h pupils const rict . When light is t hen sw ung t o t he sympt omat ic eye, less light reaches t he oculomot or nucleus because of t he opt ic nerve lesion. The oculomot or nucleus senses t he less int ense light and shut s off t he parasympat het ic response,
result ing in paradoxical pupillary dilat at ion. I n 1902 Robert Marcus G unn (1850 1 909), a Scot t ish opht halmologist , observed t he react ion of bot h eyes t o st imulat ion of one of t hem, w hile Levat in described t he sw inging f lashlight t est and observed t he paradoxical dilat at ion of t he pupil of t he aff ect ed eye w hen t he light w as sw ung t o it f rom t he normal eye. Mollaret's triangle. The t riangular space f ormed by t he red nucleus, inf erior olive, and dent at e nucleus of cerebellum. Named af t er Pierre Mollaret , a French physician. O culomotor nerve (Latin ocul us, e ye ; motor, m over ) . The t hird cranial nerve aff ect s movement s of t he eye. Parinaud's syndrome. Paralysis of upw ard gaze associat ed w it h pret ect al lesions. Described by Henri Parinaud, a French neuro-opht halmologist , in 1883. Parkinson's disease. A chronic progressive degenerat ive disease charact erized by t remor, rigidit y, and akinesia. I t w as init ially described in 1817 by t he English physician James Parkinson under t he rubric shaki ng pal sy. Parvicellular nucleus (Latin parvus, s mall ; cel l ul a, c ell ) . The parvicellular nucleus is composed of small cells. Perlia's nucleus. A component of t he aut onomic oculomot or nuclear complex relat ed t o ocular conversion. Described by Richard Perlia, a G erman opht halmologist , in 1899. Ptosis (G reek ptosi s, f all ) . Drooping of t he upper lid f rom oculomot or nerve palsy (levat or palpebrae muscle paralysis) or sympat het ic nerve palsy (t arsal plat e paralysis) as in Horner's syndrome. Saccades (French, j erking ) . Abrupt , rapid movement s or jerks of t he eyes w hen one is changing point s of f ixat ion. Tectum ( r ooflike structure ) . A st ruct ure t hat f orms t he roof of t he midbrain. Tegmentum (Latin tegmenta, c overing ) . A st ruct ure t hat covers t he cerebral peduncles. Trochlear nerve (Latin trochl eari s, r esembling a pulley ) . The f ourt h cranial nerve supplies t he superior oblique eye muscle, w hose t endon angles t hrough a ligament ous sling like a pulley. Achillini and Vesalius included t his nerve w it h t he t hird pair of nerves. I t w as described as a separat e root by Fallopius and w as named t he t rochlear nerve by William Molins, an English surgeon, in 1670.
Vicq d'Azyr, Felix (1748 1 794). French physician t o Q ueen Marie Ant oinet t e. Described t he ant erior, middle, and post erior lobes of t he cerebral cort ex (corresponding t o t he f ront al, pariet al, and occipit al), t he insula (island of Reil) w ell bef ore Reil, t he subst ant ia nigra, and t he mamillot halamic t ract (t ract of Vicq d'Azyr).
SUGGESTED READINGS Af if i AK, Kaelber WW: Eff erent connect ions of t he subst ant ia nigra: An experiment al st udy in cat s. Exp Neurol 1965; 11: 474 4 82. Anderson ME, Yoshida M: Axonal branching pat t erns and locat ion of nigrot halamic and nigrocollicular neurons in t he cat . J Neurophysi ol 1980; 43: 883 8 95. Bhidayasiri R et al: A hypot het ical scheme f or t he brainst em cont rol of vert ical gaze. Neurol ogy 2000; 54: 1985 1 993. Blok BF: Cent ral pat hw ays cont rolling mict urit ion and urinary cont inence. Urol ogy 2002; 59(Suppl 1): 13 1 7. Bogousslavsky J et al: Pure midbrain inf arct ion: Clinical syndromes, MRI , and et iologic pat t erns. Neurol ogy 1994; 44: 2032 2 040. Brando ML et al: Neurochemical mechanisms of t he def ensive behavior in t he dorsal midbrain. Neurosci Behav Rev 1999; 23: 863 8 75. Brandt T et al: Post erior cerebral art ery t errit ory inf arct s: clinical f eat ures, inf arct t opography, causes and out come. Mult icent er result s and a review of t he lit erat ure. Cerebrovasc Di s 2000; 10: 170 1 82. Breen LA et al: Pupil-sparing oculomot or nerve palsy due t o midbrain inf arct ion. Arch Neurol 1991; 48: 105 1 06. Cast ro O et al: I solat ed inf erior oblique paresis f rom brain-st em inf arct ion: Perspect ive on oculomot or f ascicular organizat ion in t he vent ral midbrain t egment um. Arch Neurol 1990; 47: 235 2 37. Dehaene I , Lammens M: Paralysis of saccades and pursuit : Clinicopat hologic st udy. Neurol ogy 1991; 41: 414 4 15. DeKeyser J et al: The mesoneocort ical dopamine neuron syst em. Neurol ogy
1990; 40: 1660 1 662. Deleu D et al: Vert ical one-and-a-half syndrome: Supranuclear dow ngaze paralysis w it h monocular elevat ion palsy. Arch Neurol 1989; 46: 1361 1 363. Doraisw amy PM et al: Morphomet ric changes of t he human midbrain w it h normal aging: MR and st ereologic f indings. AJNR 1992; 13: 383 3 86. Fallon JH, Moore RY: Cat echolamine innervat ion of t he basal f orebrain: I V. Topography of t he dopamine project ion t o t he basal f orebrain and neost riat um. J Comp Neurol 1978; 180: 545 5 80. Felice KJ et al: R ubral gait at axia. Neurol ogy 1990; 40: 1004 1 005. Fog M, Hein-Sřrenson O : Mesencephalic syndromes. I n Vinken PJ, Bruyn G W (eds): Handbook of Cl i ni cal Neurol ogy, vol 2. Amst erdam, Nort h-Holland, 1969: 272 2 85. G ale K: Role of t he subst ant ia nigra in G ABA-mediat ed ant iconvulsant act ions. Adv Neurol 1986; 44: 343 3 64. G alet t a SL et al: Pret ect al eyelid ret ract ion and lag. Ann Neurol 1993; 33: 554 5 57. G ebhart G F, Toleikis JR: An evaluat ion of st imulat ion-produced analgesia in t he cat . Exp Neurol 1980; 62: 570 5 79. G onzalez-Vegas JA: Nigro-ret icular pat hw ay in t he rat : An int racellular st udy. Brai n Res 1981; 207: 170 1 73. Haber SN, Fudge JL: The primat e subst ant ia nigra and VTA: int egrat ive circuit ry and f unct ion. Cri t Rev Neurobi ol 1997; 11: 323 3 42. Halmagyi G M et al: Tonic cont raversive ocular t ilt react ion due t o unilat eral meso-diencephalic lesion. Neurol ogy 1990; 40: 1503 1 509. Hart mann-von Monakow K et al: Project ions of precent ral and premot or cort ex t o t he red nucleus and ot her midbrain areas in Macaca f asci cul ari s. Exp Brai n Res 1979; 34: 91 1 05. Hat t ori N et al: I mmunohist ochemical st udies on complexes I , I I , I I I , and I V of
mit ochondria in Parkinson's disease. Ann Neurol 1991; 30: 563 5 71. Hommel M, Bogousslavsky J: The spect rum of vert ical gaze palsy f ollow ing unilat eral brain st em st roke. Neurol ogy 1991; 41: 1229 1 234. Hopf HC, G ut man L: Diabet ic 3rd nerve palsy: Evidence f or a mesencephalic lesion. Neurol ogy 1990; 40: 1041 1 045. Juncos JL et al: Mesencephalic cholinergic nuclei in progressive supranuclear palsy. Neurol ogy 1991; 41: 25 3 0. Kaelber WW, Af if i AK: Nigroamygdaloid f iber connect ions in t he cat . Am J Anat 1977; 148: 129 1 35. Kaplan PW, Lesser RP: Vert ical and horizont al epilept ic gaze deviat ion and nyst agmus. Neurol ogy 1989; 39: 1391 1 393. Keane JR: I solat ed brain-st em t hird nerve palsy. Arch Neurol 1988; 45: 813 8 14.
Keane JR: The pret ect al syndrome: 206 pat ient s. Neurol ogy 1990; 40: 684 6 90. Lepore FE, G laser JS: Misdirect ion revisit ed. A crit ical appraisal of acquired oculomot or nerve synkinesis. Arch O phthal mol 1980; 98: 2206 2 209. Liu G T et al: Unilat eral oculomot or palsy and bilat eral pt osis f rom paramedian midbrain inf arct ion. Arch Neurol 1991; 48: 983 9 86. Liu G T et al: Midbrain syndromes of Benedikt , Claude, and Not hnagel: Set t ing t he record st raight . Neurol ogy 1992; 42: 1820 1 822. Marshall RS et al: Dissociat ed vert ical nyst agmus and int ernuclear opht halmoplegia f rom a midbrain inf arct ion. Arch Neurol 1991; 48: 1304 1 305. McKenna KE: Cent ral nervous syst em pat hw ays involved in t he cont rol of penile erect ion. Annu Rev Sex Res 1999; 10: 157 1 83. Mehler MF: The neuro-opht halmologic spect rum of t he rost ral basilar art ery syndrome. Arch Neurol 1988; 45: 966 9 71.
Meibach RC, Kat zman R: O rigin, course and t erminat ion of dopaminergic subst ant ia nigra neurons project ing t o t he amygdaloid complex in t he cat . Neurosci ence 1981; 6: 2159 2 171. Messé SR et al: O culomot or synkinesis f ollow ing a midbrain st roke. Neurol ogy 2001; 57: 1106 1107. Moore RY: Cat echolamine neuron syst ems in t he brain. Ann Neurol 1982; 12: 321 3 27. O yanagi K et al: Q uant it at ive invest igat ion of t he subst ant ia nigra in Hunt ingt on's disease. Ann Neurol 1989; 26: 13 1 9. Pierrot -Deseilligny CH et al: Parinaud's syndrome. Elect ro-oculographic and anat omical analysis of six vascular cases w it h deduct ions about vert ical gaze organizat ion in t he premot or st ruct ures. Brai n 1982; 105: 667 6 96. Pryce-Phillips W: Compani on to Cl i ni cal Neurol ogy. Bost on, Lit t le, Brow n, 1995. Pullicino P et al: Abnormal vergence w it h upper brainst em inf arct s: pseudoabducens palsy. Neurol ogy 2000; 55: 352 3 58. Pusat eri TJ et al: I solat ed inf erior rect us muscle palsy f rom a solit ary met ast asis t o t he oculomot or nucleus. Arch O phthal mol 1987; 105: 675 6 77. Ranalli PJ et al: Palsy of upw ard and dow nw ard saccadic, pursuit , and vest ibular movement s w it h a unilat eral midbrain lesion: Pat hophysiologic correlat ions. Neurol ogy 1988; 38: 114 1 22. Remy P et al: Peduncular r ubral t remor and dopaminergic denervat ion: A PET st udy. Neurol ogy 1995; 45: 472 4 77. Skinner HL: The O ri gi n of Medi cal Terms. Balt imore, Williams & Wilkins, 1961. Smit h JL: The nuclear t hird quest ion. J Cl i n Neuroophthal mol 1982; 2: 61 6 3. St eiger HJ, But t ner-Ennever JA: O culomot or nucleus aff erent s in t he monkey demonst rat ed w it h horseradish peroxidase. Brai n Res 1979; 160: 1 1 5.
Thurst on SE, Saul RF: Superior oblique myokymia: Q uant it at ive descript ion of t he eye movement . Neurol ogy 1991; 41: 1679 1 681. Trojanow ski JQ , Wray SH: Vert ical gaze opht halmoplegia: Select ive paralysis of dow ngaze. Neurol ogy 1980; 30: 605 6 10. Usunoff KG et al: Elect ron microscopic evidence f or t he exist ence of a cort iconigral t ract in t he cat . J Hi rnf orsch 1982; 23: 17 2 3. Vanoot eghem P et al: Combined t rochlear nerve palsy and int ernuclear opht halmoplegia. Arch Neurol 1992; 49: 108 1 09. Walberg F, Nordby T: A re-examinat ion of t he rubro-olivary t ract in t he cat , using horseradish peroxidase as a ret rograde and an ant erograde neuronal t racer. Neurosci ence 1981; 6: 2379 2 391. Warren W et al: At ypical oculomot or paresis. J Cl i n Neuroophthal mol 1982; 2: 13 1 8. Weber JT et al: The precise origin of t he t ect ospinal pat hw ay in t hree common laborat ory animals: A st udy using t he horseradish peroxidase met hod. Neurosci Lett 1979; 11: 121 1 27.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 10 - Mes enc ephalon ( Midbr ain) : C linic al C or r elates
10 Mesencephalon (Midbrain): Clinical Correlates
Mesencephalic Vascular Syndrom es Syndrome of W eber Syndrome of Benedikt Claude's Syndrome Nothnagel's Syndrome Plus-Minus Lid Syndrome Parinaud's Syndrome W alleyed Syndrome Vertical One-and-a-Half Syndrome Locked-in Syndrome Top of the Basilar Syndrome Peduncular Hallucinosis Syndrome Akinetic Mutism Decerebrate Rigidity KEY CONCEPTS The syndrome of Weber consists of oculomotor nerve paralysis ipsilateral to the midbrain lesion and contralateral hemiplegia. The syndrome of Benedikt consists of oculomotor nerve paralysis ipsilateral to the midbrain lesion and contralateral tremor. Contralateral hemianesthesia
may occur. Claude's syndrome consists of oculomotor nerve paralysis ipsilateral to the midbrain lesion and contralateral ataxia and tremor. Nothnagel's syndrome is variably described as consisting of bilateral oculomotor nerve paralysis, ipsi- or contralateral gait ataxia, and vertical gaze palsy. Parinaud's syndrome consists of upgaze palsy, pupillary abnormalities, lid retraction, and convergence retraction nystagmus on upward gaze. The walleyed syndrome consists of exotropic gaze and an absence of ocular adduction. This syndrome is also known as the walleyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome. The vertical one-and-a-half syndrome consists of bilateral impairment of downgaze and monocular paralysis of eye elevation. A variant syndrome consists of bilateral impairment of upgaze and monocular downgaze paralysis. The locked-in syndrome consists of mute quadriplegia, preservations of consciousness, and communication by ocular movement and blinking. The top of the basilar syndrome consists of a variety of visual defects, abnormalities of eye movements, pupillary abnormalities, and behavioral disturbances. The peduncular hallucinosis syndrome consists of hallucinations and somnolence. Akinetic mutism characterized by complete immobility except in the eyes occurs with lesions in the midbrain reticular formation. Decerebrate rigidity is associated with midbrain
lesions caudal to the red nucleus, between it and the vestibular nuclei.
M ESENCEPHALIC VASCULAR SYNDROM ES Midbrain inf arct s have not been st udied ext ensively. There have been only a f ew report s of single cases, w ell described clinically and by magnet ic resonance imaging (MRI ), of isolat ed midbrain inf arct s (Table 10-1). The most commonly aff ect ed region is t he middle midbrain, and t he most f requent ly involved t errit ory is t he paramedian t errit ory, f ollow ed by t he post erior cerebral art ery t errit ory and t he t errit ory int ermediat e bet w een t he t w o. I nvolvement of t he t errit ory of t he superior cerebellar art ery is rare. Pat ient s w it h middle midbrain inf arct s have a localizing clinical pict ure t hat is linked t o involvement of t he t hird nerve or it s nucleus. Paramedian inf arct s are associat ed w it h t he nuclear syndrome of t he oculomot or nerve, w hereas more lat eral inf arct s are associat ed w it h f ascicular involvement of t he t hird nerve in isolat ion or w it h cont ralat eral hemiparesis (syndrome of Weber) or hemiat axia (Claude's syndrome). Tabl e 10-1. Midbrain Vascular Syndromes
Syndrom e
Ipsilateral
Contralateral
Lesio
W eber's
Oculomotor palsy
Hemiparesis
CN III,
Benedikt
Oculomotor palsy
Tremor ą hemianesthesia
CN III, ML, ST
Claude's
Oculomotor palsy
Tremor and ataxia
CN III,
Nothnagel's
Oculomotor palsy and ataxia
Oculomotor palsy ą ataxia
CN III,
Plus-minus lid syndrome
Parinaud's
Ptosis
Lid retraction
Upward gaze paralysis Pupillary abnormalities Large pupil Light-near dissociation Covergence retraction nystagmus on upgaze Lid retraction (Collier's sign)
CN III f to the le palpebr muscle. Nucleus posterio commis
Pretecta region
W alleyed
Internuclear ophthalmoplegia (MLF syndrome)
Internuclear ophthalmoplegia (MLF syndrome)
MLF, bi
Vertical one-and-ahalf
Downgaze palsy Monocular elevation palsy
Downgaze palsy
Efferent RiMLF,
Locked-in Peduncular hallucinosis
Mute quadriplegia
Ventral mesenc
Hallucinations, somnolence
Tegmen CP
NOTE: CN, cranial nerve; CP, cerebral peduncle; RN, red n BC, brachium conjunctivum; ML, medial lemniscus; ST,
spinothalamic tract; MLF, medial longitudinal fasciculus; RiM rostral interstitial nucleus of the medial longitudinal fascicul CBF, corticobulbar fibers. Pat ient s w it h rost ral or caudal midbrain inf arct s have a less localizing neurologic pict ure except f or vert ical gaze impairment in t hose w it h dorsal rost ral midbrain inf arct s. I psilat eral t rochlear nerve palsy, Horner's syndrome, and cont ralat eral at axia point t o t he t errit ory of t he superior cerebellar art ery. Hand-f oot -mout h hyperest hesia is due t o involvement of t he medial lemniscus and t he vent ral ascending t ract of t he t rigeminal nerve.
Syndrome of Weber I n t he syndrome of Weber t he pat ient present s w it h signs of ipsilat eral oculomot or nerve paralysis and cont ralat eral upper mot or neuron paralysis t hat includes t he low er f ace. The vascular lesion, usually an inf arct , aff ect s root let s of t he oculomot or nerve and t he underlying cerebral peduncle (Figure 10-1). This syndrome w as described by Adolph-Marie G ubler, a French physician, about 4 years bef ore Sir Herman David Weber, a G erman-English physician, described t he syndrome in 1863, and 17 years bef ore Ernst Vict or von Leyden, a G erman physician, described a similar syndrome in 1875. The syndrome is t heref ore ref erred t o by some as t he G ubler-Weber syndrome, Leyden paralysis, and Leyden syndrome. O t her synonyms include t he cerebral peduncle syndrome, hemiplegia alt ernans superior peduncularis, and syndrome of t he cerebral peduncle.
Syndrome of Benedikt I n t he syndrome of Benedikt t he pat ient present s w it h signs of ipsilat eral oculomot or nerve paralysis and cont ralat eral t remor. The vascular lesion aff ect s root let s of t he oculomot or nerve w it hin t he t egment um of t he mesencephalon and t he underlying red nucleus (Figure 10-1). Cont ralat eral hemianest hesia has been described by some researchers and is at t ribut ed t o involvement of t he medial lemniscus and spinot ha-lamic t ract . This syndrome w as f irst described by a Viennese physician, Morit z Benedikt , in 1889. The t remor in t his syndrome has been called rubral t remor on t he basis of damage t o t he red nucleus or t he superior cerebellar peduncle. The t remor is usually of low f requency and may have rest ing, post ural, and kinet ic component s. The kinet ic component may be explained by t he involvement of t he superior cerebellar peduncle or t he red nucleus. The rest ing and post ural component s are due t o t he involvement of dopaminergic nigrost riat al f ibers t hat arise f rom t he pars compact a of t he subst ant ia nigra and run vent ral t o t he red nucleus and t hrough f ield H of Forel (prerubral) on t heir w ay t o t he hypot halamus and
st riat um. This component of t he t remor responds w ell t o t reat ment w it h levodopa.
Claude's Syndrome Described by t he French psychiat rist and neurologist Henry Claude in 1912, t his syndrome is very rare. Claude's original case had midbrain inf arct ion t hat involved t he medial half of t he red nucleus, t he adjacent decussat ing f ibers of superior cerebellar peduncle, and oculomot or nerve f ascicles. Pat ient s present w it h ipsilat eral oculomot or nerve palsy and cont ralat eral t remor and at axia. O culomot or nerve palsy is part ial in most pat ient s. The medial rect us is most commonly involved, f ollow ed in order of f requency by t he levat or palpebrae, superior rect us, inf erior oblique, and inf erior rect us. The pupil is spared in t he majorit y of pat ient s. Alt hough t he t remor and at axia are generally at t ribut ed t o a lesion in t he red nucleus, it has recent ly been show n t hat t he main pat hology is in t he superior cerebellar peduncle, just below and medial t o t he red nucleus, and t hat t he red nucleus cont ribut es lit t le t o t he syndrome. I nf arct ion in t he t errit ory of t he ant eromedial branches of t he post erior cerebral art ery is t he cause of t he syndrome in t he majorit y of pat ient s.
Nothnagel's Syndrome Not hnagel's syndrome has been variably described by diff erent aut hors. I n 1879, Not hnagel, an Aust rian physician, described a pat ient w it h bilat eral asymmet ric oculomot or palsies of varying degree and gait at axia. Subsequent ly, t he syndrome w as variously described in pat ient s w it h oculomot or nerve palsy and ipsilat eral or cont ralat eral at axia and pat ient s w it h oculomot or nerve palsy and vert ical gaze palsy. The lesion in t he original report involved t he superior and inf erior colliculi. Subsequent report s described pat hology in t he oculomot or nerve f ascicles and t he brachium conjunct ivum. The syndrome may be regarded as a variant of t he dorsal midbrain (Parinaud's) syndrome or as Benedikt syndrome w it h added vert ical gaze palsy.
Fi gure 10-1. Schemat ic diagram show ing lesions of t he oculomot or nerve in it s int ra- and ext ra-axial course and t heir respect ive clinical manif est at ions.
Plus-Minus Lid Syndrome Described by G aymard and colleagues in 1992, t his syndrome consist s of unilat eral pt osis and cont ralat eral lid ret ract ion due t o a small lesion in t he rost ral midbrain involving t he nucleus of t he post erior commissure and oculomot or f ascicles t o t he ipsilat eral levat or palpebrae muscle as t hey emerge f rom t he cent ral caudal subnucleus. I psilat eral pt osis is explained on int errupt ion of oculomot or f ascicles t o t he levat or palpebrae. Lid ret ract ion is explained on overact ivat ion of t he cont ralat eral levat or palpebrae muscle due t o loss of inhibit ory pat hw ays f or lid ret ract ion f rom t he nucleus of t he post erior commissure t o t he cent ral caudal subnucleus.
Parinaud's Syndrome Parinaud's syndrome is also know n as t he sylvian aqueduct syndrome, t he dorsal midbrain syndrome, Koerber-Salus-Elschnig syndrome, t he pineal syndrome, and t he syndrome of t he post erior commissure. The lesion is in t he pret ect al region. Pat ient s w it h t his syndrome present w it h upw ard gaze paralysis, pupillary abnormalit ies (large pupil, light -near dissociat ion), lid ret ract ion (Collier's sign), and convergence ret ract ion nyst agmus on upw ard gaze. This syndrome w as described in 1883 by Parinaud, w ho vaguely speculat ed about t he lesion sit e. Def init ive localizat ion of t he lesion in t he pret ect al area result ed f rom experiment al and human observat ions made bet w een 1969 and 1974 by Bender,
w ho coined t he t erm pretectal syndrome.
Walleyed Syndrome The w alleyed syndrome is also know n as t he w alleyed bilat eral int ernuclear opht halmoplegia (WEBI NO ) syndrome. The lesion is bilat eral and involves t he rost ral medial longit udinal f asciculus. This syndrome is charact erized by lat eral deviat ion of bot h eyes (exot ropic gaze) and t he absence of ocular adduct ion.
Vertical One-and-a-Half Syndrome The vert ical one-and-a-half syndrome is charact erized by bilat eral impairment of dow ngaze (t he one) and monocular paralysis of elevat ion (t he half ). The lesion usually consist s of bilat eral inf arct s in t he mesencephalic-diencephalic region t hat involve eff erent t ract s of t he rost ral int erst it ial nucleus of t he medial longit udinal f asciculus (RiMLF) bilat erally and premot or f ibers t o t he cont ralat eral superior rect us subnucleus and t he ipsilat eral inf erior oblique subnucleus bef ore or af t er decussat ion in t he post erior commissure. A variant of t his syndrome consist s of bilat eral impairment of upgaze (t he one) w it h monocular dow ngaze palsy (t he half ). The vert ical one-and-a-half syndrome w as described by Deleu, Buisseret , and Ebinger in 1989.
Locked-in Syndrome The locked-in syndrome is also know n as t he bilat eral pyramidal syst em syndrome. I t is charact erized by mut e quadriplegia, preservat ion of consciousness, and communicat ion by vert ical (not lat eral) ocular movement s and blinking. I n most pat ient s t he lesion is bilat eral in t he vent ral half of t he pons at or rost ral t o t he level of t he abducens nuclei; in some pat ient s t he lesion may be bilat eral in t he vent ral mesencephalon or bot h int ernal capsules. The t erm l ocked-i n syndrome w as proposed by Plum and Posner in 1987. This syndrome is also know n as pseudocoma, t he de-eff erent ed st at e, t he vent ral pont ine or brain st em syndrome, cerebromedullary disconnect ion, pont opseudocoma, t he pont ine disconnect ion syndrome a nd t he Mont e Crist o syndrome in ref erence t o Alexandre Dumas's novel The Count of Monte Cri sto, in w hich t he elderly Noirt ier communicat ed only by eye blinks.
Top of the Basilar Syndrome I n t he t op of t he basilar syndrome t he lesion is not limit ed t o t he mesencephalon but also involves ot her st ruct ures (t he t halamus and port ions of t he t emporal and occipit al cort ices). The conglomerat e signs and sympt oms of t his syndrome include (1) visual def ect s such as hemianopia, cort ical blindness (loss of vision w it h int act pupillary light ref lexes), and Balint 's syndrome (opt ic
at axia) caused by involvement of t he occipit al, pariet al, and t emporal cort ices, (2) abnormalit ies of eye movement s, including vert ical gaze abnormalit ies, lid ret ract ion (Collier's sign), and convergence disorder, (3) pupillary abnormalit ies, including light -near dissociat ion and a small react ive or large f ixed pupil, (4) behavioral dist urbances (somnolence, memory def ect s, agit at ion, hallucinat ion), and (5) mot or and sensory def icit s. The usual et iology of t his syndrome is occlusion of t he rost ral basilar art ery.
Peduncular Hallucinosis Syndrome The peduncular hallucinosis syndrome is charact erized by nont hreat ening hallucinat ions, of t en f ormed nonst ereot ypically, colored, and vivid, t hat usually occur in somnolent pat ient s w it h presumed t egment al and cerebral peduncle lesions. The sympt oms probably arise f rom t halamic or occipit ot emporal lesions rat her t han f rom t he midbrain. This condit ion w as f irst described by Jean Jacques Lhermit t e, a French neurologist , in 1922 in a 75-year-old w oman w it h midbrain inf arct w hose hallucinat ions consist ed of animals and people sharing t he room w it h her. The name w as suggest ed by Ludo Van Bogaert , a Belgian neurologist , in 1924.
AKINETIC M UTISM Various levels of unconsciousness occur in pat ient s w it h lesions of t he mesencephalic ret icular f ormat ion. Evidence f rom experiment al w ork point s t o a t onic role of t he mesencephalic ret icular f ormat ion in cort ical excit abilit y and t he maint enance of aw areness. Bilat eral limit ed lesions of t he mesencephalic ret icular f ormat ion have been associat ed w it h akinet ic mut ism (Cairns syndrome), a clinical condit ion charact erized by absolut e mut ism and complet e immobilit y except f or t he eyes, w hich are kept open and move in all direct ions. The pat ient appears aw ake and maint ains a sleep-w ake cycle, but no communicat ion w it h t he pat ient t hrough eit her painf ul or audit ory st imuli can be est ablished. The condit ion w as f irst report ed by an Aust ralian neurosurgeon, Sir Hugh Cairns, in 1941. This condit ion may result f rom injury t o t he mesencephalic ret icular f ormat ion caused by t ranst ent orial brain herniat ion w it h edema, hemorrhage, or occlusion of branches of t he basilar art ery. The condit ion is also know n as persist ent veget at ive st at e.
DECEREBRATE RIGIDITY Decerebrat e rigidit y in humans result s f rom lesions of t he brain st em caudal t o t he red nucleus and rost ral t o t he vest ibular nuclei. The body is f orced backw ard w it h t he head bent ext remely dorsally. The shoulders are int ernally rot at ed, t he elbow s are ext ended, and t he dist al part s of t he upper limbs are hyperpronat ed w it h f inger ext ension at t he met acarpophalangeal joint s and f lexion at t he int erphalangeal joint s. The hips and knees are ext ended; t he f eet and t oes are plant ar f lexed. This syndrome is associat ed w it h severe head
t rauma and compression of t he brain st em by herniat ion.
TERM INOLOGY Balint's syndrome. Also know n as Balint -Holmes syndrome, ocular apraxia, opt ic at axia, psychic paralysis of visual f ixat ion, and cort ical paralysis of visual f ixat ion. A rare syndrome result ing f rom bilat eral pariet o-occipit al disease and charact erized by an inabilit y t o direct t he eyes t o a cert ain point in t he visual f ield despit e int act eye movement s and vision. Discovered by Rudolph Balint , a Hungarian neurologist , in 1909. Claude's syndrome. Described by a French psychiat rist and neurologist , Henri Claude, in 1912. Collier's sign. Bilat eral lid ret ract ion seen in t he pret ect al syndrome. Horner's syndrome. Drooping of t he eyelid (pt osis), const rict ion of t he pupil (miosis), ret ract ion of t he eyeball (enopht halmos), and loss of sw eat ing on t he f ace (anhidrosis) const it ut e a syndrome described by Johann Friedrich Horner, a Sw iss opht halmologist , in 1869. The syndrome is caused by int errupt ion of descending sympat het ic f ibers. Also know n as Bernard-Horner syndrome and oculosympat het ic palsy. The syndrome w as described in animals by François du Pet it in 1727. Claude Bernard in France in 1862 and E. S. Hare in G reat Brit ain in 1838 gave precise account s of t he syndrome bef ore Horner did. Koerber-Salus-Elschnig syndrome. A syndrome of vert ical gaze palsy, anisocoria (unequal pupil sizes), light -near dissociat ion, conversion ret ract ion nyst agmus, lid ret ract ion, impaired convergence, skew ed eye deviat ion, papilledema, and lid f lut t er associat ed most commonly w it h pineal t umors or disorders of t he pret ect al region. Also know n as Parinaud's syndrome, t he sylvian aqueduct syndrome, and t he syndrome of t he post erior commissure. The best of t he original descript ions w as t hat of Salus in 1910. Nothnagel's syndrome. Described by Carl Wilhelm Hermann Not hnagel, an Aust rian int ernist , neurologist , and pat hologist , in 1879. O ptic ataxia. A rare syndrome result ing f rom bilat eral pariet o-occipit al disease and charact erized by inabilit y t o direct t he eyes t o a cert ain point in t he visual f ield despit e int act eye movement s and vision. Also know n as Balint 's syndrome, Balint -Holmes syndrome, and ocular apraxia. Parinaud's syndrome.
Described by Henri Parinaud, a French neuro-opht halmologist , in 1883. Syndrome of Benedikt. Described in a 4-year-old pat ient by Morit z Benedikt , an Aust rian physician, in 1889. Syndrome of Weber. Named af t er Sir Herman David Weber, a G erman-English physician w ho described t he syndrome in 1863.
SUGGESTED READINGS Balint R: Seelenlahmung des S chauens, opt ische At axia, raumliche st orung der Auf merskameit . Monatsschr Psychi atr Neurol 1909; 25: 51 8 1. Benedikt M: Tremblement avec paralysie croisée du mot eur oculaire commun. Bul l Soc Med Hop Pari s 1889; 3: 547 5 48. Bogousslavsky J et al: Pure midbrain inf arct ion: Clinical syndromes, MRI , and et iologic pat t erns. Neurol ogy 1994; 44: 2032 2 040. Breen LA et al: Pupil-sparing oculomot or nerve palsy due t o midbrain inf arct ion. Arch Neurol 1991; 48: 105 1 06. Cairns H et al: Akinet ic mut ism w it h an epidermoid cyst of t he 3rd vent ricle. Brai n 1941; 64: 273 2 90. Claude H: Syndrome pedunculaire de la region du noyau rouge. Rev Neurol (Pari s) 1912; 23: 311 3 13. Claude H, Loyez M: Ramollissement du noyau rouge. Rev Neurol (Pari s) 1912; 24: 49 5 1. Deleu D et al: Vert ical one-and-a-half syndrome: Supranuclear dow ngaze paralysis w it h monocular elevat ion palsy. Arch Neurol 1989; 46: 1361 1 363. Felice KJ et al: R ubral gait at axia. Neurol ogy 1990; 40: 1004 1 005. G alet t a SL et al: Unilat eral pt osis and cont ralat eral eyelid ret ract ion f rom a t ha-lamic-midbrain inf arct ion. J Cl i n Neuroophthal mol 1993; 13: 221 2 24. G aymard B et al: Plus-minus lid syndrome. J Neurol Neurosurg Psychi atry
1992; 55: 846 8 48. Keane JR: The pret ect al syndrome: 206 pat ient s. Neurol ogy 1990; 40: 684 6 90. Liu G T et al: Midbrain syndromes of Benedikt , Claude, and Not hnagel: Set t ing t he record st raight . Neurol ogy 1992; 42: 1820 1 822. Mehler MF: The neuro-opht halmologic spect rum of t he rost ral basilar art ery syndrome. Arch Neurol 1988; 45: 966 9 71. Not hnagel H: Topi sche di agnosti k der G ehi rnkrankhei ten. Berlin, Hischw alden, 1879: 220. Parinaud H: Paralysie des mouvement s associés des yeux. Arch Neurol (Pari s) 1883; 5: 145 1 72. Plum F, Posner JB: The Di agnosi s of Stupor and Coma. Philadelphia, Davis, 1987. Pryse-Phillips W: Compani on to Cl i ni cal Neurol ogy. Bost on, Lit t le, Brow n, 1995. Ranalli PJ et al: Palsy of upw ard and dow nw ard saccadic, pursuit , and vest ibular movement s w it h a unilat eral midbrain lesion: Pat hophysiologic correlat ion. Neurol ogy 1988; 38: 114 1 22. Salus R: Acquired ret ract ion movement s of t he globe. Arch Augenhei l k 1910; 68: 61 6 7. Seo SW et al: Localizat ion of Claude's syndrome. Neurol ogy 2001; 57: 2304 2 307. Weber HD: A cont ribut ion t o t he pat hology of t he crura cerebri. Med Chi r Trans 1863; 46: 121 1 39.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 11 - D ienc ephalon
11 Diencephalon
Gross Topography Divisions of Diencephalon Epithalamus Thalamus (Dorsal Thalamus) and Metathalamus Internal Capsule Subthalamus KEY CONCEPTS The term diencephalon includes the following structures: epithalamus, thalamus (including the metathalamus), hypothalamus, and subthalamus. Based on their rostrocaudal and mediolateral location, thalamic nuclei are divided into the following groups: anterior, medial, lateral, intralaminar and reticular, midline, and posterior. The anterior group of thalamic nuclei have reciprocal connections with the mamillary bodies and cingulate gyrus. They belong to the modality-specific and limbic group of thalamic nuclei. The medial group of thalamic nuclei have a reciprocal relationship with the prefrontal cortex. They belong to the multimodal associative group of
thalamic nuclei and play a role in affective behavior, memory, and the integration of somatic visceral activities. The pulvinar and lateral posterior nuclei form a single nuclear complex based on their anatomic connections and functions. The pulvinar l ateral posterior complex links subcortical visual areas with the association cortical visual areas. The pulvinar l ateral posterior complex belongs to the multimodal associative group of thalamic nuclei. The ventral anterior nucleus links the basal ganglia and the cerebral cortex. It belongs to the modalityspecific and motor groups of thalamic nuclei. The ventral lateral nucleus links the cerebellum with the cerebral cortex. It belongs to the modalityspecific and motor groups of thalamic nuclei. The ventral posterior lateral nucleus links the somatosensory (medial lemniscus and spinothalamic) neural system from the contralateral half of the body with the somatosensory cortex. The ventral posterior medial nucleus links the somatosensory neural system from the contralateral face (tri-geminothalamic) and taste system with the somatosensory cortex. The intralaminar, reticular, and midline nuclei belong to the nonspecific system of thalamic nuclei. They are concerned with arousal, motor control, and the awareness of sensory experiences. The medial geniculate nucleus is a relay station in the auditory pathway. It belongs to the modalityspecific and sensory groups of thalamic nuclei. The lateral geniculate nucleus is a relay station in
the visual pathway. It belongs to the modality-specific and sensory groups of nuclei. The posterior thalamic nucleus belongs to the multimodal associative group of thalamic nuclei. It is a convergence center for multimodal sensory modalities. Based on their neural connectivity, thalamic nuclei are grouped into the following categories: modalityspecific, multimodal associative, nonspecific, and reticular. Based on their function, thalamic nuclei are grouped into the following categories: motor, sensory, and limbic. Vascular lesions in the posterior limb of the internal capsule are associated with contralateral hemiplegia and hemisensory loss. Lesions that involve the visual and auditory radiations are in addition associated with contralateral visual loss and hearing deficit. Lesions that involve the genu are associated with cranial nerve signs. The thalamus receives its blood supply from four parent vessels: basilar, posterior cerebral, posterior communicating, and internal carotid. Vascular lesions in the thalamus are associated with a characteristic pain syndrome, the thalamic syndrome. Lesions of the subthalamic nucleus or of the subthalamopallidal pathways are associated with contralateral hemiballismus. The H fields of Forel contain pallidal and cerebellar efferents to the thalamus.
GROSS TOPOGRAPHY (Figures 11-1, 11-2, and A5-17) The diencephalon, or i n-bet w een brain, is complet ely surrounded by t he cerebral hemispheres except at it s vent ral surf ace. I t is limit ed post eriorly by t he post erior commissure and ant eriorly by t he lamina t erminalis and t he f oramen of Monro. The post erior limb of t he int ernal capsule limit s t he diencephalon lat erally. Medially, t he diencephalon f orms t he lat eral w all of t he t hird vent ricle. The dorsal surf ace f orms t he f loor of t he lat eral vent ricle and is marked medially by a band of nerve f ibers, t he st ria medullaris t halami. The vent ral surf ace cont ains hypot halamic st ruct ures. A groove ext ending bet w een t he f oramen of Monro and t he aqueduct of Sylvius (t he hypot halamic sulcus) divides t he dienceph-alon int o a dorsal port ion, t he t halamus, and a vent ral port ion, t he hypot halamus. The t w o t halami are connect ed across t he midline in about 70 percent of humans t hrough t he int ert halamic adhesion (massa int ermedia). The diencephalon develops f rom t he caudal vesicle of t he embryologic prosencephalon.
DIVISIONS OF DIENCEPHALON The diencephalon is divided int o f our major subdivisions. These are (1) t he epit halamus, (2) t he t halamus and met at halamus, (3) t he subt halamus, and (4) t he hypot halamus. The f irst t hree subdivisions w ill be discussed in t his chapt er. The f ourt h subdivision, t he hypot halamus, w ill be discussed in Chapt er 19.
Epithalamus The epit halamus occupies a posit ion dorsal t o t he t halamus and includes t he f ollow ing st ruct ures (Figure 11-1).
A. STRIA M EDULLARIS THALAM I This band of nerve f ibers courses dorsomedial t o t he t halamus and connect s t he sept al (medial olf act ory) area, locat ed underneat h t he rost ral end of t he corpus callosum in t he f ront al lobe, w it h t he habenular nuclei.
B. HABENULAR NUCLEI These nuclei are locat ed in t he caudal diencephalon; one is on each side, dorsomedial t o t he t halamus. They receive t he st ria medullaris and project via t he habenulo-int erpeduncular t ract (f asciculus ret rof lexus of Meynert ) t o t he int erpeduncular nucleus of t he midbrain. The t w o habenular nuclei are connect ed by t he habenular commissure. The habenular nuclei, part of a neural net w ork t hat includes t he limbic and olf act ory syst ems, are concerned w it h mechanisms of
emot ion and behavior.
Fi gure 11-1. Schemat ic diagram show ing t he subdivisions of t he diencephalon as seen in a midsagit t al view.
Fi gure 11-2. Schemat ic diagram show ing t he subdivisions of t he diencephalon as seen in a composit e coronal view.
C. PINEAL GLAND This endocrine gland is locat ed just rost ral t o t he superior colliculi in t he roof of t he t hird vent ricle. The f unct ions of t he pineal gland are not w ell underst ood. I t
may have roles in gonadal f unct ion and circadian rhyt hm. I t secret es t he biogenic amines serot onin, norepinephrine, and melat onin and cont ains several hypot halamic pept ides including t hyrot ropin-releasing hormone (TRH), leut einizing hormone r eleasing hormone (LHRH), and somat ost at in r elease inhibit ory f act or (SRI F). I t synt hesizes melat onin f rom serot onin in a rhyt hmic f ashion t hat f luct uat es w it h t he daily cycle of light . The pineal gland usually calcif ies af t er t he age of 16 years. This f act is used in t he det ect ion of midline shif t s in skull x-rays. I n normal skull x-rays, pineal calcif icat ions are seen in t he midline. Shif t s of pineal calcif icat ion aw ay f rom t he midline suggest t he presence of space-occupying lesions displacing t he pineal. Such a lesion could be blood in t he subdural or epidural space, a hemat oma w it hin t he brain, or a brain t umor. Pineal gland t umors (pinealomas) depress gonadal f unct ion and delay t he onset of pubert y. I n cont rast , lesions t hat dest roy t he pineal gland may be associat ed w it h precocious onset of pubert y, suggest ing t hat t he pineal gland exert s an inhibit ory inf luence on gonadal f unct ion. Tumors in t he region of t he pineal gland usually int erf ere w it h vert ical gaze. This loss of vert ical gaze, know n as Parinaud's syndrome, result s f rom pressure of t he pineal lesion on t he pret ect al area and/ or t he post erior commissure.
Thalamus (Dorsal Thalamus) and Metathalamus The t erm thal amus derives f rom a G reek w ord t hat means i nner chamber. Use of t he t erms opti c thal amus and chamber of vi si on relat es t o t he t racing, in t he second cent ury A. D. , of opt ic nerve f ibers t o t he t halamus by G alen. The pref ix opti c w as dropped w hen it w as discovered t hat sensory modalit ies ot her t han vision are also processed in t he t halamus. The t halamus is t he largest component of t he diencephalon, w it h a rost rocaudal dimension in humans of about 30 mm, height of about 20 mm, w idt h of about 20 mm, and an est imat ed 10 million neurons in each hemisphere. I t is subdivided int o t he f ollow ing major nuclear groups (Figure 11-3) on t he basis of t heir rost rocaudal and mediolat eral locat ion w it hin t he t halamus: 1. Ant erior 2. Medial 3.
Lat eral
4. I nt ralaminar and ret icular 5. Midline 6. Post erior The t halamus is t raversed by a band of myelinat ed f ibers, t he int ernal medullary lamina, w hich runs along t he rost rocaudal ext ent of t he t halamus. The int ernal medullary lamina separat es t he medial f rom t he lat eral group of nuclei. Rost rally
and caudally, t he int ernal medullary lamina split s t o enclose t he ant erior and int ralaminar nuclear groups, respect ively. The int ernal medullary lamina cont ains int rat halamic f ibers connect ing t he diff erent nuclei of t he t halamus w it h each ot her. Anot her medullat ed band, t he ext ernal medullary lamina, f orms t he lat eral boundary of t he t halamus medial t o t he int ernal capsule. Bet w een t he ext ernal medullary lamina and t he int ernal capsule is t he ret icular nucleus of t he t halamus. The ext ernal medullary lamina cont ains nerve f ibers leaving or ent ering t he t halamus on t heir w ay t o or f rom t he adjacent capsule. Lit erat ure on t he t halamus in general, and on t halamic surgery in part icular, is diff icult t o read because diff erent nomenclat ures are in use. Most available nomenclat ures are derived f rom st udies in primat es. The diff erent nomenclat ures are based eit her on t he cyt oarchit ect onic def init ion of nuclei or on t heir subcort ical aff erent s. Human t halamic nomenclat ure is based ent irely on cyt oarchit ect onic subdivisions and on t ransf er of know ledge by analogy f rom monkey t o human. Problems, how ever, have arisen w hen t rying t o t ransf er t he det ailed know ledge f rom t he monkey t o t he human brain.
Fi gure 11-3. Schemat ic diagram show ing t he major nuclear groups of t he t halamus.
A. ANTERIOR NUCLEAR GROUP The ant erior t ubercle of t he t halamus (dorsal surf ace of t he most rost ral part of t he t halamus) is f ormed by t he ant erior nuclear group. I n humans, t he ant erior nuclear group of t ha-lamic nuclei consist s of t w o nuclei: principal
ant erior and ant erodorsal. The principal ant erior nucleus of humans corresponds t o t he ant eromedial and ant erovent ral nuclei of ot her species. The ant erior group of t halamic nuclei has reciprocal connect ions (Figure 11-4) w it h t he hypot halamus (mamillary bodies) and t he cerebral cort ex (cingulat e gyrus). The ant erior group also receives signif icant input f rom t he hippocampal f ormat ion of t he cerebral cort ex (subiculum and presubiculum) via t he f ornix. The reciprocal f ibers bet w een t he ant erior t halamic nuclear group and t he mamillary bodies t ravel via t he mamillot halamic t ract (t ract of Vicq d'Azyr). The project ions f rom t he mamillary bodies t o t he ant erior group of t halamic nuclei is t opographically organized such t hat t he medial mamillary nucleus project s t o t he ipsilat eral principal ant erior nucleus, w hereas t he lat eral mamillary nucleus project s t o bot h ant erodorsal nuclei. The reciprocal connect ions bet w een t he ant erior nuclear group and t he cingulat e gyrus accompany t he ant erior limb of t he int ernal capsule. The project ion f rom t he ant erior t halamic group t o t he cingulat e gyrus is t opographically organized such t hat t he medial part of t he principal ant erior nucleus project s t o rost ral part s of t he cingulat e gyrus, w hereas t he lat eral part of t he principal nucleus and t he ant erodorsal nucleus project t o caudal part s of t he cingulat e gyrus. The ant erior nuclear group of t he t halamus is part of t he limbic syst em, w hich is concerned w it h emot ional behavior and memory mechanisms. Discret e damage t o t he mamillot halamic t ract has been associat ed w it h def icit s in a specif ic t ype of memory, episodic longt erm memory, w it h relat ive sparing of short -t erm memory and int ellect ual capacit ies.
B. M EDIAL NUCLEAR GROUP O f t he medial nuclear group, t he dorsomedial nucleus is t he most highly developed in humans. I n hist ologic sect ions st ained f or cells, t hree divisions of t he dorsomedial nucleus are recognized: a dorsomedial magnocellular division locat ed rost rally, a dorsolat eral parvicellular division locat ed caudally, and a paralaminar division adjacent t o t he int ernal medullary lamina. The dorsomedial nucleus develops in parallel w it h and is reciprocally connect ed w it h t he pref ront al cort ex (areas 9, 10, 11, and 12), via t he ant erior t halamic peduncle, and t he f ront al eye f ields (area 8) (Figure 11-5). I t also receives input s f rom t he t emporal neocort ex (via t he inf erior t halamic peduncle), amygdaloid nucleus and subst ant ia nigra pars ret iculat a, and adjacent t halamic nuclei, part icularly t he lat eral and int ralaminar groups. The dorsomedial nucleus belongs t o a neural syst em concerned w it h aff ect ive behavior, decision making and judgment , memory, and t he int egrat ion of somat ic and visceral act ivit y. Bilat eral lesions of t he dorsomedial nucleus result in a syndrome of lost physical self -act ivat ion, manif est ed by apat hy, indiff erence, and poor mot ivat ion. The reciprocal connect ions bet w een t he pref ront al cort ex and t he dorsomedial nucleus can be int errupt ed surgically t o relieve severe anxiet y st at es and ot her psychiat ric disorders. This operat ion, know n as pref ront al lobot omy (ablat ion of pref ront al
cort ex) or pref ront al leukot omy (severance of t he pref ront al-dorsomedial nucleus pat hw ay), is rarely pract iced now adays, having been replaced largely by medical t reat ment t hat achieves t he same result w it hout undesirable side eff ect s.
Fi gure 11-4. Schemat ic diagram show ing t he reciprocal connect ions among t he ant erior nucleus of t he t halamus, mamillary body, and cingulat e gyrus.
C. LATERAL NUCLEAR GROUP The lat eral nuclear group of t he t halamus is subdivided int o t w o groups, dorsal and vent ral.
1. Dorsal Subgroup This subgroup includes, f rom rost ral t o caudal, t he lat eral dorsal, lat eral post erior, and pulvinar nuclei. The lat eral dorsal nucleus, alt hough anat omically part of t he dorsal t ier of t he lat eral group of t halamic nuclei, is f unct ionally part of t he ant erior group of t halamic nuclei, w it h w hich it collect ively f orms t he limbic t halamus. Similar t o t he ant erior group of t halamic nuclei, t he lat eral dorsal nucleus receives input s f rom t he hippocampus (via t he f ornix) and an uncert ain input f rom t he mamillary bodies and project s t o t he cingulat e gyrus. I n hist ologic sect ions st ained f or myelin, t he lat eral dorsal nucleus is charact erized by a dist inct capsule of myelinat ed f ibers surrounding it .
Fi gure 11-5. Schemat ic diagram show ing t he major aff erent and eff erent connect ions of t he dorsomedial nucleus of t he t halamus.
The borderline bet w een t he lat eral post erior nucleus and t he pulvinar nucleus is vague, and t he t erm pul vi nar l ateral posteri or compl ex has been used t o ref er t o t his nuclear complex. The pulvinar l at eral post erior complex has reciprocal connect ions caudally w it h t he lat eral geniculat e body and rost rally w it h t he associat ion areas of t he pariet al, t emporal, and occipit al cort ices (Figure 11-6). I t also receives
input s f rom t he pret ect al area and superior colliculus. The pulvinar is t hus a relay st at ion bet w een subcort ical visual cent ers and t heir respect ive associat ion cort ices in t he t emporal, pariet al, and occipit al lobes. The pulvinar has a role in select ive visual at t ent ion. There is evidence t hat t he pulvinar nucleus plays a role in speech mechanisms. St imulat ion of t he pulvinar nucleus of t he dominant hemisphere has produced anomia (nominal aphasia). The pulvinar nucleus also has been show n t o play a role in pain mechanisms. Lesions in t he pulvinar nucleus have been eff ect ive in t he t reat ment of int ract able pain. Experiment al st udies have demonst rat ed connect ions bet w een t he pulvinar nucleus and several cort ical and subcort ical areas concerned w it h pain mechanisms.
Fi gure 11-6. Schemat ic diagram show ing t he major aff erent and eff erent connect ions of t he pulvinar.
The pulvinar l at eral post erior complex and t he dorsomedial nucleus are know n collect ively as mult imodal associat ion t ha-lamic nuclei. They all have t he f ollow ing in common:
1. They do not receive a direct input f rom t he long ascending t ract s. 2. Their input is mainly f rom ot her t halamic nuclei. 3. They project mainly t o t he associat ion areas of t he cort ex.
2. Ventral Subgroup This subgroup includes t he vent ral ant erior, vent ral lat eral, and vent ral post erior nuclei. The neural connect ivit y and f unct ions of t his subgroup are much bet t er underst ood t han t hose of t he dorsal subgroup. I n cont rast t o t he dorsal subgroup, w hich belongs t o t he mult imodal associat ion t halamic nuclei, t he vent ral subgroup belongs t o t he modalit y-specif ic t halamic nuclei. These nuclei share t he f ollow ing charact erist ics: 1. They receive a direct input f rom t he long ascending t ract s. 2. They have reciprocal relat ionships w it h specif ic cort ical areas. 3. They degenerat e on ablat ion of t he specif ic cort ical area t o w hich t hey project .
a. Ven tral an terior n u cleu s This is t he most rost rally placed of t he vent ral subgroup. I t receives f ibers f rom several sources (Figure 11-7). G l obus pal l i dus. A major input t o t he vent ral ant erior nucleus is f rom t he int ernal segment of globus pallidus. Fibers f rom t he globus pallidus f orm t he ansa and lent icular f asciculi and reach t he nucleus via t he t halamic f asciculus. Pallidal f ibers t erminat e in t he lat eral port ion of t he vent ral ant erior nucleus. Substanti a ni gra pars reti cul ata. Nigral aff erent s t erminat e in t he medial port ion of t he nucleus in cont rast t o t he pallidal aff erent s, w hich t erminat e in it s lat eral port ion. Intral ami nar thal ami c nucl ei. Premotor and pref rontal corti ces (areas 6 and 8) The input s f rom globus pallidus and subst ant ia nigra are G ABAergic inhibit ory. The input s f rom t he cerebral cort ex are excit at ory. The major out put of t he vent ral ant erior nucleus goes t o t he premot or cort ices and t o w ide areas of t he pref ront al cort ex, including t he f ront al eye f ields. I t also has reciprocal connect ions w it h t he int ralaminar nuclei. A project ion t o t he primary mot or cort ex has been described.
Thus t he vent ral ant erior nucleus is a major relay st at ion in t he mot or pat hw ays f rom t he basal ganglia t o t he cerebral cort ex. As such, it is involved in t he regulat ion of movement . The medial (magnocellular) part of t he vent ral ant erior nucleus is concerned w it h cont rol of volunt ary eye, head, and neck movement s. The lat eral (parvicellular) part of t he nucleus is concerned w it h cont rol of body and limb movement s. Lesions in t his nucleus and adjacent areas of t he t halamus have been placed surgically (t halamot omy) t o relieve disorders of movement , especially parkinsonism.
Fi gure 11-7. Schemat ic diagram show ing t he major connect ions of t he vent ral ant erior nucleus of t he t halamus.
b. Ven tral lateral n u cleu s
This nucleus is locat ed caudal t o t he vent ral ant erior nucleus and, similar t o t he lat t er, plays a major role in mot or int egrat ion. The vent ral ant erior and vent ral lat eral nuclei t oget her comprise t he mot or t halamus. The aff erent f ibers t o t he vent ral lat eral nucleus come f rom t he f ollow ing sources (Figure 11-8).
Fi gure 11-8. Schemat ic diagram show ing t he major aff erent and eff erent connect ions of t he nucleus vent ralis lat eralis of t he t halamus.
Deep cerebel l ar nucl ei. The dent at ot halamic syst em const it ut es t he major input t o t he vent ral lat eral nucleus. As det ailed in Chapt er 15, t his f iber syst em originat es in t he deep cerebellar nuclei (mainly dent at e), leaves t he cerebellum via t he superior cerebellar peduncle, and decussat es in t he mesencephalon. Some f ibers synapse in t he red nucleus, w hile ot hers bypass it t o reach t he t halamus.
G l obus pal l i dus (i nternal segment). Alt hough t he pallidot ha-lamic f iber syst em project s primarily on vent ral ant erior neurons, some f ibers reach t he ant erior (oral) port ion of t he vent ral lat eral nucleus. Pri mary motor cortex. There is a reciprocal relat ionship bet w een t he primary mot or cort ex (area 4) and t he vent ral lat eral nucleus. The eff erent f ibers of t he vent ral lat eral nucleus go primarily t o t he primary mot or cort ex in t he precent ral gyrus. O t her cort ical t arget s include nonprimary somat osensory areas in t he pariet al cort ex (areas 5 and 7) and t he premot or and supplement ary mot or cort ices. The pariet al cort ical t arget s play a role in decoding sensory st imuli t hat provide spat ial inf ormat ion f or t arget ed movement s. Thus t he vent ral lat eral nucleus, like t he vent ral ant erior nucleus, is a major relay st at ion in t he mot or syst em linking t he cerebellum, t he basal ganglia, and t he cerebral cort ex. Deep cerebellar nuclei have been show n t o project exclusively t o vent ral lat eral t halamic nuclei, w hereas t he project ion f rom t he globus pallidus t arget s mainly t he vent ral ant erior nucleus. Physiologic st udies have show n t hat t he cerebellar and pallidonigral project ion zones in t he t halamus are separat e; very f ew cells have been ident if ied t hat respond t o bot h cerebellar and pallidonigral st imulat ion. As in t he case of t he vent ral ant erior nucleus, lesions in t he vent ral lat eral nucleus have been produced surgically t o relieve disorders of movement manif est ed by t remor. Physiologic re-cordings during surgical procedures (t halamot omy) f or relief of parkinsonian t remor have ident if ied f our t ypes of neurons in t he vent ral t halamic nuclear group (Table 11-1): (1) cells w it h act ivit y relat ed t o somat osensory st imulat ion (sensory cells), (2) cells w it h act ivit y relat ed t o act ive movement (volunt ary cells), (3) cells w it h act ivit y relat ed t o bot h somat osensory st imulat ion and act ive movement (combined cells), and (4) cells w it h act ivit y relat ed t o neit her somat osensory st imulat ion nor act ive movement (no-response cells). Combined volunt ary and no-response cells are locat ed in t he region of t he t halamus, w here a lesion w ill st op t remor, and ant erior t o t he region, w here sensory cells w ere f ound. These f indings suggest t hat t halamic cells unresponsive t o somat osensory st imulat ion (volunt ary and noresponse cells) and t hose responsive t o somat osensory st imulat ion (combined cells) are involved in t he mechanism of parkinsonian t remor. Act ivit y in sensory cells lags behind t remor, w hile act ivit y of combined cells leads t he t remor.
c. Ven tral posterior n u cleu s This nucleus is locat ed in t he caudal part of t he t halamus. I t receives t he long ascending t ract s conveying sensory modalit ies (including t ast e) f rom t he cont ralat eral half of t he body and f ace. These t ract s (Figure 11-9) include t he medial lemniscus, t rigeminal lemniscus (secondary t rigeminal t ract s), and spinot halamic t ract .
Vest ibular inf ormat ion is relayed t o t he cort ex via t he vent ral post erior as w ell as t he int ralaminar and post erior group of t halamic nuclei. The vent ral post erior nucleus is made up of t w o part s: t he ventral posteri or medi al ( VPM) nucl eus, w hich receives t he t rigeminal lemniscus and t ast e f ibers, and t he ventral posteri or l ateral ( VPL) nucl eus, w hich receives t he medial lemniscus and spinot halamic t ract s. Bot h nuclei also receive input f rom t he primary somat osensory cort ex. A visceral nocicept ive input t o t he VPL has been described. The VPL nucleus is divided int o t w o subnuclei: pars oralis (VPLo ) and pars caudalis (VPLc ). Pars oralis is f unct ionally a part of t he vent ral lat eral nucleus (mot or f unct ion) and like VL receives input f rom t he cerebellum and project s t o t he primary mot or cort ex. Tabl e 11-1. Motor T halamus Cell Population
Activation Cell type
Active m ovem ent
Som atosensory stim ulation
Voluntary cells a
+
-
Sensory cells
-
+
Combined cells b
+
+
No-response cell
-
-
a Cells involved in parkinsonian tremor. b Site of tremor-relieving lesion.
Fi gure 11-9. Schemat ic diagram show ing t he major aff erent and eff erent connect ions of t he vent ral post erior lat eral and vent ral post erior medial nuclei of t he t halamus.
The out put f rom bot h nuclei is t o t he primary somat osensory cort ex (SI ) in t he post cent ral gyrus (areas 1, 2, and 3). The project ion t o t he cort ex is somat ot opically organized in such a w ay t hat f ibers f rom t he vent ral post erior medial nucleus project t o t he f ace area, w hile diff erent part s of t he vent ral post erior lat eral nucleus project t o corresponding areas of body represent at ion in t he cort ex. A cort ical project ion f rom t he part of t he vent ral post erior medial nucleus t hat receives t ast e f ibers t o t he pariet al operculum (area 43) has been demonst rat ed. A group of cells locat ed vent rally bet w een t he vent ral post erior lat eral and vent ral post erior medial nuclei comprises t he ventral posteri or i nf eri or ( VPI) nucl eus. Cells in t his nucleus provide t he major t halamic project ion t o somat osensory area I I (SI I ). The vent ral post erior lat eral and vent ral post erior medial nuclei are collect ively ref erred t o as t he ventrobasal compl ex.
D. INTRALAM INAR, M IDLINE, AND RETICULAR NUCLEI
The int ralaminar nuclei, as t heir name suggest s, are enclosed w it hin t he int ernal medullary lamina in t he caudal t halamus. The ret icular nuclei occupy a posit ion bet w een t he ext ernal medullary lamina and t he int ernal capsule (Figure 11-3).
1. Intralaminar Nuclei The int ralaminar nuclei include several nuclei, divided int o caudal and rost ral groups. The caudal group includes t he cent romedian and paraf ascicular nuclei, w hich are t he most import ant f unct ionally in humans. The rost ral group includes t he paracent ral, cent rolat eral, and cent romedial nuclei. The int ralaminar nuclei have t he f ollow ing aff erent and eff erent connect ions.
1. Afferen t con n ection s (Figu re 11-10) Fibers project ing on t he int ralaminar nuclei come f rom t he f ollow ing sources.
(1) Reticular formation of the brain stem This const it ut es t he major input t o t he int ralaminar nuclei.
(2) Cerebellum The dent at orubrot halamic syst em project s on t he vent ral lat eral nucleus of t he t halamus. Collat erals of t his syst em project on t he int ralaminar nuclei.
(3) Spinothalamic and trigeminal lemniscus Aff erent f ibers f rom t he ascending pain pat hw ays project largely on t he vent ral post erior nucleus but also on t he int ralaminar nuclei.
Fi gure 11-10. Schemat ic diagram show ing t he major aff erent and eff erent connect ions of t he int ralaminar nuclei of t he t halamus.
(4) Globus pallidus Pallidot halamic f ibers project mainly on t he vent ral ant erior nucleus. Collat erals
of t his project ion reach t he int ralaminar nuclei.
(5) Cerebral cortex Cort ical f ibers arise primarily f rom t he mot or and premot or areas. Fibers originat ing in t he mot or cort ex (area 4) t erminat e on neurons in t he cent romedian, paracent ral, and cent rolat eral nuclei. Those originat ing f rom t he premot or cort ex (area 6) t erminat e on t he paraf ascicular and cent rolat eral nuclei. I n cont rast t o ot her t ha-lamic nuclei, t he connect ions bet w een t he int ralaminar nuclei and cerebral cort ex are not reciprocal.
(6) Other Afferent Connections Ret rograde t ransport st udies of horseradish peroxidase have ident if ied aff erent connect ions t o t he int ralaminar nuclei f rom t he vest ibular nuclei, periaqueduct al gray mat t er, superior colliculus, pret ect um, and t he locus ceruleus.
2. Efferen t Con n ection s The int ralaminar nuclei project t o t he f ollow ing st ruct ures.
(1) Other thalamic nuclei The int ralaminar nuclei inf luence cort ical act ivit y t hrough ot her t halamic nuclei. There are no direct cort ical connect ions f or t he int ralaminar nuclei. O ne except ion has been demonst rat ed, w it h bot h t he horseradish peroxidase t echnique and aut oradiography show ing a direct project ion f rom one of t he int ralaminar nuclei (cent rolat eral) t o t he primary visual cort ex (area 17). The signif icance of t his f inding is t w of old. First , it show s t hat int ralaminar nuclei, cont rary t o previous concept s, do project direct ly t o cort ical areas. Second, it explains t he report ed response of area 17 neurons t o nonvisual st imuli (e. g. , pinprick or sound); such responses w ould be mediat ed t hrough t he int ralaminar nuclei.
(2) The striatum (caudate and putamen) The st riat al project ion is t opographically organized such t hat t he cent romedian nucleus project s t o t he put amen and t he paraf ascicular nucleus t o t he caudat e nucleus.
2. Midline Nuclei Consist of numerous cell groups, poorly developed in humans, locat ed in t he medial border of t he t halamus along t he banks of t he t hird vent ricle. They include t he paravent ral, cent ral, and reunien nuclei. Their input includes project ions f rom t he hypot halamus, brain st em nuclei, amygdala, and parahippocampal gyrus. Their out put is t o t he limbic cort ex and vent ral st riat um. They have a role in emot ion, memory, and aut onomic f unct ion.
The int ralaminar and midline nuclei comprise t he nonspeci f i c thal ami c nucl ear group.
3. Reticular Nuclei The reti cul ar nucl eus is a cont inuat ion of t he ret icular f ormat ion of t he brain st em int o t he diencephalon. I t receives input s f rom t he cerebral cort ex and ot her t halamic nuclei. The f ormer are collat erals of cort icot halamic project ions, and t he lat t er are collat erals of t halamocort ical project ions. The ret icular nucleus project s t o ot her t halamic nuclei. The inhibit ory neurot ransmit t er in t his project ion is gamma-aminobut yric acid (G ABA). The ret icular nucleus is unique among t halamic nuclei in t hat it s axons do not leave t he t halamus. Based on it s connect ions, t he ret icular nucleus plays a role in int egrat ing and gat ing act ivit ies of t halamic nuclei. Thus t he int ralaminar nuclei and ret icular nucleus collect ively receive f ibers f rom several sources, mot or and sensory, and project diff usely t o t he cerebral cort ex (t hrough ot her t halamic nuclei). Their mult isource input s and diff use cort ical project ions enable t hem t o play a role in t he cort ical arousal response. The int ralaminar nuclei, by virt ue of t heir basal ganglia connect ions, are also involved in mot or cont rol mechanisms, and by virt ue of t he input f rom ascending pain-mediat ing pat hw ays, t hey are also involved in t he aw areness of painf ul sensory experience. The aw areness of sensory experience in t he int ralaminar nuclei is poorly localized and has an emot ional qualit y, in cont rast t o cort ical aw areness, w hich is w ell localized.
E. M ETATHALAM US The t erm met at halamus ref ers t o t w o t halamic nuclei, t he medial geniculat e and lat eral geniculat e.
1. Medial Geniculate Nucleus This is a relay t halamic nucleus in t he audit ory syst em. I t receives f ibers f rom t he lat eral lemniscus direct ly or, more f requent ly, af t er a synapse in t he inf erior colliculus. These audit ory f ibers reach t he medial geniculat e body via t he brachium of t he inf erior colliculus (inf erior quadrigeminal brachium). The medial geniculat e nucleus also receives f eedback f ibers f rom t he primary audit ory cort ex in t he t emporal lobe. The eff erent out f low f rom t he medial geniculat e nucleus f orms t he audit ory radiat ion of t he int ernal capsule (sublent icular part ) t o t he primary audit ory cort ex in t he t emporal lobe (areas 41 and 42). Small hemorrhagic inf arct ions in t he medial geniculat e nucleus are associat ed w it h audit ory illusions such as hyperacusis and palinacusis and complet e ext inct ion of t he cont ralat eral ear input . The medial geniculat e may have roles in spect ral analysis of sound, sound pat t ern recognit ion, audit ory memory, and localizat ion of sound in space, in addit ion t o mat ching audit ory inf ormat ion w it h ot her modalit ies.
2. Lateral Geniculate Nucleus This is a relay t halamic nucleus in t he visual syst em. I t receives f ibers f rom t he opt ic t ract conveying impulses f rom bot h ret inae. The lat eral geniculat e nucleus is laminat ed, and t he inf low f rom each ret ina project s on diff erent laminae (ipsilat eral ret ina t o laminae I I , I I I , and V; cont ralat eral ret ina t o laminae I , I V, and VI ). Feedback f ibers also reach t he nucleus f rom t he primary visual cort ex (area 17) in t he occipit al lobes. The eff erent out f low f rom t he lat eral geniculat e nucleus f orms t he opt ic radiat ion of t he int ernal capsule (ret rolent icular part ) t o t he primary visual cort ex in t he occipit al lobe. Some of t he eff erent out f low project s t o t he pulvinar nucleus and t o t he secondary visual cort ex (areas 18 and 19). Thalamic nuclei and t heir cort ical t arget s are illust rat ed in Figure 11-11.
F. POSTERIOR THALAM IC NUCLEAR GROUP This group embraces t he caudal pole of t he vent ral post erior group of t halamic nuclei medial t o t he pulvinar nucleus and ext ends caudally t o merge w it h t he medial geniculat e body and t he gray mat t er medial t o it . I t receives input s f rom all somat ic ascending t ract s (medial lemniscus and spinot halamic), as w ell as f rom t he audit ory pat hw ays and possibly t he visual pat hw ays. Neurons in t his part of t he t halamus are mult imodal and respond t o a variet y of st imuli. The out f low f rom t he post erior group project s t o t he associat ion cort ices in t he pariet al, t emporal, and occipit al lobes. The post erior nuclear group is t hus a convergence cent er f or varied sensory modalit ies. I t lacks t he modal and spat ial specif icit y of t he classic ascending sensory syst ems but allow s f or int eract ion among t he divergent sensory syst ems t hat project on it . Unlike t he specif ic sensory t halamic nuclei, t he post erior group does not receive reciprocal f eedback connect ions f rom t he cerebral cort ex.
G. NOM ENCLATURE There are several nomenclat ure syst ems f or t halamic nuclei based on shared f eat ures of f iber connect ivit y and f unct ion. Tw o such nomenclat ure syst ems are used commonly. The f irst nomenclat ure syst em groups t halamic nuclei int o t hree general cat egories: (1) modalit y-specif ic, (2) mult imodal associat ive, and (3) nonspecif ic and ret icular. The modalit y-specif ic group of nuclei shares t he f ollow ing f eat ures in common: (1) t hey receive direct input s f rom long ascending t ract s concerned w it h somat osensory, visual, and audit ory inf ormat ion (vent ral post erior lat eral and medial, lat eral geniculat e, medial geniculat e) or else process inf ormat ion derived f rom t he basal ganglia (vent ral ant erior, vent ral lat eral), t he cerebellum (vent ral lat eral), or t he limbic syst em (ant erior, lat eral dorsal); (2) t hey have reciprocal connect ions w it h w elldef ined cort ical areas (primary somat osensory, audit ory, and visual areas,
premot or and primary mot or areas, cingulat e gyrus); and (3) t hey undergo degenerat ion on ablat ion of t he specif ic cort ical area t o w hich t hey project .
Fi gure 11-11. Schemat ic diagram of t halamic nuclei and t heir cort ical t arget s. A, ant erior nucleus; DM, dorsomedial nucleus; I ML, int ernal medullary lamina; LP, lat eral post erior nucleus; Pul, pulvinar nucleus; MG , medial geniculat e nucleus; LG , lat eral geniculat e nucleus; VP, vent ral post erior nucleus; VL, vent ral lat eral nucleus, VA, vent ral ant erior nucleus; CC, corpus callosum.
The mult imodal associat ive group, in cont rast , receives no direct input s f rom long ascending t ract s and project s t o associat ion cort ical areas in t he f ront al, pariet al, and t emporal lobes. These nuclei include t he dorsomedial nucleus and t he pulvinar l at eral post erior nuclear complex. The nonspecif ic and ret icular group of nuclei are charact erized by diff use and w idespread indirect cort ical project ions and by input s f rom t he brain st em ret icular f ormat ion. These nuclei include t he int ralaminar, midline, and ret icular nuclei. Low -f requency st imulat ion of t he modalit y-specif ic t halamic nuclei result s in a charact erist ic cort ical response know n as t he augment ing response. This response consist s of a primary excit at ory post synapt ic pot ent ial (EPSP) f ollow ed
by augment at ion of t he amplit ude and lat ency of t he primary EPSP recorded f rom t he specif ic cort ical area t o w hich t he modalit y-specif ic nucleus project s. St imulat ion of t he nonspecif ic nuclear group, on t he ot her hand, gives rise t o t he charact erist ic recruit ing response in t he cort ex. This is a bilat eral generalized cort ical response (in cont rast t o t he localized augment ing response) charact erized by a predominant ly surf ace-negat ive EPSP t hat increases in amplit ude and, w it h cont inued st imulat ion, w ill w ax and w ane. The ot her nomenclat ure syst em groups t halamic nuclei int o t he f ollow ing cat egories: (1) mot or, (2) sensory, (3) limbic, (4) associat ive, and (5) nonspecif ic and ret icular. The mot or group receives mot or input s f rom t he basal ganglia (vent ral ant erior, vent ral lat eral) or t he cerebellum (vent ral lat eral) and project s t o t he premot or and primary mot or cort ices. The sensory group receives input s f rom ascending somat osensory (vent ral post erior lat eral and medial), audit ory (medial geniculat e), and visual (lat eral geniculat e) syst ems. The limbic group is relat ed t o limbic st ruct ures (mamillary bodies, hippocampus, cingulat e gyrus). The associat ive and nonspecif ic and ret icular groups correspond t o t he same groupings in t he ot her nomenclat ure syst em. Table 11-2 combines t he t w o nomenclat ure syst ems.
H. NEUROTRANSM ITTERS AND NEUROPEPTIDES The f ollow ing neurot ransmit t ers have been ident if ied in t he t halamus: (1) G ABA is t he inhibit ory neurot ransmit t er in t erminals f rom t he globus pallidus, in local circuit neurons, and in project ion neurons of t he ret icular nucleus and lat eral geniculat e nucleus; and (2) glut amat e and aspart at e are t he excit at ory neurot ransmit t ers in cort icot halamic and cerebellar t erminals and in t halamocort ical project ion neurons. Several neuropept ides have been ident if ied in t erminals of long ascending t ract s. They include subst ance P, somat ost at in, neuropept ide Y, en-kephalin, and cholecyst okinin.
I. NEURONAL CIRCUITRY Thalamic nuclei cont ain t w o t ypes of neurons. The predominant t ype is t he principal (project ion) neuron, w hose axon project s on ext rat halamic t arget s. The ot her neuron is t he local-circuit int erneuron. I nput s t o t halamic nuclei f rom subcort ical and cort ical sit es f acilit at e bot h t he project ion and local-circuit neurons, t he neurot ransmit t er being glut amat e or aspart at e. An except ion t o t his is t he subcort ical input f rom t he basal ganglia, w hich is inhibit ory G ABAergic. The local-circuit neuron, in t urn, inhibit s t he project ion neuron. The neurot ransmit t er is G ABA. Thus aff erent input s t o t he t halamus inf luence project ion (t halamocort ical) neurons via t w o pat hw ays: a direct excit at ory pat hw ay and an indirect (via t he local-circuit neuron) inhibit ory pat hw ay (Figure 11-12). The local-circuit neuron t hus modulat es act ivit y of t he project ion neuron.
Project ion neurons send t heir axons t o t he ext rat halamic t arget s (cerebral cort ex, st riat um). Neurons in t he ret icular nucleus act like local-circuit neurons. They are f acilit at ed by collat erals of cort icot halamic and t halamocort ical project ions, and t hey, in t urn, inhibit project ion neurons by G ABAergic t ransmission (Figure 11-12). Tabl e 11-2. T halamus Nuclear G roups
Modalityspecific
Multim odal associative
Nonspecific and reticular
Motor Ventral anterior
X
Ventral lateral
X
Ventral posterior
X
Lateral geniculate
X
Medial geniculate
X
X
Sensory
Limbic Anterior
Lateral dorsal
X
Associative Dorsomedial
X
Pulvinar
X
Posterior
X
Reticular/nonspecific Reticular
X
Intralaminar
X
Midline nuclei
X
Fi gure 11-12. Schemat ic diagram show ing neuronal circuit ry w it hin t he t halamus.
Internal Capsule (Figure 11-13) The int ernal capsule is a broad, compact band of nerve f ibers t hat are cont inuous rost rally w it h t he corona radiat a and caudally w it h t he cerebral peduncles. I t cont ains aff erent and eff erent nerve f ibers passing t o and f rom t he brain st em t o t he cerebral cort ex. I n axial sect ions of t he cerebral hemispheres, t he int ernal capsule is bent w it h a lat eral concavit y t o f it t he w edge-shaped lent if orm nucleus. I t is divided int o an ant erior limb, genu, post erior limb, ret rolent icular part , and sublent icular part . The ant erior limb is sandw iched bet w een t he head of t he caudat e nucleus medially and t he lent if orm nucleus (put amen and globus pallidus) lat erally. I t cont ains f ront opont ine, t halamocort ical, and cort icot halamic bundles; t he lat t er t w o bundles reciprocally connect t he dorsomedial and ant erior t halamic nuclei w it h t he pref ront al cort ex and cingulat e gyrus, respect ively. Some invest igat ors add t he caudat oput amenal int erconnect ions t o component s of t he ant erior limb. The genu of t he int ernal capsule cont ains cort icobulbar and cort icoret iculobulbar f ibers t hat t erminat e on cranial nerve nuclei of t he brain st em. Evidence obt ained f rom st imulat ion of t he int ernal capsule during st ereot axic surgery and f rom vascular lesions of t he int ernal capsule suggest s, how ever, t hat cort icobulbar f ibers are locat ed in t he post erior t hird of t he post erior limb rat her t han in t he genu. The post erior limb is bounded medially by t he t halamus and lat erally by t he lent if orm nucleus. I t cont ains cort icospinal and cort icorubral f ibers, as w ell as f ibers t hat reciprocally connect t he lat eral group of t halamic nuclei (vent ral ant erior, vent ral lat eral, vent ral post erior, and pulvinar) w it h t he cerebral cort ex. The cort icospinal bundle is somat ot opically organized in such a w ay t hat t he f ibers t o t he upper ext remit y are locat ed more ant eriorly, f ollow ed by f ibers t o t he t runk and t he low er ext remit y. Recent dat a suggest t hat t he cort icospinal f iber bundle is largely conf ined t o t he caudal half of t he post erior limb. The t halamocort ical project ions f rom t he vent ral ant erior nucleus t o premot or cort ex (area 6), f rom vent ral lat eral nucleus t o t he precent ral gyrus (area 4), f rom t he vent ral post erior nucleus t o t he post cent ral gyrus (areas 1, 2, and 3), and f rom t he pulvinar t o t emporal and visual cort ices are segregat ed in t he int ernal capsule, w it h t he cort ical project ion f rom vent ral ant erior nucleus most rost ral f ollow ed by t hose f rom vent ral lat eral nucleus, vent ral post erior nucleus, and pulvinar nucleus. Small f ocal capsular lesions may select ively involve one of t hese t halamocort ical project ions.
The ret rolent icular part of t he int ernal capsule cont ains cort icot ect al, cort iconigral, and cort icot egment al f ibers, as w ell as part of t he visual radiat ion. The sublent icular part of t he int ernal capsule cont ains cort icopont ine f ibers, t he audit ory radiat ion, and part of t he visual radiat ion. Because of t he crow ding of cort icot halamic and t halamocort ical f ibers in t he int ernal capsule, lesions in t he capsule produce more w idespread clinical signs t han similar lesions elsew here in t he neuraxis. Vascular lesions in t he post erior limb of t he int ernal capsule are associat ed w it h cont ralat eral hemiplegia and hemisensory loss. Lesions in t he most post erior region w ill, in addit ion, be associat ed w it h cont ralat eral visual loss (hemianopsia) and hearing def icit (hemihypacusis). Lesions involving t he genu of t he int ernal capsule w ill be associat ed w it h cranial nerve signs.
Fi gure 11-13. Schemat ic diagram show ing component part s of t he int ernal capsule and t he f iber bundles w it hin each component .
A. BLOOD SUPPLY OF THALAM US Blood supply of t he t halamus is derived f rom f our parent vessels: basilar root of t he post erior cerebral, post erior cerebral, post erior communicat ing, and int ernal carot id. The basilar root of t he post erior cerebral art ery, via paramedian branches, supplies t he medial t halamic t errit ory. The post erior cerebral art ery, via it s geniculot halamic branch, supplies t he post erolat eral t halamic t errit ory.
The post erior communicat ing art ery, via t he t uberot ha-lamic branch, supplies t he ant erolat eral t halamic t errit ory. The int ernal carot id art ery, via it s ant erior choroidal branch, supplies t he lat eral t halamic t errit ory. Because diff erent aut hors use diff erent t erminology t o ref er t o t he same vessel, account s of blood supply of t he t halamus may be conf using. Table 11-3 is a summary of blood supply of t he t halamus and clinical manif est at ions of t halamic inf arct s.
B. BLOOD SUPPLY OF INTERNAL CAPSULE (FIGURE 1114) The ant erior limb of t he int ernal capsule is supplied by t he st riat e branches of t he ant erior and middle cerebral art eries. The genu is supplied by st riat e branches of t he middle cerebral and int ernal carot id art eries. The bulk of t he post erior limb is supplied by st riat e branches of t he middle cerebral art ery. The ant erior choroidal art ery provides supply t o t he caudal port ion of t he post erior limb.
C. FUNCTIONS The f unct ion of t he t halamus is t o int egrat e sensory and mot or act ivit ies. I n addit ion, it has roles t o play in arousal and consciousness, as w ell as in aff ect ive behavior and memory. I n a sense, it is t he gat ew ay t o t he cort ex. The t halamus plays a cent ral role in sensory int egrat ion. All somat ic and special senses, except olf act ion, pass t hrough t he t halamus bef ore reaching t he cerebral cort ex. Sensory act ivit y w it hin t he t halamus is channeled in one of t hree rout es. The f irst rout e is t hrough t he modalit y-specif ic sensory relay nuclei (medial geniculat e, lat eral geniculat e, and vent ral post erior). Sensat ions relayed in t he modalit y-specif ic sensory relay nuclei have direct access t o t he respect ive sensory cort ical areas. They are st rict ly organized w it h regard t o t opographic and modal specif icit ies and are discriminat ive and w ell localized. The second rout e is t hrough t he nonspecif ic nuclei. Wit h it s many sources of input and diff use project ions t o t he cort ex, t his rout e serves t he low ext reme of t he modalit y-specif icit y gradient . The t hird rout e is t hrough t he post erior nuclear group. This rout e receives f rom mult iple sensory sources and project s t o t he associat ion cort ical areas. I t plays an int ermediat e role bet w een t he modalit y-specif ic and nonspecif ic rout es described above.
Tabl e 11-3. Blo
T halam ic
Blood supply
Synonym s
territory
Posterolateral
Geniculothalamic
Posterolateral Thalamogeniculate
Polar
P ce (P
Anterolateral
Tuberothalamic
Medial
Paramedian
Lateral
Anterior choroidal
Anterior internal optic Premamillary pedicle
Posteromedial Deep interpeduncular profunda Posterior internal optic Thalamoperforating
P co
B P
In ca
Posterior
Posterior choroidal
P
NOTE: AV, anterior ventral; BV, blood vessel; CM, centrome pallidus; IC, internal capsule; LG, lateral geniculate; MG, m lateral; Pf, parafascicular; pul, pulvinar; ret, reticular; VA, ve VPM, ventral posterior medial; L, left; R, right.
Fi gure 11-14. Schemat ic diagram of int ernal capsule show ing sources of blood supply. Cd, caudat e nucleus; Put , put amen nucleus; G P, globus pallidus nucleus; Th, t halamus; MCA, middle cerebral art ery; ACA, ant erior cerebral art ery.
Some sensory modalit ies are perceived at t he t halamic level and are not aff ect ed by ablat ion of t he sensory cort ex. Follow ing sensory cort ical lesions, all sensory modalit ies are lost , but soon pain, t hermal sense, and crude t ouch ret urn. The sense of pain t hat ret urns is t he aching, burning t ype of pain t hat is carried by C-f ibers. I t is t his t ype of pain t hat is believed t o t erminat e in t he t halamus, w hereas t he pricking, w ell-localized pain carried by t he A-f ibers t erminat es in t he sensory cort ex and is lost w it h it s ablat ion. I n pat ient s w it h int ract able pain, placement of a surgical lesion in t he vent ral post erior or int ralaminar nuclei (cent romedian) may provide relief . Vascular lesions of t he t halamus result in a charact erist ic clinical syndrome know n as t he t halamic syndrome. Follow ing an init ial period of loss of all sensat ions cont ralat eral t o t he t halamic lesion, pain, t hermal sense, and some crude t ouch ret urn. How ever, t he t hreshold of st imulat ion t hat elicit s t hese sensat ions is elevat ed, and t he sensat ions are exaggerat ed and unpleasant w hen perceived. The syndrome is usually associat ed w it h a marked aff ect ive response at t ribut ed t o t he int act dorsomedial nucleus, usually unaff ect ed by t he vascular lesion. The role of t he t halamus in mot or cont rol is evident f rom t he input it receives f rom t he cerebellum, basal ganglia, and mot or areas of t he cort ex. Based on st riat ot halamic, t halamost riat e, and t halamocort ical connect ions, it has been suggest ed t hat t he t halamus may be a place f or int eract ion bet w een t he input and out put syst ems of t he basal ganglia. I t is proposed t hat t he inf ormat ion processed by t he basal ganglia and direct ed t o t he cerebral cort ex t hrough t he t halamus could be reaching t he basal ganglia again via t he st riat um (t halamost riat e connect ions) and t hus inf luencing it s overall organizat ion. A t remorogenic cent er has been post ulat ed f or t he vent ral lat eral nucleus. Lesions have been placed in t he vent ral lat eral nucleus t o relieve abnormal movement result ing f rom cerebellar and basal ganglia disorders. The t halamus, as part of t he ascending ret icular act ivat ing syst em, has a cent ral role in t he conscious st at e and at t ent ion. The role of t he t halamus as essent ial f or arousal and w akef ulness has been challenged, in part by t he recognit ion t hat t he cerebral cort ex can be act ivat ed direct ly by cholinergic, serot onergic, noradrenergic, and hist aminergic arousal syst ems t hat originat e in brain st em, basal f orebrain, or hypot halamus and do not pass t hrough t he t halamus. The connect ions of t he medial t halamus w it h t he pref ront al cort ex ref lect it s role in aff ect ive behavior and execut ive f unct ion. Ablat ion of t he pref ront al cort ex or it s connect ions w it h t he dorsomedial nucleus causes changes in personalit y charact erized by lack of drive, f lat aff ect , indiff erence t o pain, and def ect s in decision making and judgment . The connect ions of t he ant erior t halamic nuclei w it h t he hypot halamus and cingulat e gyrus enable t hem t o play a role in memory, visceral f unct ion, and emot ional behavior. Damage t o several and dist inct areas of t he t halamus (ant erior t halamic nucleus,
mamillot halamic t ract , dorsomedial nucleus, int ralaminar nuclei, and midline nuclei) cont ribut e t o memory def icit s (amnesia). Discret e damage t o t he mamillot halamic t ract has been associat ed w it h def icit s in a specif ic t ype of memory, episodic long-t erm memory, w it h relat ive sparing of short -t erm memory and int ellect ual capacit y.
D. ROLE OF THALAM US IN PAIN The t halamus receives and processes all nocicept ive inf ormat ion dest ined t o reach t he cort ex. The t halamus has a role in percept ion of pain and in t he pat hophysiology of cent ral pain and ot her t ypes of chronic pain. Nocicept ive inf ormat ion reaches t he t halamus via t he spinot halamic t ract s (lat eral and ant erior) and t he t rigeminot halamic pat hw ays. Some nocicept ive input t o t he t halamus is mediat ed via ot her spinal pat hw ays and f rom t he brain st em, but t heir role and import ance in pain has not been est ablished. The regions of t he t halamus involved in pain and w here responses t o noxious st imuli are recorded include t he VPL, VPM, VPI , cent rolat eral (CL), paraf ascicular (PF), and t he dorsomedial (DM) nuclei. Most of t he t halamic nuclei t hat receive nocicept ive input have project ions t o cort ical areas implicat ed in pain. Vent ral post erior lat eral and medial nuclei project t o somat osensory cort ex (SI ), vent ral post erior inf erior nucleus project s t o t he secondary somat osensory cort ex (SI I ), and t he dorsomedial nucleus t o t he ant erior cingulat e cort ex. Most of t he neurons in VPL and VPM are relay neurons f or t act ile inf ormat ion. Ten percent of neurons are nocicept ive neurons of t he w ide dynamic range (WDR) t ype t hat discharge maximally t o noxious mechanical and noxious heat st imuli. VPI neurons are of t he w ide dynamic range t ype as w ell as nocicept ive-specif ic (NS) t ype. They t end t o have larger recept ive f ields t han t hose of VPL and VPM. The int ralaminar nuclei (CL, Pf ) and t he dorsomedial nucleus (DM) mediat e, in part icular, t he aff ect ive mot ivat ional aspect of pain as w ell as cent ral pain.
Subthalamus The subt halamus is a mass of gray and w hit e subst ance in t he caudal diencephalon. I t is bordered medially by t he hypot halamus, lat erally by t he int ernal capsule, dorsally by t he t halamus, and vent rally by t he int ernal capsule. The subt halamus consist s of t hree main st ruct ures; t hese are t he subt halamic nucleus, t he f ields of Forel, and t he zona incert a.
A. SUBTHALAM IC NUCLEUS (FIGURE 11-15) The subt halamic nucleus (of Luys) is a biconvex gray mass t hat replaces t he subst ant ia nigra in caudal diencephalic levels. The subt halamic nucleus receives a massive G ABAergic (inhibit ory) input f rom t he ext ernal segment of globus pallidus and a glut amat ergic (excit at ory) input f rom t he cerebral cort ex (areas 4 and 6). The input f rom t he
globus pallidus t ravels in t he subt halamic f asciculus, w hereas t he input f rom t he cerebral cort ex t ravels in t he int ernal capsule. O t her input s include t hose f rom t he t halamus (primarily f rom t he int ralaminar nuclei) and t he brain st em ret icular f ormat ion. The t w o subt halamic nuclei communicat e via t he supramamillary commissure. Project ions t o t he subt halamic nucleus are arranged in dist inct sensorimot or, associat ive, and limbic t errit ories similar t o t hose report ed f or ot her basal ganglionic nuclei. The out put f rom t he subt halamic nucleus is t o bot h segment s of t he globus pallidus and t o t he subst ant ia nigra pars ret iculat a. The neurot ransmit t er in bot h t hese project ions is glut amat e (excit at ory). I t has been show n t hat t he project ions t o t he ext ernal and int ernal segment s of t he globus pallidus arise f rom diff erent subt halamic neurons.
Fi gure 11-15. Schemat ic diagram of t he subt halamic region show ing it s component part s and t he major aff erent and eff erent connect ions of t he subt halamic nucleus.
I nt errupt ion of t he subt halamopallidal pat hw ays or t he subt halamic nucleus is responsible f or t he involunt ary violent hyperkinesia of t he cont ralat eral upper and low er ext remit ies know n as hemiballismus. Facial and neck muscles may be involved.
B. FIELDS OF FOREL (FIGURE 11-16) This t erm ref ers t o f iber bundles cont aining pallidal and cerebellar eff erent s t o t he t halamus. Pallidot halamic f ibers f ollow one of t w o rout es. Some t raverse t he int ernal capsule and gat her dorsal t o t he subt halamic nucleus as t he lent icular f asciculus (H2 f ield of Forel); ot hers make a loop around t he int ernal capsule as t he ansa lent icularis. Bot h groups of f ibers join t he dent at ot halamic f ibers in t he prerubral f ield (H f ield of Forel) and t hen join t he t halamic f asciculus (H1 f ield of Forel) t o reach t heir respect ive t halamic nuclei. The f ields of Forel are named af t er August Forel, t he Sw iss psychiat rist , neurologist , and anat omist w ho is best remembered f or his anat omic st udies on t he basal ganglia and subt halamic region. The H is f rom t he G erman w ord Haube, meaning a cap or hood.
C. ZONA INCERTA The zona incert a (Figure 11-15) is t he rost ral cont inuat ion of t he mesencephalic ret icular f ormat ion t hat ext ends lat erally int o t he ret icular nucleus of t he t halamus. I t is sandw iched bet w een t he lent icular f asciculus and t he t halamic f asciculus. The zona incert a has been implicat ed in a variet y of f unct ions, including locomot ion, eye movement s, sociosexual behavior, f eeding and drinking, arousal, and at t ent ion, and in aspect s of visual, nocicept ive, and somat osensory processing. The precise role of t he zona incert a in many of t hese f unct ions is not cert ain. The diversit y of f unct ions ascribed t o zona incert a ref lect s it s w idespread connect ivit y. Reciprocal connect ions have been described in diff erent species t o almost all part s of t he neuraxis, including t he neocort ex, t halamus, brain st em, basal ganglia, cerebellum, hypot halamus, basal f orebrain, and spinal cord. Chronic, high-f requency, deep-brain st imulat ion of t he zona incert a in humans and non-human primat es has been show n t o suppress limb t remor. G ABAergic neurons in t he zona incert a have been show n t o pause immediat ely prior t o onset of and during saccades, suggest ing an inhibit ory role of t hese neurons on saccadic eye movement s. These neurons have been show n t o project t o deep layers of t he superior colliculus and t he nucleus of Darkschew it sch, w hich are import ant in cont rolling saccades. The zona incert a has also been show n t o project t o t he pret ect al area. The incert opret ect al pat hw ay is believed t o play a role in t he guidance of t ect ally init iat ed saccades by somat osensory st imuli. The zona incert a has been show n t o receive collat erals f rom cort icot halamic f ibers and t o send G ABAergic project ions t o t halamic relay neurons.
Fi gure 11-16. Schemat ic diagram of t he f ields of Forel.
TERM INOLOGY Diencephalon (G reek di a, b etween ; enkephal os, b rain ) . The part of t he cent ral nervous syst em bet w een t he t w o hemispheres. I t includes t he epit halamus, t halamus (including t he met at halamus), subt halamus, and hypot halamus. The diencephalon is t he post erior of t he t w o brain vesicles f ormed f rom t he prosencephalon of t he developing embryo. Epithalamus (G reek epi , u pon ; thal amos, i nner chamber ) . Part of t he diencephalon dorsal t o t he t halamus. I t includes t he st ria medullaris t halami, habenular nucleus, and pineal gland. Forel, August Henri (1848 1 931). Sw iss neuropsychiat rist w ho described t he f iber bundles of t he subt halamus (H f ields of Forel). G alen, Claudius (A. D. 130 2 00). Hellinist ic physician w ho pract iced mainly in Rome and Pergamon. He w as t he leading medical aut horit y of t he Christ ian w orld f or 1400 years. The great cerebral vein is named af t er him. G eniculate (Latin geni cul are, t o bend the knee ) . Abrupt ly bent , as in lat eral and medial geniculat e nuclei of t he t halamus. G enu (Latin k nee ) . A kneelike st ruct ure. The genu of t he corpus callosum. Habenula (Latin diminutive of habena, a small strap or rein ) . The habenular nuclei are part of t he epit halamus.
Hemiballismus (G reek hemi , h alf ; bal l i smos, j umping about ) . Violent f linging involunt ary movement s of one side of t he body due t o a lesion in t he cont ralat eral subt halamic nucleus. Hypacusis (G reek hypo, u nder, below ; akousi s, h earing ) . Decreased hearing. Hyperacusis. Abnormal percept ion of sound as being loud. Hypothalamus (G reek hypo, u nder, below ; thal amos, i nner chamber ) . The region of t he diencephalon below t he t halamus. Luys, Jules Bernard (1828 1 895). French clinical neurologist w ho described t he subt halamic nucleus (nucleus of Luys). Mamillary bodies (Latin diminutive of mamma, b reast, nipple ) . A pair of small round sw ellings on t he vent ral surf ace of t he hypot halamus mimicking t he mammas. Massa intermedia. Bridge of gray mat t er t hat connect s t he t halami of t he t w o sides across t he t hird vent ricle; also called i nterthal ami c adhesi on. Metathalamus (G reek meta, a fter ; thal amos, i nner chamber ) . The met at halamus includes t he lat eral and medial geniculat e bodies. Meynert, T heodor Hermann (1833 1 892). Aust rian psychiat rist and neurologist . Described t he habenuloint erpeduncular t ract in 1867. Palinacusis. (G reek pal i n, b ackward or a gain ; curi s, h earing, sound ) . Audit ory perseverat ion. The pat hologic cont inuance or recurrence of an audit ory sensat ion af t er t he st imulus is gone. Parinaud, Henri (1844 1 905). French opht halmologist . De-scribed t he Parinaud syndrome in 1883. Wrot e ext ensively about ocular movement s, having had access t o t he large numbers of Charcot pat ient s at t he Salpęt ričre hospit al in Paris. He is regarded as t he f at her of neuro-opht halmology. Pineal gland (Latin pi nea, a pine cone ) . A small midline organ shaped like a pine cone. Pulvinar (Latin pul vi nar, a cushioned reclining seat ) . The pulvinar nucleus is locat ed in t he post erior pole of t he t halamus overhanging t he superior colliculus and geniculat e bodies. Subthalamus (Latin sub, u nder ; G reek thal amos, i nner chamber ) . Region of t he diencephalon beneat h t he t halamus.
T halamus (G reek thal amos, i nner chamber ) . Also meant a bridal couch, so t he pulvinar nucleus is it s cushion or pillow. Part of t he diencephalon on each side of t he t hird vent ricle and above t he hypot halamic sulcus. G alen made up t he w ord thal amus, and Willis w as t he f irst t o use t he t erm in it s modern sense. Zona incerta (Latin zona, z one, belt ; i ncerta, i n between ) . A rost ral ext ension of t he brain st em ret icular f ormat ion int o t he subt halamus. I nsert ed bet w een t he lent icular and t halamic f asciculi.
SUGGESTED READINGS Bart ho P et al: Select ive G ABAergic innervat ion of t halamic nuclei f rom zona incert a. Eur J Neurosci 2002; 16: 999 1 014. Behrens TEJ et al: Non-invasive mapping of connect ions bet w een human t halamus and cort ex using diff usion imaging. Nat Neurosci 2003; 6: 750 7 57. Bert rand G : St imulat ion during st ereot act ic operat ion f or dyskinesia. J Neurosurg 1996; 24: 419 4 23. Blum PS et al: Thalamic component s of t he ascending vest ibular syst em. Exp Neurol 1979; 64: 587 6 03. Carpent er MB et al: I nt erconnect ions and organizat ion of pallidal and subt halamic nucleus neurons in t he monkey. J Comp Neurol 1981; 197: 579 6 03. Carpent er MB et al: Connect ions of t he subt halamic nucleus in t he monkey. Brai n Res 1981; 224: 1 2 9. Cramon DY et al: A cont ribut ion t o t he anat omical basis of t halamic amnesia. Brai n 1985; 108: 993 1 008. Donnan G A et al: A prospect ive st udy of lacunar inf arct ion using comput erized t omography. Neurol ogy 1982; 32: 49 5 6. Dost rovsky JO : Role of t halamus in pain. Progr Brai n Res 2000; 129: 245 2 57. Englander RN et al: Locat ion of human pyramidal t ract in t he int ernal capsule: Anat omic evidence. Neurol ogy 1975; 25: 823 8 26.
Fukut ake T, Hat t ori T: Audit ory illusions caused by a small lesion in t he right medial geniculat e body. Neurol ogy 1998; 51: 1469 1 471. G imenez-Amaya JM, Scarnat i E: The t halamus as a place f or int eract ion bet w een t he input and t he out put syst ems of t he basal ganglia: A comment ary. J Cl i n Neuroanat 1999; 16: 149 1 52. G oldman PS: Cont ralat eral project ions t o t he dorsal t halamus f rom f ront al associat ion cort ex in t he rhesus monkey. Brai n Res 1979; 166: 166 1 71. G raff -Radf ord NR et al: Nonhaemorrhagic t halamic inf arct ion: Clinical, neuropsychological and elect rophysiological f indings in f our anat omical groups def ined by comput erized t omography. Brai n 1985; 108: 485 5 16. G root huis DR et al: The human t halamocort ical sensory pat h in t he int ernal capsule: Evidence f rom a small capsular hemorrhage causing a pure sensory st roke. Ann Neurol 1977; 2: 328 3 31. Hanaw ay J et al: Localizat ion of t he pyramidal t ract in t he int ernal capsule. Neurol ogy 1981; 31: 365 3 66. Hart man-von Monakow R et al: Project ions of t he precent ral mot or cort ex and ot her cort ical areas of t he f ront al lobe t o t he subt halamic nucleus in t he monkey. Exp Brai n Res 1978; 33: 395 4 03. Hendry SHC et al: Thalamic relay nuclei f or cerebellar and cert ain relat ed f iber syst ems in t he cat . J Comp Neurol 1979; 185: 679 7 14. Herrero M-T et al: Funct ional anat omy of t halamus and basal ganglia. Chi l d Nerv Syst 2002; 18: 386 4 04. Hirai T, Jones EG : A new parcellat ion of t he human t halamus on t he basis of hist ochemical st aining. Brai n Res Rev 1989; 14: 1 3 4. Hirayama K et al: The represent at ion of t he pyramidal t ract in t he int ernal capsule and basis pedunculi: A st udy based on t hree cases of amyot rophic lat eral sclerosis. Neurol ogy 1962; 12: 337 3 42. I linsky I A, Kult as-I linsky K: An aut oradiographic st udy of t opographical relat ionships bet w een pallidal and cerebellar project ions t o t he cat t halamus. Exp Brai n Res 1984; 54: 95 1 06.
I linsky I A et al: Q uant it at ive evaluat ion of crossed and uncrossed project ions f rom basal ganglia and cerebellum t o t he cat t halamus. Neurosci ence 1987; 21: 207 2 27. Krack P et al: Surgery of t he mot or t halamus: Problems w it h t he present nomenclat ure. Movement Di s 2002; 17(Suppl): S2 S 8. Kult as-I linsky K et al: A descript ion of t he G ABAergic neurons and axon t erminals in t he mot or nuclei of t he cat t halamus. J Neurosci 1985; 5: 1346 1 369. Lenz FA et al: Single unit analysis of t he human vent ral t halamic nuclear group: Tremor-relat ed act ivit y in f unct ionally ident if ied cells. Brai n 1994; 117: 531 5 43. Ma TP: Saccade-relat ed omnivect oral pause neurons in t he primat e zona incert a. Neuroreport 1996; 7: 2713 2 716. Macchi G et al: Tow ard an agreement on t erminology of nuclear and subnuclear divisions of t he mot or t halamus. J Neurosurg 1997; 86: 77 9 2. Madarasz M et al: A combined horseradish peroxidase and G olgi st udy on t he aff erent connect ions of t he vent robasal complex of t he t halamus in t he cat . Cel l Ti ssue Res 1979; 199: 529 5 38. May PJ et al: Recriprocal connect ions bet w een t he zona incert a and t he pret ect um and superior colliculus of t he cat . Neurosci ence 1997; 77: 1091 1114. McG uiness CM, Kraut hamer G M: The aff erent project ions t o t he cent rum medianum of t he cat as demonst rat ed by ret rograde t ransport of horseradish peroxidase. Brai n Res 1980; 184: 255 2 69. Mennemeir M et al: Cont ribut ions of t he lef t int ralaminar and medial t ha-lamic nuclei t o memory: Comparisons and report of a case. Arch Neurol 1992; 49: 1050 1 058. Miller JW, Benevent o LA: Demonst rat ion of a direct project ion f rom t he int ralaminar cent ral lat eral nucleus t o t he primary visual cort ex. Neurosci Lett 1979; 14: 229 2 34.
Mit rof anis J, deFonseka R: O rganisat ion of connect ions bet w een t he zona incert a and t he int erposed nucleus. Anat Embryol 2001; 204: 153 1 59. Nandi D et al: Brainst em mot or loops in t he cont rol of movement . Movement Di s 2002; 17(Suppl): S22 S 27. Naut a HJW, Cole M: Eff erent project ions of t he subt halamic nucleus: An aut oradiographic st udy in monkey and cat . J Comp Neurol 1978; 180: 1 1 6. Nomura S et al: Topographical arrangement of t halamic neurons project ing t o t he orbit al gyrus in t he cat . Exp Neurol 1980; 67: 601 6 10. O nodera S, Hicks TP: Project ions f rom subst ant ia nigra and zona incert a t o t he cat 's nucleus of Darkschew it sch. J Comp Neurol 1998; 396: 461 4 82. Pow er BD et al: Evidence f or a large project ion f rom t he zona incert a t o t he dorsal t halamus. J Comp Neurol 1999; 404: 554 5 65. Pow er BD et al: Evidence f or a visual subsect or w it hin t he zona incert a. Vi s Neurosci 2001; 18: 179 1 86. Royce G J: Cells of origin of subcort ical aff erent s t o t he caudat e nucleus: A horseradish peroxidase st udy in t he cat . Brai n Res 1978; 153: 465 4 75. Sakai ST et al: Comparison of cerebellot halamic and pallidot halamic project ions in t he monkey (Macaca f uscata): A double ant erograde labeling st udy. J Comp Neurol 1996; 368: 215 2 28. Sandson TA et al: Front al lobe dysf unct ion f ollow ing inf arct ion of t he lef t sided medial t halamus. Arch Neurol 1991; 48: 1300 1 303. Schell G R, St rick PL: The origin of t halamic input s t o t he arcuat e premot or and supplement ary mot or areas. J Neurosci 1984; 4: 539 5 60. Smit h Y et al: Eff erent project ions of t he subt halamic nucleus in t he squirrel monkey as st udied by t he PHA-L ant erograde t racing met hod. J Comp Neurol 1990; 294: 306 3 23. Tekian A, Af if i AK: Eff erent connect ions of t he pulvinar nucleus in t he cat . J Anat 1981; 132: 249 2 65.
Van der Werf Y D et al: Def icit s of memory, execut ive f unct ioning and at t ent ion f ollow ing inf arct ion in t he t halamus: A st udy of 22 cases w it h localized lesions. Neuropsychol ogi a 2003; 41: 1330 1 344.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 12 - D ienc ephalon: C linic al C or r elates
12 Diencephalon: Clinical Correlates
Clinical Correlates of T halam ic Anatom y T halam ic Infarcts Posterolateral Thalamic Territory Anterolateral Thalamic Territory Medial Thalamic Territory Lateral Thalamic Territory Posterior Thalamic Territory Thalamic Pain Syndromes Memory Deficits Thalamus and Arousal The Cheiro-Oral Syndrome The Alien Hand Syndrome Thalamic Acalculia Language Deficits Clinical Correlates of Subthalam ic Anatom y Hemiballismus KEY CONCEPTS Posterolateral (thalamogeniculate) thalamic territory lesions are characterized by pansensory loss associated with thalamic pain, the Dejerine-Roussy syndrome.
Anterolateral (tuberothalamic) thalamic territory lesions are characterized by neuropsychological impairment. Medial (paramedian) thalamic territory lesions are characterized by alteration in state of consciousness. Akinetic mutism and the Kleine-Levin syndrome occur with lesions in this thalamic territory. Lateral (anterior choroidal) thalamic territory lesions are characterized by hemiparesis and dysarthria. Posterior (posterior choroidal) thalamic territory lesions are characterized by hemisensory dysfunction and visual field defects. Four types of thalamic pain syndromes have been described based on the presence or absence of each of tha-lamic pain, proprioceptive and exteroceptive sensations, and abnormalities in somatosensory evoked potentials. Encoding memory defects, severe distractibility, and verbal memory disturbances have been described in tha-lamic lesions. The thalamus is one (indirect) of two mechanisms for cortical activation. The other (direct) mechanism is via cholinergic, serotonergic, noradrenergic, and histaminergic nonthalamic systems. Language deficits occur with dominant thalamic lesions and are transient. A violent dyskinesia (hemiballismus) occurs with lesions in the subthalamic nucleus or its connections with globus pallidus.
CLINICAL CORRELATES OF THALAM IC ANATOM Y A mult iplicit y of neurologic signs and sympt oms has been report ed in disorders of t he t halamus. These ref lect (1) t he anat omic and f unct ional het erogeneit y of t he t halamus, (2) simult aneous involvement of several nuclei even by discret e vascular lesions due t o t he f act t hat art erial vascular t errit ories in t he t halamus cross nuclear boundaries, and (3) simult aneous involvement of neighboring areas such as t he midbrain in paramedian t halamic vascular lesions, t he int ernal capsule in lat eral t halamic vascular lesions, and t he subt halamus in post erior t halamic vascular lesions. The conglomerat e of signs and sympt oms associat ed w it h t ha-lamic lesions includes t he f ollow ing: sensory dist urbances, t halamic pain, hemiparesis, dyskinesias, dist urbances of consciousness, memory dist urbances, aff ect ive dist urbances, and disorders of language. Correlat ion of signs and sympt oms w it h aff ect ed t halamic t errit ory is best w it h vascular lesions (inf arct s) of t he t halamus (Table 12-1). Clinicoanat omic correlat ion in pat ient s w it h occlusion of t halamic art eries has been great ly f acilit at ed by neuro-imaging met hods (comput ed t omography and magnet ic resonance imaging). The diff erent vascular t errit ories of t he t halamus and associat ed neurologic signs and sympt oms are out lined in t he next sect ions. Most t halamic inf arct s are report ed in t he post erolat eral and t he medial t halamic t errit ories supplied by t he geniculot ha-lamic and paramedian art eries, respect ively. O nly a f ew cases are report ed in t he ant erolat eral and post erior t errit ories supplied by t he t uberot halamic and post erior choroidal art eries, respect ively.
THALAM IC INFARCTS Posterolateral Thalamic Territory (Figure 12-1) I nf arct s in t his t halamic t errit ory are due t o occlusion of t he geniculot halamic (t halamogeniculat e, post erolat eral) art ery, a branch of t he post erior cerebral art ery. Thalamic st ruct ures involved by t he inf arct are t he primary sensory t halamic nuclei, w hich include t he vent ral post erior lat eral, vent ral post erior medial, medial geniculat e, pulvinar, and cent romedian nuclei. O t her nuclei t hat are inconsist ent ly involved include t he dorsomedial, post erior lat eral, ret icular, paraf ascicular, and lat eral geniculat e nuclei. The clinical hallmark of post erolat eral t halamic t errit ory inf arct s is a pansensory loss cont ralat eral t o t he lesion, parest hesia, and t halamic pain. I n addit ion, one or more of t he f ollow ing may occur: t ransient hemiparesis, homonymous hemianopsia, hemiat axia, t remor, choreif orm movement s, and spat ial neglect , all cont ralat eral t o t he lesion in t he t halamus. An at het oid post ure of t he cont ralat eral hand (t halamic hand) may appear 2 or more w eeks f ollow ing lesions in t his t errit ory. The hand is f lexed and
pronat ed at t he w rist and met acarpophalangeal joint s and ext ended at t he int erphalangeal joint s. The f ingers may be abduct ed. The t humb is eit her abduct ed or pushed against t he palm. The conglomerat e of signs and sympt oms associat ed w it h post erolat eral t halamic t errit ory inf arct s comprises t he t halamic syndrome of Dejerine and Roussy. I n t his syndrome, severe, persist ent , paroxysmal, and of t en int olerable pain (t ha-lamic pain) resist ant t o analgesic medicat ions occurs at t he t ime of injury or f ollow ing a period of t ransient hemiparesis, hemiat axia, choreif orm movement s, and hemisensory loss. Cut aneous st imuli t rigger paroxysmal exacerbat ions of t he pain t hat out last t he st imulus. Because t he percept ion of e picrit ic pain (f rom a pinprick) is reduced on t he painf ul areas, t his sympt om is know n as anest hesia dolorosa, or painf ul anest hesia. The syndrome is named af t er Joseph-Jules Dejerine, a French neurologist , and his assist ant , G ust ave Roussy, a Sw iss-French neuropat hologist , w ho described t he t halamic syndrome in 1906 in six pat ient s w it h a vascular t halamic lesion w ho present ed w it h a charact erist ic clust er of sympt oms: hemihypoest hesia, int ract able pain, slight t ransient hemiparesis, hemiat axia, and choreoat het ot ic movement s. The et iology of t he t halamic pain syndrome is not clear but may be t he result of alt erat ions in f requencies and pat t erns of input s t o t he t halamus, qualit ies of injured neurons, or changes in qualit y of out put t o t he cort ex.
Anterolateral Thalamic Territory I nf arct s in t he ant erolat eral t errit ory of t he t halamus are usually secondary t o occlusion of t he t uberot halamic branch of t he post erior
communicat ing art ery. Synonyms f or t his branch include t he polar, ant erior int ernal opt ic, and t he premamillary pedicle. Thalamic nuclei involved in t he inf arct include t he vent ral ant erior, vent ral lat eral, dorsomedial, and ant erior. The clinical manif est at ions include cont ralat eral hemiparesis, visual f ield def ect s, f acial paresis w it h emot ional st imulat ion, and rarely, hemisensory loss. Severe, usually t ransient neuropsychological impairment s predominat e in lesions in t his t halamic t errit ory. Abulia, lack of spont aneit y and init iat ive, and reduced quant it y of speech are t he predominant f indings. O t her impairment s consist of def ect s in int ellect , language, and memory in lef t -sided lesions and visuospat ial def icit s in right -sided lesions.
Fi gure 12-1. T2-w eight ed axial magnet ic resonance image (MRI ) show ing an inf arct (arrow ) in t he post erolat eral t halamic t errit ory.
Tabl e 12-1. Blo
T halam ic territory
Blood supply
Synonym s
Posterolateral
Anterolateral
Geniculothalamic
Posterolateral Thalamogeniculate
P ce (P
Tuberothalamic
Polar Anterior internal optic Premamillary pedicle
P co ar
Posteromedial
Deep interpeduncular profunda Posterior internal optic Thalamoperforating
B P
Medial
Paramedian
Lateral
Anterior choroidal
In ca
Posterior
Posterior choroidal
P
NOTE: AV, anterior ventral; BV, blood vessel; CM, centrome
pallidus; IC, internal capsule; LG, lateral geniculate; MG, m lateral; Pf, parafascicular; pul, pulvinar; ret, reticular; VA, ve VPM, ventral posterior medial; L, left; R, right.
Medial Thalamic Territory (Figure 12-2) I nf arct s in t he medial t errit ory of t he t halamus are associat ed w it h occlusion of t he paramedian branches of t he basilar root of t he post erior cerebral art ery. These branches include t he post eromedial, deep int erpeduncular prof unda, post erior int ernal opt ic, and t halamoperf orat ing. The t halamic nuclei involved include t he int ralaminar (cent romedian, paraf ascicular) and dorsomedial, eit her unilat erally or bilat erally. The paramedian t errit ory of t he midbrain is of t en involved by t he lesion. The f ollow ing nuclei are inconsist ent ly involved: t he vent ral lat eral, ant erior, and vent ral post erior. The hallmark of t he clinical pict ure is drow siness. I n addit ion, t here are abnormalit ies in recent memory, at t ent ion, int ellect , vert ical gaze, and occasionally, mild hemiparesis or hemiat axia. No sensory def icit s are as a rule associat ed w it h lesions in t his t errit ory. Ut ilizat ion behavior (inst rument ally correct but highly exaggerat ed response t o environment al cues and object s) t hat is charact erist ic of f ront al lobe damage has been report ed in medial t halamic t errit ory inf arct s. Tw o syndromes have also been report ed in medial t halamic t errit ory inf arct s: akinet ic mut ism and t he Kleine-Levin syndrome. I n akinet ic mut ism (persist ent veget at ive st at e), pat ient s appear aw ake and maint ain a sleep-w ake cycle but are unable t o communicat e in any w ay. I n addit ion t o t halamic inf arct s, akinet ic mut ism has been report ed t o occur w it h lesions in t he basal ganglia, ant erior cingulat e gyrus, and pons. The Kleine-Levin syndrome (hypersomnia-bulimia syndrome) is charact erized by recurrent periods (last ing 1 t o 2 w eeks every 3 t o 6 mont hs) in adolescent males of excessive somnolence, hyperphagia (compulsive eat ing), hypersexual behavior (sexual disinhibit ion), and impaired recent memory, and event ually ending w it h recovery. A conf usional st at e, hallucinosis, irrit abilit y, or a schizophrenif orm st at e may occur around t he t ime of t he at t acks. The syndrome w as f irst report ed by Ant imoff in 1898 but more f ully by Willi Kleine in 1925 in G erman and by Max Levin 4 years lat er in English.
Lateral Thalamic Territory (Figure 12-3) I nf arct s in t he lat eral t errit ory of t he t halamus are associat ed w it h occlusion of t he ant erior choroidal branch of t he int ernal carot id art ery. St ruct ures involved in t he lesion include t he post erior limb of t he int ernal capsule, lat eral t halamic nuclei (lat eral geniculat e, vent ral post erior lat eral, pulvinar, ret icular), and medial t emporal lobe. The clinical hallmarks of t he inf arct are cont ralat eral hemiparesis and dysart hria. Lesions in t he lat eral t halamic t errit ory may manif est w it h only pure mot or hemiparesis. O t her clinical manif est at ions include
hemisensory loss of pain and t ouch, occasional visual f ield def ect s, and neuropsychological def ect s. The lat t er consist of memory def ect s in lef t sided lesions and visuospat ial def ect s in right -sided lesions.
Fi gure 12-2. T2-w eight ed axial MRI show ing an inf arct (arrow ) in t he medial t halamic t errit ory.
Fi gure 12-3. Prot on densit y MRI show ing an inf arct (arrow ) in t he lat eral t halamic t errit ory.
Posterior Thalamic Territory (Figure 12-4) I nf arct s in t he post erior t halamic t errit ory are associat ed w it h occlusion of t he post erior choroidal branch of t he post erior cerebral art ery. Thalamic nuclei involved include t he lat eral geniculat e, pulvinar, and dorsolat eral nuclei. The f ollow ing st ruct ures are inconsist ent ly involved in t he lesion: dorsomedial and ant erior t halamic nuclei, hippocampus, and rost ral midbrain. Clinical manif est at ions include cont ralat eral homonymous quadrant anopsia and hemihypest hesia, as w ell as neuropsychological def icit s, including memory def ect s and t ranscort ical aphasia. I nconsist ent signs include cont ralat eral hemiparesis and choreoat het osis.
Thalamic Pain Syndromes Four t ypes of pain syndromes have been described in associat ion w it h t halamic lesions (Table 12-2). The f our t ypes are diff erent iat ed f rom each ot her on t he basis of t he presence or absence in each of cent ral (t halamic) pain, propriocept ive sensat ions (vibrat ion, t ouch, joint ), ext erocept ive sensat ions (pain and t emperat ure), and abnormalit ies in somat osensory evoked pot ent ials. I n t ype I (analget ic t ype), cent ral pain is absent , bot h propriocept ive and ext erocept ive sensat ions are lost , and no somat osensory evoked pot ent ials are
elicit able. I n t ype I I , bot h cent ral pain and ext erocept ive sensat ions are present , w hereas propriocept ive sensat ions are lost and somat osensory evoked pot ent ials are absent . I n t ype I I I , cent ral pain as w ell as propriocept ive and ext erocept ive sensat ions are present , w hereas somat osensory evoked pot ent ials are reduced in amplit ude. I n t ype I V (pure alget ic), cent ral pain is present , propriocept ive and ext erocept ive sensat ions are unimpaired, and somat osensory evoked pot ent ials are normal.
Memory Deficits Discret e lesions of t he t halamus can cause severe and last ing memory def icit s. Alt hough it remains uncert ain w hich t halamic st ruct ures are crit ical f or memory, evidence f rom human and animal research suggest s t hat one or more of t he f ollow ing st ruct ures are import ant : ant erior nuclei, midline and int ralaminar nuclei, dorsomedial nucleus, and mamillot halamic t ract . There are t hree dist inct behavioral and anat omic t ypes of memory impairment associat ed w it h diencephalic lesions: (1) Severe encoding def ect s are associat ed w it h lesions in t he mamillary bodies, mamillot halamic t ract s, midline t halamic nuclei, and t he dorsomedial nucleus. Perf ormance of such pat ient s never approximat es normal memory. (2) A milder f orm of memory def icit charact erized by severe dist ract ibilit y occurs in lesions of t he int ralaminar and medial t halamic nuclei. (3) Dist urbances in verbal memory (ret rieval, regist rat ion, and ret ent ion) occur in lesions of t he lef t t halamus t hat include t he vent rolat eral and int ralaminar nuclei and t he mamillot halamic t ract . Memory dist urbances, w hich may be t ransient or permanent , are most common w it h bilat eral t halamic lesions but do occur w it h unilat eral lesions of eit her side.
Fi gure 12-4. T2-w eight ed MRI show ing an inf arct (arrow ) in t he post erior t halamic t errit ory.
Thalamus and Arousal The essent ial role of t he t halamus as t he sole mechanism f or cort ical arousal has been challenged. I t is now acknow ledged t hat cort ical act ivat ion is mediat ed by t w o mechanisms: (1) an indirect mechanism, via t he t halamus, comprised of t he ascending ret icular act ivat ing syst em (ARAS), and (2) a direct mechanism (nont halamic), via cholinergic, serot onergic, noradrenergic, and hist aminergic arousal syst ems t hat originat e in t he brain st em, basal f orebrain, or hypot halamus and do not pass t hrough t he t halamus.
The Cheiro-Oral Syndrome This syndrome consist s of sensory dist urbances conf ined t o one hand and t o t he ipsilat eral mout h region. I t is associat ed w it h f ocal lesions in t he vent ral post erior t halamic nucleus. A similar syndrome has been report ed w it h lesions in t he somat osensory cort ex, border of t he post erior limb of t he int ernal capsule and corona radiat a, midbrain, and pons. The involvement of t he hand and mout h areas suggest s t hat t he sensory represent at ion of t hese t w o areas is cont iguous not only in t he primary somat osensory cort ex but also elsew here in t he neuraxis.
The Alien Hand Syndrome The alien hand syndrome is def ined as unw illed, uncont rollable movement s of an upper limb t oget her w it h f ailure t o recognize ow nership of a limb in t he absence of visual cues. The syndrome w as f irst described by G oldst ein in 1908. Most cases are associat ed w it h lesions in t he corpus callosum and mesial f ront al area, alone or in combinat ion. The condit ion has also been report ed in inf arct s involving t he post erolat eral and ant erolat eral t halamic t errit ories (supplied by t he geniculot halamic and t uberot halamic art eries, respect ively). The lesion usually involves t he vent ral post erior, vent ral lat eral, and dorsomedial nuclei.
Thalamic Acalculia I nf arct ions in t he lef t ant erolat eral t halamic t errit ory supplied by t he t uberot halamic art ery have been report ed t o produce acalculia. The lesion usually involves t he vent ral lat eral and dorsomedial t halamic nuclei.
Tabl e 12-2. T halamic Pain Syndromes Subtypes
Type
Central pain
Vibration, Som atos Pain, touch, evok tem perature joint potent
I (analgetic)
Absent
Lost
Lost
Absent
II
Present
Lost
Present
Absent
III
Present
Present
Present
Reduced
IV (pure algetic)
Present
Present
Present
Normal
Language Deficits Dominant hemisphere t halamic lesions may cause a t ransient def icit in language. Three t ypes have been described: (1) medial, (2) ant erolat eral, and (3) lat eral. I n t he medial t ype, involving t he dorsomedial and cent romedian nuclei (medial t halamic t errit ory), t he language def icit is charact erized by anomia and at t ent ionally induced language impairment . Lesions in t his area are associat ed w it h memory and at t ent ion def icit s. I n t he ant erolat eral t ype, t he lesion involves vent ral ant erior and ant erior vent ral nuclei (ant erolat eral t halamic t errit ory). This t ype is associat ed w it h an aphasic syndrome resembling t ranscort ical aphasia. I n t he t hird t ype, t he lesion involves t he lat eral t halamic t errit ory. The language def icit in t his t ype is charact erized by mild anomia. Several aut hors have suggest ed t hat t halamic language dist urbances are due t o cort ical hypoperf usion and hypomet abolism.
CLINICAL CORRELATES OF SUBTHALAM IC ANATOM Y Hemiballismus Lesions in t he subt halamic nucleus or in t he pallidosubt halamic syst em are associat ed w it h violent , involunt ary, f linging, ballist ic movement s of t he cont ralat eral half of t he body. The abnormal movement involves primarily t he ext remit ies; t he head and neck also may be involved.
TERM INOLOGY Abulia (G reek a, w ithout ; boul é, w ill ) . A st at e in w hich t he pat ient manif est s lack of init iat ive and spont aneit y w it h preserved consciousness. Aphasia (G reek a, w ithout ; phasi s, s peech ) . Def ect in communicat ion by language. Ataxia (G reek a, w ithout ; taxi s, o rder ) . Loss of muscle coordinat ion w it h irregularit y of movement . Contralateral (Latin contra, o pposite ; l ateri s, o f a side ) . O f t he ot her side of t he body. Dysarthria (G reek dys, d ifficult ; arthroun, t o articulate ) . Diff icult y in speaking. Exteroceptor (Latin exterus, e xternal ; receptor, r eceiver ) . Sensory recept or t hat serves t o acquaint t he individual w it h t he ext ernal environment . I ncludes pain and t emperat ure recept ors. Hemianopsia (G reek hemi , h alf ; an, n egative ; opsi s, v ision ) . Def ect of half t he f ield of vision. Hemiballismus (G reek hemi , h alf ; bal l i smos, j umping about ) . Violent f linging movement of one side of t he body due t o a lesion in t he cont ralat eral subt halamic nucleus. Infarction (Latin i nfarci re, t o stuff into ) . Vascular occlusion leading t o deat h of t issue. Kleine, Willi. G erman neuropsychiat rist w ho, in 1925, report ed f ive cases of periodic somnolence and morbid hunger at t ribut ed t o hypot halamic lesion. The syndrome had been previously described in 1898 by Ant imoff . Lesion (Latin l aesum, h urt or wounded ) . The t erm is applied t o an abnormalit y t hat may dest roy t issue, as in inf arct ion, hemorrhage, or t umor, or t hat may st imulat e t issue, as in epilepsy. Levin, Max. American neuropsychiat rist of Lat vian origin. I n 1929, he described a case of Kleine-Levin syndrome 4 years af t er Kleine described his cases. I n 1936, he summarized t he f eat ures of seven cases as a new syndrome of periodic somnolence and morbid hunger. Paresthesia (G reek para, b eside, near, beyond ; ai sthesi s, p erception ) . Dist ort ed sensat ion, t ingling, p ins and needles.
Proprioceptor (Latin propri us, o ne's own ; receptor, r eceiver ) . Sensory endings in muscles, t endons, and joint s t hat provide inf ormat ion about movement and posit ion of body part s. Syndrome (G reek syndromos, a running together, combining ) . A group of co-occurring sympt oms and signs t hat charact erize a disease.
SUGGESTED READINGS Beric A: Cent ral pain: New syndromes and t heir evaluat ion. Muscl e Nerve 1993; 16: 1017 1 024. Biller J et al: Syndrome of t he paramedian t halamic art eries: Clinical and neuroimaging correlat ion. J Cl i n Neuroophthal mol 1985; 5: 217 2 23. Bjornst ad B et al: Paroxysmal sleep as a present ing sympt om of bilat eral paramedian t halamic inf arct ion. Mayo Cl i n Proc 2003; 78: 347 3 49. Bogousslavsky J et al: Thalamic inf arct s: Clinical syndromes, et iology, and prognosis. Neurol ogy 1988; 38: 837 8 48. Bogousslavsky J et al: Loss of psychic self -act ivat ion w it h bit halamic inf arct ion: Neurobehavioral, CT, MRI , and SPECT correlat es. Acta Neurol Scand 1991; 83: 309 3 16. Brandt T et al: Post erior cerebral art ery t errit ory inf arct s: Clinical f eat ures, inf arct t opography, causes and out come. Cerebrovasc Di s 2000; 10: 170 1 82. Caplan LR: Top of t he basilar syndrome. Neurol ogy 1980; 30: 72 7 9. Cast aigne P et al: Paramedian t halamic and midbrain inf arct s: Clinical and neuropat hological st udy. Ann Neurol 1981; 10: 127 1 48. Engelborghs S et al: Funct ional anat omy, vascularisat ion and pat hology of t he human t halamus. Acta Neurol Bel g 1998; 98: 252 2 65. Eslinger PJ et al: F ront al lobe ut ilizat ion behavior associat ed w it h paramedian t halamic inf arct ion. Neurol ogy 1991; 41: 450 4 52. G ent ilini M et al: Bilat eral paramedian t halamic art ery inf arct s: Report of eight cases. J Neurol Neurosurg Psychi atry 1987; 50: 900 9 09.
G raff -Radf ord NR et al: Nonhemorrhagic t halamic inf arct ion. Brai n 1985; 108: 485 5 16. G uberman A, St uss D: The syndrome of bilat eral paramedian t halamic inf arct ion. Neurol ogy 1983; 33: 540 5 45. I sono O et al: Cheiro-oral t opography of sensory dist urbances due t o lesions of t halamocort ical project ions. Neurol ogy 1993; 43: 51 5 5. Kinney HC et al: Neuropat hological f indings in t he brain of Karen Ann Q uinlan: The role of t he t halamus in t he persist ent veget at ive st at e. N Engl J Med 1994; 330: 1469 1 475. Marey-Lopez J et al: Post erior alien hand syndrome af t er a right t halamic inf arct . J Neurol Neurosurg Psychi atry 2002; 73: 447 4 49. Mauguiere F, Desmedt JE: Thalamic pain syndrome of Dejerine-Roussy: Diff erent iat ion of f our subt ypes assist ed by somat osensory evoked pot ent ials dat a. Arch Neurol 1988; 45: 1312 1 320. Mendez MF et al: Thalamic acalculia. J Neuropsychi atry Cl i n Neurosci 2003; 15: 115 116. Mennemeier M et al: Cont ribut ions of t he lef t int ralaminar and medial t halamic nuclei t o memory. Arch Neurol 1992; 49: 1050 1 058. Miw a H et al: Thalamic t remor: Case report s and implicat ions of t he t remorgenerat ing mechanism. Neurol ogy 1996; 46: 75 7 9.
Mori E et al: Lef t t halamic inf arct ion and dist urbances of verbal memory: A clinicoanat omical st udy w it h a new met hod of comput ed t omographic st ereot axic lesion localizat ion. Ann Neurol 1986; 20: 671 6 76. Nea JP, Bogousslavsky J: The syndrome of post erior choroidal art ery t errit ory inf arct ion. Ann Neurol 1996; 39: 779 7 88. Reilly M et al: Bilat eral paramedian t halamic inf arct ion: A dist inct but poorly recognized st roke syndrome. Q J Med 1992; 29: 63 7 0. Roit berg BZ et al: Bilat eral paramedian t halamic inf arct in t he presence of an
unpaired t halamic perf orat ing art ery. Acta Neurochi r 2002; 144: 301 3 04. Szczudlik A et al: Vascular t halamic syndromes c linical and t opographic analysis. Neur Neurochi r Pol 1996; 30(Suppl 2): 55 6 3. Wallesch CW et al: Neuropsychological def icit s associat ed w it h small unilat eral t halamic lesions. Brai n 1983; 106: 141 1 52.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 13 - The B as al Ganglia
13 The Basal Ganglia
Definitions and Nom enclature Neuronal Population, Synaptic Relations, and Internal Organization Neostriatum (Striatum) Globus Pallidus and Substantia Nigra Pars Reticulata Neostriatal Input Neostriatal Output Pallidal and Nigral Inputs Pallidal and Nigral Outputs Subthalamic Nucleus Ventral (Limbic) Striatum Corticostriatothalamocortical Loops Split Pathways Basal Ganglia Function Motor Function Gating Function Cognitive Function Emotion and Motivation Function Spatial Neglect Com plem entarity of Basal Ganglia and Cerebellum in Motor Function
Blood Supply KEY CONCEPTS The terms corpus striatum, striatum, dorsal striatum, neostriatum, ventral striatum, pallidum, paleostriatum, and lentiform nucleus refer to welldefined components of the basal ganglia as summarized in Table 13-1. The striatum receive inputs from the cerebral cortex (major source) and subcortical structures (substantia nigra compacta, thalamus, raphe nuclei, locus ceruleus, and external segment of globus pallidus). The striatum projects to the output nuclei (globus pallidus internus and substantia nigra reticulata) via two pathways; direct and indirect. The striatum is the principal receptive structure and the globus pallidus is the principal output structure of the basal ganglia. Lesions of subthalamic nucleus result in ballism, and stimulation relieves the symptoms of Parkinsonism. Corticostriatothalamocortical connections are organized into five parallel and segregated loops and/or three split circuits. The role of the basal ganglia in motor control includes the preparation for and execution of cortically initiated movement. The basal ganglia subserve roles in cognitive function, emotion, and motivation. Blood supply of the basal ganglia is derived from
lenticulostriate branches of the middle and anterior cerebral arteries and the anterior choroidal branch of the internal carotid artery.
The neural cont rol of movement is t he product of int eract ions w it hin and among a number of cort ical and subcort ical neural st ruct ures (Figure 13-1). Among t he various subcort ical st ruct ures, t hree are of part icular signif icance. They are t he basal ganglia, cerebellum, and t he dopaminergic mesencephalic syst em. Whereas lesions in t he mot or cort ex result in loss of movement , such as occurs in st roke, lesions in t he basal ganglia or cerebellum result in incoordinat ed and disorganized movement , such as occurs in Parkinsonism and Hunt ingt on's chorea. Recent experiment al st udies and clinical observat ions have f ocused on a new role f or t he basal ganglia in nonmot or f unct ions, including cognit ion and behavior.
Fi gure 13-1. Simplif ied schemat ic diagram of major cort ical and subcort ical neural st ruct ures involved in movement : 1, cort icospinal t ract ; 2, cerebrocerebellar pat hw ays; 3, cort icost riat e pat hw ays; 4, dent at ot halamic pat hw ays; 5, st riat ot halamic pat hw ays; 6, t halamocort ical pat hw ays; and 7, dopaminergic pat hw ays.
DEFINITIONS AND NOM ENCLATURE The basal gangl i a are a group of int erconnect ed nuclei involved in mot or and nonmot or f unct ions. Anat omically, t he t erm ref ers t o t he f ollow ing nuclei: caudat e, put amen, globus pallidus, nucleus accumbens sept i, and olf act ory
t ubercle, all of w hich are t opographically locat ed in t he b asement of t he brain (Figure 13-2). Funct ionally, t he subst ant ia nigra and subt halamic nucleus are included w it hin t he basal ganglia. The anat omic net w ork of basal ganglia w as not out lined w it h precision unt il t he 20t h cent ury. G alen used t he t erm b ut t ocks t o ref er t o cellular masses (caudat e nuclei) prot ruding int o t he lat eral vent ricles. Prior t o 1786, t he basal ganglia w ere lumped w it h t he t halamus in t he s t riat ed body . A major st ep in it s def init ion w as made w hen t he t halamus w as separat ed f rom t he st riat ed body by t he French anat omist Felix Vicq d'Azir in 1786. The t erm basal gangl i a w as f irst int roduced in t he English language by Ferrier in 1876. The dist inct ion bet w een st riat um and pallidum w as made at t he beginning of t he 20t h cent ury, and t he import ance of t he cort icost riat al connect ions w ere recognized in t he lat e 1960s. As revealed by magnet ic resonance imaging (MRI ), basal ganglia volume is signif icant ly larger on t he right side, irrespect ive of handedness and gender. The t erm corpus st riat um ref ers t o t he caudat e, put amen, and globus pallidus. The t erms stri atum, dorsal stri atum, and neostri atum ref er t o t he caudat e and put amen. The t erms pallidum and paleost riat um ref er t o globus pallidus. The put amen and globus pallidus t oget her compose t he lent if orm nucleus. The t erm ventral stri atum ref ers t o t he vent ral part s of caudat e and put amen, t he nucleus accumbens sept i, and t he st riat al part of t he olf act ory t ubercle (Table 13-1). The t erm ext rapyramidal syst em, coined in 1912 by Brit ish neurologist Kinnier Wilson, ref ers t o t he basal ganglia and an array of brain st em nuclei (red nucleus, subt halamic nucleus, subst ant ia nigra, ret icular f ormat ion) t o w hich t hey are connect ed. This conglomerat e of neural st ruct ures plays an import ant role in mot or cont rol.
NEURONAL POPULATION, SYNAPTIC RELATIONS, AND INTERNAL ORGANIZATION Neostriatum (Striatum) The t erms neost riat um and st riat um ref er t o t he caudat e nucleus and put amen. Bot h nuclei are of t elencephalic origin. During ont ogenesis, t he caudat e nucleus f ollow s t he curvat ure of t he t elencephalic vesicle and t hus becomes a C-shaped st ruct ure w it h an expanded rost ral ext remit y, t he head, w hich t apers dow n in size t o f orm a body and a t ail. The head of t he caudat e nucleus bears a charact erist ic relat ionship t o t he ant erior horn of t he lat eral vent ricle (Figure 132). This part of t he caudat e charact erist ically bulges int o t he lat eral vent ricle. I n degenerat ive cent ral nervous diseases involving t he caudat e nucleus, such as Hunt ingt on's chorea, described by t he American general pract it ioner G eorge Hunt ingt on in 1872, t he charact erist ic bulge of t he caudat e nucleus int o t he lat eral vent ricle is lost . While t he head and body of t he caudat e nucleus maint ain a relat ionship t o t he lat eral w all of t he ant erior horn and body of t he lat eral vent ricle, respect ively, t he t ail of t he caudat e occupies a posit ion in t he roof of
t he inf erior horn of t he lat eral vent ricle (Figure 13-3). The t ail of t he caudat e is very small in humans. The put amen is locat ed lat eral t o t he globus pallidus and medial t o t he ext ernal capsule (Figure 13-2). I t is separat ed f rom t he caudat e nucleus by t he int ernal capsule, except rost rally, w here t he head of t he caudat e and t he put amen are cont inuous around t he ant erior limb of t he int ernal capsule (Figure 13-4). Neost riat al neurons are of t w o t ypes: aspiny and spiny. Aspiny neurons (4 percent ) are int rinsic neurons (int erneurons). They are divided int o f our t ypes: large cholinergic, small G ABAergic and parvalbumin-cont aining (largest populat ion), somat ost at in and neuropept ide Y c ont aining, and calret inin immunoreact ive neurons. I n addit ion, immunocyt ochemical st udies demonst rat e t he presence of int rinsic dopaminergic int erneurons in t he st riat um. They are f ew in number in t he normal st riat um but increase in number w hen t he dopaminergic input t o t he st riat um is int errupt ed, as in Parkinson's disease.
Fi gure 13-2. Parasagit t al A and coronal B sect ions of t he brain show ing t he anat omic component s of t he basal ganglia.
Spiny neurons, t he neost riat al project ion (principal) neurons, const it ut e t he great majorit y (96 percent ) of neost riat al neurons. They cont ain G ABA, t aurine, and a number of neuropept ides, including subst ance P, enkephalin, neurot ensin, dynorphin, and cholecyst okinin. Spiny neurons are silent at rest and discharge w hen st imulat ed by cort ical or ot her input s. Spiny project ion neurons and t he large cholinergic aspiny int erneurons are lost in Hunt ingt on's chorea.
Tabl e 13-1. Basal G anglia Nomenclature
Striatum , Corpus dorsal Ventral Pallidu striatum striatum , striatum paleostria neostriatum
Caudate
+
+
+
Putamen
+
+
+
Globus pallidus
+
+
Nucleus accumbens
+
Olfactory tubercle
+
Molecular biology t echniques have ident if ied at least six dopamine recept or isof orms grouped int o t w o subf amilies (D1 -like and D2 -like). D1 and D2 recept ors are f ound in t he st riat um. D2 recept ors mediat e t he ant ipsychot ic eff ect s of neurolept ic drugs and exert f eedback cont rol on dopaminergic t ransmission. I n Parkinson's disease, D1 recept ors are reduced, w hile D2 recept ors are signif icant ly increased. Colocalizat ion of D1 and D2 recept ors has been report ed in virt ually all st riat al neurons. Axons f rom t he cerebral cort ex t erminat e on dist al spines of project ion neurons. Axons f rom subst ant ia nigra, t halamus, and int rast riat al sit es (int erneurons and ot her spiny neurons) t erminat e on dendrit ic shaf t s and cell bodies of project ion neurons (Figure 13-5). This pat t ern of t erminat ion allow s cort ical input t o be modulat ed or inhibit ed by t he ot her input s t o t he project ion neurons.
Fi gure 13-3. Axial sect ion of t he brain show ing t he head and t ail of t he caudat e nucleus, and t heir relat ionships t o t he ant erior and inf erior (t emporal) horns of t he lat eral vent ricle.
Fi gure 13-4. Coronal sect ion of t he brain show ing cont inuit y of t he put amen w it h t he head of t he caudat e around t he ant erior limb of t he int ernal capsule.
The adult neost riat um is made up of t w o compart ment s: The pat ches (st riosomes) compart ment cont ains cells t hat st ain w eakly f or acet ylcholine est erase and is int erspersed bet w een st rongly st aining areas, t he mat rix compart ment . Besides diff erences in acet ylcholine est erase react ivit y, t he t w o compart ment s diff er in t heir input , out put , neurot ransmit t ers, neuromodulat ors, sources of dopaminergic input , and dist ribut ion of dopaminergic recept or subt ypes (Table 13-2).
Fi gure 13-5. Schemat ic diagram of st riat al medium spiny project ion neuron show ing t he diff erent pat t erns of t erminat ion of cort ical, nigral, t halamic, and int rast riat al neurons on dendrit es and soma. S, soma; D, dendrit e; Sp, dendrit ic spine. (Modif ied f rom Trends in Neurosci-ence 13: 259 2 65, 1990, f igure 3, w it h permission f rom Elsevier Science Lt d. )
Tabl e 13-2. Characteristics of Striosome and Matrix Compartments
Striosom es
Matrix
Acetylcholinesterase staining
Light
Heavy
Cell development
Early
Late
Input
Medial frontal cortex, limbic cortex, substantia nigra pars compacta, ventral substantia nigra pars reticulata
Sensorimotor cortex, supplementary motor cortex, association cortex, limbic cortex, intralaminar thalamic nuclei, ventral tegmental area, dorsal substantia nigra pars compacta
Output
Substantia nigra pars compacta
Substantia nigra pars reticulata, globus pallidus
Neurotransmitter
GABA
GABA
Neuromodulators
Neurotensin, dynorphin, substance P
Somatostatin, enkephalin, substance P
Dopamine receptor
D1
D2
Globus Pallidus and Substantia Nigra Pars Reticulata The globus pallidus is a w edge-shaped nuclear mass locat ed bet w een t he put amen and int ernal capsule. A lamina of f ibers (ext ernal pallidal lamina) separat es t he globus pallidus f rom t he put amen. Anot her lamina (int ernal pallidal lamina) divides t he globus pallidus int o a larger lat eral (out er) and a smaller medial (inner) segment (Figure 13-2A). The ent opeduncular nucleus of nonprimat e mammals is part of t he medial pallidal segment in primat e mammals. The subst ant ia nigra pars ret iculat a occupies t he vent ral zone of t he subst ant ia nigra and cont ains iron compounds. Morphologically and chemically, t he globus pallidus and t he subst ant ia nigra pars ret iculat a are similar. The lat t er is considered t he part of t he globus pallidus cont aining head and neck represent at ion, w hereas t he int ernal segment of globus pallidus has arm and leg represent at ion. Most neurons in t he globus pallidus and subst ant ia nigra pars ret iculat a are large mult ipolar project ion neurons. I nt erneurons are inf requent . All pallidal and nigral neurons use G ABA as t he inhibit ory neurot ransmit t er. Pallidal and nigral neurons are about 100 t imes less numerous t han spiny st riat al neurons, t hus providing convergence of input f rom t he st riat um t o t he pallidum. About 90 percent of t he input t o pallidal and nigral neurons originat es f rom t he st riat um.
Subthalamic Nucleus Subt halamic nucleus neurons are cyt ologically homogenous, use glut amat e as t heir neurot ransmit t er, have only f ew spines, and are int ermediat e in t heir dendrit ic arborizat ion bet w een t hose of st riat al and pallidal neurons.
Neostriatal Input A. CORTICOSTRIATE PROJECTIONS Project ions f rom t he cerebral cort ex t o t he st riat um are bot h direct and indirect . Direct cort icost riat e project ions reach t he neost riat um via t he int ernal and ext ernal capsules and via t he subcallosal f asciculus. The indirect pat hw ays include t he cort icot halamost riat e pat hw ay, collat erals of t he cort ico-olivary pat hw ay, and collat erals of t he cort icopont ine pat hw ay (Figure 13-6). The cort icost riat e project ion comprises t he most massive st riat al aff erent s. Almost all cort ical areas cont ribut e t o t his project ion. Cort ical areas int erconnect ed via cort icocort ical f ibers t end t o share common zones of t erminat ion in t he neost riat um. Cort icost riat al f ibers are t opographically organized int o t hree dist inct st riat al t errit ories: (1) sensorimot or (post commissural put amen), (2) associat ive (caudat e and pre-commissured put amen), and (3) limbic (nucleus accumbens). The sensorimot or t errit ory receives it s input s f rom sensory and mot or cort ical areas. The associat ive t errit ory receives
f ibers f rom t he associat ion cort ices. The limbic t errit ory receives input f rom limbic and paralimbic cort ical areas. The cingulat e cort ex project s t o bot h t he sensorimot or and limbic st riat um. I t t hus serves t o modulat e mot or responses based on limbic inf ormat ion. Cort icost riat e pat hw ays are also somat ot opically organized such t hat cort ical associat ion areas project t o t he caudat e nucleus, w hereas sensorimot or cort ical areas pref erent ially project t o t he put amen. Cort icoput amenal project ions are f urt her organized in t hat t he cort ical arm, leg, and f ace areas project t o corresponding areas w it hin t he put amen. The somat ot opic organizat ion of cort icost riat e project ion is replicat ed t hroughout t he basal ganglia. The excit at ory neurot ransmit t er of cort icost riat e project ions is glut amat e.
B. M ESENCEPHALOSTRIATE PROJECTIONS The principal mesencephalost riat e project ion originat es f rom dopaminecont aining cells of t he subst ant ia nigra pars compact a. Dopamine has a net excit at ory eff ect on D1 st riat al neurons t hat project t o t he int ernal segment of globus pallidus and subst ant ia nigra pars ret iculat a and a net inhibit ory eff ect on D 2 st riat al neurons t hat project t o t he ext ernal segment of globus pallidus (Figure 13-7). Collat erals f rom nigrost riat e project ions have recent ly been t raced t o globus pallidus and subt halamic nucleus. These collat erals provide t he anat omic basis f or nigral dopaminergic neurons t o direct ly aff ect t he pallidum and subt halamic nucleus.
Fi gure 13-6. Schemat ic diagram of t he direct (1) and indirect (2, 3, 4) cort icost riat e project ions.
Fi gure 13-7. Schemat ic diagram of nigrost riat al pat hw ay show ing t he f acilit at ory act ion (+) of dopamine on st riat al neurons t hat project t o subst ant ia nigra pars ret iculat a and int ernal segment of globus pallidus, and t he inhibit ory act ion ( ) of dopamine on st riat al neurons t hat project t o t he ext ernal segment of globus pallidus. D1 , dopamine 1 class recept or neuron; D 2 , dopamine 2 class recept or neuron; DA, dopamine; G ABA, gammaaminobut yric acid; G Pe, ext ernal segment of globus pallidus; G Pi, int ernal segment of globus pallidus; SNr, subst ant ia nigra pars ret iculat a. (Modif ied f rom J Child Neurol 9: 249 2 60, 1994, f igure 1, w it h permission f rom Decker Periodicals. )
I n addit ion t o t he subst ant ia nigra, t he f ollow ing mesencephalic dopaminergic nuclear groups project t o t he st riat um: t he vent ral t egment al area of Tasi (area A-10) and t he ret rorubral nucleus (subst ant ia nigra pars dorsalis, area A-8).
C. THALAM OSTRIATE PROJECTIONS Thalamost riat e project ions are t he second most prominent aff erent s t o t he st riat um. The cent romedian nucleus project s mainly t o t he sensorimot or st riat al t errit ory, w hile t he paraf ascicular nucleus project s t o t he associat ive and limbic st riat al t errit ories. O t her t halamic sources of input t o t he st riat um include vent ral ant erior, vent ral lat eral, and post erior t halamic nuclei. Thalamost riat e project ions f rom vent ral ant erior and vent ral lat eral nuclei overlap ext ensively w it h cort icost riat e project ions f rom f ront al mot or cort ical areas. Thalamost riat e f ibers are believed t o be excit at ory. The neurot ransmit t er is glut amat e.
D. OTHER PROJECTIONS O t her project ions t o t he neost riat um include t hose f rom t he raphe nuclei (serot onergic), t he locus ceruleus (noradrenergic), and ext ernal segment of globus pallidus. Figure 13-8 is a schema of t he major input s t o t he neost riat um. The main t arget of st riat al aff erent s is t he G ABAergic medium-size spiny project ion neuron. Alt hough less massively innervat ed, t he aspiny int erneurons also receive direct cort ical, t halamic, and nigral input s.
Fi gure 13-8. Schemat ic diagram of major sources of input t o t he sensorimot or, associat ion, and limbic zones of t he neost riat um. G lu, glut amine; DA, dopamine.
Neostriatal Output The neost riat um project s t o t he subst ant ia nigra pars ret iculat a, bot h segment s of t he globus pallidus, and t he vent ral pallidum. There is also a small project ion f rom t he neost riat um t o t he subst ant ia nigra pars compact a. The neost riat al project ions t o t he diff erent t arget areas, alt hough cont aining one neurot ransmit t er (G ABA), have diff erent neuropept ides (Table 13-3). The st riat al out put t o t he globus pallidus and t he subst ant ia nigra pars ret iculat a is organized int o direct and indirect project ions (Figure 13-9). The direct project ion is f rom t he neost riat um t o t he int ernal segment of t he globus pallidus and t he subst ant ia nigra pars ret iculat a (out put nuclei). The indirect project ion is f rom t he neost riat um t o t he ext ernal segment of t he globus pallidus and via t he subt halamic nucleus t o t he int ernal segment of t he globus pallidus and t he subst ant ia nigra pars ret iculat a. The t w o pat hw ays have opposing eff ect s on t he out put nuclei and t heir t halamic t arget s. Act ivat ion of t he direct pat hw ay leads t o a net disinhibit ory (f acilit at ory) eff ect on t he t halamus and an increase in mot or behavior. Act ivat ion of t he indirect pat hw ay leads t o increased inhibit ion of t he t halamus and decreased mot or act ivit y. Enhanced act ivit y of t he indirect pat hw ay may be responsible f or t he povert y of movement (hypokinesia) of some basal ganglia disorders (Parkinson's disease), w hereas reduced act ivit y in t he direct pat hw ay may result in excessive act ivit y (hyperkinesia) of some basal ganglia disorders (Hunt ingt on's chorea). The concept of separat e direct and indirect pat hw ays has been challenged by t he f ollow ing recent f indings: (1) direct project ions f rom t he ext ernal pallidal segment t o t he out put nuclei and t o t he st riat um, (2) subt halamic nucleus
project ions t o t he st riat um, ext ernal pallidal segment , and subst ant ia nigra pars compact a, (3) abundant collat eralizat ion of st riat al axons t erminat ing in several t arget nuclei, and (4) int erconnect ion of st riat al neurons giving rise t o t he direct and indirect pat hw ays and t he convergence of bot h pat hw ays at single out put neurons. The indirect pat hw ay is f unct ionally immat ure in childhood, w hereas t he direct pat hw ay is f unct ionally mat ure in childhood. Tabl e 13-3. Neurotransmitters and Neuromodulators Involved in Striatal O utput
To GPi To Gpe To SNr To SNc
GABA
+
Substance P
+
Enkephalin Dynorphin Neurotensin
+
+
+
+ +
+
+ +
+ +
Pallidal and Nigral Inputs A. STRIATOPALLIDAL AND STRIATONIGRAL PROJECTIONS The input t o bot h segment s of t he globus pallidus is primarily f rom t he put amen and t he subt halamic nucleus, w hereas t he input t o t he subst ant ia nigra pars ret iculat a is primarily f rom t he caudat e and t he subt halamic nucleus. The input f rom t he neost riat um is G ABAergic (inhibit ory). The input f rom t he subt ha-lamic nucleus is glut amat ergic (excit at ory).
B. OTHER PROJECTIONS O t her, less signif icant pallidal aff erent s include t hose f rom dopaminergic and serot onergic neurons of t he brain st em.
Pallidal and Nigral Outputs (Figure 13-10) A. M AJOR OUTPUT The major out put f rom t he int ernal segment of t he globus pallidus and t he subst ant ia nigra pars ret iculat a (out put nuclei) is t o t he t halamus. Pallidot halamic f ibers f ollow one of t w o rout es. Some t raverse t he int ernal capsule and gat her dorsal t o t he subt halamic nucleus as t he lent icular f asciculus (H2 f ield of Forel, af t er t he Sw iss neuropsychiat rist August Henri Forel, w ho described t hese bundles); ot hers pass around t he int ernal capsule (ansa lent icularis). Bot h groups of f ibers gat her t oget her t o f orm t he prerubral f ield (H f ield of Forel) and t hen join t he t halamic f asciculus (H1 f ield of Forel) t o reach t he t arget t halamic nuclei. The t arget t halamic nuclei are t he vent ral ant erior, vent ral lat eral, dorsomedial, and int ralaminar nuclei. The neurot ransmit t er is G ABA. Pallidal out put t hus inhibit s t he excit at ory t halamocort ical loop. The pallidot halamic and nigrot halamic project ions const it ut e t he link bet w een t he neost riat um and t he cerebral cort ex. The int ralaminar nuclei (cent romedian and paraf ascicular) are crucial element s in t he st riat ot halamocort ical circuit ry. The cent romedian nucleus f orms a nodal point in sensorimot or, and t he paraf ascicular nucleus an import ant relay in t he associat ive-limbic component s of t he circuit .
Fi gure 13-9. Schemat ic diagram of t he direct and indirect st riat opallidal pat hw ays. G ABA, gamma-aminobut yric acid; G Pe, ext ernal segment of globus pallidus; G Pi, int ernal segment of globus pallidus; SNr, subst ant ia nigra pars ret iculat a; +, f acilit at ory pat hw ay; -, inhibit ory pat hw ay.
B. M INOR OUTPUT Minor out put s f rom t he int ernal segment of t he globus pallidus and t he subst ant ia
nigra pars ret iculat a go t o t he f ollow ing areas.
1. Nucleus Tegmenti Pedunculopontis. This project ion serves t o link t he basal ganglia w it h t he spinal cord via t he ret iculospinal t ract . The project ion t o t he nucleus t egment i pedunculopont is assumes part icular signif icance because of t he mult iple connect ions and f unct ions of t his nucleus, t he best know n being mot or f unct ion (mesencephalic locomot or cent er), arousal, and sleep. O t hers include mot ivat ion, at t ent ion, and learning.
Fi gure 13-10. Schemat ic diagram of t he eff erent connect ions of int ernal segment of globus pallidus and subst ant ia nigra pars ret iculat a. G Pe, ext ernal segment of globus pallidus; G Pi, int ernal segment of globus pallidus; SNr, subst ant ia nigra pars ret iculat a. (From J Child Neurol 9: 249 2 60, 1994, f igure 2, w it h permission f rom Decker Periodicals. )
2. Habenular Nucleus Via t his connect ion, t he basal ganglia are linked w it h t he limbic syst em.
3. Superior Colliculus. Through t his pat hw ay, t he basal ganglia are linked (via t he t ect ospinal t ract ) t o t he spinal cord and (via t he t ect oret icular t ract ) t o brain st em nuclei relat ed t o head and eye movement s.
C. SIDE TRACK OUTPUT
This out put reciprocally relat es t he ext ernal segment of t he globus pallidus w it h t he subt halamic nucleus. The neurot ransmit t er is G ABA. The input s and out put s of t he basal ganglia are schemat ically summarized in Figure 13-11. The basal ganglia and it s relat ed neural syst ems may be view ed as composed of (1) a core and (2) regulat ors of t he core. The core is composed of t he st riat um and it s pallidal and nigral t arget s. The regulat ors of t he core f all int o t w o cat egories: (1) regulat ors of t he st riat um and (2) pallidonigral regulat ors (Figure 13-12).
Subthalamic Nucleus (Figure 13-13) Like t he st riat um, t he subt halamic nucleus is divided int o sensorimot or, associat ive, and limbic t errit ories. I t receives input s f rom t he f ollow ing sources: Corticosubthalamic Projection. Alt hough t he st riat um is t he main sit e of cort ical input , t he subt halamic nucleus receives excit at ory glut amat ergic project ions primarily f rom t he primary mot or area, w it h minor cont ribut ions f rom pref ront al, premot or, and supplement ary mot or cort ices. They are somat ot opically and t opographically organized, similar t o t he cort icost riat e project ions. Pallidosubthalamic Projection. A massive G ABAergic project ion f rom t he ext ernal segment of globus pallidus t o t he subt halamic nucleus plays an import ant role in t he indirect pat hw ay t hat links input and out put nuclei of t he basal ganglia. T halamosubthalamic Projection. Cent romedian and paraf ascicular nuclei comprise t he major sources of t his project ion. Nigrosubthalamic Projection. This dopaminergic pat hw ay originat es f rom t he subst ant ia nigra pars compact a and t he vent ral t egment al area as collat eral branches f rom t he nigrost riat al pat hw ay. Reticulosubthalamic Projection. The dorsal nucleus of t he raphe is t he main source of t his serot onergic project ion. The major out f low f rom t he subt halamic nucleus is t o bot h segment s of globus pallidus and t o t he subst ant ia nigra pars ret iculat a. Subt halamic nucleus lesions or lesions int errupt ing t he subt halamic p allidal connect ion are responsible f or t he violent hyperkinesia of ballism. The subt halamic nucleus has been a f avorable sit e f or deep brain st imulat ion in t reat ment of Parkinson's disease. I nf ormat ion f low t hrough t he st riat um and t he subt halamic nucleus is diff erent . Cort ical input t o t he subt halamic nucleus is f rom t he f ront al lobe, w hereas t he st riat um receives f rom virt ually all cort ical areas. The out put f rom t he st riat um is G ABAergic (inhibit ory) and slow, w hereas subt halamic nucleus
out put is glut amat ergic (excit at ory) and f ast . Subt halamic project ion t o t he out put nuclei int eract s w it h many out put neurons, w hereas st riat al project ion is f ocused on a single neuron. The pat hw ay t hrough t he subt halamic nucleus t hus provides a f ast , divergent excit at ion, w hereas t he pat hw ay t hrough t he st riat um provides f ocused inhibit ion of t he out put nuclei. These t w o pat hw ays provide t he anat omic basis f or t he model of f ocused inhibit ion and surround excit at ion of out put nuclei.
Ventral (Limbic) Striatum Current ly, t he t erm ventral stri atum ref ers t o t he f ollow ing nuclei: nucleus accumbens sept i, st riat e-like deep port ions of t he olf act ory t ubercle and vent ral part s of t he caudat e nucleus, and t he put amen (Table 13-1). The vent ral st riat um receives f ibers f rom t he f ollow ing sources: hippocampus, amygdala, ent orhinal and perirhinal cort ices (areas 28 and 35), ant erior cingulat e cort ex (area 24), medial orbit of ront al cort ex, and w idespread sources w it hin t he t emporal lobe. Dopaminergic input t o t he vent ral st riat um is subst ant ial. The out put f rom t he vent ral st riat um is t o t he vent ral pallidum. As is evident f rom it s connect ions, t he vent ral st riat um is relat ed t o t he limbic syst em. The vent ral st riat um has been t he f ocus of various st udies suggest ing t hat t he nucleus accumbens sept i plays a prominent role in mediat ing rew ard and mot ivat ion, w it h pot ent ial involvement in drug addict ion and ment al disorders such as schizophrenia and Touret t e syndrome.
Fi gure 13-11. Simplif ied schemat ic summary diagram of aff erent and eff erent connect ions of t he basal ganglia show ing t hat t he st riat um is t he major receiving area, w hereas t he int ernal segment of globus pallidus and
subst ant ia nigra pars ret iculat a const it ut e t he major out put nuclei. +, f acilit at ion; -, inhibit ion; DA, dopamine; Ser, serot onin; NA, noradrenaline; G Pe, ext ernal segment of globus pallidus; G Pi, int ernal segment of globus pallidus; SNr, subst ant ia nigra pars ret iculat a; VA, vent ral ant erior nucleus; VL, vent rolat eral nucleus; CM, cent romedian nucleus; DM, dorsomedial nucleus. (Modif ied f rom J Child Neurol 9: 249 2 60, 1994, f igure 3, w it h permission f rom Decker Periodicals. )
Fi gure 13-12. Schemat ic diagram show ing t he organizat ion of t he basal ganglia a ssociat ed neural syst em int o a core made up of t he st riat um and it s pallidonigral t arget s, and regulat ors act ing eit her on t he st riat um or pallidonigral component s of t he core.
Corticostriatothalamocortical Loops Cort icost riat ot halamocort ical connect ions are organized in f ive parallel and largely segregat ed loops (circuit s): mot or, oculomot or, dorsolat eral pref ront al, lat eral orbit of ront al, and limbic (Figure 13-14). Their names ref lect t he major cort ical area(s) of origin and/ or f unct ion of each. I nf ormat ion f low in each circuit passes f rom it s cort ical area of origin t o t he st riat um (caudat e, put amen, or vent ral st riat um), pallidum (dorsal or vent ral), and t halamus bef ore ret urning t o t he major cort ical area(s) f rom w hich each circuit originat ed. According t o t his model, cort ical areas t hat are t arget s of out put f rom a channel are t he cort ical areas f rom w hich t he major input t o t he channel originat ed. I njury t o a circuit result s in select ive dist urbance in mot or, cognit ive, or emot ional behavior.
A. M OTOR LOOP PATHWAY The mot or loop pat hw ay is cent ered on t he put amen and it s connect ions (Figure 13-14A). The put amen of primat es receives somat ot opically organized (arm, leg, f ace) input s f rom t he primary mot or, primary sensory, somat osensory associat ion, premot or, and supplement ary mot or cort ices. Wit hin each of t hese anat omic subchannels, f urt her levels of f unct ional organizat ion exist pert aining t o such behavioral variables as t arget locat ion, limb kinemat ics, and muscle pat t ern. The put amen project s t o bot h segment s of t he globus pallidus and t o t he subst ant ia nigra pars ret iculat a. The int ernal pallidal segment project s t o vent ral lat eral, vent ral ant erior, and cent romedian nuclei of t he t halamus, w hereas t he subst ant ia nigra pars ret iculat a project s t o t he vent ral ant erior t halamic nucleus. The mot or loop is complet ed by t halamocort ical project ions t o t he supplement ary mot or, premot or, and primary mot or cort ices.
Fi gure 13-13. Schemat ic diagram of t he input and out put of t he subt halamic nucleus. G lu, glut amat ergic pat hw ay; DA, dopaminergic pat hw ay; Ser, serot onergic pat hw ay; G ABA, G ABAergic pat hw ay.
Fi gure 13-14. Schemat ic diagrams show ing t he anat omic subst rat es of t he mot or loop A, oculomot or loop B, dorsolat eral pref ront al loop C, lat eral orbit of ront al loop D, and t he limbic loop E. MC, primary mot or cort ex (area 4); SC, primary sensory cort ex (areas 3, 1, and 2); SSA, somat osensory associat ion cort ex (area 5); PM, premot or cort ex; SMA, supplement ary mot or area; G Pi, int ernal segment of globus pallidus; SNr, subst ant ia nigra pars ret iculat a; STh, subt halamic nucleus; G Pe, ext ernal segment of globus pallidus; VLo, vent rolat eral nucleus of t halamus, pars oralis; VApc, vent ral ant erior nucleus of t halamus, pars parvicellularis; VAmc, vent ral ant erior nucleus of t halamus, pars magnocellularis; CM, cent romedian nucleus of t halamus; FEF, f ront al eye f ield (area 8); SEF, supplement ary eye f ield; DLPC, dorsolat eral pref ront al cort ex (areas 9 and 10); PPC, post erior pariet al cort ex; DMpm, dorsomedial nucleus of t halamus, pars mult if ormis; SC, superior colliculus; LO FC, lat eral orbit of ront al cort ex; DMmc, dorsomedial nucleus of t halamus, pars magnocellularis; ACC, ant erior
cingulat e cort ex; MO FC, medial orbit of ront al cort ex. (From J Child Neurology 9: 352 3 61, 1994, f igures 2, 3, 4, 5, t o 6, w it h permission f rom Decker Periodicals. )
An off shoot f rom t he pallidot halamic component of t he mot or loop is a project ion f rom t he int ernal segment of t he globus pallidus t o t he pedunculopont ine nucleus. A side loop in t his mot or pat hw ay passes f rom t he put amen t o t he ext ernal segment of t he globus pallidus and f rom t here t o t he subt halamic nucleus and back t o t he int ernal segment of t he globus pallidus.
B. OCULOM OTOR LOOP PATHWAY The oculomot or loop pat hw ay (Figure 13-14B) is cent ered on t he caudat e nucleus. Cort ical sources of input t o t he caudat e nucleus include t he f ront al eye f ield, supplement ary eye f ield, dorsolat eral pref ront al cort ex, and post erior pariet al cort ex. The caudat e, in t urn, project s t o t he int ernal segment of t he globus pallidus and t he subst ant ia nigra pars ret iculat a. The t halamic t arget s of t he oculomot or loop include t he vent ral ant erior and dorsomedial nuclei. The oculomot or loop is complet ed by t ha-lamocort ical project ions t o f ront al eye f ield and supplement ary eye f ield.
C. DORSOLATERAL PREFRONTAL LOOP PATHWAY The dorsolat eral pref ront al loop pat hw ay (Figure 13-14C) is also cent ered on t he caudat e nucleus. Cort icost riat e input t o t his pat hw ay originat es f rom t he dorsolat eral pref ront al cort ex and post erior pariet al cort ex. The caudat e nucleus project s t o t he int ernal segment of t he globus pallidus and t he subst ant ia nigra pars ret iculat a. The t halamic t arget s of t his pat hw ay are t he vent ral ant erior and dorsomedial nuclei. The loop is complet ed by t halamic project ions t o t he dorsolat eral pref ront al cort ex.
D. LATERAL ORBITOFRONTAL PREFRONTAL LOOP PATHWAY The lat eral orbit of ront al pref ront al loop pat hw ay (Figure 13-14D) is similarly cent ered on t he caudat e nucleus. The cort ico-st riat e project ion originat es f rom t he lat eral orbit of ront al cort ex. The caudat e nucleus project s t o t he int ernal segment of t he globus pallidus and t he subst ant ia nigra pars ret iculat a. The t halamic t arget s of t his pat hw ay are t he dorsomedial and vent ral ant erior nuclei. The loop is complet ed by t halamic project ions t o t he lat eral orbit of ront al cort ex.
E. LIM BIC LOOP PATHWAY
The limbic loop pat hw ay (Figure 13-14E) is cent ered on t he vent ral st riat um. Cort icost riat e project ions originat e f rom t he ant erior cingulat e cort ex, medial orbit of ront al cort ex, and w idespread areas in t he t emporal lobe. The vent ral st riat um project s t o vent ral pallidum. The t halamic t arget of t his pat hw ay is t he dorsomedial nucleus. The loop is complet ed by t halamic project ions t o ant erior cingulat e and medial orbit of ront al cort ices. A role f or t he limbic circuit in t he genesis of schizophrenia has been proposed. Each of t he f ive circuit s has a direct and an indirect pat hw ay f rom t he st riat um t o t he out put nuclei (int ernal segment of t he globus pallidus and subst ant ia nigra pars ret iculat a). The direct pat hw ay cont ains G ABA and subst ance P and direct ly connect s t he st riat um w it h t he out put nuclei (Figure 13-15). The indirect pat hw ay (Figure 13-16) connect s t he st riat um w it h t he out put nuclei via relays in t he ext ernal segment of globus pallidus and t he subt halamic nucleus. Act ivat ion of t he direct pat hw ay t ends t o disinhibit t halamocort ical t arget neurons. Act ivat ion of t he indirect syst em has a net eff ect of increasing t he inhibit ion of t halamocort ical t arget neurons.
Split Pathways The preceding f ive circuit s (loops) are charact erized by parallel, segregat ed, and closed connect ions, in w hich lit t le, if any, int ercommunicat ion t akes place. An alt ernat e model has been proposed t hat allow s f or cross-communicat ion bet w een circuit s. I n t his model, t hree circuit s are proposed: mot or, associat ive, and limbic. Wit hin each of t hese circuit s, t here are bot h closed and open loops (Figures 13-17). The novel f eat ure of t he open and closed loops (split circuit ry) model is t hat in each split circuit t he engaged st riat al area can inf luence, via it s open loop, a cort ical f ield t hat does not project t o it . Thus, it allow s f or t he coexist ence of diff erent sympt oms and signs (mot or, cognit ive, and emot ional) as a result of a lesion in only one of t he circuit s. I nt eract ion bet w een split circuit s can occur at t w o levels, t he cerebral cort ex and t he subst ant ia nigra.
Fi gure 13-15. Schemat ic diagram show ing t he anat omic subst rat es of t he direct st riat opallidal pat hw ay. G l, glut amat e; G ABA, gamma-aminobut yric acid; G Pi, int ernal segment of globus pallidus; SNR, subst ant ia nigra pars ret iculat a; +, f acilit at ion; -, inhibit ion. (Modif ied f rom J Child Neurol 9: 352 3 61, 1994, f igure 7, w it h permission f rom Decker Periodicals. )
BASAL GANGLIA FUNCTION The basal ganglia have long been considered cent ral in t he cont rol of movement . I t is now w idely accept ed t hat t hey also play a role in nonmot or behavior, including cognit ion and emot ion.
Motor Function The basal ganglia play a role in t he aut omat ic execut ion of learned mot or plan and in t he preparat ion f or movement . St udies t hat t ime neuronal discharge in relat ion t o onset of st imulus-t riggered movement suggest t hat act ivit y w it hin t he basal ganglia is init iat ed at cort ical levels. I n t he cort ically init iat ed movement , inf ormat ion f low f rom t he cort ex t o t he basal ganglia (Figure 13-18) begins w it h a command f rom t he cort ex t o t he st riat um t hat init iat es act ion of st riat al neurons. The nigral input t o t he st riat um provides a cont inuous damping eff ect so t hat cort ical commands w ill be f ocused. The input f rom t he t halamus and ot her sit es inf orms and updat es t he st riat um of t he act ivit y in ot her syst ems concerned w it h movement . The st riat um int egrat es and f eeds inf ormat ion t o t he globus pallidus and t he subst ant ia nigra pars ret iculat a. These in t urn inf luence act ivit y of t he t halamus and ot her t arget s (i. e. , superior colliculus, ret icular f ormat ion). According t o Marsden, t he basal ganglia are responsible f or t he aut omat ic execut ion of a learned mot or plan. As a mot or skill is learned, t he basal ganglia t ake over t he role of aut omat ically execut ing t he learned st rat egy. When basal ganglia are damaged, t he individual must revert t o a slow er, less aut omat ic, and less accurat e cort ical mechanism f or mot or behavior.
Fi gure 13-16. Schemat ic diagram show ing t he anat omic subst rat es of t he direct st riat opallidal pat hw ay. G l, glut amat e; G ABA, gamma-aminobut yric acid; ENK, enkephalin; G Pe, ext ernal segment of globus pallidus; G Pi, int ernal segment of globus pallidus; SNr, subst ant ia nigra pars ret iculat a; STh, subt halamic nucleus; +, f acilit at ion; -, inhibit ion. (Modif ied f rom J Child Neurol 9: 352 3 61, 1994, f igure 8, w it h permission f rom Decker Periodicals. )
Fi gure 13-17. Schemat ic diagram of split mot or circuit show ing t he closed loop and t he open loop of t he circuit . (Modif ied f rom Neuroscience 63: 363 3 79, 1994, f igure 3, w it h permission f rom Elsevier Science Lt d. )
O t her roles f or t he basal ganglia in mot or cont rol include t he preparat ion f or movement . During bot h t he preparat ion and execut ion of movement , separat e populat ions of neurons w it hin t he mot or loop discharge select ively in relat ion t o eit her t arget locat ion in space, direct ion of limb movement , or muscle pat t ern. Similarly, in t he oculomot or loop, populat ions of neurons have been described t hat discharge in relat ion t o visual f ixat ion, saccadic eye movement , or passive visual st imuli. A subset of caudat e neurons has been show n t o part icipat e in t he rew ard-based cont rol of visual at t ent ion. The recognit ion t hat basal ganglia neurons respond t o st imuli colored by memory or signif icance indicat es t hat t his region of t he brain is concerned w it h higherorder mot or cont rol. A role f or t he basal ganglia in Touret t e syndrome, a chronic t ic disorder described by t he French neuropsychiat rist G eorge G illes de la Touret t e in 1885, has been proposed. A hypot het ical model f or basal ganglia reorganizat ion in t ic disorders and Touret t e syndrome has also been proposed.
Gating Function
Several lines of evidence support a role of t he basal ganglia in gat ing of sensory inf ormat ion f or mot or cont rol. The benef it of ext ernal sensory cues in Parkinson's disease and t he sensory t rick in dyst onia support such a role. According t o t he gat ing hy-pot hesis, in normal subject s, dopamine (inhibit ory) and cort ical sensorimot or (excit at ory) input s t o t he st riat um are in physiologic balance. The inhibit ory out put of t he pallidum t hus regulat es sensorimot or access. I n Parkinson's disease, t he loss of dopamine (inhibit ory) w ill allow cort ical f acilit at ion a f ree hand t o st imulat e t he inhibit ory basal ganglia out put . This limit s access of sensory inf ormat ion t o t he mot or syst em and decreases mot or act ivit y (hypokinesia). I n Hunt ingt on's chorea, loss of basal ganglia neurons result s in a decrease in inhibit ory out put of t he basal ganglia, w it h a result ing increase in access of sensory inf ormat ion t o t he mot or syst em and increased act ivit y.
Fi gure 13-18. Schemat ic diagram of inf ormat ion f low in t he basal ganglia (1) Command f rom cort ex init iat es act ion in st riat um. (2) Nigral input f rom SNc t o st riat um provides cont inuous damping of st at ic so t hat cort ical command w ill be f ocused. (3) I nput f rom t he t halamus and ot her sit es updat es and inf orms st riat um of act ivit y in ot her syst ems. (4) St riat um has an int egrat or role and f eeds it s result s t o G P and SNr. (5) G P and SNr inf luence (f acilit at e or inhibit ) act ivit y of t halamus and ot her t arget s (superior colliculus, ret icular f ormat ion, et c). SNc, subst ant ia nigra pars compact a; G P, globus pallidus; SNr subst ant ia nigra pars ret iculat a. (Modif ied f rom J Child Neurol 9: 352 3 61, 1994, f igure 9 w it h permission f rom Decker Periodicals. )
Cognitive Function I n addit ion t o t heir role in mot or cont rol, t he basal ganglia subserve cognit ive f unct ion. Lesions of t he dorsolat eral pref ront al circuit (loop) result in cognit ive def icit s and def icit s on t asks t hat require spat ial memory. The basal ganglia play a role in ret rieval of episodic and semant ic inf ormat ion f or explicit
memory and in implicit t asks t hat require t he init iat ion or modif icat ion of cent ral mot or programs. Lesions in t he dorsolat eral pref ront al circuit in humans have been linked t o cognit ive dist urbances in schizophrenia, Hunt ingt on's chorea, and Parkinson's disease. Lesions in t he lat eral orbit of ront al circuit have been linked t o obsessive-compulsive behavior.
Emotion and Motivation Function The limbic loop plays a role in emot ional and mot ivat ional processes. A role f or t he limbic loop in schizophrenia and depression has also been proposed. Decrease in size of t he basal ganglia has been report ed in bipolar disorders.
Fi gure 13-19. Simplif ied schemat ic diagram show ing varied t ypes of inf ormat ion received by t he cerebral cort ex, and t he complement arit y of basal ganglia and cerebellar roles in mot or f unct ion.
Spatial Neglect Various st udies have implicat ed t he put amen (and t o a lesser ext ent , t he caudat e) in spat ial neglect w it h right -sided basal ganglia lesions. Bot h nuclei are direct ly connect ed w it h t he superior t emporal gyrus, w hich plays a cent ral role in spat ial neglect .
COM PLEM ENTARITY OF BASAL GANGLIA AND CEREBELLUM IN M OTOR FUNCTION
Review of basal ganglia and cerebellar st ruct ure, connect ivit y, and organizat ion reveals many f eat ures in common. Bot h are component s of t he mot or syst em, bot h inf luence cerebral cort ical act ivit y via t he t halamus, bot h are linked w it h t he cerebral cort ex via recurrent loops, bot h have int ernal (local) circuit ry t hat modulat es loop act ivit y, and bot h receive modulat ing input s t hat inf luence t heir act ivit ies (climbing f ibers in t he cerebellum and dopaminergic input in t he basal ganglia). The emerging concept (Figure 13-19) of t he complement arit y of basal ganglia and cerebellum in mot or f unct ion suggest s t hat t he basal ganglia f unct ion as cont ext encoders, providing t o t he cerebral cort ex inf ormat ion t hat could be usef ul in planning and gat ing of act ion. The cerebellum, in cont rast , f unct ions as pat t ern generat or and execut or. According t o t his concept , t he cerebral cort ex, w hich receives diverse sensory inf ormat ion f rom t he periphery via t he diff erent ascending t ract s, as w ell as complex inf ormat ion already processed w it hin t he basal ganglia and cerebellum, serves t w o f unct ions: a reposit ory f unct ion t o receive t his diverse inf ormat ion, comput e it , and share it w it h t he basal ganglia and cerebellum and an execut ive f unct ion t o implement t he act ion emanat ing f rom it s collect ive comput at ion process. Tabl e 13-4. Blood Supply of Basal G anglia
Middle cerebral, lateral striate branch
Caudate nucleus
Anterior cerebral, m edial striate branch
Head
×
Body
×
×
Tail
Putamen
Internal carotid, anterior choroidal
×
Rostral
×
Caudal
Globus pallidus
Lateral Medial
×
×
×
×
BLOOD SUPPLY (Table 13-4) The basal ganglia receive t heir blood supply f rom perf orat ing (lent iculost riat e) branches of t he middle and ant erior cerebral art eries and t he ant erior choroidal branch of t he int ernal carot id art ery. The caudat e and put amen nuclei (t he st riat um) are supplied mainly by t he lat eral st riat e branches of t he middle cerebral art ery. Rost romedial part s of t he head of t he caudat e nucleus receive blood supply f rom t he medial st riat e art ery (of Huebner), a branch of t he ant erior cerebral art ery. The t ail of t he caudat e nucleus and caudal part of t he put amen receive branches of t he ant erior choroidal art ery. Most of t he globus pallidus is supplied by t he ant erior choroidal branch of t he int ernal carot id art ery. The lat eral (out er) segment of t he globus pallidus receives blood supply also f rom t he lat eral st riat e branch of t he middle cerebral art ery.
TERM INOLOGY Ballism (G reek bal l i smos, j umping ) . Violent involunt ary movement due t o a lesion in t he subt halamic nucleus. Caudate nucleus (Latin, h aving a tail ). The caudat e nucleus is so named because it has a long ext ension or t ail. Chorea (Latin from G reek choros, a dance ). Disorder of t he neost riat um causing irregular, involunt ary movement s of t he limbs or f ace. Formerly called St . Vit us dance. Corpus striatum (Latin corpus, b ody stri atu, s triped ) . G ray mat t er comprising caudat e, put amen, and globus pallidus w it h st riped appearance produced by myelinat ed f ibers t raversing t he gray mat t er.
Extrapyramidal system. Vague t erm int roduced but not def ined by t he Brit ish neurologist Kinnier Wilson. Current ly used t o ref er t o t he basal ganglia and t heir connect ions. Ferrier, Sir David (1843 1 928). Scot t ish neurophysiologist and neurologist w ho made many signif icant cont ribut ions t o cerebral localizat ion, including localizat ion of audit ory f unct ion t o t he superior t emporal gyrus among ot her sensory and mot or areas. G alen, Claudius (A. D. 130 2 00). Founder of t he galenic syst em of medicine. Described t he great cerebral vein (of G alen) and t he choroid vein among many ot her brain st ruct ures, including seven pairs of cranial nerves. He localized ment al f unct ions in t he cerebrum rat her t han in t he vent ricles. G lobus pallidus (Latin gl obus, a ball or round mass, pal l i dus, p ale ) . The paler inner part of t he lent if orm nucleus. Lentiform nucleus (Latin l ens, l entil forma, s hape ) . Lent if orm nucleus (put amen and globus pallidus) so named because it is shaped like a lent il. Neostriatum (G reek neos, n ew ; Latin stri atus, s triped ) . The phylogenet ically new er part of t he corpus st riat um comprises t he caudat e and put amen nuclei. Paleostriatum (G reek pal ai os, a ncient ; Latin stri atus, s triped ) . The phylogenet ically older part of t he corpus st riat um comprises t he globus pallidus. Pallidum (Latin pal l i dus, p ale ) . The paler part of t he basal ganglia comprises t he globus pallidus. Putamen (Latin, s hell ). Lat eral part of t he lent if orm nucleus. Striatum (Latin stri atus, s triped ) . The caudat e and put amen, so named because of t heir st riped appearance in sect ions. Substantia nigra (Latin, b lack substance ). G roup of neurons bet w een t he cerebral peduncle and midbrain t egment um. So named because of t heir melanin-cont aining neurons. Vicq d'Azir, Felix (1748 1 794). French physician t o queen Marie Ant oinet t e. Among his many cont ribut ions are his descript ions of t he insula (bef ore Reil), t he subst ant ia nigra, and t he mamillot halamic t ract (t ract of Vicq d' Azir).
SUGGESTED READINGS Af if i AK: Basal ganglia: Funct ional anat omy and physiology. Part I . J Chi l d Neurol 1994; 9: 249 2 60. Af if i AK: Basal ganglia: Funct ional anat omy and physiology. Part I I . J Chi l d Neurol 1994; 9: 352 3 61. Af if i AK, Uc EY: Cort ical s ubcort ical circuit ry f or movement , cognit ion and behavior. I n CE Coff ey, RA Brumback (eds): Textbook of Pedi atri c Neuropsychi atry. Washingt on, American Psychiat ric Press, 1998: 65 1 00. Albin RL et al: The f unct ional anat omy of basal ganglia disorders. Trends Neurosci 1989; 12: 366 3 75. Alexander G E et al: Basal ganglia t halamocort ical circuit s: Parallel subst rat es f or mot or, oculomot or, p ref ront al and l imbic f unct ions. Prog Brai n Res 1990; 85: 119 1 46. But t ers N et al: Specif icit y of t he memory def icit s associat ed w it h basal ganglia dysf unct ion. Rev Neurol 1994; 150: 580 5 87. Carpent er MB et al: Connect ions of t he subt halamic nucleus in t he monkey. Brai n Res 1981; 224: 1 2 9. Cosset t e M, Levesque M, Parent A: Ext rast riat al dopaminergic innervat ion of human basal ganglia. Neurosci Res 1999; 34(Suppl): 51 5 4. Flahert y AW, G raybiel AM: Anat omy of basal ganglia. I n Marsden CD, Fahn S (eds): Movement Di sorders. Bost on, But t erw ort h-Heinemann, 1994: 3 2 7. G oldman-Rakic PS: Cyt oarchit ect onic het erogeneit y of t he primat e neost riat um: Subdivision int o island and mat rix cellular compart ment s. J Comp Neurol 1982; 205: 398 4 13. G raybiel AM: Neurot ransmit t ers and neuromodulat ors in t he basal ganglia. Trends Neurosci 1990; 13: 244 2 54. G raybiel AM: The basal ganglia. Curr Bi ol 2000; 10: R509 5 11. Haber S, McFarland NR: The place of t he t halamus in f ront al cort ical b asal
ganglia circuit s. Neurosci enti st 2001; 7: 315 3 24. Houk JC, Wise SP: Dist ribut ed modular archit ect ures linking basal ganglia, cerebellum, and cerebral cort ex: Their role in planning and cont rolling act ion. Cerebral Cortex 1995; 2: 95 110. Joel D, Weiner I : The organizat ion of t he basal ganglia t halamocort ical circuit s: O pen int erconnect ed rat her t han closed segregat ed. Neurosci ence 1994; 63: 363 3 79. Kampe KK et al: Rew ard value of at t ract iveness and gaze. Nature 2001; 413: 589. Lynd-Balt a E, Haber SN: The organizat ion of midbrain project ions t o t he st riat um in t he primat e: Sensorimot or-relat ed st riat um versus vent ral st riat um. Neurosci ence 1994; 59: 625 6 40. Marsden CD: Movement disorders and t he basal ganglia. Trends Neurosci 1986; 9: 512 5 15. McG eer EG et al: Neurot ransmit t ers in t he basal ganglia. Can J Neurol Sci 1984; 11: 89 9 9. Naut a HJW, Cole M: Eff erent project ions of t he subt halamic nucleus: An aut oradiographic st udy in monkey and cat . J Comp Neurol 1978; 180: 1 1 6. O 'Connor WT: Funct ional neuroanat omy of basal ganglia as st udied by dualprobe microdialysis. Nucl Med Bi ol 1998; 25: 743 7 46. Parent A: Ext rinsic connect ions of t he basal ganglia. Trends Neurosci 1990; 13: 254 2 58. Penney JB, Young AB: G ABA as t he pallidot halamic neurot ransmit t er: I mplicat ions f or basal ganglia f unct ion. Brai n Res 1981; 207: 195 1 99. Prensa L et al: Dopaminergic innervat ion of human basal ganglia. J Chem Neuroanat 2000; 20: 207 2 13. Rolls E: Neurophysiology and cognit ive f unct ions of t he st riat um. Rev Neurol 1994; 150: 648 6 60.
Sadikot AF et al: The cent er median and paraf ascicular t halamic nuclei project respect ively t o t he sensorimot or and associat ive-limbic st riat al t errit ories in t he squirrel monkey. Brai n Res 1990; 510: 161 1 65. Schneider JS et al: Def icit s in orof acial sensorimot or f unct ion in Parkinson's disease. Ann Neurol 1986; 19: 275 2 82. Segaw a M: Development of t he nigrost riat al dopamine neuron and t he pat hw ays in t he basal ganglia. Brai n Dev 2000; 22(Suppl): S1 S 4. Selemon LD, G oldman-Rakic PS: Common cort ical and subcort ical t arget s of t he dorsolat eral pref ront al and post erior pariet al cort ices in t he rhesus monkey: Evidence f or a dist ribut ed neural net w ork subserving spat ially guided behavior. J Neurosci 1988; 8: 4049 4 068. Selemon LD, G oldman-Rakic PS: Longit udinal t opography and int erdigit at ions of cort icost riat al project ions in t he rhesus monkey. J Neurosci 1985; 5: 776 7 94. Smit h AD, Bolam JP: The neural net w ork of t he basal ganglia as revealed by t he st udy of synapt ic connect ions of ident if ied neurones. Trends Neurosci 1990; 13: 259 2 65. St aines WA et al: Neurot ransmit t ers cont ained in t he eff erent s of t he st riat um. Brai n Res 1980; 194: 391 4 02. St eckler T et al: The pedunculopont ine t egment al nucleus: A role in cognit ive processes? Brai n Res Rev 1994; 19: 298 3 18. St oet t er B et al: Funct ional neuroanat omy of Touret t e syndrome: Limbic-mot or int eract ions st udied w it h FDG PET. Adv Neurol 1992; 58: 213 2 26. Yelnik J: Funct ional anat omy of t he basal ganglia. Movement Di s 2002; 17 Suppl 3: S15 S 21.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 14 - B as al Ganglia: C linic al C or r elates
14 Basal Ganglia: Clinical Correlates
Hyperkinetic Disorders Chorea Athetosis Ballism Dystonia Tic Disorder Tourette Syndrome Hypokinetic Disorders @CC2:Parkinsonism KEY CONCEPTS Movement disorders associated with basal ganglia lesions are of two categories: hyper- and hypokinetic or akinetic. There are two varieties of chorea: benign reversible Sydenham's chorea and malignant progressive Huntington's chorea. Athetosis frequently accompanies chorea (choreoathetosis) and involves predominantly distal parts of extremities. Ballism, a violent flinging movement of extremities contralateral to a lesion in the subthalamic nucleus.
Dystonia may be focal (writer's cramp), regional (torticollis), or generalized. Tourette syndrome is a conglomerate of signs and symptoms that includes motor and vocal tics and behavioral abnormalities (attention, compulsiveness, etc.). Parkinson's disease is characterized by tremor, rigidity, and akinesia or hypokinesia. Depletion of dopaminergic neurons in the substantia nigra and, secondarily, dopamine stores in the striatum are the pathologic landmarks of Parkinson's disease.
Diseases of t he basal ganglia are associat ed w it h abnormal involunt ary movement s t hat t ypically occur at rest and disappear in sleep. They are generally divided int o t w o cat egories: hyperki neti c, charact erized by excessive involunt ary movement and hypoki neti c, charact erized by slow movement (bradykinesia) or absence or diff icult y in init iat ing movement (akinesia). The hyperkinet ic variet y is seen in such disorders as chorea, at het osis, ballism, dyst onia, t remor, and t ics. The hypokinet ic variet y is seen largely in Parkinson's disease. Despit e voluminous lit erat ure on basal ganglia, clinicoanat omic correlat ions are not available f or all basal ganglia disorders. How ever, t he f ollow ing anat omic loci f or pat hology are agreed on: subst ant ia nigra in Parkinson's disease, caudat e nucleus in chorea, and subt halamic nucleus in ballism. Discret e lesions in t he caudat e nucleus are more likely t o cause behavioral and cognit ive manif est at ions, w hereas similar lesions in t he put amen are more likely t o be associat ed w it h mot or manif est at ions. These observat ions are consist ent w it h know n anat omic connect ions of t hese nuclei. Abulia (a syndrome of apat hy and loss of init iat ive, spont aneous t hought , and emot ional response) has been described in associat ion w it h discret e lesions in t he caudat e nucleus. The genet ic basis of many movement disorders is being increasingly recognized. Familiarit y w it h such disorders is import ant in making accurat e diagnoses and in f amily counseling.
HYPERKINETIC DISORDERS
Chorea Chorea is a disorder of movement charact erized by sudden, f requent , involunt ary, purposeless, and quick jerks of t he t runk, ext remit ies, and head associat ed w it h f acial grimaces. The t erm chorea is derived f rom t he G reek w ord chorei a, f or d ance. The lesion producing chorea is believed t o be in t he caudat e nucleus (Figure 14-1), alt hough t he pat hology is of t en diff use and mult iple involving ot her neural st ruct ures. At t he cellular level, reduced levels of t he f ollow ing neurot ransmit t ers and neuropept ides have been report ed: gamma-aminobut yric acid (G ABA), acet ylcholine, enkephalin, subst ance P, dynorphin, and cholecyst okinin. Loss of noradrenergic neurons in t he locus ceruleus also has been report ed. Tw o variet ies of chorea are know n t o occur.
Fi gure 14-1. Coronal brain sect ion f rom a pat ient w it h Hunt ingt on's chorea show ing at rophy of t he caudat e nucleus.
These are a benign, reversible variet y (Sydenham's chorea) occurring in children as a complicat ion of rheumat ic f ever and a malignant variet y (Hunt ingt on's chorea) t hat is a heredit ary (aut osomal dominant ) disorder linked t o a single gene def ect on chromosome 4 and associat ed w it h progressive ment al and cognit ive det eriorat ion. Appendicular musculat ure is predominant ly involved in t he Sydenham's variet y, w hereas t runcal musculat ure is predominant ly involved in t he Hunt ingt on's variet y. Choreic pat ient s are of t en unable t o sust ain a t ight hand grip (milkmaid's grip) and cannot maint ain a prot ruded t ongue, w hich t ends t o dart in and out irregularly (t rombone t ongue). Figure 14-2 is a diagram show ing how t he st riat al lesion in Hunt ingt on's chorea result s in random expression of unw ant ed
movement . A variet y of chorea associat ed w it h pregnancy (chorea gravidarum) usually occurs during t he second t rimest er of pregnancy in pat ient s w it h a previous hist ory of Sydenham's chorea.
Athetosis At het osis is a disorder of movement charact erized by slow, w rit hing, cont inuous, w ormlike movement s of t he dist al part s of t he ext remit ies, chief ly t he f ingers, w hich show bizarre post uring. The t erm athetosi s is derived f rom t he G reek w ord athetos, meaning w it hout posit ion. The lesion producing at het osis is probably in t he put amen. Diff erent iat ion of at het osis f rom chorea may at t imes be diff icult because it is common t o see pat ient s w it h mixed choreoat het osis.
Ballism Ballism is a disorder of movement usually caused by a vascular lesion in t he subt halamic nucleus. The t erm bal l i sm is derived f rom t he G reek w ord bal l i smos, meaning j ump or t hrow. The movement s of t he limbs in t his disorder are sudden, quick, cont inuous, unusually violent , and f linging in nat ure. The hyperkinesia is usually conf ined t o one side of t he body (hemiballismus) cont ralat eral t o t he lesion in t he subt halamic nucleus.
Fi gure 14-2. Schemat ic diagram show ing how t he st riat al lesion in Hunt ingt on's chorea aff ect s t he indirect st riat opallidal pat hw ay and result s in random expression of movement . (1) Loss of mat rix neurons project ing t o ext ernal segment of globus pallidus (G Pe). (2) Disinhibit ion of G Pe. (3) Excess inhibit ion of subt halamic nucleus (STh). (4) Decreased excit at ion of int ernal segment of globus pallidus (G Pi) and subst ant ia nigra pars ret iculat a
(SNr). (5) Less inhibit ion of t halamus. (6) Random expression of unw ant ed movement . (Modif ied f rom Adel K. Af if i: Basal ganglia: Funct ional anat omy and physiology. Part I I . J Child Neurol 9: 352 3 61, 1994, f igure 12, w it h permission f rom Decker Periodicals. )
Dystonia Dyst onia is charact erized by a t w ist ing, slow, cont ort ing, involunt ary movement t hat is somew hat sust ained and of t en repet it ive. The t erm dystoni a is derived f rom t he G reek w ords dys and tonos, f or b ad t one. The aff ect ed body part may, w it h t ime, develop a f ixed abnormal post ure. Dyst onia may be f ocal (involving a single body part such as t he hand), segment al (involving t w o or more adjacent body part s such as t he neck and arm), or generalized. Writ er's cramp, an involunt ary cont ract ion of hand or f inger muscles w hile w rit ing, is an example of f ocal dyst onia. Tort icollis (involunt ary t urning or t ilt ing of head) combined w it h f acial dyst onia const it ut es segment al dyst onia. I diopat hic t orsion dyst onia, a heredit ary (aut osomal dominant ) disorder t hat begins in childhood, is an example of generalized dyst onia. No obvious specif ic pat hology has been def ined in t he basal ganglia in heredit ary idiopat hic dyst onia. How ever, discret e lesions in t he st riat um (Figure 14-3) caused by st roke, t umor, or t rauma have been associat ed w it h t he development of dyst onia.
Fi gure 14-3. Comput ed t omography scan of brain show ing a lesion in t he caudat e nucleus and put amen in a pat ient w it h dyst onia.
Tic Disorder Tics are brief , sudden, rapid, and int ermit t ent movement s (mot or t ics) or sounds (vocal t ics). Tics may be simple or complex. Simple t ics are caused by cont ract ions of only one group of muscles (e. g. , eye blinking) or a single meaningless sound (e. g. , a h ) . Complex t ics consist of coordinat ed sequenced movement of more t han one group of muscles (e. g. , eye blinking and shoulder shrug) or meaningf ul verbalizat ions. Tics may be t ransient (days t o w eeks) or chronic (mont hs t o years), and t hey may be a prelude t o Touret t e syndrome.
Tourette Syndrome Touret t e syndrome is charact erized by mot or and vocal t ics. Mot or t ics are sudden, brief involunt ary movement s involving muscles in diff erent body part s such as eye blinking and shoulder shrugging. Vocal t ics consist of gut t eral sounds, grunt s, or verbalizat ion of w ords and phrases. The mot or manif est at ions are of t en associat ed w it h behavioral abnormalit ies such as at t ent ion def icit s and compulsive rit ualist ic behaviors. Previously considered a psychiat ric or emot ional disorder, Touret t e syndrome is current ly believed t o have organic et iology. Morphomet ric magnet ic resonance imaging (MRI ) st udies in Touret t e syndrome reveal volume reduct ion in t he caudat e nucleus and t he lent icular nucleus. Post mort em st udies in Touret t e syndrome brains, alt hough limit ed in number, report a decrease in overall volume of t he st riat um coupled w it h an increase in t he number of small neurons and decreased dynorphin in st riat opallidal axons. Based on t he mot or manif est at ions of Touret t e syndrome (t ics), t he mot or circuit of t he basal ganglia or some subunit s of it have been proposed as t he primary sit e of pat hology. The associat ed behavioral manif est at ions lend credence t o involvement of t he limbic basal ganglia circuit . An inhibit ory limbic syst em drive act ing on t he mot or cort ex and mot or st riat um (Figure 14-4) has been proposed as inst rument al in t he genesis of t ics. Touret t e syndrome is named af t er G illes de la Touret t e, a French physician w ho described t he syndrome in 1885. The f irst aff lict ed suff erer w as report edly t he French prince of Condé, w ho had t o st uff clot hes int o his mout h t o st op himself f rom barking (vocal t ics) at King Louis XI V.
Fi gure 14-4. Schemat ic diagram depict ing t he roles of t he limbic syst em drive, cerebral cort ex, and subcort ical mot or cent ers in t he genesis of t ics. I n early st ages of t ics A, t he cerebral cort ex plays t he major role in t ic generat ion (t hick arrow ), w hile subcort ical mot or cent ers play a minor role (t hin arrow ). I n lat e st ages of t ics B, bot h t he cort ex and subcort ical cent ers are equally capable of generat ing t ics. (From A. E. Lang, et al: S igning t ics : I nsight s int o t he pat hophysiology of sympt oms in Touret t e's syndrome. Ann Neurol 33: 212 2 15, 1993, f igures A and B, w it h permission. )
Fi gure 14-5. Schemat ic diagram show ing how dopamine deplet ion in Parkinson's disease aff ect s t he direct and indirect st riat opallidal pat hw ays and movement . A: Slow ness and povert y of movement . (1) Loss of excit at ory dopamine (DA) input t o st riat al neurons project ing t o int ernal segment of globus pallidus (G Pi) and subst ant ia nigra pars ret iculat a (SNr). (2) Decreased inhibit ion of G Pi and SNr neurons. (3) Decreased disinhibit ion of t halamic neurons. (4) Slow ness and povert y of movement . B: I nhibit ion of unw ant ed movement ; diff icult y sw it ching t o new behavior. (1) Loss of
inhibit ory DA input t o st riat al neurons project ing t o ext ernal segment of globus pallidus (G Pe). (2) I ncreased inhibit ion of G Pe neurons. (3) Disinhibit ion of subt ha-lamic nucleus (STh) input t o G Pi and SNr. (4) Reinf orcing inhibit ion of unw ant ed movement . (Modif ied f rom Adel K. Af if i: Basal ganglia: Funct ional anat omy and physiology. Part I I . J Child Neurol 9: 352 3 61, 1994, f igure 11, w it h permission f rom Decker Periodicals. )
HYPOKINETIC DISORDERS Parkinsonism Parkinson's disease is charact erized by t remor, rigidit y, and hypokinesia or akinesia. The t remor of Parkinson's disease is rhyt hmic f ine t remor recurring at t he rat e of 3 t o 6 cycles per second and is best seen w hen t he ext remit y is in a f ixed post ure rat her t han in mot ion (in cont radist inct ion t o cerebellar t remor, w hich is seen during movement of an ext remit y). The rigidit y is charact erized by resist ance t o passive movement of a joint t hroughout t he range of mot ion (cogw heel rigidit y), result ing f rom an increase in t one of muscles w it h opposing act ion (agonist s and ant agonist s). Hypokinesia or akinesia is manif est ed by a diminut ion or loss of associat ed movement s (e. g, sw inging of upper ext remit ies w hen w alking), diff icult y in init iat ing movement , and slow movement . The hypokinesia of t en causes diff icult ies f or pat ient s in get t ing dressed, f eeding, and maint aining personal hygiene. The coexist ence of rigidit y and hypokinesia in f acial muscles account s f or decreased blinking rat e and t he expressionless mask f acies. The lesion producing Parkinson's disease is w idespread in t he cent ral nervous syst em but aff ect s t he dopaminergic neurons in t he subst ant ia nigra pars compact a most consist ent ly. The lesion t hus aff ect s t he dopaminergic nigrost riat al f iber syst em and deplet es t he st riat al dopamine st ores. The disease t hus can be ameliorat ed by administ rat ion of L-dopa. Figure 14-5 is a diagram show ing how dopamine deplet ion cont ribut es t o t he povert y of movement and t he diff icult y in sw it ching t o new behaviors. I n addit ion t o t he deplet ion of dopamine, reduct ion in concent rat ion of t he f ollow ing neuropept ides occurs: enkephalin, somat ost at in, neurot ensin, subst ance P, and bombesin. Decrease in angiot ensin I I binding sit es and loss of adrenergic neurons in t he locus ceruleus also have been report ed. Prior t o t he discovery of t he signif icance of L-dopa in parkinsonism, t he t remor and rigidit y of parkinsonism w ere t reat ed by surgical lesions in t he globus pallidus or t halamus. The f ormer w as more eff ect ive in t he relief of rigidit y and
t he lat t er in t he relief of t remor. Surgical approaches t o t reat ment became less popular f ollow ing t he int roduct ion of L-dopa t herapy. Based on recent physiologic and anat omic dat a, it is now recognized t hat hyperact ivit y of t he subt halamic nucleus is an import ant f eat ure of Parkinson's disease. Hyperact ivit y of t he subt halamic nucleus increases t he excit at ory drive ont o t he int ernal segment of globus pallidus and subst ant ia nigra pars ret iculat a, w hich, in t urn, overinhibit s t he mot or project ions t o t he t halamus. Thus, t he subt halamic nucleus and int ernal segment of globus pallidus have become t he pref erred surgical t arget s t o t reat select ed drug-ref ract ory pat ient s. Lesions in t hese sit es (pallidot omy and subt halamic nucleot omy) or f unct ional blockade (by deep brain st imulat ion) have been increasingly used.
TERM INOLOGY Abulia (G reek, w ithout will ). A st at e in w hich t he pat ient manif est s lack of init iat ive and spont aneit y w it h preserved consciousness. Akinesia (G reek a, n egative, without ki nesi s, m ovement ) . Lack of spont aneous movement as seen in Parkinson's disease. Athetosis (G reek athetos, w ithout position or place ). I nvolunt ary movement disorder charact erized by irregular, slow, w rit hing movement s of dist al part s of ext remit ies. The condit ion w as described by William Hammond in 1871. Ballism (G reek bal l i smos, j umping, throwing ) . Violent f linging movement s usually of one side of t he body due t o a lesion in t he cont ralat eral subt halamic nucleus. Bradykinesia (G reek brady, sl ow ; ki nesi s, m ovement ) . Abnormal slow ness of movement as seen in Parkinson's disease. Chorea (Latin choros, a dance ). I rregular involunt ary movement s of t he limbs or f ace secondary t o st riat al lesion. The names of f our saint s (Vit us, Valent ine, Modest i, and John) have been associat ed w it h chorea over t he ages. The most used is St. Vi tus's dance. Cogwheel rigidity. The arrhyt hmic, repet it ive alt erat ion of resist ance t o passive st ret ch occurring during passive movement of a joint ; palpable t remor. A sign of basal ganglia disorder. Dystonia. Sust ained and pat t erned muscle cont ract ions of agonist s and ant agonist muscles leading t o t w ist ing involunt ary movement s. The clinical condit ion w as f irst described by G erman physician Marcus Walt er Schw albe in 1908.
Huntington's chorea. Progressive neurodegenerat ive disorder inherit ed as an aut osomal dominant t rait . The disease w as import ed t o America f rom Suff olk in t he Unit ed Kingdom by t he emigrant w if e of an Englishman in 1630. Her f at her w as choreic, and his f at her disapproved of t he mat ch because of t he bride's f at her's illness. The disorder is named af t er G eorge Sumner Hunt ingt on, a general pract it ioner w ho described t he disease. Hypokinesia. Povert y of w illed movement . Milkmaid's grip. Variabilit y in t he isomet ric f orce exert ed by t he w rist and by individual f ingers during at t empt s t o grasp an object . The sign is present in chorea. Parkinsonism. A chronic progressive degenerat ive disease charact erized by t remor, rigidit y, and akinesia. I t w as described init ially by English physician James Parkinson under t he rubric s haking palsy published in 1817. Earlier descript ions w ere made by G alen, Boet ius, and ot hers. Sydenham's chorea. An acut e, benign, and self -limit ed chorea, a manif est at ion of rheumat ic f ever. Named af t er Thomas Sydenham, t he English physician w ho f irst described t he disorder in 1686. T ics. Sudden, brief , repet it ive involunt ary movement s t hat may be suppressed f or a period by eff ort or w ill. Torticollis (Latin tortere, t o twist col l i s, n eck ) . A f ocal dyst onia causing int ermit t ent or persist ent rot at ion of t he neck. Tourette syndrome. A dominant ly inherit ed syndrome charact erized by mot or and vocal t ics and a variet y of behavioral sympt oms and signs t hat include at t ent ion def icit s and obsessive-compulsive behaviors. The syndrome is named af t er G eorge-EdmondAlbert -Brut us G illes de la Touret t e, t he French neuropsychiat rist w ho described t he condit ion in 1885. The f irst recorded suff erer w as t he French prince of Condé, w ho st uff ed clot hes int o his mout h t o st op himself f rom barking at King Louis XI V. Trombone tongue. Repet it ive prot rusion and replacement of t he t ongue seen charact erist ically in Hunt ingt on's disease. Writer's cramp. A f ocal (hand) occupat ional dyst onia precipit at ed by w rit ing or t yping. When f irst
described by Bell in 1830, it w as considered a psychiat ric disorder.
SUGGESTED READINGS Bhat ia KP, Marsden CD: The behavioral and mot or consequences of f ocal lesions of t he basal ganglia in man. Brai n 1994; 117: 859 8 76. Ceballos-Baumann AO et al: Rest orat ion of t halamocort ical act ivit y af t er post erovent ral pallidot omy in Parkinson's disease. Lancet 1994; 344: 814. Dogali M et al: St ereot act ic vent ral pallidot omy f or Parkinson's disease. Neurol ogy 1995; 45: 753 7 61. Koller WC: Chorea, hemichorea, hemiballismus, choreoat het osis and relat ed disorders of movement . Curr O pi n Neurol Neurosurg 1991; 4: 350 3 53. Lavoie B et al: I mmunohist ochemical st udy of t he basal ganglia in normal and parkinsonian monkeys. Adv Neurol 1992; 58: 115 1 21. Lozano AM et al: Eff ect of G Pi pallidot omy on mot or f unct ion in Parkinson's disease. Lancet 1995; 346: 1387 1 388. Munro-Davis LE et al: The role of t he pedunculopont ine region in basalganglia mechanism of akinesia. Exp Brai n Res 1999; 129: 511 5 17. O beso JA et al: Pat hophysiologic basis of surgery f or Parkinson's disease. Neurol ogy 2000; 55(Suppl 6): S7 S 12. Pet erson B et al: Reduced basal ganglia volumes in Touret t e's syndrome using t hree-dimensional reconst ruct ion t echniques f rom magnet ic resonance images. Neurol ogy 1993; 43: 941 9 49. Rice JE, Thompson PD: Movement disorders I I : The hyperkinet ic disorders. Med J Aust 2001; 174: 413 4 19. Sw edo SE et al: Sydenham's chorea: Physical and psychological sympt oms of St . Vit us dance. Pedi atri cs 1993; 91: 706 7 13. Wilson SAK: Progressive lent icular degenerat ion: A f amilial nervous disease associat ed w it h cirrhosis of t he liver. Brai n 1912; 34: 295 5 09.
Yoshida M: The neural mechanism underlying Parkinsonism and dyskinesia: Diff erent ial roles of t he put amen and caudat e nucleus. Neurosci Res 1991; 12: 31 4 0. Young AB, Penney JB: Neurochemical anat omy of movement disorders. Neurol Cl i n 1984; 2: 417 4 33.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 15 - C er ebellum
15 Cerebellum
Gross Features Lobes and Subdivisions Somatotopic Representation Microscopic Structure Cerebellar Cortex Principal (Purkinje) Neuron Intrinsic Neurons Cerebellar Glomerulus Cerebellar Input Inferior Cerebellar Peduncle Middle Cerebellar Peduncle Superior Cerebellar Peduncle Internal Cerebellar Circuitry Mossy Fiber Input Climbing Fiber Input Cerebellar Output Deep Cerebellar Nuclei Dentate Nucleus Interposed Nuclei Fastigial Nucleus Cerebrocerebellar and Cerebellocerebral Circuitries Neurotransm itters
Cerebellar Physiology Cerebellar Cortex Deep Cerebellar Nuclei Cerebellar Function Historical Perspective Motor Functions of the Cerebellum Neocerebellar Signs Archicerebellar and Paleocerebellar Signs Ocular Motor Signs Cerebellum and Epilepsy Complementarity of Basal Ganglia and Cerebellum in Motor Function Nonmotor Functions of the Cerebellum The Cerebellum and Autism Sensory System s and Cerebellum Arterial Supply Venous Drainage KEY CONCEPTS The cerebellum is divided into three imperfectly delineated lobes or zones based on morphology, connectivity, function, or phylogeny. The cerebellar cortex has three layers and contains five cell types (one principal and four intrinsic). The major inputs to the cerebellum are from three sources: spinal cord, vestibular system, and cerebral cortex. Within the cerebellum, various inputs are segregated into one of three fiber systems. Cerebellar inputs excite Purkinje cells directly via climbing fibers and indirectly via granule cell axons.
Intrinsic cerebellar neurons are excited by cerebellar inputs and in turn inhibit Purkinje cells. Deep cerebellar nuclei provide cerebellar output to extracerebellar targets. Extracerebellar targets include the vestibular and reticular nuclei, red nucleus, and thalamus. Signs of cerebellar disorders include asynergia (dyssynergia), dysarthria, adiadochokinesis, dysmetria, tremor, muscular hypotonia, ataxia, and nystagmus. Nonmotor roles for the cerebellum in autonomic regulation, behavior, cognition, and learning are being increasingly documented. Blood supply of the cerebellum is provided by three arteries from the vertebral b asilar arterial system. They are the posterior inferior cerebellar, anterior inferior cerebellar, and superior cerebellar.
GROSS FEATURES The cerebellum, or s mall brain, develops f rom t he embryologic rhombic lip, a zone of cells bet w een t he alar and roof plat es at t he level of t he pont ine f lexure. Alt hough it develops f rom a s ensory region (t he rhombic lip), t he cerebellum is concerned primarily (but not exclusively) w it h mot or f unct ion. The cerebellum is locat ed in t he post erior f ossa of t he skull, separat ed f rom t he occipit al lobes by a dural f old, t he t ent orium cerebelli. I t overlies t he dorsal surf aces of t he pons and medulla oblongat a and cont ribut es t o t he f ormat ion of t he roof of t he f ourt h vent ricle. The cerebellum consist s of a midline vermis and t w o lat erally placed hemispheres. The part s of t he hemispheres adjacent t o t he vermis are know n as t he paravermal or int ermediat e zones (Figure 15-1). The dorsal cerebellar surf ace is rat her f lat ; t he demarcat ion of vermis and hemispheres is not evident on t his surf ace (Figure 15-2). The vent ral surf ace is convex w it h a deep groove (vallecula) in t he midline t hrough w hich t he vermis is
apparent (Figure 15-3). The adult human cerebellum w eighs approximat ely 150 g (10 percent of brain w eight ) and has a surf ace area of approximat ely 1000 cm2 (40 percent of t he cerebral cort ex). The cerebellum is connect ed t o t he midbrain, pons, and medulla oblongat a by t hree pairs of peduncles (Figure 15-4). 1. The superior cerebellar peduncle (brachium conjunct ivum) connect s t he cerebellum w it h t he midbrain. 2. The middle cerebellar peduncle (brachium pont is) connect s t he pons w it h t he cerebellum. 3. The inf erior cerebellar peduncle (rest if orm and juxt arest if orm bodies) connect s t he medulla w it h t he cerebellum. The cont ent s of each of t hese peduncles are discussed in t he chapt ers on t he mesencephalon (Chapt er 9), pons (Chapt er 7), and medulla oblongat a (Chapt er 5). The cerebellum consist s of a highly convolut ed layer of gray mat t er, t he cerebellar cort ex, surrounding a core of w hit e mat t er t hat cont ains t he aff erent and eff erent t ract s. The branching pat t ern of t he w hit e mat t er w as ref erred t o by early anat omist s as t he arbor vit ae (t ree of lif e) (Figure 15-4). Hence t he cort ical convolut ions in t he cerebellum are ref erred t o as f olia (leaves) inst ead of gyri (t erm used t o describe cort ical convolut ions in t he cerebral cort ex). Embedded in t he w hit e mat t er core are f our pairs of deep cerebellar nuclei arranged f rom lat eral t o medial (Figure 15-5).
Fi gure 15-1. Schemat ic diagram of vent ral surf ace of t he cerebellum show ing it s subdivision int o vermis, paravermis, and hemisphere.
1. Dent at e nucleus 2. Embolif orm nucleus 3. G lobose nucleus 4. Fast igial nucleus The globose and embolif orm nuclei are ref erred t o collect ively as t he int erposed nucleus. A commonly used mnemonic t o recall t he deep cerebellar nuclei is D on't Eat G reasy Food.
Lobes and Subdivisions (Table 15-1) The cerebellum is divided anat omically by t w o t ransverse f issures (ant erior and post erolat eral or prenodular) int o t hree lobes: ant erior, post erior, and f locculonodular. The demarcat ion of t he t hree lobes is best seen in midsagit t al sect ions (Figure 15-6). The post erior lobe cont ains, on it s inf erior surf ace, t he cerebellar t onsils (Figure 15-3). I n cases of increased int racranial pressure such as occurs in brain t umors, int racranial hemorrhage, or severe head t rauma, t he cerebellar t onsils may herniat e t hrough t he f oramen magnum. This t onsillar herniat ion is a lif e-t hreat ening neurologic emergency due t o compromise of vit al cent ers in t he brain st em.
Fi gure 15-2. Phot ograph of dorsal surf ace of t he cerebellum. (From
G luhbegovic and Williams: The Human Brain, A Phot ographic G uide. Harper and Row Publishers, 1980, court esy of t he aut hors. )
Fi gure 15-3. Phot ograph of vent ral surf ace of t he cerebellum. (From G luhbegovic and Williams: The Human Brain, A Phot ographic G uide. Harper and Row Publishers, 1980, court esy of t he aut hors. )
The cerebellum is also subdivided int o t hree longit udinal zones, based on t he arrangement of project ions f rom t he cerebellar cort ex t o deep cerebellar nuclei (Figure 15-1). These are t he midline (vermis) zone, t he int ermediat e (paravermal) zone, and t he lat eral (hemisphere) zone. The cort ex of t he vermis project s t o t he f ast igial deep cerebellar nucleus, t hat of t he paravermis t o t he int erposed deep nuclei (embolif orm and globose), and t hat of t he cerebellar hemisphere t o t he dent at e nucleus. The borders t hat separat e each of t he t ransverse and longit udinal lobes and zones are f ar f rom precise. Clear f unct ional subdivisions are t hus scarcely possible w it h ref erence t o eit her t he t ransversely orient ed lobes or t he longit udinally orient ed zones.
Fi gure 15-4. Sect ion t hrough t he cerebral hemisphere and cerebellum show ing t he t hree cerebellar peduncles (superior, middle, inf erior). Show n also are t he arbor vit ae and f olia of t he cerebellum.
Fi gure 15-5. Schemat ic diagram of unf olded cerebellum show ing t he f our cerebellar nuclei.
Based on f iber connect ivit y, how ever, t hree f unct ional subdivisions of t he cerebellum have been delineat ed:
1. The vest ibulocerebellum (corresponds best w it h t he f locculonodular lobe) has reciprocal connect ions w it h vest ibular and ret icular nuclei and plays a role in cont rol of body equilibrium and eye movement . 2. The spinocerebellum (corresponds best t o t he ant erior lobe) has reciprocal connect ions w it h t he spinal cord and plays a role in cont rol of muscle t one as w ell as axial and limb movement s, such as t hose used in w alking and sw imming. 3. The cerebrocerebellum or pont ocerebellum (corresponds best t o t he post erior lobe) has reciprocal connect ions w it h t he cerebral cort ex and plays a role in planning and init iat ion of movement s, as w ell as t he regulat ion of discret e limb movement s. Phylogenet ically, t he cerebellum is divided int o t hree zones: The archicerebellum, t he oldest zone, corresponds t o t he f locculonodular lobe. The paleocerebellum, of more recent phylogenet ic development t han t he archicerebellum, corresponds t o t he ant erior lobe and a small part of t he post erior lobe. The neocerebellum, t he most recent phylogenet ically, corresponds t o t he post erior lobe.
Somatotopic Representation (Figure 15-7) Somat ot opic represent at ion of body part s in t he cerebellum w as f irst described in 1943 by Adrian and lat er conf irmed by ot hers. I n t he ant erior lobe, t he body appears invert ed, w it h hindlimbs represent ed rost ral t o t he f orelimbs and f ace. I n t he post erior lobe, t he body appears noninvert ed and dually represent ed on each side of t he midline, w it h f ace ant eriorly and legs post eriorly represent ed. I n general, t he t runk is represent ed in t he midline, and t he ext remit ies are represent ed more lat erally in t he hemispheres. Thus, in disorders predominant ly aff ect ing t he midline cerebellum, dist urbances of movement w ill be manif est primarily in t runk musculat ure and w ould aff ect body equilibrium. I n cont rast , in disorders primarily aff ect ing t he cerebellar hemispheres, dist urbances of movement w ill manif est primarily in ext remit y movement .
M ICROSCOPIC STRUCTURE Cerebellar Cortex The cerebellar cort ex is made up of t he f ollow ing t hree layers. 1. O ut er molecular layer (about 300 ľm in t hickness) 2. Middle Purkinje cell layer (about 100 ľm in t hickness) 3. I nnermost granule cell layer (about 200 ľm in t hickness) Five cell t ypes (Table 15-2) are dist ribut ed in t he diff erent cort ical layers.
Basket and st ellat e cells are in t he molecular layer, Purkinje cells are in t he Purkinje cell layer, and granule and G olgi cells are in t he granule cell layer. O f t hese f ive cell t ypes, t he Purkinje cell const it ut es t he principal neuron of t he cerebellum, since it is t he only cerebellar neuron t hat sends it s axons out side t he cerebellum (project ion neuron). All t he ot her cells are int rinsic neurons and est ablish connect ions w it hin t he cerebellum. Tabl e 15-1. Cerebellar Lobes and Subdivisions
A
Anatomic subdivisions Transverse plane Longitudinal plane
Anterior lobe Vermis
Posterior lobe Paravermis
B
Functional subdivisions
Spinocerebellum
Cerebrocerebellum
C
Phylogenetic subdivisions
Paleocerebellum
Neocerebellum
Fi gure 15-6. Schemat ic diagram of midsagit t al view of t he cerebellum and brain st em show ing t he t hree anat omic lobes of t he cerebellum.
Principal (Purkinje) Neuron (Table 15-2) Described in 1837 by t he Bohemian priest and physiologist Johannes Purkinje, cell bodies of Purkinje cells are arranged in a single row at t he border zone bet w een t he molecular and granule cell layers. The cell is f lask-shaped w hen view ed in t he t ransverse plane and is narrow and vert ical w hen view ed in longit udinal sect ions. The Purkinje cell measures approximat ely 30 t o 35 ľm in t ransverse diamet er. Adjacent Purkinje cells are separat ed by 50 ľm in t he t ransverse plane and by 50 t o 100 ľm in t he longit udinal plane. Each Purkinje cell has an elaborat e dendrit ic t ree t hat st ret ches t hroughout t he ext ent of t he molecular layer and is arranged at right angles t o t he long axis of t he f olium. The dendrit ic t ree is made up of a sequence of primary, secondary, and t ert iary branches, w it h t he smaller dendrit ic branches prof usely covered w it h dendrit ic spines or gemmules. I t is est imat ed t hat each Purkinje cell has over 150, 000 spines on it s dendrit ic t ree.
Fi gure 15-7. Schemat ic diagram of unf olded cerebellum show ing somat ot opic represent at ion of body part s in t he cerebellum. H, head; UE, upper ext remit y; LE, low er ext remit y; T, t runk.
Each Purkinje cell has a single axon t hat courses t hrough t he granule cell layer and deep w hit e mat t er t o project on deep cerebellar nuclei. Some Purkinje cell axons (f rom t he vermis) bypass t he deep cerebellar nuclei t o reach t he lat eral vest ibular nucleus. Recurrent collat eral axonal branches arise f rom Purkinje cell axons and project on adjacent Purkinje cells as w ell as on basket , st ellat e, and G olgi cells in neighboring or even dist ant f olia. I t is est imat ed t hat t here are about 15 million Purkinje cells in t he human cerebellum.
Intrinsic Neurons (Table 15-2) A. BASKET CELL Basket cells are sit uat ed in deeper part s of t he molecular layer in close proximit y t o Purkinje cells. Dendrit ic arborizat ions of basket cells are disposed in t he t ransverse plane of t he f olium in a manner similar t o but less elaborat e t han t he Purkinje cells. The axon courses in t he molecular layer in t he t ransverse plane of t he f olium just above t he cell bodies of Purkinje cells. Each axon gives rise t o several descending branches t hat surround Purkinje cell perikarya and init ial segment s of t heir axons in t he f orm of a basket , hence t heir name. Each basket cell axon covers t he t errit ory of about 10 Purkinje cells. Basket f ormat ion, how ever, skips t he Purkinje cell immediat ely adjacent t o t he basket cell and descends on t he second Purkinje cell and onw ard in t he row. I n addit ion, axonal branches ext end in t he longit udinal plane of t he f olium t o reach an
addit ional t hree t o six row s of Purkinje cells on bot h sides of t he main axons. As a result of t his, a single basket cell may reach as many as 200 Purkinje cells. More t han one basket cell may cont ribut e t o a single basket f ormat ion around one Purkinje cell. While t he descending branches of basket cell axons est ablish cont act w it h Purkinje cell perikarya and init ial segment s of t heir axons, ascending branches of basket cell axons ascend in t he molecular layer t o reach t he proximal dendrit es of Purkinje cells. I t is est imat ed t hat t here are about 7 million basket cells in t he human cerebellum. Tabl e 15-2. Cerebellar Cortex Neurons
Neuron
Type
Layer
Projection
Synaptic action
Inhibitory
Purkinje
Principal (projection)
Purkinje
Deep cerebellar nuclei Lateral vestibular nucleus Other Purkinje cells Intrinsic neurons
Basket
Interneuron
Molecular
Purkinje cell
Inhibitory
Stellate
Interneuron
Molecular
Purkinje cell
Inhibitory
Purkinje cell Basket
Granule
Interneuron
Granule
Golgi
Interneuron
Granule
cell Stellate cell Golgi cell Granule cell
Excitatory
Inhibitory
B. STELLATE CELL St ellat e cells are locat ed in t he superf icial and deeper part s of t he molecular layer. Axons of st ellat e cells are also disposed t ransversely in t he f olium and t erminat e on Purkinje cell dendrit es. I t is est imat ed t hat t here are 12 million st ellat e cells in t he human cerebellum. The basket and st ellat e cells can be considered as belonging t o t he same class. Bot h receive t he same input , and bot h act on Purkinje cells. The diff erence lies in t he f act t hat st ellat e cells est ablish cont act w it h t he dendrit es of Purkinje cells, w hereas basket cells est ablish cont act w it h dendrit es, perikarya, and axons of Purkinje cells.
C. GRANULE CELL G ranule cells are among t he smallest cells in t he brain (6 t o 9 ľm) and f ill t he granule cell layer. Each cell gives rise t o about t hree t o f ive dendrit es t hat est ablish synapt ic cont act s w it h axons in a synapt ic zone (t he glomerulus) w it hin t he granule cell layer. Axons of granule cells ascend in t he granule cell layer, Purkinje layer, and molecular layer, w here t hey bif urcat e in a T f ashion and run parallel t o t he surf ace t o f orm t he parallel f iber syst em. Parallel f ibers run horizont ally in t he molecular layer perpendicular t o t he plane of t he Purkinje dendrit es. Each parallel f iber branch is 1 t o 1. 5 mm in lengt h; t hus t he axon of a single granule cell spans an area of approximat ely 3 mm. The parallel f ibers est ablish cont act w it h dendrit es of Purkinje cells, G olgi cells, st ellat e cells, and basket cells. G enerally, a parallel f iber comes in cont act w it h a Purkinje cell only once or, rarely, t w ice. The individual parallel f ibers are t hus not a st rong drive t o t he Purkinje neuron. A single Purkinje cell, how ever, can receive up t o 100, 000 parallel f ibers. Alt hough a single parallel f iber is not a st rong drive t o t he Purkinje neuron, cont act by 100, 000 parallel f ibers can provide a pow erf ul drive t o t his neuron. The t ot al number of granule cells is est imat ed t o be on t he order of 2. 2 billion.
D. GOLGI TYPE II CELL G olgi neurons occupy t he superf icial part of t he granule cell layer adjacent t o t he Purkinje cells. They are large neurons, about t he same size as t he Purkinje cell bodies. Dendrit es of G olgi neurons arborize in eit her t he molecular or t he granule cell layer. Those w hich remain in t he granule cell layer cont ribut e t o t he glomeruli of t hat layer. Those w hich reach t he molecular layer arborize w idely and overlap t he t errit ories of t hree Purkinje cells in bot h t he t ransverse and longit udinal planes. The G olgi neuron dendrit ic arborizat ion is t hus t hree t imes t hat of t he Purkinje cell. Axons of G olgi cells t ake part in t he f ormat ion of t he glomer-ulus. They are charact erized by a dense arborizat ion of short axonal branches t hat span t he ent ire granule cell layer. The f ield of axonal arborizat ion approaches t hat of dendrit ic arborizat ion. The axonal arborizat ion of t he G olgi neurons is among t he most unique in t he brain. The G olgi neuron f orms t he cent ral point of a f unct ional hexagon t hat includes about 10 Purkinje cells. I t is est imat ed t hat t here are 4 million G olgi cells.
Cerebellar Glomerulus I n hist ologic sect ions of t he cerebellar cort ex t here are islands bet w een granule cells t hat st ain light er t han t he rest of t he granule cell layer. These are t he cerebellar glomeruli (Figure 15-8). They are t he sit es of synapt ic cont act bet w een t he incoming cerebellar f ibers (mossy f iber syst em) and processes of neurons w it hin t he granule cell layer. The element s t hat f orm a cerebellar glomerulus are 1. Cerebellar input via t he mossy f iber syst em (origins of t his syst em w ill be discussed lat er) 2. Dendrit es of granule cells 3. Axon t erminals of G olgi neurons 4. Proximal part s of G olgi dendrit es Elect ron micrographs have show n t hat t he mossy f iber axonal t erminal is t he cent ral element in t he glomerulus (t erminal roset t es), around w hich are clust ered dendrit es of granule cells and axons of G olgi neurons. Bot h mossy f iber axons and G olgi axons act on t he dendrit es of granule cells. I n addit ion, mossy f iber axons project on dendrit es of G olgi neurons. The w hole complex is surrounded by a glial envelope. I t is est imat ed t hat a glomerulus cont ains about 100 t o 300 dendrit ic t erminals f rom some 20 granule cells.
CEREBELLAR INPUT
Cont aining more t han half t he neurons in t he brain, t he cerebellum is one of t he busiest neuronal int ersect ions in t he brain, receiving input f rom and sending signals back t o every major part of t he cent ral nervous syst em. I nput t o t he cerebellum originat es f rom a variet y of sources. The t hree major sources of aff erent s, how ever, are t he spinal cord, vest ibular syst em, and cerebral cort ex.
Fi gure 15-8. Schemat ic diagram of a cerebellar glomerulus show ing t he diff erent sources of converging f ibers.
I nput s f rom t he spinal cord are t ransmit t ed t o t he cerebellum (Figure 15-9) via t he dorsal and vent ral spinocerebellar t ract s and t he rost ral ext ension of t he dorsal spinocerebellar t ract , t he cuneocerebellar t ract . These t ract s provide t he cerebellum w it h inf ormat ion relat ed t o t he posit ion and condit ion of muscles, t endons, and joint s. I nput s f rom t he vest ibular syst em (Figure 15-10) arise f rom t he primary vest ibular end organ in t he vest ibular labyrint h, as w ell as f rom vest ibular nuclei (inf erior and medial) in t he brain st em. Vest ibulocerebellar input s provide inf ormat ion relat ed t o body equilibrium.
Cort ical input s t o t he cerebellum originat e in neocort ical as w ell as paleocort ical and archicort ical areas. These include primary mot or and sensory cort ices as w ell as associat ion and limbic cort ices. I nput s f rom neocort ical areas (Figure 1511) reach t he cerebellum af t er relays in t he pont ine nuclei (t he vast majorit y) and inf erior olive. I nput s f rom paleocort ical and archicort ical areas est ablish relays in t he ret icular nuclei and hypot halamus prior t o reaching t he cerebellum. Cort icocerebellar input s provide inf ormat ion relat ed t o t he planning and init iat ion of movement . O t her f iber input s t o t he cerebellum include a noradrenergic project ion f rom t he locus ceruleus (A-6 cell group of primat es), a dopaminergic project ion f rom t he vent ral t egment al area of Tsai in t he midbrain (A-10 cell group of primat es), and a serot onergic project ion f rom t he raphe nuclei (B-5 and B-6 cell groups of primat es) in t he brain st em. The input f rom t he locus ceruleus project s on Purkinje cell dendrit es and exert s an inhibit ory eff ect on Purkinje cell act ivit y. I t has been post ulat ed t hat t he input f rom t he locus ceruleus plays a role in t he development of Purkinje cells. The t erminals f rom t he locus ceruleus develop prior t o Purkinje cell mat urat ion. Dest ruct ion of t he locus ceruleus result s in immat ure development of Purkinje cells. I n t he past f ew years, a series of invest igat ions has revealed t he exist ence of a complex net w ork of direct and indirect pat hw ays bet w een t he hypot halamus and t he cerebellum. The project ions are bilat eral w it h ipsilat eral preponderance. They originat e f rom various hypot halamic nuclei and areas but principally f rom t he lat eral, dorsal, and post erior hypot halamic areas and t he dorsomedial, vent romedial, supramamillary, lat eral mamillary, and t uberomamillary nuclei. The indirect pat hw ay reaches t he cerebellum af t er relays in a number of brain st em nuclei. Hypot halamocerebellar f ibers t erminat e in relat ion t o neurons in all layers of t he cerebellar cort ex. The hypot halamocerebellar net w ork may provide t he neuroanat omic subst rat e f or t he aut onomic responses elicit ed f rom cerebellar st imulat ion. Fiber input s t o t he cerebellum f rom t he preceding various sources arrive via t hree cerebellar peduncles: t he inf erior (rest if orm body), t he middle (brachium pont is), and t he superior (brachium conjunct ivum). Figure 15-12 is a composit e schemat ic diagram of input s t o t he cerebellum.
Inferior Cerebellar Peduncle The f iber syst ems reaching t he cerebellum via t his peduncle are t he f ollow ing: 1. Dorsal spinocerebellar t ract f rom t he dorsal nucleus of Clarke 2. Cuneocerebellar t ract f rom t he accessory cuneat e nuclei 3. O livocerebellar t ract f rom t he inf erior olivary nuclei (major component )
4. Ret iculocerebellar t ract f rom t he ret icular nuclei of t he brain st em 5. Vest ibulocerebellar t ract (bot h primary aff erent s f rom t he vest ibular end organ and secondary aff erent s f rom t he vest ibular nuclei) 6. Arcuat ocerebellar t ract f rom t he arcuat e nuclei of t he medulla 7. Trigeminocerebellar t ract f rom t he spinal and main sensory nuclei of t he t rigeminal nerve
Middle Cerebellar Peduncle The f iber syst ems reaching t he cerebellum via t his rout e are t he f ollow ing: 1. Pont ocerebellar (cort icopont ocerebellar) t ract f rom t he pont ine nuclei (major component ) 2. Serot onergic f ibers f rom t he raphe nuclei
Fi gure 15-9. Schemat ic diagram of spinocerebellar input . DSCT, dorsal spinocerebellar t ract s; VSCT, vent ral spinocerebellar t ract ; ACN, accessory cuneat e nucleus; CCT, cuneocerebellar t ract .
Fi gure 15-10. Schemat ic diagram of vest ibular input t o t he cerebellum.
Superior Cerebellar Peduncle The f iber input t o t he cerebellum via t his rout e includes t he f ollow ing: 1. Vent ral spinocerebellar t ract 2. Trigeminocerebellar t ract f rom t he mesencephalic t rigeminal nucleus 3. Cerulocerebellar t ract f rom t he nucleus ceruleus 4. Tect ocerebellar t ract f rom t he superior and inf erior colliculi The various input s t o t he cerebellum are segregat ed w it hin t he cerebellum int o one of t hree f iber syst ems: climbing, mossy, and a recent ly described mult ilayered.
A. CLIM BING FIBER SYSTEM (Figure 15-13) I t is generally believed t hat t he olivocerebellar t ract is t he major component of t his syst em. Climbing f ibers est ablish synapses on dendrit es of t he principal neuron of t he cerebellum (t he Purkinje cell), as w ell as on dendrit es of int rinsic neurons (G olgi, basket , and st ellat e) (Table 15-3). The climbing f iber input is know n t o exert a pow erf ul excit at ory eff ect on a single Purkinje cell and a much less pow erf ul eff ect on int rinsic neurons. The relat ionship of climbing f ibers t o principal neurons is so int imat e t hat one climbing f iber is rest rict ed t o one Purkinje cell and f ollow s t he branches of t he Purkinje cell dendrit es like a grapevine. The climbing f iber eff ect on a Purkinje cell is t hus one-t o-one, all-or-none excit at ion. I t is est imat ed t hat one climbing f iber est ablishes 1000 t o 2000 synapt ic cont act s w it h it s Purkinje cell. St imulat ion of t he climbing f iber syst em elicit s a prolonged burst of highf requency act ion pot ent ials (complex spike) f rom t he Purkinje cell capable of overriding any ongoing act ivit y in t hat cell. Several lines of evidence suggest t hat olivocerebellar input via t he climbing f iber pat hw ay is pow erf ully modulat ed during act ive movement s. Available dat a suggest t hat access of sensory signals f rom t he spinal cord t o t he cerebellum via t he inf erior olive (spino-olivocerebellar pat hw ay) and t he climbing f iber syst em is pow erf ully gat ed and is subject t o cent ral cont rol. The import ance of t he climbing f iber syst em is evident by t he f act t hat ablat ion of t he inf erior olive (source of climbing f iber pat hw ay) result s in movement disorder similar t o t he mot or def icit s t hat f ollow direct damage t o t he cerebellum. O ne not able aspect of t he olivocerebellar project ion is it s highly ordered t opography.
Fi gure 15-11. Schemat ic diagram show ing neocort ical input t o t he cerebellum w it h relay in t he pont ine nuclei and inf erior olive. MCP, middle cerebellar peduncle (brachium pont is); I CP, inf erior cerebellar peduncle (rest if orm body).
Fi gure 15-12. Composit e schemat ic diagram show ing major sources of input t o t he cerebellum.
B. M OSSY FIBER SYSTEM The mossy f iber syst em includes all aff erent s t o t he cerebellum except t hose w hich cont ribut e t o t he climbing f ibers and t he mult ilayered f iber syst em. Like t he climbing f ibers, mossy f ibers ent er t he cerebellum via t he core of deep w hit e mat t er. They t hen diverge int o t he f olia of t he cerebellum, w here t hey branch out int o t he granule cell layer. Wit hin t he granule cell layer, mossy f ibers divide int o several subbranches of t erminal roset t es t hat occupy t he cent er of each glomerulus, w here t hey come in cont act w it h dendrit es of granule and G olgi neurons (Figure 15-13 and Table 15-3). I t is est imat ed t hat each mossy f iber est ablishes cont act w it h approximat ely 400 granule cell dendrit es w it hin a single f olium and t hat each t erminal mossy roset t e cont act s approximat ely 20 diff erent granule cells. O n t he ot her hand, each granule cell receives synapt ic cont act s f rom f our t o f ive diff erent mossy f iber t erminals. The mossy f iber is believed t o st imulat e t he largest number of cells t o be act ivat ed by a single aff erent f iber. Thus, in cont rast t o t he climbing f iber input , w hich is highly specif ic and sharply f ocused on t he Purkinje cell, t he mossy f iber input is diff use and complex (Figure 15-13). I n addit ion t o t heir cont ribut ion t o t he Purkinje and granule cells of t he cerebellar cort ex, bot h climbing and mossy f ibers send collat erals t o t he deep cerebellar nuclei (Figure 15-13). These collat erals are excit at ory in nat ure and help maint ain a const ant background discharge of t hese deep nuclei.
C. M ULTILAYERED FIBER SYSTEM This recent ly described f iber syst em includes aff erent s t o t he cerebellum f rom t he hypot halamus, as w ell as t he serot onergic input
f rom t he raphe nuclei, t he noradrenergic input f rom t he nucleus locus ceruleus, and t he dopaminergic input f rom t he mesencephalic dopaminergic neurons. Similar t o t he climbing and mossy f iber syst ems, t he mult ilayered f iber syst em project s on neurons in t he cerebellar cort ex and t he deep cerebellar nuclei.
Fi gure 15-13. Schemat ic diagram comparing t he climbing and mossy f iber syst ems w it hin t he cerebellum.
INTERNAL CEREBELLAR CIRCUITRY (Figures 15-14 and 15-15) Mossy Fiber Input A mossy f iber input excit es dendrit es of a group of granule cells. The discharge f rom t hese granule cells w ill be t ransmit t ed t hrough t heir axons (parallel f ibers), w hich bif urcat e in a T conf igurat ion in t he molecular layer, coming in cont act w it h dendrit es of Purkinje, st ellat e, basket , and G olgi neurons. I f t he excit ed parallel f iber bundle is w ide enough t o cover t he Purkinje cell dendrit ic f ield, act ivat ion w ill result in a f iring of a single row of Purkinje cells and in t he relat ed basket and st ellat e cells. The act ivat ion of t he basket and st ellat e cells w ill inhibit a w ide zone of Purkinje cells on each side of t he row of
act ivat ed Purkinje cells. Thus t he mossy f iber input w ill produce a row of act ivat ed Purkinje cells f lanked on each side by a st rip of inhibit ed Purkinje cells. The inhibit ed row s of Purkinje cells, by silencing surrounding act ivit y, help t he process of neural sharpening w it hin t he act ivat ed row of Purkinje cells. I f t he act ivat ed bundle of parallel f ibers becomes w ide enough t o span t he dendrit ic f ield of a G olgi neuron, t he G olgi cell is t hen excit ed and, t hrough it s axon in t he glomerulus, w ill inhibit t he granule cell. Thus, a mossy f iber excit at ory input t o t he granule cell w ill be t ransf erred int o inhibit ion via one of t w o mechanisms (Figure 15-14): 1. Mossy f iber t o granule cell dendrit e t o granule cell axon (parallel f ibers) t o basket and st ellat e cells dendrit es t o basket and st ellat e cells axons t o Purkinje cell body (basket cells axons) and dendrit es (st ellat e cells axons) 2. Mossy f ibers t o granule cell dendrit e t o granule cell axon (parallel f ibers) t o G olgi cell dendrit es, t o G olgi cell axon, t o granule cell dendrit es. A t hird inhibit ory mechanism of t he mossy f iber syst em (Figure 15-15) is via mossy f iber input t o G olgi cell dendrit es t o G olgi cell axon and back t o granule cell dendrit es. Tabl e 15-3. Climbing and Mossy Fibers
Projection targets Fiber type
Deep Purkinje Basket Stellate Granule G nuclei
Climbing
X
Mossy
X
X
X
X
X
Fi gure 15-14. Schemat ic diagram show ing how an excit at ory mossy f iber input can be t ransf ormed int o inhibit ion via granule cell axon. MF, mossy f iber; G , granule cell; G O , G olgi cell; B, basket cell; S, st ellat e cell; PC, Purkinje cell; ML, molecular layer; PCL, Purkinje cell layer; G CL, granule cell layer; PF, parallel f ibers; A, axon; D, dendrit e; +, f acilit at ion; -, inhibit ion.
Fi gure 15-15. Schemat ic diagram show ing how an excit at ory mossy f iber input can be t ransf ormed int o inhibit ion via G olgi cell axon. MF, mossy f iber; G , granule cell; G O , G olgi cell; ML, molecular layer; PCL, Purkinje cell layer; G CL, granule cell layer; PF, parallel f ibers; A, axon; D, dendrit e; +, f acilit at ion; -, inhibit ion.
The mossy f iber input has bot h high divergence and convergence rat ios. A single mossy f iber has 40 roset t es, each roset t e connect s w it h t he dendrit ic t erminals of 20 granule cells, and a single granule cell connect s t hrough t he parallel f ibers w it h 100 t o 300 Purkinje cells. This gives a divergence rat io of about 1: 100, 000 t o 1: 300, 000 f rom one mossy f iber t o Purkinje cells. O n t he ot her hand, each Purkinje cell has about 100, 000 dendrit ic spines in synapt ic cont act w it h parallel f ibers (granule cells) and hence a large rat io of convergence.
Climbing Fiber Input Similarly, a climbing f iber input w ill excit e Purkinje cells as w ell as st ellat e, basket , and G olgi neurons. The eff ect on t hese diff erent cells is similar t o t hat described f or t he mossy f iber input and helps t o f ocus on t he act ivat ion of t he Purkinje cell amid a zone of inhibit ion induced by basket , st ellat e, and G olgi
neurons. I n cont rast t o t he mossy f iber syst em, t he convergence and divergence f act ors f or t he climbing f iber input are small (1: 1). I ncoming f ibers (climbing and mossy) t o t he cerebellum t hus excit e Purkinje and granule cells of t he cerebellar cort ex, as w ell as t he deep cerebellar nuclei. Purkinje cells are excit ed direct ly by climbing f ibers and indirect ly (via t he granule cell) by mossy f ibers. The excit at ion of Purkinje cells is modulat ed by several f eedback circuit s (via basket and st ellat e inhibit ory int erneurons) t hat inhibit Purkinje cell act ivit y and suppress t ransmission of impulses f rom Purkinje cells t o deep cerebellar nuclei. The out put of Purkinje cells t o t he deep cerebellar nuclei is t hus a f inely modulat ed inhibit ory signal. The out put of t he deep cerebellar nuclei t o ext racerebellar t arget s is t hus t he product of excit at ory input f rom climbing and mossy f ibers and inhibit ory project ions f rom Purkinje cells (Figure 15-16). The mossy f iber pat hw ays conduct f ast er t han t he climbing f iber pat hw ays. How ever, t he ult imat e inhibit ory pot ent ials produced by t he mossy f iber syst em develop slow ly so t hat by t he t ime t he climbing f iber input arrives in t he cerebellum, t he f ull eff ect of t he mossy f iber inhibit ory pot ent ials has not yet developed. This allow s t he climbing f iber syst em t o act on t he background act ivit y of excit at ion and inhibit ion init iat ed by t he mossy f iber input . Thus, of all t he cells of t he cerebellar cort ex, only t he granule cell is excit at ory; all ot hers, including t he Purkinje cells, are inhibit ory. Recent st udies on t he cerebellum have given t he G olgi neuron a cent ral role in cerebellar organizat ion. Through it s cont act w it h bot h t he mossy f ibers in t he glomerulus and t he climbing f iber collat erals, t he G olgi neuron is able t o select w hat input w ill reach t he Purkinje cell at any one t ime.
CEREBELLAR OUTPUT The cerebellar out put syst em has t w o component s: int racerebellar and ext racerebellar. The int racerebellar component comprises t he inhibit ory project ions of Purkinje cells t o deep cerebellar nuclei. These project ions are somat ot opically organized (Figure 15-17). Purkinje cells in t he vermis project t o t he nucleus f ast igii, w hile t hose in t he paravermal and cerebellar hemisphere zones project , respect ively, t o t he int erposed nucleus (embolif orm and globose) and t he dent at e nucleus. The vast majorit y of t he ext racerebellar component comprises t he project ions of deep cerebellar nuclei t o ext racerebellar t arget s. A smaller part of it originat es f rom a group of Purkinje cells in t he vest ibulocerebellum w hose axons bypass t he deep cerebellar nuclei and project on t he lat eral vest ibular nucleus in t he brain st em. Ext racere-bellar t arget s of deep cerebellar nuclei (Figures 15-18, 15-19, 15-20) include t he vest ibular and ret icular nuclei of t he brain st em (f rom t he nucleus f ast igii), t he red nucleus in t he midbrain and t he inf erior olivary nucleus in t he medulla (f rom t he int erposed nucleus), t he t halamus (f rom t he dent at e and int erposed nuclei), and t he hypot halamus (f rom all deep cerebellar nuclei).
Eff erent s f rom t he cerebellum leave via t he inf erior and superior cerebellar peduncles (Figure 15-21). Cerebellovest ibular and cerebelloret icular f ibers t ravel via t he inf erior cerebellar peduncle, w hereas t he cerebellot halamic, cerebellorubral, and cerebello-olivary f ibers t ravel via t he superior cerebellar peduncle. The superior cerebellar peduncle crosses in t he midbrain t egment um (at t he inf erior colliculus level) and project s on t he cont ralat eral red nucleus and vent rolat eral nucleus of t he t halamus. A small f ascicle f rom t his crossed syst em descends t o t he inf erior olivary nucleus. The cerebellum exert s it s most import ant inf luence on t he mot or and premot or cort ices via t he vent rolat eral nucleus of t he t halamus. Elect rophysiologic st udies show t hat pyramidal t ract neurons in t he mot or and premot or cort ices receive di-synapt ic or t risynapt ic excit at ory input s f rom t he dent at e and int erposed nuclei af t er relays in t he vent rolat eral t halamic nucleus. O t her cort icof ugal neurons in t he mot or and premot or cort ices, such as t hose w hich project t o t he red nucleus, pont ine nuclei, and spinal cord, also receive cerebellar f ibers. I n addit ion t o t he mot or and premot or cort ices, t he cerebellum project s t o t he pariet al and t emporal associat ion cort ices.
Fi gure 15-16. Schemat ic diagram of t he int rinsic cerebellar circuit ry. +, excit at ion; -, inhibit ion.
Fi gure 15-17. Schemat ic diagram show ing t opographic project ions of Purkinje cells of diff erent cerebellar zones int o t he respect ive deep cerebellar nuclei.
DEEP CEREBELLAR NUCLEI The deep cerebellar nuclei are embedded in t he w hit e mat t er core of t he cerebellum. There are f our pairs of nuclei arranged f rom lat eral t o medial as f ollow s: dent at e, embolif orm, globose, and f ast igi (Figure 15-5). A mnemonic used f requent ly t o remember t he lat eral t o medial order of deep cerebellar nuclei is L ucky Dude Engages G irl From Mont ana w here L is f or lat eral, D f or dent at e, E f or embolif orm, G f or globose, F f or f ast igii, and M f or medial.
Dentate Nucleus The dent at e nucleus is composed of mult ipolar neurons and resembles t he inf erior olive in conf igurat ion. I t receives t he axons of Purkinje cells locat ed in t he lat eral part of t he cerebellar hemispheres and collat erals of climbing and mossy f ibers. The Purkinje cell input is inhibit ory, w hereas t he input s f rom climbing and mossy f ibers are excit at ory t o t he dent at e nucleus (Figure 15-18).
Fi gure 15-18. Schemat ic diagram show ing t he aff erent and eff erent connect ions of t he dent at e nucleus. +, f acilit at ion; -, inhibit ion; CF, Climbing f iber; MF, mossy f iber; BC, brachium conjunct ivum.
Fi gure 15-19. Schemat ic diagram show ing t he aff erent and eff erent connect ions of t he int erposed nuclei. +, f acilit at ion; -, inhibit ion; CF, climbing f iber; MF, mossy f iber; BC, brachium conjunct ivum.
Fi gure 15-20. Schemat ic diagram show ing t he aff erent and eff erent connect ions of t he nucleus f ast igii. +, f acilit at ion; -, inhibit ion.
The bulk of axons of t he dent at e nucleus project via t he superior cerebellar peduncle (brachium conjunct ivum) t o t he cont ralat eral vent rolat eral nucleus of t he t halamus. A relat ively small number of axons project t o t he int ralaminar nuclei of t he t halamus (mainly t he cent ral lat eral nucleus), t o t he rost ral t hird of t he red nucleus (origin of rubroolivary t ract ), and, via t he descending limb of t he brachium conjunct ivum, t o t he ret iculot egment al nucleus and inf erior olive. The expansion of t he dent at e nucleus and t he lat eral cerebellar hemisphere in t he course of hominid evolut ion provided t he neural basis f or novel cerebellar t raject ories and new f unct ions. The phylogenet ically older part of t he dent at e nucleus (t he dorsomedial part ) maint ains connect ions w it h t he mot or cort ex via t he mot or t halamus (vent rolat eral nucleus) and w it h t he spinal cord via t he red nucleus, in line w it h t he t radit ionally est ablished role of t he cerebellum in mot or cont rol. The phylogenet ically new er part of t he dent at e nucleus (t he vent rolat eral part ), in cont rast , has connect ions, in addit ion t o t he mot or cort ex, w it h t he pref ront al cort ex, w hich has expanded in parallel w it h t he dent at e nucleus in t he
course of hominid evolut ion. Evidence is accumulat ing in f avor of a nonmot or f unct ion of t he neodent at e nucleus.
Interposed Nuclei These nuclei include t he embolif orm nucleus, locat ed medial t o t he hilum of t he dent at e nucleus, and t he globose nucleus, locat ed medial t o t he embolif orm nucleus (Figure 15-5). The int erposed nuclei receive aff erent f ibers f rom t he f ollow ing sources (Figure 15-19): 1. Axons of Purkinje cells in t he paravermal (int ermediat e) zone of t he cerebellum t hat are inhibit ory in f unct ion 2. Collat erals f rom climbing and mossy f iber syst ems t hat are excit at ory in f unct ion Axons of int erposed nuclei leave t he cerebellum via t he superior cerebellar peduncle (brachium conjunct ivum). The bulk project s on neurons in t he caudal t w o-t hirds of t he red nucleus (t he part t hat gives rise t o t he rubrospinal t ract ). A smaller number of axons project on t he vent rolat eral nucleus of t he t halamus and, via t he descending limb of t he brachium conjunct ivum, t o t he inf erior olive.
Fastigial Nucleus This nucleus is locat ed in t he roof of t he f ourt h vent ricle medial t o t he globose nucleus; hence it is called t he roof nucleus. I t receives aff erent f ibers f rom t he f ollow ing sources (Figure 15-20): 1. Axons of Purkinje cells in t he vermis of t he cerebellum t hat are inhibit ory in f unct ion 2. Collat erals of mossy and climbing f iber syst ems t hat are excit at ory I n cont rast t o eff erent s f rom t he dent at e and t he int erposed nuclei, eff erent s of t he f ast igial nucleus do not t ravel via t he brachium conjunct ivum. A large number of f ast igial eff erent s cross w it hin t he cerebellum and f orm t he uncinat e f asciculus. Uncrossed f ast igial f ibers join t he juxt arest if orm body. The bulk of f ast igial eff erent s project on t he vest ibular nuclei (lat eral and inf erior) and several ret icular nuclei of t he brain st em. Fast igial project ions t o vest ibular nuclei are bilat eral. Fast igioret icular f ibers are mainly crossed. A small number of f ast igial eff erent s course rost rally in t he brain st em t o project on t he superior colliculus, nuclei of t he post erior commissure, and t he vent rolat eral t halamic nucleus.
Fi gure 15-21. Schemat ic summary diagram show ing t he cerebellar out put via t he superior cerebellar peduncle (SCP) and inf erior cerebellar peduncle (I CP). CBL, cerebellum.
I n addit ion t o t he eff erent project ions of t he deep cerebellar nuclei described above, all deep cerebellar nuclei have been show n t o send axon collat erals t o t he areas of t he cerebellar cort ex f rom w hich t hey receive f ibers; t hus t he nucleus f ast igii sends axon collat erals t o t he cerebellar vermis, t he int erposed nuclei t o t he paravermal region, and t he dent at e nucleus t o lat eral part s of t he cerebellar hemispheres. Alt hough deep cerebellar nuclei receive axons of Purkinje cells, t heir axon collat erals do not project direct ly on Purkinje cells but on neuronal element s in t he granule cell layer via t he mossy f iber syst em. The exact cell t ype in t he granule cell layer t hat receives t hese axon collat erals has not been ident if ied w it h cert aint y. Thus all t he deep cerebellar nuclei receive a dual input ; t hese are an excit at ory
input f rom ext racerebellar sources (mossy and climbing f ibers) and an inhibit ory input f rom t he cerebellar cort ex (axons of Purkinje cells). I n cont rast , t he out put of t he deep cerebellar nuclei is excit at ory.
CEREBROCEREBELLAR AND CEREBELLOCEREBRAL CIRCUITRIES The cerebral cort ex communicat es w it h t he cerebellum via a mult it ude of pat hw ays, of w hich t he f ollow ing are w ell recognized (Figure 15-22): 1. Cort icoolivocerebellar via t he red nucleus and inf erior olivary nucleus 2. Cort icopont ocerebellar via t he pont ine nuclei 3. Cort icoret iculocerebellar via t he ret icular nuclei of t he brain st em The f irst t w o pat hw ays convey t o t he cerebellum precisely localized and somat ot opically organized inf ormat ion. O f t hese t w o, t he pat hw ay via t he pont ine nuclei is quant it at ively more impressive. The pat hw ay via t he ret icular nuclei is part of a syst em w it h diff use input and out put (ret icular f ormat ion), in w hich inf ormat ion of cort ical origin is int egrat ed w it h inf ormat ion f rom ot her sources bef ore t ransmission t o t he cerebellum. The cerebellum inf luences t he cerebrum mainly via t he dent at ot halamic syst em. The cerebellocerebral pat hw ays are modest in number w hen compared w it h t he cerebrocerebellar pat hw ays (approximat ely 1: 3). This is a ref lect ion of t he eff iciency of t he cerebellar machinery t hat makes it possible f or t he cerebellum t o regulat e cort ically originat ing signals f or movement . Cort icocerebellar f ibers originat e f rom mot or and nonmot or (associat ive and limbic) areas of t he cerebral cort ex. Similarly, cerebellar out put f ibers t arget bot h mot or and nonmot or cerebral cort ical areas.
NEUROTRANSM ITTERS The f ollow ing neurot ransmit t ers have been ident if ied in t he cerebellum: gammaaminobut yric acid (G ABA), t aurine, glut amat e, aspart at e, acet ylcholine, norepinephrine, serot onin, and dopamine.
Fi gure 15-22. Schemat ic diagram of cerebrocerebellar and cerebellocerebral connect ions. Heavy arrow s denot e quant it at ively signif icant pat hw ay.
G ABA is liberat ed f rom axons of Purkinje, basket , and G olgi neurons and exert s an inhibit ory eff ect on t arget neurons. Taurine is believed t o be t he inhibit ory neurot ransmit t er of t he superf icial st ellat e cells; t aurine levels are high in t he molecular layer and drop subst ant ially w hen st ellat e cell development is blocked by x-irradiat ion. G lut amat e is believed t o be t he excit at ory neurot ransmit t er of granule cells; glut amat e levels in t he granule cell layer drop subst ant ially in t he agranular cerebellum of virus-inf ect ed and mut ant mice. G lut amat e has also been report ed t o be t he excit at ory neurot ransmit t er in climbing and mossy f ibers. Acet ylcholine has been report ed in granule cells, G olgi cells, and mossy f ibers. G lycine, enkephalin, and somat ost at in have been report ed in G olgi cells. Norepinephrine is t he inhibit ory neurot ransmit t er of t he locus ceruleus project ion on Purkinje cell dendrit es. I n addit ion t o it s presumed role in mat urat ion of Purkinje neurons, norepinephrine seems t o modulat e Purkinje cell response t o ot her cerebellar neurot ransmit t ers. St imulat ion of t he locus ceruleus enhances sensit ivit y of Purkinje neurons t o bot h glut amat e and G ABA. Serot onin and dopamine are released in t erminals of project ions f rom t he raphe nuclei and midbrain dopamine neurons, respect ively.
CEREBELLAR PHYSIOLOGY Cerebellar Cortex Cerebellar neurons are charact erized by high rat es of rest ing impulse discharge. Purkinje cells discharge at t he rat e of approximat ely 20 t o 40 Hz, granule cells at 50 t o 70 Hz, and inhibit ory int erneurons (basket , st ellat e, and G olgi) at 7 t o 30 Hz. This high discharge rat e of cerebellar neurons is derived f rom t he nat ure
of t heir synapt ic drive. St imulat ion of t he mossy f iber syst em or of t he parallel f ibers (axons of granule cells) elicit s in t he Purkinje cell a brief excit at ory post synapt ic pot ent ial (EPSP) (si mpl e spi ke) last ing 5 t o 10 ms, f ollow ed by a prolonged inhibit ory post synapt ic pot ent ial (I PSP). The short EPSP is at t ribut ed t o t he act ivat ion of Purkinje cell dendrit es by t he parallel f ibers. The I PSP, on t he ot her hand, is at t ribut ed t o t he f eedf orw ard inhibit ion of Purkinje cells by st ellat e and basket cells t hat are act ivat ed simult aneously by t he beam of parallel f ibers (Figure 1523). St imulat ion of t he climbing f iber syst em elicit s in t he Purkinje cell an int ense and prolonged react ion charact erized by an init ial large spike f ollow ed by several small ones. This pat t ern is ref erred t o as a compl ex spi ke. This complex EPSP is f ollow ed by a prolonged I PSP. The complex spike is explained on t he basis of more t han one mechanism. O ne mechanism f or t his complex spike in t he Purkinje cell is t he repet it ive discharge emanat ing f rom inf erior olive neurons because of axonal collat erals w it hin t he inf erior olive. Anot her mechanism f or t he complex response of Purkinje cells lies in t he int rinsic propert y of t heir membranes. The I PSP t hat f ollow s t he complex EPSP is at t ribut ed t o simult aneous act ivat ion of st ellat e and basket cells by t he climbing f ibers, w hich in t urn inhibit t he Purkinje cell by a f eedf orw ard pat hw ay. Bot h mossy and climbing f ibers f acilit at e t he G olgi cell, w hich in t urn inhibit s t he granule cell and can t hus cont ribut e t o Purkinje cell inhibit ion. Af t er t heir init ial act ivat ion by t he mossy and climbing f iber input , int rinsic neurons (basket , st ellat e, and G olgi) ult imat ely are inhibit ed by Purkinje axon collat erals. The act ion of t he recurrent Purkinje axon collat erals is t hus t o disinhibit t he Purkinje cell.
Fi gure 15-23. Schemat ic diagram show ing t he mechanism of generat ion of excit at ory (EPSP) and inhibit ory (I PSP) post synapt ic act ion pot ent ials in t he Purkinje cell. MF, mossy f iber; CF, climbing f iber; PF, parallel f ibers; SS, simple spike; CS, complex spike.
I t becomes evident f rom t he preceding t hat t he mossy and climbing input f ibers are excit at ory t o t he granule and Purkinje cells, w hereas t he act ion of all ot her cells w it hin t he cerebellum (except t he granule cell) is inhibit ory. I t is t hus not possible f or cerebellar act ivit y in response t o an aff erent input t o be sust ained. Several invest igat ors have st udied t he eff ect s of cerebellar st imulat ion in humans. The result s of such st imulat ion are similar t o t hose described above.
Deep Cerebellar Nuclei Like t he Purkinje cells, deep nuclei have high rat es of impulse discharge at rest . Also like t he Purkinje cells, t he deep cerebellar nuclei receive bot h excit at ory and inhibit ory input s, t he f ormer arriving via t he climbing and mossy f ibers and t he lat t er by axons of Purkinje cells (Figure 15-16). Thus a mossy f iber input , f or
example, w ill cause f irst a high-f requency burst in t he deep cerebellar nuclei f ollow ed by a low ering of t he f requency as a result of inhibit ion arriving t hrough t he slow er Purkinje cell loop. Purkinje cell inhibit ion is mediat ed by gammaaminobut yric acid (G ABA).
CEREBELLAR FUNCTION Historical Perspective The cerebellum has puzzled and f ascinat ed anat omist s, physiologist s, and clinicians since it s early descript ion by Arist ot le and G alen. Early observers at t ribut ed t o it roles as cont roller of mot or nerves, seat of memory, direct or of aut omat ic and involunt ary visceral movement s, and t he seat of sexual act ivit y. Fluorens' experiment s f rom 1822 t o 1824 show ed t hat t he cerebellum w as concerned w it h coordinat ion of movement . Fraser in 1880 considered it t he seat of sexual appet it e.
A. PHRENOLOGIC ERA I n phrenologic maps of t he brain, t he cerebellum w as t he primary anat omic locus of amat ive (sexual) love. The overlying occipit al pole w as t he locus of mat ernal/ pat ernal love. Analysis of cerebellar morphology w as an import ant prenupt ial check. Cagey lovers w ere report ed t o perf orm a discret e examinat ion of t he crania of prospect ive part ners t o check on t he degree of prominence of t heir occipit al ridge. Circulat ed report s at t he t ime described a w ell-know n societ y physician w it h a markedly prominent occipit al ridge w ho out lived t hree w ives and required t he at t ent ion of f our mist resses. Anot her described a Viennese f ort une t eller, f amous f or his libidinous desires, w hose aut opsy revealed a marked degree of cerebellar hypert rophy. I t w as also believed at t he t ime t hat t he cerebellum and ext ernal genit alia w ere lat eralized and reciprocally act ivat ing such t hat an injury t o t he lef t t est icle w as expect ed t o result in at rophy of t he cont ralat eral cerebellar hemisphere.
B. EXPERIM ENTAL ERA (19TH CENTURY) The experiment al era of cerebellar f unct ion w as ushered in by t he st udies of Magendie, Cuvier, and Rolando. The experiment alist s described t he phrenologist perspect ive as a collect ion of absurdit ies, incoherence, and gross ignorance. Surgical lesions in cerebella of experiment al animals result ed in various degrees of ipsilat eral w eakness, disequilibrium, and loss of mot or coordinat ion.
C. HUM AN BRAIN INJURIES G ordon Holmes, in t he f irst quart er of t he 20t h cent ury, concept ualized about cerebellar f unct ion f rom observat ions made on pat ient s w ho received bullet w ound injuries t o t he cerebellum during t he f irst w orld w ar. Thus w as coined t he
Holmes t riad of ast henia, at axia, and at onia.
D. THE ERA OF IM AGING The use of imaging (comput erized axial t omography and magnet ic resonance imaging) in t he mid-1970s and 1980s permit t ed a bet t er correlat ion of lesions and dist urbance of f unct ion.
Motor Functions of the Cerebellum The cerebellum t radit ionally has been relegat ed a mot or f unct ion. As early as 1822, Flourens show ed t hat t he cerebellum w as concerned w it h coordinat ion of movement , and in 1891, I t alian physiologist Luigi Luciani described t he t riad of cerebellar signs: at onia, ast henia (w eakness), and ast asia (mot or incoordinat ion). Lat er he added a f ourt h sign, dysmet ria. Based on st udies conduct ed by G ordon Holmes in t he f irst quart er of t he 20t h cent ury on pat ient s w it h w ound injuries t o t he cerebellum, t he Holmes mot or t riad of ast henia (easy f at igabilit y), at axia, and at onia became synonymous w it h cerebellar disease. Subsequent clinical and experiment al st udies conf irmed a role f or t he cerebellum in cont rol and int egrat ion of mot or act ivit y.
Neocerebellar Signs The cerebellum is generally t hought t o int egrat e mot or commands and sensory inf ormat ion t o help coordinat e movement . The incoordinat ion of movement not ed in diseases of t he neocerebellum is t he result of dist urbances in speed, range, f orce, or t iming of movement . These are manif est ed clinically in t he f ollow ing neocerebellar signs: dyssynergia or asynergia, dysart hria, adiadochokinesis, dysmet ria, t remor, muscular hypot onia, at axia, and nyst agmus. The lack of unif orm velocit y is responsible f or t he irregular and jerky movement s of ext remit ies (dyssynergia or asynergia) of cerebellar disease. Asynergy of muscles of art iculat ion is responsible f or t he slow, slurred speech (dysart hria) of cerebellar disorders. Proper t iming in init iat ion and t erminat ion of movement is also essent ial in t he execut ion of smoot h movement . A delay in t he init iat ion of each successive movement w ill lead t o t he adiadochokinesis (dist urbance in perf ormance of rapid movement using ant agonist ic muscle groups) of cerebellar disease. A delay in t he t erminat ion of movement result s in dysmet ria. Dysmet ria can manif est as overshoot ing int ended t arget (hypermet ria), or undershoot ing int ended t arget (hypomet ria). Thus, adiadochokinesis and dysmet ria are t he result of an error in t iming. I nt ent ion (volit ional) t remor is due t o def ect ive f eedback cont rol f rom t he cerebellum on cort ically init iat ed movement . Normally, cerebellar f eedback mechanisms cont rol t he f orce and t iming of cort ically init iat ed movement . Failure
of t hese mechanisms in cerebellar disease result s in t remor. The cerebellum is able t o exert it s correct ive inf luence on cort ically originat ing movement by virt ue of t he input it receives f rom t he cerebral cort ex and periphery. The cerebral cort ex inf orms t he cerebellum of int ended movement via t he cerebrocerebellar pat hw ays described previously. During movement , t he cerebellum receives also a const ant f low of inf ormat ion, bot h propriocept ive and ext erocept ive, f rom peripheral recept ors (e. g. , muscle spindle, G olgi t endon organ) concerning movement in progress. The cerebellum correlat es peripheral inf ormat ion on movement in progress w it h cent ral inf ormat ion on int ended movement and correct s errors of movement accordingly. The cerebellum t hus serves t o opt imize cort ically originat ing movement using sensory inf ormat ion. Based on t he cerebellar role in sensorymot or int egrat ion, it has been suggest ed t hat t he cerebellum might be involved in generat ing t he predict ion of t he sensory consequences of movement . Such a role may explain w hy w e cannot t ickle ourselves. I n addit ion, t he cerebellum may be involved in mot or learning and t he init iat ion of movement . Long-last ing changes in synapt ic eff icacy may t ake place in t he cerebellar cort ex during mot or learning, suggest ing t hat t he cerebellum may be capable of remembering w hat w as done and t hereby adapt ing it s inf luence on mot or neurons in accordance w it h t he out come of movement . Experiment al evidence suggest s t hat deep cerebellar nuclei f ire simult aneously w it h pyramidal cort ical neurons prior t o movement . The cerebellum also inf luences movement via it s eff ect s on t he gamma syst em. The cerebellum normally increases t he sensit ivit y of muscle spindles t o st ret ch. Cerebellar lesions are associat ed w it h a depression of gamma mot or neuron act ivit y t hat leads t o erroneous inf ormat ion in t he gamma syst em about t he degree of muscle st ret ch. The erroneous inf ormat ion conveyed by t he muscle spindle t o t he alpha mot or neuron result s in dist urbances in discharge of t he alpha mot or neuron and is manif est ed by a dist urbance in f orce and t iming of movement . The depression of t onic act ivit y of gamma mot or neurons in cerebellar disease is also t he basis of t he hypot onia associat ed w it h neocerebellar syndromes. The at axia of neocerebellar lesions are usually appendicular (unst eady limb movement ). The nyst agmus (rhyt hmic oscillat ion of eye movement s) seen in neocerebellar lesions is apparent w it h horizont al ocular movement and ref lect s dysmet ria of eye t racking.
Archicerebellar and Paleocerebellar Signs The archicerebellum and paleocerebellum inf luence spinal act ivit y via t he vest ibulospinal and ret iculospinal t ract s. Archicerebellar signs are usually associat ed w it h lesions in t he f locculonodular lobe and are manif est ed by t runcal at axia (st aggering gait and unst eady post ure w hile st anding) and nyst agmus
(rhyt hmic oscillat ion of t he eyes at rest and/ or w it h ocular movement s). Paleocerebellar lesions are rare in humans and usually aff ect t he ant erior lobe. The increase in myot at ic and post ural ref lexes associat ed w it h t he ant erior lobe syndrome is due t o an increase in mot or signals t o t he alpha mot or neurons and a simult aneous decrease in signals t o t he gamma syst em. Thus, t he rigidit y of cerebellar disease is an alpha t ype of rigidit y. I n humans, unst eadiness of gait (gait at axia) may be t he only manif est at ion of paleocerebellar lesions.
Ocular Motor Signs The cerebellum is necessary f or t he product ion of bot h accurat e saccadic and smoot h pursuit movement s. Evidence is accumulat ing f or a role of t he cerebellum in vergence eye movement s. Saccades are t he volunt ary rapid eye movement s t hat move our eyes f rom one visual t arget t o anot her. The object ive of smoot h pursuit eye movement s is t o reduce t he slip of a visual image over t he f ovea t o velocit ies slow enough t o allow clear vision. Vergence is simult aneous movement of bot h eyes in diff erent direct ions. Convergence is movement of bot h eyes nasally; divergence is movement of bot h eyes t emporally. Convergence and divergence occur in response t o changes in posit ion of a visual t arget along t he f ar near axis. The post erior lobe vermis (oculomot or vermis) and t he caudal nucleus f ast igii t o w hich it project s are necessary f or horizont al saccades and make t hem f ast , accurat e, and consist ent . I n lesions of t he caudal f ast igial nucleus, saccades are inaccurat e, slow, and abnormally variable in size and speed. The caudal f ast igial nucleus inf luences saccadic machinery via it s project ions t o saccade-relat ed neurons in t he brain st em (excit at ory burst neurons, inhibit ory burst neurons, omnipause neurons). The int erposit us nucleus is relat ed t o vert ical saccades. Bot h t he caudal f ast igial nucleus and t he f loccculus/ paraf locculus are necessary f or normal smoot h pursuit eye movement s. The caudal f ast igial nucleus is believed t o be import ant in pursuit init iat ion and t he f locculus in pursuit maint enance. I n addit ion t o playing a role in saccades and smoot h pursuit , t he caudal f ast igial nucleus and int erposit us nucleus also inf luence vergence eye movement s.
Cerebellum and Epilepsy Cerebellar st imulat ion has been show n t o have benef icial eff ect s on bot h experiment ally induced epilepsy and human epilepsy. The result s are variable, and more st udy is needed bef ore t he role of t he cerebellum in t he cont rol of epilepsy can be def ined clearly.
Complementarity of Basal Ganglia and Cerebellum in Motor Function Review of basal ganglia and cerebellar st ruct ure, connect ivit y, and organizat ion
reveals many f eat ures in common. Bot h are component s of t he mot or syst em, inf luence cerebral cort ical act ivit y via t he t halamus, are linked w it h t he cerebral cort ex via recurrent loops, have int ernal (local) circuit ry t hat modulat es loop act ivit y, receive modulat ing input s t hat inf luence t heir act ivit ies (climbing f ibers in t he cerebellum and dopaminergic input in t he basal ganglia), have a high convergence rat io of input s on t heir principal neurons (spiny neuron in t he basal ganglia and Purkinje cell in t he cerebellum), and play a role in pat t ern recognit ion. The emerging concept (Figure 15-24) of t he complement arit y of basal ganglia and cerebellar roles in mot or f unct ion suggest s t hat t he basal ganglia f unct ion as det ect ors of specif ic cont ext s, providing t o t he cerebral cort ex inf ormat ion t hat could be usef ul in planning and gat ing of act ion. The cerebellum, in cont rast , f unct ions in programming, execut ion, and t erminat ion of act ions. According t o t his concept , t he cerebral cort ex, w hich receives diverse sensory inf ormat ion f rom t he periphery via t he diff erent ascending t ract s as w ell as complex inf ormat ion already processed w it hin t he basal ganglia and cerebellum, serves t w o f unct ions: a reposit ory f unct ion t o receive t his diverse inf ormat ion, comput e it , and share it w it h t he basal ganglia and cerebellum and an execut ive f unct ion t o implement t he act ion emanat ing f rom it s collect ive comput at ion process. Anot her complement arit y model (Figure 15-25), based on t he roles of t he cerebellum and basal ganglia in bot h mot or and cognit ive f unct ions, suggest s t hat cerebellum, basal ganglia, and cerebral cort ex are specialized f or diff erent t ypes of learning. According t o t his model, t he cerebellum is specialized f or supervised (error-based) learning, guided by t he error signal encoded in t he climbing f iber input f rom t he inf erior olive. The basal ganglia are specialized f or reinf orcement (rew ard-based) learning, guided by t he rew ard signals encoded in t he dopaminergic input f rom t he subst ant ia nigra. The cerebral cort ex is specialized f or unsupervised learning guided by t he st at ist ical propert ies of t he input signal regulat ed by ascending neuromodulat ory input s.
Fi gure 15-24. Schemat ic diagram show ing t he complement arit y of t he cerebellum and basal ganglia in mot or f unct ion.
Nonmotor Functions of the Cerebellum A grow ing body of dat a suggest a nont radit ional role f or t he cerebellum in t he regulat ion of aut onomic f unct ion, behavior, and cognit ion. Follow ing cerebellar ablat ion or st imulat ion, a mult it ude of visceral and aff ect ive responses has been report ed, including cardiovascular and endocrine changes; alt ered respirat ion, int est inal mot ilit y, and bladder t one; reduced aggressiveness; mood changes; and alert ing react ions. These visceral and aff ect ive responses w ere believed t o be mediat ed t hrough cerebellar connect ions w it h brain st em ret icular nuclei. Evidence f or a complex net w ork of pat hw ays bet w een t he hypot halamus and cerebellum suggest s an alt ernat e mechanism f or t hese responses.
Fi gure 15-25. Schemat ic diagram show ing error-based cerebellar and rew ard-based basal ganglia f eedback input s t o t he cerebral cort ex.
The possibilit y t hat t he cerebellum may be involved in nonmot or f unct ion w as f irst suggest ed by phrenologist s in t he eight eent h and ninet eent h cent uries and by lat er st udies dat ing back almost half a cent ury. The f ounder of phrenology, Franz G all, considered t he primary f unct ion of t he cerebellum t o be a locus of t he emot ion of love. Report s of neuropsychological dysf unct ion in pat ient s w it h development al and acquired cerebellar pat hology and neuroimaging st udies in normal adult s have given credence t o t he proposed involvement of t he cerebellum in higher-order nonmot or processes. Psychiat ric disorders (schizophrenia, manic depression, and dement ia) have been report ed in associat ion w it h cerebellar agenesis or hypoplasia by some aut hors but not by ot hers. Damage t o t he cerebellum has been show n t o impair rapid and accurat e ment al shif t s of at t ent ion bet w een and w it hin sensory modalit ies. I ncreased planning and w ord-ret rieval t ime have been described in pat ient s w it h cort ical cerebellar at rophy; prof ound def icit s in pract ice-relat ed nonmot oric learning have been report ed in associat ion w it h right -sided cerebellar inf arct s; and t ransient mut ism has been report ed f ollow ing post erior f ossa craniect omy f or cerebellar t umors and f ollow ing bilat eral st ereot act ic lesions of t he dent at e nucleus. Mut ism and agrammat ic, Broca's aphasia-like speech have also been described w it h right cerebellar inf arct s. Dat a f rom posit ron-emission t omography (PET), f unct ional magnet ic resonance imaging (f MRI ), and single phot on emission comput ed t omography (SPECT) seem t o conf irm a role f or t he cerebellum in nonmot or f unct ion. Neocerebellar areas are met abolically act ive during language and cognit ive processes such as t he associat ion of verbs t o nouns, ment al imagery, ment al arit hmet ic, mot or ideat ion, and learning t o recognize complicat ed f igures, w hereas vermal and paravermal st ruct ures are met abolically act ive during panic and anxiet y st at es. Development al dyslexia and aut ism have been report ed in development al cerebellar disorders. Tabl e 15-4. Functions of Cerebellum
Region
Motor function (established)
Nonm otor function (proposed) Primitive autonomic
Archicerebellum
Neocerebellum
Equilibrium and posture
Coordination of extremity movement
responses, emotion, affect, sexuality, affectively important memory ( l imbic cerebellum) Modulation of thought, planning, strategy formation, spatial and temporal parameters, learning, memory, language
St imulat ion of t he f ast igial nucleus in animals has been report ed t o produce an alert ing react ion, grooming response, savage predat ory at t ack, and out burst s of sham rage, suggest ing t hat t he f ast igial nucleus may serve a modulat ory role f or emot ional react ions. Follow ing lesions in t he cerebellar vermis, aggressive monkeys are report ed t o have become docile, and chronic cerebellar st imulat ion in humans has been report ed t o reduce anxiet y, t ension, and aggression. The report ed associat ion bet w een cerebellar disorders and cognit ion and behavior does not necessarily imply causalit y, how ever. Whet her t he cognit ive and behavioral manif est at ions report ed in cerebellar disorders are due t o t he cerebellar lesion it self or are secondary t o associat ed cerebral hemisphere dysf unct ion remains unset t led. The cerebellum and cerebral cort ex are closely relat ed anat omically and f unct ionally. Based on t he available behavioral and cognit ive dat a, a new concept of cerebellar f unct ion has evolved t hat assigns t o each cerebellar lobe a role in behavior and cognit ion (Table 15-4). Thus t he archicerebellum may be concerned not only w it h cont rol of equilibrium and post ure but also w it h primit ive def ense mechanism such as t he f ight or f light response, emot ion, aff ect , and sexualit y, w hereas t he neocerebellum may be concerned, in addit ion t o coordinat ion of rapid movement of t he ext remit ies, w it h modulat ion of t hought , planning, st rat egy f ormat ion, spat ial and t emporal paramet ers, learning, memory, and language.
The Cerebellum and Autism I n 1987, Courchesne and colleagues w ere t he f irst t o report hypoplasia of cerebellar vermis and hemispheres in MRI scans of aut ist ic pat ient s and t o suggest t hat t he abnormalit y may be responsible f or t he def icit s in at t ent ion,
sensory modulat ion, and mot or and behavioral init iat ion seen in t his disorder. I n subsequent imaging st udies, vermal hypoplasia and hyperplasia as w ell as normal cerebellar morphology have been report ed. Neuropat hologic st udies of aut ist ic pat ient s describe loss of Purkinje and granule cells in t he vermis and hemispheres as w ell as neurons in nucleus f ast igii of possible prenat al onset . The cerebellum, how ever, is not t he only sit e in t he cent ral nervous syst em t o be impaired in aut ist ic disorders. O t her st udies have show n reduct ion in t he size of t he brain st em, post erior port ion of corpus callosum, pariet al lobes, amygdala, and hippocampus.
Fi gure 15-26. Phot ograph of t he vent ral surf aces of t he cerebellum show ing t he t errit ories of art erial supply.
Fi gure 15-27. Phot ograph of t he dorsal surf aces of t he cerebellum show ing t he t errit ories of art erial supply.
SENSORY SYSTEM S AND CEREBELLUM Alt hough t he cerebellum is generally regarded as a mot or cent er, st udies suggest t hat it has a role in sensory mechanisms. The cerebellum has been show n t o receive t act ile, visual, and audit ory impulses. Furt hermore, reciprocal connect ions have been demonst rat ed bet w een t he cerebral and cerebellar t act ile, visual, and audit ory areas.
ARTERIAL SUPPLY The cerebellum is supplied by t hree long circumf erent ial art eries arising f rom t he vert ebral basilar syst em: (1) t he post erior inf erior cerebellar art ery (PI CA), (2) t he ant erior inf erior cerebellar art ery (AI CA), and (3) t he superior cerebellar art ery (SCA). The post erior inf erior cerebellar art ery (PI CA) arises f rom t he rost ral end of t he vert ebral art ery and supplies most of t he inf erior surf ace of t he cerebellum (Figure 15-26), including t he cerebellar hemispheres, inf erior vermis, and t he t onsils. I t also supplies t he choroid plexus of t he f ourt h vent ricle and gives collat erals f rom it s medial branch t o supply t he dorsolat eral medulla. The ant erior inf erior cerebellar art ery (AI CA) arises f rom t he caudal t hird of t he basilar art ery. Because of it s usual small size, it supplies a small area of t he ant erolat eral part of t he inf erior surf ace of t he cerebellum (Figure 15-26). Proximal branches of t he art ery usually supply t he lat eral port ion of t he pons,
including t he f acial, t rigeminal, vest ibular, and cochlear nuclei, t he root s of t he f acial and cochleovest ibular cranial nerves, and t he spinot ha-lamic t ract . When t here is a large AI CA, t he ipsilat eral PI CA is usually hypoplast ic, and t he AI CA t errit ory t hen encompasses t he w hole ant eroinf erior aspect of t he cerebellum. The superior cerebellar art ery (SCA) is t he most const ant in caliber and t errit ory of supply. I t arises f rom t he rost ral basilar art ery. The SCA supplies most of t he superior surf ace of t he cerebellar hemisphere and vermis (Figure 15-27) as w ell as t he deep cerebellar nuclei. Along it s course, branches of t he SCA supply t he lat eral t egment um of t he rost ral pons, including t he superior cerebellar peduncle, spinot halamic t ract , lat eral lemniscus, descending sympat het ics, and more dorsally, t he root of t he t rochlear nerve. The t hree circumf erent ial art eries and t heir branches are connect ed by numerous f ree cort ical anast omoses t hat help limit t he size of t he inf arct w it h cerebellar, vert ebral, or basilar art ery occlusions.
VENOUS DRAINAGE The cerebellum is drained by t hree veins: superior, post erior, and ant erior. The superior vein drains t he ent ire superior surf ace of t he cerebellum and empt ies int o t he great cerebral vein of G alen. The post erior vein drains t he post erior part of t he inf erior surf ace and empt ies int o t he st raight or t ransverse sinus. The ant erior vein, know n t o neurosurgeons as t he pet rosal vein, is a const ant vein t hat drains t he inf eroant erior surf ace of t he cerebellum and empt ies int o t he superior or inf erior pet rosal sinus.
TERM INOLOGY Archicerebellum (G reek arche, b eginning ) . Phylogenet ically old part of t he cerebellum concerned w it h equilibrium and post ure. Astasia (G reek a, w ithout stasi s, stand). Mot or incoordinat ion. Asthenia. (G reek a, w ithout sthenos, s trength ) . The ast henic habit us is a t hin, f rail person. Asynergia (G reek synergi a, c ooperation ) . Lack of coordinat ion among part s. Dist urbance of proper associat ion in t he cont ract ion of muscles t hat ensures t hat t he diff erent component s of an act f ollow in proper sequence and at t he proper moment so t hat t he act is execut ed accurat ely. Ataxia (G reek taxi s, o rder ) . Want of order; lack of coordinat ion, result ing in unst eadiness of movement . The t erm w as used by Hippocrat es and G alen f or any morbid st at e, especially one
w it h disordered or irregular act ion of any part , such as irregularit y of t he pulse. Brachium (Latin a rm ). Denot es a discret e bundle of int erconnect ing f ibers. Cerebellum (Latin l ittle brain ) . The hind brain, locat ed in t he post erior f ossa. Cuvier, Baron de la (1769 1 832). French anat omist and nat uralist . He is best know n f or classif icat ion of t he animal w orld in his La Régne Ani mal published in 1817. Dentate nucleus (Latin dentatus, t oothed ) . Like a t oot h. Dysmetria (G reek dys, d ifficult metron, a measure ). Diff icult y in accurat ely cont rolling (measuring) t he range of movement . O ccurrence of errors in judgment of dist ance w hen a limb is made t o perf orm a precise movement . Emboliform nucleus (G reek embol os, p lug Latin forma, f orm ) . Plug-shaped. The embolif orm nucleus plugs t he opening of t he dent at e nucleus. Fastigial nucleus (Latin fasti gi um, a pex of a gabled, pointed roof ). The roof nucleus. The nucleus f ast igii is locat ed in t he point ed roof of t he f ourt h vent ricle. Fluorens, Marie-Jean-Pierre (1794 1 867). French comparat ive anat omist w ho suggest ed t hat f unct ions w ere precisely locat ed in many part s of t he cerebral cort ex. He ident if ied t he cerebellum as concerned w it h mot or coordinat ion, alt hough he w rongly supposed t hat t his cont rol is exert ed cont ralat erally. He correct ly ascribed t o t he vest ibular syst em a role in vert igo and nyst agmus. G all, Franz (1758 1 829). Viennese physician and anat omist . Founder of t he discipline of phrenology, and f at her of cerebral localizat ion. Described t he cervical and lumbar enlargement s of t he spinal cord, diff erent iat ed gray f rom w hit e mat t er, and described t he origins of t he opt ic, oculomot or, t rochlear, and abducens cranial nerves. He is best know n, how ever, f or cerebral localizat ion of f unct ion. He isolat ed 26 brain areas and relat ed t hem t o int ellect , sent iment s, and ment al at t ribut e m ost of w hich t urned out t o be ill-f ounded. Af t er decades of success, t he discipline of phrenology f ell int o disreput e w hen it w as claimed as a met hod f or select ing members of parliament among ot hers. G lobose nucleus (Latin gl obus, a ball ). Rounded. The globose nucleus is rounded (spherical) in shape. G lomerulus (Latin gl omero, t o wind into a ball ).
Small, rounded synapt ic conf igurat ion around mossy f iber roset t es. G olgi, Camillo (1844 1 926). I t alian anat omist w hose st aining met hod (developed in his kit chen) allow ed t he f ull descript ion of neuronal morphology. Described t w o t ypes of cort ical cells in 1880. The G olgi neuron of t he cerebellum is t he t ype I I G olgi neuron. Type I neurons have long axons t hat t erminat e at a dist ance. He w as t he f irst t o describe dendrit es and shared t he Nobel prize f or 1906 w it h Ramon y Cajal, w it h w hom his relat ionship w as poor. Holmes, Sir G ordon (1876 1 965). I rish neurologist . Had int erest in spinal cord t ract s and t heir connect ions. As consult ant neurologist t o t he Brit ish army during World War O ne, he and Sir Percy Sargent , his neurosurgical colleague, t reat ed hundreds of soldiers w it h head injuries. This experience provided him an opport unit y t o st udy t he eff ect s of lesions in specif ic brain regions on balance, vision, and bladder f unct ion. Luciani, Luigi (1840 1 919). I t alian physiologist . Pioneer in cerebellar physiology. He made many import ant cont ribut ions t o t he physiology of t he nervous syst em, including t he cerebellar t riad of at onia, ast henia, and ast asia as w ell as cort ical pat hogenesis of epilepsy. He is best know n f or t w o monographs: t he physi-ology of st arvat ion in man and t he physiology and pat hology of t he cerebellum. Magendie, Francois (1783 1 855). French physiologist . Credit ed w it h int roducing t he met hods of experiment al physiology int o pharmacology and pat hology. Wit h Sir Charles Bell, he developed t he Bell-Magendie law (ant erior spinal root s being mot or and post erior spinal root s sensory). He described t he CSF in 1827, and t he f oramen of Magendie in t he roof of t he f ourt h vent ricle in 1842. Neocerebellum (G reek neos, n ew Latin cerebel l um, s mall brain ). Phylogenet ically new part of t he cerebellum. Nystagmus (G reek nystagmos, n odding in sleep ). Rhyt hmic involunt ary oscillat ory movement s of t he eyes. The t erm is said t o have been f irst used by Plenck. The associat ion of t hese eye movement s w it h vert igo w as f irst not ed by Purkinje and f urt her invest igat ed by Flourens. Paleocerebellum (G reek pal ai os, a ncient Latin cerebel l um, l ittle brain ). Phylogenet ically old part of t he cerebellum. Peduncle (Latin peduncul us, l ittle foot ). St emlike or st alklike process by w hich an anat omic part is joined t o t he main organ. The cerebellar peduncles connect t he brain st em w it h t he cerebellum. Purkinje, Johannes Evangelista von (1787 1 869). Bohemian priest and prof essor of physiology at Breslau and Prague. Described t he Purkinje cells in t he cerebellum in 1837. Besides his prof essional dut ies, he
served as new spaper edit or and member of t he Czech parliament . His int erest in experiment at ion led him t o induce seizures in himself by t aking camphor. Because of his et hnicit y and his eclect ic research, he w as know n as t he g ypsy physiologist . Restiform body (Latin resti s, c ord or rope forma, f orm or shape ). The inf erior cerebellar peduncle has a cordlike appearance on t he dorsolat eral surf ace of t he medulla. The rest if orm body w as described and named by Humphrey Ridley (1653 1 708), an English anat omist , in Anatomy of the Brai n (London, 1695, p. 78). Rolando, Luigi (1773 1 831). I t alian anat omist . Best know n f or describing t he cent ral sulcus in 1825 (named af t er him by Leurat in 1839). Leurat w as unaw are of t he earlier descript ion by Vicq d'Azir. He also is accredit ed f or describing t he subst ant ia gelat inosa of t he spinal cord and ipsilat eral mot or f unct ion of t he cerebellum. Tentorium cerebelli (Latin tentori um, a tent ). Horizont al dural f old bet w een t he cerebellum and cerebral hemisphere. The t erm w as adopt ed near t he end of t he 18t h cent ury. Vermis (Latin a worm ). The midline port ion of t he cerebellum. The appearance of it s f olia bears a resemblance t o t he segment ed body of a w orm.
SUGGESTED READINGS Ackermann H et al: Speech def icit s in ischaemic cerebellar lesions. J Neurol 1992; 239: 223 2 27. Amarenco P: The spect rum of cerebellar inf arct ions. Neurol ogy 1991; 41: 973 9 79. Appollonio I M et al: Memory in pat ient s w it h cerebellar degenerat ion. Neurol ogy 1993; 43: 1536 1 544. Apps R: Movement -relat ed gat ing of climbing f iber input t o cerebellar cort ical zones. Prog Neurobi ol 1999; 57: 537 5 62. Blakemore SJ et al: Why can't you t ickle yourself ? Neuro Report 2000; 11: R11 R 16. Brodal P, Bjaalie JG : Salient anat omic f eat ures of t he cort ico-pont ocerebellar pat hw ay. Prog Br Res 1997; 114: 227 2 49.
Brow n-G ould B: The organizat ion of aff erent s t o t he cerebellar cort ex in t he cat : Project ions f rom t he deep cerebellar nuclei. J Comp Neurol 1979; 184: 27 4 2. Chaves CJ et al: Cerebellar inf arct s. Curr Neurol 1994; 14: 143 1 77. Cody FWJ, Richardson HC: Mossy and climbing f iber project ions of t rigeminal input s t o t he cerebellar cort ex in t he cat . Brai n Res 1978; 153: 352 3 56. Courchesne E et al: Abnormal neuroanat omy in a nonret arded person w it h aut ism: Unusual f indings w it h magnet ic resonance imaging. Arch Neurol 1987; 44: 335 3 41. Courville J, Faraco-Cant in F: O n t he origin of t he climbing f ibers of t he cerebellum: An experiment al st udy in t he cat w it h an aut oradiographic t racing met hod. Neurosci ence 1978; 3: 797 8 09.
Daum I , Ackermann H: Cerebellar cont ribut ions t o cognit ion. Behav Brai n Res 1995; 67: 201 2 10. Diamond A: Close int errelat ion of mot or development and cognit ive development and of t he cerebellum and pref ront al cort ex. Chi l d Dvl pt 2000; 71: 44 5 6. Diet richs E et al: Hypot halamocerebellar and cerebellohypot halamic project ions: Circuit s f or regulat ing nonsomat ic cerebellar act ivit y? Hi stol Hi stopathol 1994; 9: 603 6 14. Doya K: Complement ary roles of basal ganglia and cerebellum in learning and mot or cont rol. Curr O p Neurobi ol 2000; 10: 732 7 39. Est anol B et al: Eff ect of cerebellect omy on eye movement s in man. Arch Neurol 1979; 36: 281 2 84. Fiez JA: Cerebellar cont ribut ions t o cognit ion. Neuron 1996; 16: 13 1 5. G helarducci B, Sebast iani L: Cont ribut ion of t he cerebellar vermis t o cardiovascular cont rol. J Autonomi c Nerv Syst 1996; 56: 149 1 56. Haines DE et al: The cerebellar hypot halamic axis: Basic circuit s and clinical
observat ions. Int Rev Neurobi ol 1997; 41: 83 1 07. Houk JC, Wise SP: Dist ribut ed modular archit ect ures linking basal ganglia, cerebellum, and cerebral cort ex: Their role in planning and cont rolling act ion. Cerebral Cortex 1995; 2: 95 110. I t o M: Recent advances in cerebellar physiology and pat hology. I n Kark RAP et al (eds): Advances i n Neurol ogy, vol 21. New York, Raven Press, 1978: 59. I t oh K, Mizuno N: A cerebello-pulvinar project ion in t he cat as visualized by t he use of ant erograde t ransport of horseradish peroxidase. Brai n Res 1979; 171: 131 1 34. Juept ner M et al: Localizat ion of a cerebellar t iming process using PET. Neurol ogy 1995; 45: 1540 1 545. Juept ner M, Weiller C: A review of diff erences bet w een basal ganglia and cerebellar cont rol of movement s as revealed by f unct ional imaging st udies. Brai n 1998; 121: 1437 1 449. Leiner HC et al: Reappraising t he cerebellum: What does t he hindbrain cont ribut e t o t he f orebrain? Behav Neurosci 1989; 103: 998 1 008. Leiner HC et al: The human cerebro-cerebellar syst em: I t s comput ing, cognit ive, and language skills. Behav Brai n Res 1991; 44: 113 1 28. Leiner HC et al: The role of t he cerebellum in t he human brain. TINS 1993; 16: 453 4 54. Leiner HC et al: Cognit ive and language f unct ions of t he human cerebellum. TINS 1993; 16: 444 4 47. Macklis RM, Macklis JD: Hist orical and phrenologic ref lect ions on t he nonmot or f unct ions of t he cerebellum: Love under t he t ent ? Neurol ogy 1992; 42: 928 9 32. Manni E, Pet rosini L: Luciani's w ork on t he cerebellum a cent ury lat er. TIN 1997; 20: 112 116. Marien P et al: The lat eralized linguist ic cerebellum: A review and a new hypot hesis. Brai n & Language 2001; 79: 580 6 00.
Marien P et al: Cerebellar neurocognit ion: A new avenue. Acta Neurol Bel gi ca 2001; 101: 96 1 09. Mauk MD et al: Cerebellar f unct ion: Coordinat ion, learning or t iming? Curr Bi ol 2000; 10: R522 R 525. Middlet on FA, St rick PL: Anat omical evidence f or cerebellar and basal ganglia involvement in higher cognit ive f unct ion. Sci ence 1994; 266: 458 4 61. Middlet on FA, St rick PL: Basal ganglia and cerebellar loops: Mot or and cognit ive circuit s. Br Res-Br Res Rev 2000; 31: 236 2 50. Murat ori F et al: Aut ism and cerebellum. An unusual f inding w it h MRI . Panmi nerva Medi ca 2001: 43: 311 3 15. Nadvornik P et al: Experiences w it h dent at omy. Conf i n Neurol 1972; 34: 320 3 24. Nicolson R et al: Development al dyslexia: The cerebellar def icit hypot hesis. TIN 2001; 24: 508 5 11. Pet rosini L et al: The cerebellum in t he spat ial problem solving: A co-st ar or a guest st ar? Prog Neurobi ol 1998; 56: 191 2 10. Rapoport M et al: The role of t he cerebellum in cognit ion and behavior: A select ive review. J Neuropsychi at Cl i n Neurosci 2000; 12: 193 1 98. Rekat e HL et al: Mut eness of cerebellar origin. Arch Neurol 1985; 42: 697 6 98. Robinson FR, Fuchs AF: The role of t he cerebellum in volunt ary eye movement s. Ann Rev Neurosci 2001; 24: 981 1 004. Roland PE: Part it ion of t he human cerebellum in sensory-mot or act ivit ies, learning and cognit ion. Can J Neurol Sci 1993; 20(suppl 3): S75 S 77. Ryding E et al: Mot or imagery act ivat es t he cerebellum regionally: A SPECT rCBF st udy w it h Tc -HMPAO . Cogn Brai n Res 1993; 1: 94 9 9. Sasaki K et al: Project ions of t he cerebellar dent at e nucleus ont o t he f ront al associat ion cort ex in monkeys. Exp Brai n Res 1979; 37: 193 1 98.
Schmahmann JD: An emerging concept : The cerebellar cont ribut ion t o higher f unct ion. Arch Neurol 1991; 48: 1178 1187. Shinoda Y et al: Thalamocort ical organizat ion in t he cerebello-t halamo-cort ical syst em. Cerebral Cortex 1993; 3: 421 4 29. van Dongen HR et al: The syndrome of c erebellar mut ism and subsequent dysart hria. Neurol ogy 1994; 44: 2040 2 046. Voogd J: The morphology of t he cerebellum: The last 25 years. Eur J Morphol 1992; 30: 81 9 6.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 16 - C er ebellum : C linic al C or r elates
16 Cerebellum: Clinical Correlates
Clinical Manifestations Cerebellar Syndrom es Experimental Animals Humans Vascular Syndrom es Superior Cerebellar Artery (SCA) Syndrome Anterior Inferior Cerebellar Artery (AICA) Syndrome Posterior Inferior Cerebellar Artery (PICA) Syndrome Developm ental Syndrom es Chiari Malformation Dandy-W alker Malformation Cerebellar Hypoplasia KEY CONCEPTS Signs of cerebellar disease are ipsilateral to the side of the cerebellar lesion. Lesions of the vermis are manifest by abnormalities in trunk movements, whereas lesions of the cerebellar hemispheres are manifested by abnormalities of movement in the extremities. Midline cerebellar syndrome is manifested by
unsteadiness of gait and nystagmus. Lateral (hemispheral, neocerebellar) syndrome is manifested by ataxia, dysmetria, dyssynergia, dysdiadochokinesia, intention tremor, muscular hypotonia, dysarthria, and nystagmus. Three vascular cerebellar syndromes are well defined: superior cerebellar artery (SCA) syndrome, anterior inferior cerebellar artery (AICA) syndrome, and posterior inferior cerebellar artery syndrome (PICA). The SCA and PICA syndromes are more frequently encountered than the AICA syndrome.
Early descript ions of cerebellar clinical sympt oms and signs came f rom st udies of pat ient s w it h heredof amilial (e. g. , Friedreich's at axia) and demyelinat ing (e. g. , mult iple sclerosis) disorders, bot h of w hich involve, in addit ion t o t he cerebellum, many ext racerebellar areas in t he brain st em and spinal cord. I n t he f irst quart er of t he 20t h cent ury, G ordon Holmes est ablished t he t riad of cerebellar signs of ast henia (f at igabilit y), at axia (incoordinat ion, unst eadiness), and at onia (decreased muscle t one). He derived his t riad f rom observat ion of pat ient s w it h cerebellar injuries during World War I . At t empt s at anat omicoclinical correlat ions of cerebellar signs ut ilizing pat ient s w it h cerebellar st rokes w ere not rew arding. Localizing signs could not be elicit ed in unconscious st roke pat ient s and w ere present in less t han half t he conscious pat ient s. The int roduct ion in t he mid1970s of comput ed t omography (CT) scans and in t he 1980s of magnet ic resonance imaging (MRI ) and magnet ic resonance art eriography (MRA), coupled w it h bet t er def init ion of cerebellar vascular t errit ories, permit t ed a more accurat e anat omicoclinical correlat ion in cerebellar disorders.
CLINICAL M ANIFESTATIONS Clinical cerebellar disorders are associat ed w it h a variet y of et iologies: congenit al malf ormat ions, heredit ary, met abolic, inf ect ious, t oxic, vascular, demyelinat ing, and neoplast ic. Cerebellar disorders share t he f ollow ing clinical charact erist ics: 1.
I psilat eral signs
2. Abnormalit ies in limb movement s (appendicular at axia) associat ed w it h lat eral cerebellar hemisphere lesions
3.
Abnormalit ies in t runk movement s (t runcal at axia) associat ed w it h midline vermis lesions
4. Lesions in deep cerebellar nuclei or t he superior cerebellar peduncle producing more severe signs t han lesions in t he cerebellar cort ex 5. Signs of cerebellar disease t ending t o improve w it h t ime, especially w hen t he lesion occurs in childhood and t he underlying disease is nonprogressive
CEREBELLAR SYNDROM ES The classically described archicerebellar, paleocerebellar, and neocerebellar syndromes in experiment al animals f ollow ing ablat ion of t he respect ive lobes of t he cerebellum are not ordinarily observed in humans. I nst ead, in humans, t w o cerebellar syndromes are clearly delineat ed: midline (archicerebellar and paleocerebellar) and lat eral cerebellar hemisphere (neocerebellar).
Experimental Animals A. ARCHICEREBELLAR SYNDROM E The archicerebellum (f locculonodular lobe) is relat ed t o t he vest ibular syst em. I t receives f ibers f rom t he vest ibular nuclei and nerve and project s t o t he vest ibular and ret icular nuclei, w hich in t urn project t o t he spinal cord (via t he vest ibulospinal and ret iculospinal t ract s) and ocular mot or syst em (via t he medial longit udinal f asciculus). The f unct ion of t his syst em is t he cont rol of body equilibrium and eye movement s. Ablat ion of t he f locculonodular lobe in experiment al animals produces nyst agmus and dist urbances in body equilibrium (t runcal at axia).
B. PALEOCEREBELLAR SYNDROM E The paleocerebellum is f unct ionally relat ed t o t he spinal cord and is concerned w it h post ure, muscle t one, and gait . Ablat ion of t he paleocerebellum in animals produces decerebrat e rigidit y and an increase in myot at ic and post ural ref lexes.
C. NEOCEREBELLAR SYNDROM E The neocerebellum is f unct ionally relat ed t o t he cerebral cort ex and plays a role in planning and init iat ion of movement as w ell as t he regulat ion of discret e limb movement s.
Humans A. M IDLINE SYNDROM E
A pict ure corresponding t o t he archicerebellar (f locculonodular lobe) syndrome is of t en seen in children w it h a special t ype of t umor, t he medulloblast oma. This t umor almost alw ays arises in t he most post erior part of t he vermis and is manif est ed by unst eadiness of gait and nyst agmus. The paleocerebellar syndrome as described in experiment al animals is usually not encount ered in humans. How ever, some pat ient s w it h at rophy of t he cerebellum demonst rat e unst eadiness of gait and increased myot at ic ref lexes in t he low er limbs. I t is believed t hat in such pat ient s t he ant erior lobe is aff ect ed primarily by t he at rophy.
B. CEREBELLAR HEM ISPHERE SYNDROM E Lesions of t he cerebellar hemispheres (neocerebellum) produce t he f ollow ing manif est at ions: Ataxia: A drunken, unst eady gait . Dysmetria: I nabilit y t o est imat e t he range of volunt ary movement . I n at t empt ing t o t ouch t he t ip of t he f inger t o t he t ip of t he nose, a pat ient w ill overshoot t he f inger past t he nose t o t he cheek or ear. Decomposition of movement (dyssynergia): Jerky and t remulous volunt ary movement s. I n at t empt ing t o t ouch t he nose w it h t he f inger or t o move t he heel over t he shin, t he pat ient 's movement s are uneven and jerky t hroughout t he range of mot ion. Adiadochokinesia (dysdiadochokinesia): I nabilit y t o perf orm rapid successive movement s such as t apping one hand on t he ot her in an alt ernat ing supinat ion and pronat ion sequence. Intention tremor: Terminal t remor as t he moving limb approaches it s t arget . Muscular hypotonia: Decrease in muscular t one and in t he resist ance t o passive st ret ching of muscles. Dysarthria: Slurred, hesit at ing t ype of speech. Nystagmus: Nyst agmus is f requent ly observed in cerebellar hemisphere lesions w it h t he f ast component t o t he side of t he cerebellar lesion.
C. PANCEREBELLAR SYNDROM E This syndrome is a combinat ion of t he preceding t w o syndromes and is charact erized by bilat eral signs of cerebellar dysf unct ion involving t he t runk, limbs, and eyes. The cerebellum is w ell know n f or it s abilit y t o compensat e f or it s def icit s. The compensat ion is especially marked in children. The mechanisms underlying t his abilit y t o compensat e are not know n. The assumpt ion of lost cerebellar f unct ions
by ot her noncerebellar st ruct ures or by remaining part s of t he cerebellum are t w o explanat ions f or t his compensat ion.
VASCULAR SYNDROM ES Superior Cerebellar Artery (SCA) Syndrome (Figure 161) This is t he most f requent ly encount ered vascular syndrome of t he cerebellum. Clinical signs include ipsilat eral dysmet ria, limb at axia, and Horner's syndrome, cont ralat eral pain and t hermal sensory loss, and cont ralat eral t rochlear nerve palsy. Horner's syndrome, t he pain and t hermal sensory def icit s, and t rochlear nerve palsy are due t o involvement of t he brain st em t egment um. Dysart hria is common and is charact erist ic of rost ral cerebellar lesions, w hereas vert igo is not as common in SCA inf arct s and is more charact erist ic of t he post erior inf erior cerebellar art ery (PI CA) syndrome. I solat ed dysart hria (w it hout ot her cerebellar signs) has been report ed in occlusion of t he medial branch of t he superior cerebellar art ery w it h an inf arct limit ed t o t he paravermal area. Prognosis f or recovery in SCA syndrome is usually good.
Fi gure 16-1. T1-w eight ed parasagit t al MR image show ing a cerebellar inf arct (arrow) in t he dist ribut ion of t he superior cerebellar art ery (SCA).
Anterior Inferior Cerebellar Artery (AICA) Syndrome O cclusion of t he ant erior inf erior cerebellar art ery (AI CA) is uncommon, and of t en is misdiagnosed as t he lat eral medullary syndrome (PI CA syndrome). I t is
charact erized by ipsilat eral dysmet ria, vest ibular signs, Horner's syndrome, f acial sensory impairment , cont ralat eral pain and t hermal sensory loss in t he limbs, and at t imes, dysphagia. O t her signs seen in t his syndrome and unusual in t he lat eral medullary syndrome include ipsilat eral severe f acial mot or palsy, deaf ness, lat eral gaze palsy, and mult imodal sensory impairment over t he f ace due t o involvement of f acial, cochleovest ibular, abducens, and t rigeminal nerves and/ or nuclei, respect ively. AI CA occlusion also can be manif est by purely cerebellar signs.
Posterior Inferior Cerebellar Artery (PICA) Syndrome (Figure 16-2) This syndrome is as f requent as t he superior cerebellar art ery (SCA) syndrome. Clinical f eat ures of t he syndrome are described in t he chapt er on clinical correlat es of t he medulla oblongat a (Chapt er 6). O cclusion of t he medial branch of t he PI CA may be clinically silent or may present w it h one of t he f ollow ing t hree pat t erns: (1) isolat ed vert igo of t en misdiagnosed as inner ear disease (labyrint hit is), (2) vert igo, ipsilat eral axial lat eropulsion (involunt ary t endency t o go t o one side w hile in mot ion), and dysmet ria or unst eadiness, or (3) classic lat eral medullary syndrome w hen t he medulla is also involved in t he lesion.
Fi gure 16-2. T1-w eight ed parasagit t al MR image show ing a cerebellar inf arct (arrow) in t he dist ribut ion of t he post erior inf erior cerebellar art ery (PI CA).
Clinical manif est at ions of occlusion of t he lat eral branch of t he PI CA are unknow n, since report ed cases have been chance aut opsy f indings w it h no available clinical inf ormat ion.
DEVELOPM ENTAL SYNDROM ES Chiari Malformation (Figure 16-3) The Chiari malf ormat ion w as f irst described by Cleland in 1883. Chiari provided det ailed neuropat hologic descript ions in 1891 and 1896, and he proposed a classif icat ion syst em t hat is st ill used. Three t ypes of Chiari malf ormat ion are recognized. Type I. I n t his t ype, t he inf erior pole of t he cerebellar hemispheres prot rude t hrough t he f oramen magnum. Most pat ient s are asympt omat ic, and t he malf ormat ion is of t en f ound incident ally on MRI . O ccasionally, pat ient s present w it h headache, usually associat ed w it h occipit al and neck pain and exacerbat ed by coughing and st raining. Hydromyelia or syringomyelia may be associat ed w it h Chiari malf ormat ion. Type II. I n t his t ype, in addit ion t o t he prot rusion of t he cerebellum, t he medulla oblongat a prot rudes t hrough t he f oramen magnum, result ing in kinking of t he cervical medullary junct ion. Part of t he f ourt h vent ricle is also displaced caudally. The f oramina of Magendie and Luschka are occluded. The malf ormat ion is f requent ly associat ed w it h hydromyelia or syringomyelia, hydrocephalus, and meningomyelocele. Type I I Chiari malf ormat ion is f requent ly ref erred t o as t he Arnold-Chiari malf ormat ion. The t erm w as coined in 1907 by t w o st udent s of Arnold based on Arnold's descript ion of t he malf ormat ion in 1895. Pat ient s w it h t ype I I malf ormat ion are sympt omat ic. They present w it h dysphonia, respirat ory st ridor, sw allow ing diff icult ies, and ot her sympt oms. Type III. This malf ormat ion has f eat ures of t ypes I and I I as w ell as herniat ion of t he ent ire cerebellum int o a high cervical meningocele. Hydrocephalus is a const ant f inding.
Dandy-Walker Malformation (Figure 16-4) This malf ormat ion is charact erized by a t riad of (1) complet e or part ial agenesis of t he cerebellar vermis, (2) cyst ic dilat ion of t he f ourt h vent ricle, and (3) an enlarged post erior f ossa w it h upw ard displacement of t he t ent orium, t orcula, and t ransverse sinus. Hydrocephalus is f requent ly present . Ment al ret ardat ion is also common. The malf ormat ion w as f irst described by Dandy and Blackf an in 1914 and review ed by Taggart and Walker in 1942. The t erm Dandy-Walker malf ormat ion w as coined by Benda in 1954. The malf ormat ion had been described in 1887 by Sut t on and possibly by Virchow in 1863. Pat ient s present w it h hydrocephalus. Ment al ret ardat ion is f requent .
Cerebellar Hypoplasia
Cerebellar hypoplasia ref ers t o incomplet e development of t he cerebellum. O n imaging, t he cerebellum appears small, t he cerebellar sulci and f issures are prominent , and t he subarachnoid cerebellar cist ern (cist erna magna) and f ourt h vent ricle are markedly enlarged. Cerebellar hypoplasia may occur alone or associat ed w it h malf ormat ions elsew here in t he brain. The malf ormat ion may be sporadic, f amilial, or associat ed w it h chromosomal anomalies or met abolic disorders. Pat ient s may be asympt omat ic or may present w it h hypot onia and ot her cerebellar signs.
Fi gure 16-3. Midsagit t al MRI of brain show ing cerebellar herniat ion t hrough t he f oramen magnum (Chiari malf ormat ion) and associat ed spinal cord syrinx.
TERM INOLOGY
Arnold, Julius (1835 1 915). G erman physician w ho described t ype I I Chiari malf ormat ion in 1895. He also described superior laryngeal neuralgia. His f at her, Friedrich Arnold (1803 1 890) described t he f ront opont ine t ract and made precise diff erent iat ion bet w een t he f ront al, pariet al, occipit al, and t emporosphenoidal lobes. Ataxia (G reek taxi s, o rder ) . Want of order, lack of coordinat ion, result ing in unst eadiness of movement . The t erm w as used by Hippocrat es and G alen f or any morbid st at e, especially one w it h disordered or irregular act ion of any part , such as irregularit y of t he pulse. Chiari, Hans (1851 1 916). Aust rian pat hologist . Described t ype I Chiari malf ormat ion in 1891 and 1896. Dandy, Walter Edward (1886 1 946). American neurosurgeon and st udent of Cushing, w it h w hom he did not get along. Described t he Dandy-Walker malf ormat ion in 1914.
Fi gure 16-4. Axial MRI of t he brain show ing Dandy-Walker malf ormat ion. Dysarthria (G reek dys, d ifficult arthroun, t o articulate ). The indist inct pronunciat ion of w ords usually result ing f rom dist urbances in t he muscular cont rol of t he speech mechanism. Dysdiadochokinesia (G reek dys, d ifficult di adochos, s ucceeding ki nesi s,
m otion ) . I mpairment of t he abilit y t o perf orm rapid alt ernat ing movement s, such as sequent ial pronat ion and supinat ion of t he arm. Dysmetria (G reek dys, d ifficult metron, a measure ). Diff icult y in accurat ely cont rolling (measuring) t he range of movement . O ccurrence of errors in judgment of dist ance w hen a limb is made t o perf orm a precise movement . Dyssynergia (G reek dys, d ifficult synergi a, c ooperation ) . Dist urbance of muscular coordinat ion bet w een cont ract ion and relaxat ion of muscles t hat normally act t oget her in a group t o produce smoot h movement . Friedreich's ataxia. Progressive heredit ary degenerat ive cent ral nervous syst em disorder charact erized by combinat ion of post erior column, lat eral cort icospinal, and spinocerebellar t ract signs. Described in 1863 by Nikolaus Friedreich, t he G erman pat hologist . Nystagmus (G reek nystagmos, n odding in sleep ). Rhyt hmic involunt ary oscillat ory movement s of t he eyes. The t erm is said t o have been f irst used by Planck. The associat ion of t hese eye movement s w it h vert igo w as f irst not ed by Purkinje and f urt her invest igat ed by Flourens.
SUGGESTED READINGS Amarenco P: The spect rum of cerebellar inf arct ions. Neurol ogy 1991; 41: 973 9 79. Amarenco P et al: I nf arct ion in t he ant erior rost ral cerebellum (t he t errit ory of t he lat eral branch of t he superior cerebellar art ery). Neurol ogy 1991; 41: 253 2 58. Amarenco P et al: Paravermal inf arct and isolat ed cerebellar dysart hria. Ann Neurol 1991; 30: 211 2 13. Amarenco P et al: Ant erior inf erior cerebellar art ery t errit ory inf arct s: Mechanisms and clinical f eat ures. Arch Neurol 1993; 50: 154 1 61. Bart h A et al: The clinical and t opographic spect rum of cerebellar inf arct s: A clinical m agnet ic resonance imaging correlat ion st udy. Ann Neurol 1993; 33: 451 4 56. Chaves CJ et al: Cerebellar inf arct s. Curr Neurol 1994; 14: 143 1 77.
Niesen CE: Malf ormat ions of t he post erior f ossa. Current perspect ive. Sem Pedi atr Neurol 2002; 9: 320 3 34. Shuman RM: The Chiari malf ormat ion: A const ellat ion of anomalies. Sem Pedi atr Neurol 1995; 2: 220 2 26.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 17 - C er ebr al C or tex
17 Cerebral Cortex
Types of Cortex Isocortex (Neocortex or Homogenetic Cortex) Allocortex (Paleocortex, Archicortex, or Heterogenetic Cortex) Mesocortex (Periallocortex, Periarchicortex) Microscopic Structure Cell Types Principal (Projection) Neurons Interneurons Layers Input to Cerebral Cortex Thalamocortical Input Extrathalamic Modulatory Input Association Fiber System Commissural Fiber System Output of Cerebral Cortex Corticospinal Pathway Aberrant Pyramidal Tract Corticoreticular Pathway Corticobulbar Pathway Corticopontine Pathway Corticothalamic Pathway Corticohypothalamic Pathway
Corticostriate Pathway Other Corticofugal Pathways Intracortical Circuitry Cortical Cytoarchitectonic Areas Cortical Sensory Areas Primary Somesthetic (General Sensory, Somatosensory) Area (SI) Secondary Somesthetic Area (SII) Supplementary Sensory Area (SSA) Primary (Unimodal)Somatosensory (Somesthetic) Association Areas Primary Visual Cortex (V1 ) Primary (Unimodal) Visual Association Areas Primary Auditory Cortex Primary (Unimodal) Auditory Association Cortex Primary Gustatory Cortex Primary Olfactory Cortex Primary Vestibular Cortex Cortical Motor Areas Primary Motor Area (MI) Supplementary Motor Area (MII) Premotor Area Cortical Eye Fields Cortical Language Areas W ernicke's Area Broca's Area The Arcuate Fasciculus Sequence of Cortical Activities during Language Processing The Right Hemisphere and Language Cortical Localization of Music Other Cortical Areas Prefrontal Cortex
Major Association Cortex T he Insula (Island of Reil) Cortical Electrophysiology Evoked Potentials Somatosensory, Visual, and Auditory Evoked Responses Electroencephalography Blood Supply Arterial Supply Venous Drainage KEY CONCEPTS The cerebral cortex receives fibers from internal and external sources. Internal sources include the cortex of the same hemisphere via association fiber bundles and the contralateral hemisphere via commissural fibers. External sources of input include the thalamus and nonthalamic subcortical sources. Corticofugal fiber system includes the corticospinal, corticoreticular, corticobulbar, corticopontine, corticothalamic, corticohypothalamic, corticostriate, and others. Based on thickness of cortex, width of the different cortical layers, cell types within each layer, and nerve fiber lamination patterns, the cerebral cortex has been divided into between 20 and 200 cytoarchitectonic areas. The most widely used classification is that of Brodmann, which contains 52 areas numbered in the order in which they were studied. There are six primary sensory cortical areas: somesthetic, visual, auditory, gustatory, olfactory,
and vestibular. The primary (unimodal) somatosensory association areas are concerned with the perception of shape, size, and texture and the identification of objects by contact (stereognosis). Three motor areas have been defined: primary motor, supplementary motor, and premotor. The cerebral areas most important for saccadic control are the posterior parietal cortex, frontal eye field, supplementary eye field, and the dorsolateral prefrontal cortex. Cortical areas for smooth pursuit movement include the posterior parietal cortex or the temporooccipitoparietal region. Two cortical areas traditionally have been associated with language function: Wernicke's and Broca's areas in the left hemisphere. The prefrontal cortex plays a role in executive function, emotion, and social behavior. The major association cortex is interconnected with all the sensory cortical areas and thus functions in higher-order, complex, multisensory perception.
The cerebral cort ex is t he layer of gray mat t er capping t he w hit e mat t er core of t he cerebral hemispheres. I t s t hickness varies f rom 1. 5 t o 4. 5 mm, w it h an average t hickness of 2. 5 mm. The cerebral cort ex is t hickest in t he primary mot or area (4. 5 mm t hick) and t hinnest in t he primary visual cort ex (1. 5 mm t hick). The cort ex is irregularly convolut ed, f orming gyri separat ed by sulci or f issures. The out er layer of t he human cerebral cort ex is around 0. 2 m2 , but only one-t hird of t his area is exposed t o t he surf ace, t he rest being buried in sulci or incorporat ed in t he insula. The number of neurons in t he cerebral cort ex is est imat ed at bet w een 10 and 20 billion. Morphomet ric st udies of t he cerebral cort ex in males and f emales demonst rat e no gender-based diff erences in cort ical
t hickness. O n t he ot her hand t hey show neuronal densit y t o be higher in t he male w it h a reciprocal increase in neuropil and neuronal processes in t he f emale. A relat ively small area of t he cerebral cort ex in humans is specialized f or receiving sensory input f rom t he eyes, ears, and skin and f or project ing mot or out put dow n t he pyramidal t ract t o bring about movement . More t han 80 percent of t he cort ex in humans serves an associat ion f unct ion specially relat ed t o int egrat ive and cognit ive act ivit ies such as language, calculat ion, planning, and abst ract reasoning.
TYPES OF CORTEX O n t he basis of phylogenet ic development and microscopic st ruct ure, t he f ollow ing t hree t ypes of cort ices are recognized.
Isocortex (Neocortex or Homogenetic Cortex) This cort ex is six layered and of recent phylogenet ic development . I t is charact erist ic of mammalian species, increases in size in higher mammals, and comprises 90% of t he cerebral cort ex in humans. I socort ex in w hich t he six layers are clearly evident (such as t he primary sensory cort ex) is t ermed homot ypical cort ex. I socort ex in w hich some of t he six layers are obscured (such as t he mot or cort ex and visual cort ex) is t ermed het erot ypical cort ex. The visual cort ex is also know n as granular cort ex or koniocort ex (f rom t he G reek koni s, meaning d ust ) . The mot or cort ex, in cont rast , is know n as agranular cort ex because of t he predominance of large pyramidal neurons.
Allocortex (Paleocortex, Archicortex, or Heterogenetic Cortex) The allocort ex is t hree layered and phylogenet ically older. I t is subdivided int o paleocort ex (rost ral insular cort ex, pirif orm cort ex, and primary olf act ory cort ex) and archicort ex (hippocampal f ormat ion).
Mesocortex (Periallocortex, Periarchicortex) This t ype of cort ex is f ound in much of t he cingulat e gyrus, ent orhinal, parahippocampal, and orbit al cort ices and is int ermediat e in hist ology bet w een t he isocort ex and allocort ex. The t erms periallocort ex and periarchicort ex are used t o ref er t o t his cort ex t o denot e it s t ransit ional nat ure bet w een neocort ex and allocort ex.
M ICROSCOPIC STRUCTURE Cell Types (Figure 17-1)
At t empt s t o make a comprehensive invent ory of t ypes of cort ical neurons st art ed w it h Ramon y Cajal in 1911 and have cont inued unt il t oday. The neurons of t he cerebral cort ex are of t w o f unct ional cat egories: (1) principal (project ion) neurons and (2) int erneurons. The principal neurons provide cort icocort ical and cort icosubcort ical out put s. I nt erneurons are concerned w it h local inf ormat ion processing. Recent evidence suggest s t hat t he t w o neuronal t ypes are generat ed in dist inct prolif erat ive zones. Principal neurons are derived f rom neuroepit helium in t he vent ricular zone. I nt erneurons, in cont rast , arise f rom t he ganglionic eminence of t he vent ral t elencephalon, w hich gives rise also t o t he basal ganglia. The cerebral cort ex has it s f ull complement of neurons (10 t o 20 billion) by t he 18t h w eek of int raut erine lif e.
Fi gure 17-1. Schemat ic diagram of t he various t ypes of cort ical neurons.
Principal (Projection) Neurons Tw o t ypes of cort ical neurons belong t o t he principal cat egory. They are t he pyramidal neurons and t he f usif orm neurons. The excit at ory neurot ransmit t er in bot h is glut amat e or aspart at e. Principal neurons const it ut e more t han half of all cort ical neurons.
A. PYRAM IDAL NEURONS (FIGURE 17-1A)
These neurons derive t heir name f rom t heir shape. The apex of t he pyramid is direct ed t ow ard t he cort ical surf ace. Each pyramidal neuron has an apical dendrit e direct ed t ow ard t he surf ace of t he cort ex and several horizont ally orient ed basal dendrit es t hat arise f rom t he base of t he pyramid. Branches of all dendrit es cont ain numerous spines t hat increase t he size of t he synapt ic area. A slender axon leaves t he base of t he pyramidal neuron and project s on ot her neurons in t he same or cont ralat eral hemisphere or else leaves t he cort ex t o project on subcort ical regions. The axon gives rise w it hin t he cort ex t o t w o t ypes of axon collat erals. These are t he recurrent axon collat erals (RACs), w hich project back on neurons in more superf icial layers, and t he horizont al axon collat erals (HACs), w hich ext end horizont ally t o synapse on neurons in t he vicinit y. Pyramidal neurons are f ound in all cort ical layers except layer I . They vary in size; most are bet w een 10 and 50 ľm in height . The largest are t he giant pyramidal cells of Bet z, w hich measure about 100 ľm in height and are f ound in layer V of t he mot or cort ex.
B. FUSIFORM , SPINDLE NEURONS (Figure 17-1C) These are small neurons w it h elongat ed perikarya in w hich t he long axis is orient ed perpendicular t o t he cort ical surf ace. A short dendrit e arises f rom t he low er pole of t he perikaryon and arborizes in t he vicinit y. A longer dendrit e arises f rom t he upper pole of t he perikaryon and ext ends t o more superf icial layers. The axon ent ers t he deep w hit e mat t er. Fusif orm neurons are f ound in t he deepest cort ical laminae.
Interneurons Several t ypes of cort ical int erneurons are recognized on t he basis of dendrit ic archit ect ure. They include t he st ellat e neurons, t he horizont al cells of Cajal, and t he cells of Mart inot t i.
A. STELLATE OR GRANULE NEURONS (Figure 17-1B) These are small (4 t o 8 ľm) st ar-shaped neurons w it h short , ext ensively branched, spiny dendrit es and short axons. They are most numerous in lamina I V. St ellat e cells are t he only t ype of excit at ory int erneurons in t he cort ex. The neurot ransmit t er is glut amat e. All ot her int erneurons exert inhibit ory inf luence by gammaaminobut yric acid (G ABA).
B. HORIZONTAL CELLS OF CAJAL (Figure 17-1D) These are small f usif orm neurons w it h t heir long axes direct ed parallel t o t he cort ical surf ace. A branching dendrit e arises f rom each pole of t he perikaryon,
and an axon arises f rom one pole. The dendrit es and axon are orient ed parallel t o t he cort ical surf ace. The horizont al cells of Cajal are f ound only in lamina I and disappear or are rare af t er t he neonat al period.
C. CELLS OF M ARTINOTTI (Figure 17-1E) G iovanni Mart inot t i in 1890 f irst described cells w hose axons ascend t ow ard t he surf ace of t he cort ex. Mart inot t i neurons are mult ipolar w it h short branching dendrit es and an axon t hat project s t o more superf icial layers, giving out horizont al axon collat erals en rout e. The Mart inot t i neurons are f ound in deeper cort ical laminae.
Layers The division of t he neocort ex int o layers has been t he out come of ext ensive cyt oarchit ect onic (organizat ion based on st udies of st ained cells) and myeloarchit ect onic (organizat ion based on st udies of myelinat ed f iber preparat ions) st udies. Alt hough several such st udies are available, t he most w idely used are t he cyt oarchit ect onic classif icat ion of Brodmann and t he myeloarchit ect onic classif icat ion of t he Vogt s (Césile and O skar, w if e and husband). According t o t hese t w o classif icat ions, t he neocort ex is divided int o six layers (Table 17-1). The six layers of t he neocort ex are recognizable by about t he sevent h mont h of int raut erine lif e. The neurons in t he six cort ical layers develop in w aves f rom t he perivent ricular germinal mat rix. Successive w aves of migrat ing neuroblast s become sit uat ed progressively f art her aw ay f rom t he germinal mat rix (inside-out gradient of cort ical hist ogenesis) (Table 17-2). I nt errupt ion of t he normal process of migrat ion or it s arrest is associat ed w it h cort ical gyral malf ormat ions such as agyria, pachygyria, micropolygyria, and het erot opia. Many of t hese are associat ed w it h ment al ret ardat ion, seizures, and ot her neurologic def icit s.
A. LAYER I (M OLECULAR, PLEXIFORM ) Layer I consist s primarily of a dense net w ork of nerve cell processes among w hich are scat t ered sparse int erneurons (horizont al cells of Cajal) and neuroglia. The nerve cell processes in t his layer comprise project ion axons f rom ext racort ical sit es as w ell as axons and dendrit es of neurons in ot her cort ical areas. This layer of t he cort ex is primarily a synapt ic area. Tabl e 17-1. Cortical Layers
Layer Cytoarchitectonic nam e
Myeloarchitectonic nam e
I
Molecular
Tangential
II
External granular
Dysfibrous
III
External pyramidal
Suprastriatal
IV
Internal granular
External Baillarger
V
Internal pyramidal
Internal of Baillarger and interstriatal
VI
Multiform
Infrastriatal
Tabl e 17-2. Chronologic Age of Cortical Layers
Layer Order of neuroblast m igration I
Oldest (acellular)
II
Fifth wave
III
Fourth wave
IV
Third wave
V
Second wave
VI
First wave
B. LAYER II (EXTERNAL GRANULAR) Layer I I consist s of a dense packing of small and medium-sized pyramidal neurons and int erneurons int ermingled w it h axons f rom ot her cort ical layers of t he same and opposit e hemispheres (associat ion and commissural f ibers), as w ell as axons and dendrit es passing t hrough t his layer f rom deeper layers. The dendrit es of pyramidal neurons in t his layer project t o layer I , w hile t heir axons project t o deeper layers. This layer of t he cort ex cont ribut es t o t he complexit y of int racort ical circuit ry.
C. LAYER III (EXTERNAL PYRAM IDAL) Layer I I I consist s of pyramidal neurons t hat increase in size in deeper part s of t he layer. The dendrit es of neurons in t his layer ext end t o layer I , w hile t he axons project t o ot her layers w it hin t he same and cont ralat eral hemisphere (associat ion and commissural f ibers) or leave t he hemisphere as project ion f ibers t o more dist ant ext racort ical sit es. This layer receives primarily axons of neurons in ot her cort ical areas (associat ion and commissural f ibers), as w ell as axons of neurons in ext racort ical regions such as t he t halamus. This layer cont ains t he dist inct ive st ripes of Kaes-Bekht erev.
D. LAYER IV (INTERNAL GRANULAR) Layer I V consist s of pyramidal cells and densely packed small st ellat e cells w it h processes t hat t erminat e w it hin t he same layer, eit her on axons of ot her st ellat e cells or on axons of cort ical or subcort ical origin passing t hrough t his layer. The cell packing densit y in layer I V is t he great est of all cort ical layers. Few of t he larger st ellat e cells in t his layer project t heir axons t o deeper cort ical layers. Layer I V is especially w ell developed in primary sensory cort ical areas. I n t he primary visual (st riat e) cort ex, t his layer is t raversed by a dense band of horizont ally orient ed t ha-lamocort ical nerve f ibers know n as t he ext ernal band of Baillarger or t he st ripe of G ennari. The band of Baillarger w as described by t he ninet eent h-cent ury French neurologist and psychiat rist Jean-G abriel-Francois Baillarger. The st ripe of G ennari w as f irst described in 1782 by Francesco G ennari, an eight eent h-cent ury I t alian medical st udent , and independent ly by Vic d'Azyr in 1786. Because of t he presence of t his st ripe, t he primary visual cort ex is know n as t he st riat e cort ex. The int ernal granular layer is t he major recipient of t halamocort ical f ibers f rom modalit y-specif ic sensory relay nuclei (visual radiat ion, audit ory radiat ion, and primary sensory radiat ion).
E. LAYER V (INTERNAL PYRAM IDAL) Layer V consist s of large and medium-sized pyramidal cells, st ellat e cells, and cells of Mart inot t i. The cell packing densit y in t his layer is t he low est of all cort ical layers. The largest pyramidal cells in t he cerebral cort ex (cells of Bet z) are f ound in t his layer (hence t he name gangl i oni c layer). Dendrit es of neurons
in t his layer project t o t he more superf icial layers. Axons project on neurons in ot her cort ical areas but mainly t o subcort ical sit es (project ion f ibers) except t he t halamus, w hich receives f ibers f rom layer VI . This layer receives axons and dendrit es arising in ot her cort ical sit es or in subcort ical sit es. I t is also t raversed by a dense band of horizont ally orient ed f ibers; t his is t he int ernal band of Baillarger. Fibers originat ing in t halamic sensory nuclei cont ribut e heavily t o t he f ormat ion of t he lines of Baillarger, especially t he out er one in lamina I V. The lines of Baillarger are t hus prominent in primary cort ical sensory areas.
F. LAYER VI (M ULTIFORM ) Layer VI consist s of cells of varying shapes and sizes, including f usif orm cells and t he cells of Mart inot t i, w hich are prominent in t his layer. Dendrit es of smaller cells arborize locally or in adjacent layers, w hile t hose of large neurons reach t he molecular layer. Axons of neurons in t his layer project t o ot her cort ical laminae or t o subcort ical regions. Layers I , V, and VI are present in all t ypes of cort ex (neocort ex, paleocort ex, and archicort ex). Layers I I , I I I , and I V, how ever, are present only in neocort ex and t hus are considered of more recent phylogenet ic development . I n general, layers I t o I V are considered recept ive. The somat a of t he majorit y of cells t hat est ablish int racort ical connect ions (ipsilat erally and cont ralat erally) lie in layers I I and I I I . Layers V and VI are eff erent . Neurons in lamina V give rise t o cort icof ugal f ibers t hat t arget subcort ical areas (brain st em and spinal cord). Neurons in lamina VI give rise t o cort icof ugal f ibers t o t he t halamus. I n cont rast t o t he horizont al anat omic laminat ion, t he vert ical laminat ion described by Mount cast le seems t o be t he more f unct ionally appropriat e. The st udies of Lorent e de Nó, Mount cast le, Szent ágot hai, and ot hers have show n t hat t he f unct ional unit of cort ical act ivit y is a column of neurons orient ed vert ically t o t he surf ace of t he cort ex. Each such column or module is 300 t o 500 ľm in diamet er, w it h it s height t he t hickness of t he cort ex, and cont ains 4000 neurons, 2000 of w hich are pyramidal neurons. All neurons in a column are act ivat ed select ively by t he same peripheral st imulus. There are approximat ely 3 million such modules in t he human neocort ex. Each module sends pyramidal cell axons t o ot her modules w it hin t he same hemisphere or t o modules in t he ot her hemisphere. O f int erest is t he f act t hat act ivat ion of a module t ends t o inhibit neuronal act ivit y in adjacent modules. The columnar organizat ion of t he neocort ex is est ablished in f et al lif e, but t he synapt ic connect ions increase in number in t he post nat al period in response t o st imulat ion f rom t he ext ernal environment . Lack of ext ernal st imuli during a crit ical period of cort ical mat urat ion, usually in t he f irst year of lif e, w ill adversely aff ect normal cort ical development .
Fi gure 17-2. Schemat ic diagram show ing sources of f iber input t o t he cerebral cort ex.
INPUT TO CEREBRAL CORTEX The input t o t he cerebral cort ex originat es in f our sit es (Figure 17-2): 1. Thalamus 2. Ext rat halamic modulat ory 3. Cort ex of t he same hemisphere (associat ion f ibers) 4. Cort ex of t he cont ralat eral hemisphere (commissural f ibers)
Thalamocortical Input The input f rom t he t halamus t ravels via t w o syst ems. (1) The modalit y-specif ic t halamocort ical syst em originat es in modalit y-specif ic t halamic nuclei (e. g. , vent ral ant erior, vent ral lat eral, vent ral post erior) and project s on specif ic cort ical areas (primary mot or, premot or, and somest het ic cort ex). This f iber syst em reaches t he cort ex as an ascending component of t he int ernal capsule. The majorit y of f ibers in t his syst em project on neurons in lamina I V (Figure 173A), w it h some project ing on neurons in lamina I I I and lamina VI . (2) The nonspecif ic t halamocort ical syst em is relat ed t o t he ret icular syst em and originat es in nonspecif ic t halamic nuclei (int ralaminar, midline, and ret icular nuclei). I n t he cort ex, f ibers of t his syst em project diff usely on all laminae (Figure 17-3B) and est ablish most ly axodendrit ic t ypes of synapses. This f iber syst em is int imat ely involved in t he arousal response and w akef ulness.
Extrathalamic Modulatory Input Unt il recent ly, it w as commonly assumed t hat essent ially all aff erent s t o t he cort ex arose f rom t he t halamus. Wit h t he development of met hods t o visualize
monoaminergic and cholinergic processes, it is now clear t hat t here are at least f our subst ant ial ext rat halamic project ions t o t he cort ex. Monoaminergic and cholinergic pat hw ays reach t he cerebral cort ex direct ly w it hout passing t hrough t he t halamus.
A. M ONOAM INERGIC INPUT 1. Serotonergic Input. The serot onergic input t o t he cerebral cort ex originat es f rom t he raphe nuclei in t he mesencephalon and rost ral pons and runs in t he medial f orebrain bundle. I t t erminat es in t he same cort ical layers t hat receive t he t halamocort ical input (layers I I I , I V, and VI ). Serot onergic f ibers project w idely in t he cerebral cort ex w it h t he visual cort ex receiving an especially rich serot onergic innervat ion. The f unct ion of t he serot onergic pat hw ay t o t he cort ex is not w ell underst ood. Serot onergic pat hw ays elsew here have been relat ed t o a variet y of f unct ions, including pain cont rol, emot ion, and sleep. The serot onergic input t o t he cort ex is believed t o alt er cort ical neuronal responses t o aff erent input in response t o change in st at e. They include inhibit ion of spont aneous act ivit y, excit at ion, and volt age dependent f acilit at ion.
Fi gure 17-3. Schemat ic diagram of t he t erminat ion pat t ern of t he various input s t o cort ical laminae.
2. Dopaminergic Input. The dopaminergic input t o t he cerebral cort ex originat es f rom dopaminergic neurons in t he mesencephalon (vent ral t egment al area of Tsai and subst ant ia nigra pars compact a). I t t erminat es in all areas of t he cort ex, but especially in t he mot or, pref ront al, and t emporal associat ion areas. The dopaminergic input t o t he cort ex is believed t o play a role in orient ing behavior. The laminar and regional pat t ern of t erminat ion of t his syst em suggest s t hat it inf luences act ivit ies of cort icocort ical rat her t han t halamocort ical circuit s and higher-order int egrat ive processes t han t he more analyt ic aspect s of sensory processing. I n addit ion, it may inf luence cort ical regulat ion of mot or cont rol. Dysf unct ion in t his
syst em may be responsible f or psychiat ric sympt oms not ed in Parkinson's disease.
3. Noradrenergic Input. The noradrenergic input t o t he cerebral cort ex originat es f rom cells in t he locus ceruleus in t he rost ral pons. I t project s w idely t o t he cerebral cort ex and t erminat es in cort ical layers t hat give rise t o cort icof ugal f ibers. The noradrenergic input is implicat ed in higher-order inf ormat ion processing and t he st at e of arousal. I t is believed t o enhance t he select ivit y and vigor of cort ical responses t o sensory st imuli or ot her synapt ic input s t o t he t arget neurons in t he cort ex.
4. Histaminergic Input. The hist aminergic input t o t he cerebral cort ex originat es f rom t he t uberomamillary nucleus in t he post erolat eral hypot halamus. The f unct ion of t his syst em is not know n.
5. Cholinergic Input. The cholinergic input t o t he cerebral cort ex originat es f rom t he nucleus basalis of Meynert . This input t erminat es in all areas of t he cort ex. I t is t he most import ant syst em f or cort ical arousal and mot ivat ion. I t has been implicat ed in t he genesis of memory def icit in Alzheimer's disease.
B. GABAERGIC INPUT The G ABAergic input t o t he cerebral cort ex originat es f rom cells in t he sept um and t he diagonal band of Broca. I t t erminat es primarily in t he hippocampus.
Association Fiber System (Figure 17-2) The associat ion f ibers arise f rom nearby (short associat ion u-f ibers) and dist ant (long associat ion f ibers) regions of t he same hemisphere. They t oo project diff usely in all laminae but most ly in laminae I t o I I I (Figure 17-3). The long associat ion f iber syst em (Figure 17-4) includes such bundles as t he cingulum, superior longit udinal f asciculus, arcuat e f asciculus, inf erior longit udinal f asciculus, occipit of ront al f asciculus, and t he uncinat e f asciculus. The cingulum (Figure 17-4B and C) is t he w hit e mat t er core of t he cingulat e gyrus. I t connect s t he ant erior perf orat ed subst ance and t he parahippocampal gyrus. The superior longit udinal f asciculus (Figure 17-4A and C), locat ed in t he lat eral part of t he hemisphere above t he insula, connect s port ions of t he f ront al lobe w it h pariet al, occipit al, and t emporal lobes. The arcuat e f asciculus (Figure 17-4A) is t he part of t he superior longit udinal f asciculus t hat sw eeps around t he insula (island of
Reil) t o connect t he speech areas in t he inf erior f ront al gyrus (Broca's area) and superior t emporal gyrus (Wernicke's area). The inf erior longit udinal f asciculus (Figure 17-4A and C) is a t hin sheet of f ibers t hat runs superf icially beneat h t he lat eral and vent ral surf aces of t he t emporal and occipit al lobes. This f iber bundle is diff icult t o demonst rat e by dissect ion and t o separat e f rom ot her f iber syst ems running in it s vicinit y. The exist ence of t he inf erior longit udinal f asciculus in humans has been quest ioned. The only long f iber bundle common t o bot h t he occipit al and t emporal lobes in humans is t he opt ic radiat ion (geniculost riat e pat hw ay). I n addit ion, t he t w o lobes are int erconnect ed by a series of u-f ibers (short associat ion f ibers) t hat connect adjacent regions of occipit al and t emporal cort ices. Based on t his, it has been proposed t hat t he t erm inf erior longit udinal f asciculus be replaced by t he t erm occipit ot emporal project ion syst em. The occipit of ront al f asciculus (Figure 17-4A and C) ext ends backw ards f rom t he f ront al lobe, radiat ing int o t he t emporal and occipit al lobes. Tw o subdivisions of t he occipit of ront al f asciculus are recognized. The superior (subcallosal) bundle (Figure 17-4C) is locat ed deep in t he hemisphere, dorsolat eral t o t he lat eral vent ricle, sandw iched bet w een t he corpus callosum, int ernal capsule, and caudat e nucleus. The inf erior bundle (Figure 17-4C) is locat ed lat eral t o t he t emporal horn of t he lat eral vent ricle and below t he insular cort ex and lent if orm nucleus. The uncinat e f asciculus (Figure 17-4A) is t he component of t he inf erior occipit of ront al f asciculus t hat courses at t he bot t om of t he sylvian f issure t o connect t he inf erior f ront al gyrus w it h t he ant erior t emporal lobe.
Fi gure 17-4. Schemat ic diagram show ing t he long associat ion f iber bundles.
Commissural Fiber System The commissural f ibers arise f rom corresponding and noncorresponding regions in t he cont ralat eral hemisphere, t ravel via t he corpus callosum and project on neurons in all laminae but most ly laminae I , I I , and I I I (Figure 17-3). St udies on t he t opographic dist ribut ion of int erhemispheric project ions in t he corpus callosum have show n t hat t he genu int erconnect s t he pref ront al cort ex, t he rost ral part of t he body int erconnect s t he premot or and supplement ary mot or cort ices, t he middle part of t he body int erconnect s t he primary mot or and primary and secondary somat ic sensory areas, t he caudal part of t he body
int erconnect s t he post erior pariet al cort ex, and t he splenium int erconnect s t emporal and occipit al cort ices. O t her int erhemispheric commissural syst ems include t he ant erior commissure, w hich int erconnect s t he t w o t emporal lobes, and t he hippocampal commissure (commissure of t he f ornix), w hich int erconnect s t he t w o hippocampi.
OUTPUT OF CEREBRAL CORTEX Eff erent out f low f rom t he cerebral cort ex is grouped int o t hree cat egories (Figure 17-5). These are (1) t he associat ion f iber syst em, (2) t he commissural f iber syst em, and (3) t he cort icof ugal f iber syst em. The laminar origin of axons of most cort ical project ions are unique. The short associat ion f ibers arise f rom lamina I I , t he long associat ion f ibers f rom laminae I I I and V, int erhemispheric commissural f ibers f rom lamina I I I , cort icot halamic f ibers f rom lamina VI , cort icospinal and cort icobulbar f ibers f rom laminae I I I and V, and cort icost riat e and cort icopont ine f ibers f rom lamina V.
Fi gure 17-5. Schemat ic diagram of t he major groups of cort ical out put .
The associat ion and commissural f iber syst ems have been described in t he sect ion on input t o t he cort ex. Essent ially, t hey represent int rahemispheric and int erhemispheric connect ions. The cort icof ugal f iber syst em includes all f iber t ract s t hat leave t he cerebral cort ex t o project on various subcort ical st ruct ures. They include t he f ollow ing pat hw ays.
Corticospinal Pathway (Figure 17-6) This cort icof ugal f iber t ract connect s t he cerebral cort ex direct ly w it h mot or neurons in t he spinal cord and is concerned w it h highly skilled volit ional
movement . I t arises f rom pyramidal neurons in layer V f rom w ide areas of t he cerebral cort ex but principally f rom t he somat ic mot or, premot or, and somat osensory cort ices. I t cont ains, on each side, roughly 1 million f ibers of various sizes (9 t o 22 ľm), about 3% of w hich are large in size and arise f rom t he giant cells of Bet z in layer V of t he mot or cort ex. The f ibers of t his syst em descend in t he int ernal capsule, t he middle part of t he cerebral peduncle, t he basis pont is, and t he pyramids bef ore gat hering in t he spinal cord as t he lat eral and ant erior cort icospinal t ract s. The f ormer (lat eral cort icospinal) const it ut es t he majorit y of t he descending cort icospinal f ibers and decussat es in t he pyramids (mot or decussat ion); t he lat t er (ant erior cort icospinal) is smaller and crosses at segment al levels in t he spinal cord. The classic not ion t hat t he cort icospinal t ract is of part icular import ance f or skilled and delicat e volunt ary movement is in essence correct , but it is obvious t hat a number of ot her indirect t ract s passing t hrough t he brain st em nuclei, ret icular f ormat ion, and cerebellum are also involved. The direct cort icospinal t ract most likely superimposes speed and agilit y on t he mot or mechanisms subserved by ot her descending indirect pat hw ays. The component of t he cort icospinal pat hw ay f rom t he somat osensory cort ex t erminat es on sensory neurons in t he dorsal horn of t he spinal cord and is concerned w it h somat osensory f unct ion possibly relat ed t o ongoing movement . A f airly large proport ion of t he sensory component of t he cort icospinal pat hw ay originat es f rom area 3a, w hich adjoins t he primary mot or cort ex and receives sensory input f rom propriocept ors.
Aberrant Pyramidal Tract This f iber t ract separat es f rom t he cort icospinal f iber syst em in t he cerebral peduncle and joins t he medial lemniscus in t he caudal midbrain ext ending t hrough t he pons t o t he middle medulla oblongat a, w here it becomes undet ect able. I t is presumed t o const it ut e a part of t he cort icobulbar t ract t hat supplies cranial nerve nuclei. I t is t hus responsible f or t he report ed supranuclear cranial nerve palsies in lesions of medial lemniscus. Some f ibers of t he t ract have been t raced t o t he spinal cord. The aberrant pyramidal t ract has been described in t he lit erat ure under t he f ollow ing synonyms: accessory f illet f ibers (Barnes, 1901), f ibre aberrant es prot uberant ielles (Dejerine, 1901), f asciculi pont ini lat eralis (Marburg, 1927), aberrant pyramidal syst em (Crosby, 1962), and f ibrae cort icot egment alis (Voogd and Van Hujizen, 1963).
Corticoreticular Pathway This f iber t ract arises f rom most if not all part s of t he cerebral cort ex but primarily f rom mot or, premot or, and somat osensory cort ices and accompanies t he cort icospinal f iber syst em, leaving it at diff erent levels of t he neuraxis t o project on ret icular neurons in t he brain st em. The cort icoret icular f ibers arising f rom one cerebral hemisphere project roughly equally t o bot h sides of t he brain st em ret icular f ormat ion. Many of t hese f ibers
ult imat ely project on cranial nerve nuclei in t he brain st em, t hus f orming t he cort icoret iculobulbar pat hw ay.
Fi gure 17-6. Schemat ic diagram of t he cort icospinal pat hw ay.
Corticobulbar Pathway Cort icobulbar f ibers originat e f rom t he f ace area of t he mot or cort ex. They project on mot or nuclei of t he t rigeminal, f acial, glossopharyngeal, vagus, accessory, and hypoglossal nerves. Direct cort icobulbar f ibers (w it hout int ermediat e synapses on ret icular neurons) are know n t o project f rom t he cerebral cort ex t o nuclei of t rigeminal (CN V), f acial (CN VI I ), and hypoglossal (CN XI I ) cranial nerves. Cort icobulbar f ibers descend in t he genu of t he int ernal capsule and occupy a dorsolat eral corner of t he cort icospinal segment of t he cerebral peduncle, as w ell as a small area in t he medial part of t he base of t he cerebral peduncle. I n t he pons, cort icobulbar f ibers are int ermixed w it h t he cort icospinal f ibers w it hin t he basis pont is. Bilat eral int errupt ion of t he cort icobulbar or cort icoret iculobulbar f iber syst em result s in paresis(w eakness) but not paralysis of t he muscles supplied by t he corresponding cranial nerve nucleus. This condit ion is know n as pseudobulbar palsy t o dist inguish it f rom bulbar palsy, w hich is a condit ion charact erized by complet e paralysis of muscles supplied by a cranial nerve nucleus as a result of a lesion of t he nucleus. The cort icobulbar input t o nuclei of t rigeminal and hypoglossal cranial nerves is bilat eral. As a result , pseudobulbar palsy result s only w hen cort icobulbar input s t o t hese nuclei f rom bot h hemispheres are int errupt ed. The cort icobulbar input t o t he f acial nucleus is bilat eral t o t he f acial subnucleus t hat supplies upper f acial muscles and is only cont ralat eral t o t he f acial subnucleus t hat supplies low er f acial muscles. As a result , inf arct s in one hemisphere (as in middle cerebral art ery occlusion) are manif est ed by cont ralat eral low er f acial paralysis and sparing of upper f acial muscles. The relat ionship bet w een t he cerebral cort ex and t he f acial nerve nucleus has been t he subject of several invest igat ions. The classical narrat ive t hat dominat ed know ledge during t he past cent ury st at ed t hat t he primary mot or cort ex (M-1) is t he source of cort icobulbar input s t o f acial nucleus, and t hat t he f acial subnucleus t hat supplies upper f acial muscles receives input s f rom bot h primary mot or cort ices, w hereas t he f acial subnucleus t hat supplies low er f acial muscles receives input only f rom t he cont ralat eral primary mot or cort ex. While t his narrat ive w as adequat e t o explain cont ralat eral low er f acial palsy in hemispheric lesions, it did not account f or t he report ed dissociat ion bet w een volunt ary and emot ional f acial movement s, emot ional f acial paralysis (amimia), or t he uncont rollable excessive emot ionally aff iliat ed f acial movement s. Several lines of research have now revealed t hat t here are f ive cort ical areas f or f ace represent at ion in human and in non-human primat es. I n addit ion t o t he w ellest ablished primary mot or cort ex (M-1), t he f ollow ing areas have f ace represent at ion: supplement ary mot or cort ex (M-2), rost ral cingulat e gyrus (M-3), caudal cingulat e gyrus (M-4), and t he vent ral lat eral premot or cort ex (LPMCV). O f t hese, t he primary mot or cort ex (M-1) and t he vent ral lat eral premot or cort ex (LPMC V) give rise t o t he heaviest project ions t o t he f acial nucleus, f ollow ed by t he supplement ary mot or cort ex (M-2), w hich sends a moderat e project ion, and
by t he cingulat e gyrus (M-3 and M-4), w hich sends a light project ion. I t has been show n t hat t he primary mot or cort ex (M-1), t he caudal cingulat e gyrus (M-4), and t he vent ral lat eral premot or cort ex (LPMCV) innervat e primarily t he cont ralat eral low er f acial subnucleus (Figure 17-7A), w hereas t he supplement ary mot or cort ex (M-2) and t he rost ral cingulat e gyrus (M-3) provide innervat ion t o bot h upper f acial subnuclei (Figure 17-7B). I t has been suggest ed t hat t he diff erent cort ical f ace represent at ions mediat e diff erent element s of f acial expression and t hat separat e neural syst ems may mediat e volunt ary and emot ional f acial movement s. Thus, volit ional f acial paresis is associat ed w it h lesions in t he primary mot or cort ex (M-2) and t he underlying subcort ical w hit e mat t er. The cingulat e gyrus (M-3 and M-4) project ions, in cont rast , subserve emot ional expressions of f acial movement s. Damage in t he ant erior cingulat e gyrus (M-3) is associat ed w it h blunt ed emot ional expression in upper f acial muscles, suggest ing t hat it cont rols emot ionally relat ed movement s of t he f ace. Funct ional neuroimaging st udies have show n t hat t he orbit of ront al cort ex plays a role in emot ional processing of pleasant f acial expressions. Enhanced responses in t he orbit of ront al cort ex are associat ed w it h recognit ion of happy f aces.
Fi gure 17-7. Schemat ic diagram show ing origins of cort icobulbar f ibers t o t he cont ralat eral low er f acial subnucleus A, and t o bot h upper f acial subnuclei B.
Corticopontine Pathway (Figure 17-8) Fibers comprising t his pat hw ay arise f rom all part s of t he cerebral cort ex but primarily f rom t he f ront al, pariet al, and occipit al lobes. Most f ibers, how ever, arise f rom t he primary mot or (precent ral gyrus) and primary sensory (post cent ral gyrus) cort ices, w it h relat ively subst ant ial cont ribut ion f rom t he premot or,
supplement ary mot or, and post erior pariet al cort ices and f ew f rom t he t emporal and pref ront al cort ices. These f ibers descend in t he int ernal capsule and occupy t he most medial and lat eral part s of t he cerebral peduncle bef ore reaching t he basis pont is, w here t hey project on pont ine nuclei. The cort icopont ine f ibers const it ut e by f ar t he largest component of t he cort icof ugal f iber syst em. I t is est imat ed t hat each cort icopont ine pat hw ay cont ains approximat ely 19 million f ibers. Wit h approximat ely t he same number of pont ine neurons on each side of t he basis pont is, t he rat io of cort icopont ine f ibers t o pont ine neurons becomes 1: 1. Cort icopont ine f ibers t erminat e in sharply delineat ed lamellae ext ending rost rocaudally. Various cort ical regions project t o separat e part s of t he pont ine nuclei, alt hough considerable overlap t akes place bet w een some project ion areas. Pont ine neurons t hat receive cort icopont ine f ibers give rise t o t he pont ocerebellar pat hw ay discussed in t he chapt er on t he pons (Chapt er 7). The cort icopont ine pat hw ay is t hus one of several pat hw ays t hat link t he cerebral cort ex w it h t he cerebellum f or t he coordinat ion and regulat ion of movement . Lesions of t he cort icopont ine pat hw ay at it s sit es of origin in t he cort ex or along it s course w ill result in incoordinat ed movement (at axia) cont ralat eral t o t he lesion. The at axia observed in some pat ient s w it h f ront al or t emporal lobe pat hology is t hus explained as an int errupt ion of t he cort icopont ine pat hw ay.
Fi gure 17-8. Schemat ic diagram of t he cort icopont ine and pont ocerebellar pat hw ays.
Corticothalamic Pathway The cort icot halamic pat hw ay arises f rom cort ical areas t hat receive t halamic project ions and t hus const it ut es a f eedback mechanism by w hich t he cerebral cort ex inf luences t halamic act ivit y. The t halamocort ical relat ionship is such t hat a t halamic nucleus t hat project s t o a cort ical area receives in t urn a project ion f rom t hat area. Examples of such reciprocal connect ions (Figure 17-9) include t he dorsomedial t halamic nucleus and pref ront al cort ex, ant erior t halamic nucleus and cingulat e cort ex, vent rolat eral t ha-lamic nucleus and mot or cort ex, post erovent ral t halamic nucleus and post cent ral gyrus, medial geniculat e nucleus and audit ory cort ex, and lat eral geniculat e nucleus and visual cort ex. The
cort icot halamic input t o t he ret icular t halamic nucleus, how ever, is not reciprocal. The ret icular nucleus receives aff erent s f rom almost all cort ical areas but does not project back t o t he cerebral cort ex. The ret icular nucleus receives collat erals f rom all t ha-lamocort ical and all cort icot halamic project ions. Thus t he ret icular nucleus is inf ormed of act ivit ies passing in bot h direct ions bet w een t he t halamus and cerebral cort ex.
Fi gure 17-9. Schemat ic diagram of t halamocort ical relat ionships.
Cort icot halamic f ibers descend in various part s of t he int ernal capsule and ent er t he t halamus in one bundle know n as t he t halamic radiat ion, w hich also includes t he reciprocal t halamocort ical f ibers.
Corticohypothalamic Pathway The cort icohypot halamic f ibers arise f rom pref ront al cort ex, cingulat e gyrus, amygdala, olf act ory cort ex, hippocampus, and sept al area.
Corticostriate Pathway Project ions f rom t he cerebral cort ex t o t he st riat um are bot h direct and indirect . Direct cort icost riat e project ions reach t he neost riat um via t he int ernal and ext ernal capsules and via t he subcallosal f asciculus. The indirect pat hw ays include t he cort icot halamost riat e pat hw ay, collat erals of t he cort icoolivary pat hw ay, and collat erals of t he cort icopont ine pat hw ay. The cort icost riat e project ion comprises t he most massive st riat al aff erent s. Almost all cort ical areas cont ribut e t o t his project ion. Cort ical areas int erconnect ed via cort icocort ical f ibers t end t o share common zones of t erminat ion in t he neost riat um. Cort icost riat al f ibers are organized t opographically int o t hree dist inct st riat al t errit ories: (1) sensorimot or, (2) associat ive, and (3) limbic. The sensorimot or t errit ory receives it s input s f rom sensory and mot or cort ical areas. The associat ive t errit ory receives f ibers f rom t he associat ion cort ices. The limbic t errit ory receives input f rom limbic and paralimbic cort ical areas. Cort icost riat e pat hw ays are also organized somat ot opically such t hat cort ical associat ion areas project t o t he caudat e nucleus, w hereas sensorimot or cort ical areas pref erent ially project t o t he put amen. Cort icoput amenal project ions are f urt her organized in t hat t he cort ical arm, leg, and f ace areas project t o corresponding areas w it hin t he put amen.
Other Corticofugal Pathways These include cort ical project ions t o several sensory brain st em nuclei, such as t he nuclei gracilis and cuneat us, t rigeminal nuclei, and ot hers. Most of t hese f ibers serve a f eedback purpose. Cort icosubt halamic project ions originat e f rom t he primary mot or and premot or cort ical areas. A cort icot ect al project ion has been described arising f rom t he f ront al eyef ields (area 8 of t he f ront al cort ex) in addit ion t o t hat f rom t he occipit al cort ex. Cort icorubral f ibers originat e f rom t he same cort ical areas as t he cort icospinal t ract and t erminat e on t he red nucleus in t he midbrain.
INTRACORTICAL CIRCUITRY Cort ical neurons may have descending, ascending, horizont al, or short axons (Figure 17-1). The descending axons cont ribut e t o t he associat ion and t he cort icof ugal f iber syst ems out lined above. The ascending, horizont al, and short axons play import ant roles in int racort ical circuit ry. Neurons w it h ascending axons are t he cells of Mart inot t i. The horizont al cells of Cajal have horizont al axons. Short axons arborizing in t he vicinit y of t he cell body are seen in st ellat e neurons. Pyramidal neurons have horizont al and recurrent axon collat erals t hat t erminat e at all levels of t he cort ex and cont ribut e signif icant ly t o int racort ical connect ions. The axon collat erals of pyramidal neurons may project on a st ellat e cell or a Mart inot t i cell t hat in t urn may inf luence ot her cort ical neurons and t hus provide f or rapid dispersion of act ivit y t hroughout a populat ion of neurons. This f act w as recognized by Cajal, w ho ref erred t o it as avalanche conduct ion. A simplif ied account of int racort ical circuit ry is illust rat ed diagrammat ically in Figure 17-10. A t halamocort ical input w ill excit e pyramidal (project ion) neurons in layer VI and int erneurons (excit at ory and inhibit ory) in layer I V (point 1 in Figure 17-10). I nhibit ory int erneurons in layer I V inhibit ot her int erneurons in t he same layer (point 2 in Figure 17-10). Excit at ory int erneurons in layer I V excit e pyramidal neurons and inhibit ory int erneurons in layers I I and I I I (point 3 in Figure 17-10). I nhibit ory int erneurons in layers I I and I I I inhibit pyramidal neurons in t he same layers (point 4 in Figure 17-10). Pyramidal neurons in layers I I and I I I excit e project ion neurons in layers I V and V (point 5 in Figure 17-10). Axon collat erals of project ion neurons in layer V excit e cort icot halamic project ion neurons in layer VI (point 6 in Figure 17-10). Axon collat erals of cort icot halamic project ion neurons in layer VI project back t o t he excit at ory int erneurons in layer I V (point 7 in Figure 17-10), t hus closing t he loop. I nt erneurons in deep cort ical layers (cells of Mart inot t i) and in superf icial cort ical layers (horizont al cells of Cajal) cont ribut e t o int racort ical circuit ry by vert ical and horizont al spread of impulses. Mart inot t i cells, excit ed by axon collat erals of pyramidal neurons, in t urn excit e eit her a pyramidal neuron or anot her int erneuron. Similarly, t he horizont ally orient ed axons of t he horizont al cells of Cajal inf luence t he vert ically orient ed processes of pyramidal neurons or int erneurons. Because of t heir paucit y or absence in t he post -neonat al period, t he horizont al cells of Cajal play a minimal role in int racort ical circuit ry in t he adult . From t he preceding it can be seen t hat an input t o t he cort ex is spread bot h horizont ally and vert ically via t he various int racort ical connect ions. The complexit y of t hese int erconnect ions is f ar f rom clear def init ion, and is t he basis of t he complexit y of human brain f unct ion.
CORTICAL CYTOARCHITECTONIC AREAS Diff erent part s of t he cort ex vary in relat ion t o t he f ollow ing paramet ers:
1. Thickness of t he cort ex 2. Widt h of t he diff erent layers of t he cort ex 3. Cell t ypes in each layer 4. Cell densit y in each layer 5. Nerve f iber laminat ion Based on t he preceding variat ions, diff erent invest igat ors have parceled t he cort ex int o f rom 20 t o 200 areas depending on t he crit eria used. The classif icat ion of t he G erman hist ologist Korbinian Brodmann, published in 1909, remains t he most w idely used. I t cont ains 52 cyt oarchit ect onic areas numbered in t he order in w hich he st udied t hem (Table 17-3).
Fi gure 17-10. Schemat ic diagram show ing int rinsic cort ical circuit ry.
Caref ul count ing of t he numbers of Brodmann areas in t ext book illust rat ions indicat es t hat numbers 13 t hrough 16 are missing. Review of Brodmann's 1909 monograph revealed t hat t he missing numbers are in t he insula (island of Reil). Areas 13 and 14 ref er t o t he ant eriorly placed t w o insulae breves, and areas 15 and 16 ref er t o t he post eriorly placed t w o insulae longes. More import ant t han t he cyt oarchit ect onic classif icat ion is t he f unct ional classif icat ion of t he cort ex int o several mot or and sensory areas. The account t hat f ollow s w ill f ocus on f unct ional areas of t he cort ex. Brodmann's t erminology w ill be used because it is t he most f requent ly cit ed. The commonly used classif icat ion of cort ical areas int o purely sensory and mot or is somew hat misleading and inaccurat e. There is ample evidence t o suggest t hat mot or responses can be elicit ed f rom so-called sensory areas. This has prompt ed t he use of t he t erm sensory mot or cort ex t o ref er t o previously designat ed sensory and mot or areas. Tabl e 17-3. Brodmann Areas
Brodm ann Area
Neuroanatom ic, functional designation
1, 2, 3
Postcentral gyrus, primary sensory cortex [intermediate (1), caudal (2), and rostral (3) parts]
4
Precentral gyrus, primary motor cortex
5
Superior parietal lobule caudal to postcentral sulcus
6
Precentral gyrus (including supplementary motor area)
7
Superior parietal lobule caudal to area 5
8
Middle frontal gyrus, rostral to area 6
9, 10
Prefrontal cortex (dorsolateral and mesial)
11, 12
Orbital gyri
13, 14
Anterior part of the insula (island of Reil)
15, 16
Posterior part of the insula (island of Reil)
17
Calcarine gyrus, primary visual (striate) cortex
18
Surrounds area 17, secondary visual association cortex
19
Surrounds area 18, tertiary visual association cortex
20
Inferior temporal gyrus, visual association cortex
21
Middle temporal gyrus, visual association cortex
22
Superior temporal gyrus, auditory association cortex, W ernicke's area
23
Ventral posterior cingulate gyrus, limbic cortex
24
Ventral anterior cingulate gyrus, limbic cortex
25
Subcallosal area, subgenu area
26
Retrosplenial area, limbic cortex
27
Presubicular area, limbic cortex
28
Entorhinal cortex
29, 30
Retrosplenial cortex, limbic cortex
31
Dorsal posterior cingulate gyrus, limbic cortex
32
Dorsal anterior cingulate gyrus and adjacent frontal area
33
Rostral cingulate gyrus (pregenu area), limbic cortex
34
Dorsal entorhinal area
35
Perirhinal area, parahippocampal gyrus
36
Ectorhinal area, lateral to the rhinal sulcus, para-hippocampal gyrus
37
Occipitotemporal area, inferolateral part of the temporal lobe, decoding of visual information
38
Temporal pole, retrieval of proper nouns
39
Angular gyrus
40
Supramarginal gyrus
41, 42
Heschl's gyrus, primary auditory cortex
43
Frontoparietal (rolandic) operculum, gustatory cortex
44
Pars opercularis of inferior frontal gyrus, Broca's area of speech
45
Pars triangularis of inferior frontal gyrus, Broca's area of speech
46
Middle frontal gyrus, dorsolateral prefrontal area, association cortex
47
Pars orbitalis of inferior frontal gyrus
48
Retrosubicular area
49
Parasubiculum
51
Prepiriform area
52
Parainsular area, superior bank of superior temporal gyrus along the posterior margin of the insula
How ever, f or didact ic purposes, t he mot or and sensory areas of t he cort ex w ill be discussed separat ely.
CORTICAL SENSORY AREAS Sensory f unct ion in t he cort ex is localized mainly in t hree lobes: pariet al, occipit al, and t emporal. There are six primary sensory areas in t he cort ex:
1.
Primary somest het ic (general sensory, somat osensory) area in t he post cent ral gyrus of t he pariet al lobe
2. Primary visual area in t he calcarine gyrus of t he occipit al lobe 3. Primary audit ory area in t he t ransverse gyri of Heschl of t he t emporal lobe 4. Primary gust at ory (t ast e) area in t he most vent ral part of t he post cent ral gyrus of t he pariet al lobe 5. Primary olf act ory (smell) area in t he pirif orm and periamygdaloid regions of t he t emporal lobe 6. Primary vest ibular area in t he t emporal lobe Each of t hese areas receives a specif ic sensory modalit y (i. e. , pain, t ouch, vibrat ion, vision, audit ion, t ast e, smell). Sensory modalit ies reaching each of t hese areas (except olf act ion) pass t hrough t he t halamus (modalit y-specif ic t halamic nucleus) prior t o reaching t he cort ex. Each of t he preceding sensory areas is designat ed as a primary sensory area. Primary sensory cort ices have rest rict ed recept ive f ields. Adjacent t o t he primary somest het ic, visual, and audit ory areas are secondary sensory areas. The secondary sensory areas are f ound by recording evoked pot ent ials in t he respect ive areas f ollow ing an appropriat e peripheral st imulus (sound, light , et c. ). I n general, t he secondary sensory areas are smaller in size t han t he primary areas, and t heir ablat ion is w it hout eff ect on t he specif ic sensory modalit y.
Primary Somesthetic (General Sensory, Somatosensory) Area (SI) This area (Figure 17-11) corresponds t o t he post cent ral gyrus of t he pariet al lobe (areas 1, 2, and 3 of Brodmann) and t he post erior part of t he paracent ral lobule. Area 3 is divided int o t w o part s: 3b on t he post erior w all of t he cent ral sulcus and 3a in t he dept h of t he sulcus. I n 1916, Dusser de Barenne applied st rychnine, a cent ral st imulant drug, t o t he post cent ral gyrus of monkeys and not ed t hat t he animals scrat ched t heir skin. Subsequent w ork by Head on World War I soldiers w it h head injuries and by t he neurosurgeons Cushing and Penf ield has added t remendously t o know ledge about t he f unct ion of t his area. Alt hough t he primary somest het ic area is concerned basically w it h sensory modalit ies, it is possible t o elicit mot or responses f ollow ing it s st imulat ion. The primary somest het ic area receives nerve f ibers f rom t he vent ral post erolat eral and vent ral post eromedial nuclei of t he t halamus. These f ibers convey general sensory (t ouch, pain, and t emperat ure) as w ell as propriocept ive sensory modalit ies (posit ion, vibrat ion, and t w o-point discriminat ion).
Fi gure 17-11. Schemat ic diagram of t he primary somest het ic cort ex.
I n addit ion t o t halamic aff erent s, t he primary somest het ic cort ex receives commissural f ibers t hrough t he corpus callosum f rom t he cont ralat eral primary somest het ic cort ex and short associat ion f ibers f rom t he adjacent primary mot or cort ex. Eff erent s f rom t he primary somest het ic cort ex project t o t he mot or cort ex, t he opposit e primary somest het ic cort ex, and t he associat ion somat osensory cort ex (areas 5 and 7) in t he post erior pariet al cort ex. The primary and secondary somest het ic areas are reciprocally int erconnect ed. I n addit ion, project ion f ibers descend w it hin t he int ernal capsule t o t he vent ral post erior nuclei of t he t halamus, post erior column nuclei of t he medulla oblongat a, and dorsal horn of t he spinal cord. The cont ralat eral half of t he body is represent ed in a precise but disproport ionat e manner (sensory homunculus) in each of t he t hree areas (1, 2, and 3) of t he som-est het ic cort ex (Figure 17-12). The pharynx, t ongue, and jaw are represent ed in t he most vent ral port ion of t he lat eral surf ace of t he somest het ic area, f ollow ed in ascending order by t he f ace,
hand, arm, t runk, and t high. The leg and f oot are represent ed on t he medial surf ace of t his area. The anal and genit al regions are represent ed in t he most vent ral port ion of t he medial surf ace just above t he cingulat e gyrus. The represent at ion of t he f ace, lips, hand, t humb, and index f inger is disproport ionat ely large in comparison w it h t heir relat ive size in t he body. This is a ref lect ion of t he f unct ional import ance of t hese part s in sensory f unct ion. St imulat ion of t he primary somest het ic cort ex in conscious pat ient s elicit s sensat ions of numbness and t ingling, a f eeling of elect ricit y, and a f eeling of movement w it hout act ual movement . These sensat ions are ref erred t o t he cont ralat eral half of t he body, except w hen t he f ace area is st imulat ed. The f ace and t ongue are represent ed bilat erally. Ablat ion of t he post cent ral gyrus w ill result , in t he immediat e post operat ive period, in loss of all modalit ies of sensat ion (t ouch, pressure, pain, and t emperat ure). Soon, how ever, pain and t emperat ure sensat ions w ill ret urn. I t is believed t hat pain and t emperat ure sensat ions are det ermined at t he t halamic level, w hereas t he source, severit y, and qualit y of such sensat ions are perceived in t he post cent ral gyrus. Thus t he eff ect s of post cent ral gyrus lesions w ould be (1) complet e loss of discriminat ive t ouch and propriocept ion and (2) crude aw areness of pain, t emperat ure, and light t ouch. Neurophysiologic st udies of t he somest het ic cort ex have revealed t he f ollow ing inf ormat ion: (1) The f unct ional cort ical unit appears t o be associat ed w it h a vert ical column of cells t hat is modalit y specif ic. Neurons w it hin a cort ical unit are act ivat ed by t he same peripheral st imulus and are relat ed t o t he same peripheral recept ive f ield. (2) Area 3b is act ivat ed by cut aneous st imuli and areas 2 and 3a by propriocept ive impulses, w hereas area 1 is act ivat ed by eit her cut aneous or propriocept ive impulses. (3) Somat osensory neurons responding t o joint movement show a marked degree of specif icit y in t hat t hey respond t o displacement in one direct ion. (4) Fast - and slow -adapt ing neuronal pools have been ident if ied in response t o hair displacement or cut aneous def ormat ion. (5) Fibers mediat ing cut aneous sensat ions t erminat e rost rally, w hile t hose mediat ing propriocept ive sensat ions t erminat e more caudally in t he somest het ic area.
Secondary Somesthetic Area (SII) A secondary somest het ic area has been described in humans and primat es. I t is locat ed on t he most inf erior aspect of t he post cent ral gyrus and in t he superior bank and dept h of t he lat eral sulcus (pariet al operculum). Body represent at ion in t his area is bilat eral, w it h cont ralat eral predominance, and is t he reverse of t hat in t he primary area so t hat t he t w o f ace areas are adjacent t o each ot her.
Fi gure 17-12. Schemat ic diagram of t he sensory homunculus.
The secondary sensory area cont ains neurons w it h recept ive f ields t hat are large, poorly demarcat ed, overlap ext ensively, and of t en have bilat eral represent at ion. Lesions of t he secondary somest het ic area and t he insula produce asymbolia f or pain, suggest ing t hat t he secondary somest het ic area is an import ant cort ical locus f or t he conscious percept ion of noxious st imuli. Posit ron-emission t omographic (PET) st udies in human volunt eers subject ed t o noxious st imuli have demonst rat ed increased met abolic act ivit y in t he secondary somest het ic area as w ell as in t he post cent ral and cingulat e gyri. Damage t o SI I or possibly t o t he post erior insula leads t o t he inabilit y of t he pat ient t o ident if y object s by t ouch (t act ile agnosia, agraphest hesia). The primary and secondary somest het ic areas are reciprocally int erconnect ed. The secondary somest het ic area cont ains no cells sensit ive t o joint movement or joint posit ion. The secondary somest het ic area has been show n t o have reciprocal connect ions w it h vent ral post eromedial and cent rolat eral nuclei of t he t halamus. I t also receives input s f rom t he ipsilat eral and cont ralat eral primary somest het ic cort ices. Eff erent connect ions project t o t he primary somest het ic and primary mot or areas w it hin t he same hemisphere. Lesions int errupt ing connect ions bet w een t he secondary somest het ic area, post erior pariet al cort ex, and vent ral post eromedial and cent rolat eral t halamic nuclei have been associat ed w it h pseudot halamic pain syndrome. The pain is spont aneous and charact erized as burning or icelike and is associat ed w it h impairment of pain and t emperat ure appreciat ion.
Supplementary Sensory Area (SSA) This area w as def ined originally by Penf ield and Jasper w it h int raoperat ive st imulat ion st udies in humans. The supplement ary sensory area lacks Brodmann's numeric designat ion, but it encompasses medial area 5 of Brodmann
and probably t he ant erior part of medial area 7. Neurons in t he supplement ary sensory area have large recept ive f ields, and some neurons are sensit ive t o pain.
Primary (Unimodal) Somatosensory (Somesthetic) Association Areas The primary somat osensory associat ion areas encompass areas 5 and 7 in t he superior pariet al lobe. They receive t heir input s mainly f rom t he primary somat osensory areas but also have recip-rocal connect ions w it h t he pulvinar nucleus of t he t halamus. Neuronal responses in t he primary somat osensory associat ion areas are complex and involve t he int egrat ion of a number of cort ical and t halamic input s. The processing of mult isensory somat osensory input s in t hese areas allow s f or t he percept ion of shape, size, and t ext ure and t he ident if icat ion of object s by cont act (st ereognosis). The primary somat osensory associat ion areas project t o mult imodal nonprimary associat ion areas (areas 39 and 40) in t he inf erior pariet al lobule t hat receive input s f rom more t han one sensory modalit y and serve int ermodal int egrat ion and mult isensory percept ions. Single-cell recordings in area 5 in monkeys suggest t hat t his area is essent ial f or t he proper use of somat osensory inf ormat ion, f or goal-direct ed volunt ary movement s, and f or t he manipulat ion of object s. Single-cell recordings in area 7 indicat e t hat t his area plays an import ant role in t he int egrat ion of visual and somat osensory st imuli, w hich is essent ial f or coordinat ion of eyes and hands in visually guided movement s. Bilat eral lesions in t he primary somat osensory associat ion areas in humans are associat ed w it h inabilit y t o move t he hand t ow ard an object t hat is clearly seen (opt ic at axia). Such pat ient s are unable t o pour w at er f rom a bot t le int o a glass and repeat edly pour t he w at er out side t he glass. Unilat eral lesions in t he primary somat osensory associat ion areas in t he nondominant hemisphere produce neglect of t he cont ralat eral half of t he body and visual space.
Primary Visual Cortex (V1 ) This area (Figure 17-13) corresponds t o t he calcarine gyrus on t he medial surf ace of t he occipit al lobe on each side of t he calcarine sulcus (area 17 of Brodmann), encompassing part s of t he lingual gyrus vent rally and cuneus gyrus dorsally. I n sect ions of f resh cort ex, t his area is charact erized by t he appearance of a prominent band of w hit e mat t er t hat can be ident if ied by t he naked eye and is named t he band of G ennari, af t er t he I t alian medical st udent w ho described it in 1782. The band of G ennari represent s a t hickened ext ernal band of Baillarger in layer I V of t he cort ex. I n myelin preparat ions, t he band of G ennari appears as a prominent dark band in t he visual cort ex, also know n as t he st riat e cort ex. The t erm st riat e ref ers t o t he presence in unst ained preparat ions of t he t hick w hit e band of G ennari.
The primary visual area receives f ibers f rom t he lat eral geniculat e nucleus. These f ibers originat e in t he ret ina, synapse in t he lat eral geniculat e nucleus, and reach t he visual cort ex via t he opt ic (geniculocalcarine) radiat ion. Each visual cort ex receives f ibers f rom t he ipsilat eral half of each ret ina (Figure 1714) t hat convey inf ormat ion about t he cont ralat eral half of t he visual f ield. Thus lesions of one visual cort ex are manif est ed by loss of vision in t he cont ralat eral half of t he visual f ield (homonymous hemianopsia). The project ions f rom t he ret ina int o t he visual cort ex are organized spat ially in such a w ay t hat macular f ibers occupy t he post erior part of t he visual cort ex, w hile peripheral ret inal f ibers occupy t he ant erior part (Figure 17-15). Fibers originat ing f rom t he superior half of t he ret ina t erminat e in t he superior part of t he visual cort ex; t hose f rom t he inf erior half of t he ret ina t erminat e in t he inf erior part (Figure 17-16). Thus lesions involving port ions of t he visual cort ex, such as t he inf erior calcarcine cort ex, produce an upper cont ralat eral quadrant anopsia in w hich blindness is limit ed t o t he cont ralat eral upper quadrant of t he visual f ield. Similarly, lesions limit ed t o t he upper calcarine cort ex produce a low er cont ralat eral quadrant anopsia in w hich blindness is limit ed t o t he cont ralat eral low er quadrant of t he visual f ield. The represent at ion of t he macula in t he visual cort ex is disproport ionat ely large in comparison w it h it s relat ive size in t he ret ina. This is a ref lect ion of it s import ant f unct ion as t he ret inal area of keenest vision.
Fi gure 17-13. Schemat ic diagram of t he primary and secondary visual cort ices.
Fi gure 17-14. Schemat ic diagram of ret inal represent at ion in t he primary visual cort ex.
Fi gure 17-15. Schemat ic diagram of ret inal represent at ion in t he primary visual cort ex.
Fi gure 17-16. Schemat ic diagram of ret inal represent at ion in t he primary visual cort ex.
St imulat ion of t he visual cort ex elicit s a crude sensat ion of bright f lashes of light ; pat ient s w it h irrit at ive lesions (such as t umors) of t he visual cort ex experience visual hallucinat ions t hat consist of bright light . Conversely, lesions t hat dest roy t he visual cort ex of one hemisphere result in loss of vision in t he cont ralat eral half of t he visual f ield. I f t he dest ruct ive lesion is of vascular origin, such as occurs in occlusions of t he post erior cerebral art ery, cent ral (macular) vision in t he aff ect ed visual f ield is spared. This phenomenon is know n clinically as macular sparing and is at t ribut ed t o t he collat eral art erial supply of t he post erior visual cort ex (macular area) f rom t he pat ent middle cerebral art ery. Funct ional magnet ic resonance imaging (f MRI ) st udies in blind persons have f ound increased responsiveness in t heir primary visual cort ex during a verbal memory t ask w it hout any sensory input . This suggest s t hat , w hile sight ed people devot e much of t heir cort ex t o visual processing, t he visual cort ex in t he blind are recruit ed f or ot her senses. Elegant neurophysiologic st udies of single neurons in t he visual cort ex have revealed t he f ollow ing inf ormat ion: 1. The visual cort ex is organized int o unit s t hat correspond t o specif ic areas in t he ret ina. 2. These unit s respond t o linear st ripe (st raight -line) conf igurat ions.
3. For each unit , a part icular orient at ion of t he st imulus is most eff ect ive. Some unit s respond only t o vert ically orient ed st ripes, w hile ot hers respond only t o horizont ally orient ed st ripes. Some unit s respond at onset of illuminat ion, w hile ot hers respond at cessat ion of illuminat ion. 4. Unit s are of t w o variet ies, simple and complex. Simple unit s react only t o st imuli in corresponding f ixed ret inal recept ive f ields. Complex unit s are connect ed t o several simple cort ical unit s. I t is presumed t hat t he complex unit s represent an advanced st age in cort ical int egrat ion. 5. Unit s t hat respond t o t he same st imulus pat t ern and orient at ion are grouped t oget her in repeat ing unit s ref erred t o as columns, similar t o t hose described f or t he somest het ic cort ex. Tw o general variet ies of f unct ional columns have been described: ocular dominance and orient at ion columns. O cular dominance columns are parallel columns arranged perpendicular t o t he cort ical surf ace and ref lect eye pref erence (right versus lef t ) of cort ical neurons. Alt ernat ing ocular dominance columns are dominat ed by input s f rom t he lef t and right eyes. O rient at ion columns comprise a sequence of cells t hat have t he same recept ive f ield axis orient at ion. 6. Visual columns respond poorly, if at all, t o diff use ret inal illuminat ion. 7. Visual unit s respond opt imally t o moving st imuli. 8. Most cort ical unit s receive f ibers f rom corresponding recept ive f ields in bot h ret inas, t hus allow ing f or single-image vision of corresponding point s in t he t w o ret inas. 9. The st riat e cort ex is organized int o vert ical and horizont al syst ems. The vert ical (columnar) syst em is concerned w it h ret inal posit ion, line orient at ion, and ocular dominance. The horizont al syst em segregat es cells of diff erent orders of complexit y. Simple cells locat ed in layer I V are driven monocularly, w hile complex and hypercomplex cells, locat ed in ot her layers, are driven by impulses f rom bot h eyes. The out put f rom t he primary visual cort ex f ollow s t w o pat hw ays or st reams: a dorsal st ream t o t he occipit opariet al cort ex (t he w here pat hw ay) and a vent ral st ream t o t he occipit ot emporal cort ex (t he w hat pat hw ay). Bilat eral lesions in t he w here pat hw ay result in t he inabilit y t o direct t he eyes t o a cert ain point in t he visual f ield despit e int act eye movement s (Balint -Holmes syndrome). Bilat eral lesions in t he w hat pat hw ay result in t he inabilit y of pat ient s, w it h normal visual percept ion, t o comprehend t he meaning of nonverbal visual st imuli (visual agnosia).
Primary (Unimodal) Visual Association Areas
Adjacent t o t he primary visual area are t he primary associat ion visual areas (ext rast riat e, prest riat e). They include areas 18 and 19 of Brodmann (Figure 1713) on t he lat eral and medial aspect s of t he hemisphere. Areas 20, 21, and 37 in t he inf erior t emporal cort ex are also dedicat ed t o visual inf ormat ion processing. The visual associat ion cort ices are concerned w it h higher-order aspect s of visual processing, as det ailed lat er. Area 18 corresponds t o t he second (V2 ) and area 19 t o t he t hird (V3 ) visual areas. V4 , in humans, is probably locat ed in t he inf erior occipit ot emporal area, in t he region of t he lingual or f usif orm gyrus. V5 in humans is probably locat ed in area 19 of Brodmann. V2 , like V1 , is ret inot opically organized. Visual areas beyond V2 are associat ed w it h varying visual f unct ions. V 3 is associat ed w it h f orm, V4 w it h color, and V5 w it h mot ion. Unit s in t he primary visual associat ion areas are of t he complex or hypercomplex t ypes. Aff erent s t o areas 18 and 19 are mainly f rom t he primary visual area (area 17) but include some direct t halamic project ions f rom t he lat eral geniculat e nucleus and pulvinar nucleus. The primary visual area project s bilat erally and reciprocally t o areas 18 and 19. The project ions f rom t he pulvinar nucleus const it ut e import ant ext rageniculat e links t o t he visual cort ex. O ut put s f rom areas 18 and 19 project t o t he post erior pariet al cort ex (area 7) and t o t he inf erot emporal cort ex (areas 20 and 21). The project ion t o area 7 is concerned w it h st ereopsis (dept h percept ion) and movement . The inf erot emporal project ion is concerned w it h analysis of f orm and color. The inf erot emporal cort ex represent s highest visual f unct ion. Elect rical st imulat ion of area 21 evokes lif elike visual hallucinat ions. Area 37, behind area 21, at t he occipit ot emporal junct ion cont ains modules devot ed t o recognit ion of f aces. Bilat eral lesions in t his area result in f ailure t o recognize f amiliar f aces (prosopagnosia). Color vision is localized inf eriorly in t he inf erior occipit ot emporal cort ex (V4 ). No color represent at ion is f ound in t he superior associat ion visual cort ex. Thus in unilat eral inf erior associat ion visual cort ex lesions t he pat ient loses color vision in t he cont ralat eral half f ield (cent ral hemiachromat opsia). Loss of color vision and f ace recognit ion usually coexist because of t he proximit y of t he areas responsible f or t hem. Connect ions of t he associat ion visual cort ex t o t he angular gyrus (area 39) play a role in recognit ion of visual st imuli. Lesions int errupt ing t his connect ion result in visual agnosia, inabilit y t o recognize object s in t he visual f ield. Bilat eral lesions of t he f if t h visual area (V5 ) are associat ed w it h a def ect in visual mot ion percept ion (akinet opsia). Project ions f rom areas 18 and 19 also reach t he f ront al eye f ields (area 8 of Brodmann) in t he f ront al lobe, as w ell as t he superior colliculus and mot or nuclei of ext raocular muscles. These project ions play a key role in conjugat e eye movement induced by visual st imuli (visual pursuit ).
Primary Auditory Cortex David Ferrier, a Brit ish physician, is credit ed w it h localizing t he primary audit ory
cort ex of monkeys t o t he superior t emporal gyrus during t he lat t er half of t he ninet eent h cent ury. This localizat ion w as not accept ed by his cont emporaries. Subsequent st udies in animals and humans, how ever, have conf irmed his early observat ions. The primary audit ory cort ex (Figure 17-17) corresponds t o t he t ransverse t emporal gyri of Heschl (areas 41 and 42 of Brodmann) locat ed in t he t emporal lobe w it hin t he lat eral f issure. Recording of primary evoked responses t o audit ory st imuli during surgery f or epilepsy provides evidence f or a rest rict ed port ion of Heschl's gyrus (it s post eromedial part ) as t he primary audit ory area. The primary audit ory cort ex receives f ibers (audit ory radiat ion) f rom t he medial geniculat e nucleus. These f ibers reach t he audit ory cort ex via t he sublent icular part of t he int ernal capsule. Audit ory f ibers originat e in t he peripheral organ of Cort i and est ablish several synapses in t he neuraxis, bot h homolat eral and cont ralat eral t o t heir side of origin, bef ore reaching t he medial geniculat e nucleus of t he t halamus. The primary audit ory cort ex, t heref ore, receives f ibers originat ing f rom bot h organs of Cort i, predominant ly f rom t he cont ralat eral side. St imulat ion of t he primary audit ory cort ex produces crude audit ory sensat ions such as buzzing, humming, or knocking. Such sensat ions are ref erred t o clinically as t innit us. Lesions of t he audit ory cort ex result in (1) impairment in sound localizat ion in space and (2) diminut ion of hearing bilat erally but most ly cont ralat erally. The f unct ional organizat ion of t he audit ory cort ex is similar t o t hat of t he somest het ic and visual cort ices. Column cells in t he audit ory cort ex share t he same f unct ional propert ies. Columnar organizat ion is t hus based on isof requency st ripes, each st ripe responding t o a part icular t onal f requency.
Fi gure 17-17. Schemat ic diagram of t he primary audit ory cort ex.
The primary audit ory cort ex is connect ed w it h t he primary (unimodal) associat ion audit ory cort ex. O t her import ant connect ions include t he audit ory cort ex of t he cont ralat eral hemisphere, t he primary somest het ic cort ex, f ront al eye f ields, Broca's area of speech in t he f ront al lobe, and t he medial geniculat e nucleus. Via it s project ion t o t he medial geniculat e body in t he t halamus, t he primary audit ory cort ex cont rols it s ow n input by changing t he excit abilit y of medial geniculat e neurons. Responses of some audit ory cort ex neurons t o sound st imuli depend on w het her t he t ype of t hese sounds w as ant icipat ed. A similar ant icipat ory response t o sound st imuli exist s in some medial geniculat e neurons, suggest ing t hat t ransmission of inf ormat ion t hrough t he audit ory t halamus (medial geniculat e nucleus) and on t o t he audit ory cort ex is cont rolled by behavioral cont ingencies. Physiologic st udies of t he primary audit ory cort ex have revealed t hat it does not play a major role in sound f requency discriminat ion but rat her in t he t emporal pat t ern of acoust ic st imuli. Frequency discriminat ion of sound is a f unct ion of subcort ical acoust ic st ruct ures. The opt imal st imulus t hat f ires audit ory cort ical unit s seems t o be a changing f requency of sound st imuli rat her t han a st eadyf requency st imulus.
Primary (Unimodal) Auditory Association Cortex Adjacent t o t he primary audit ory cort ex is t he primary (unimodal) audit ory associat ion cort ex (area 22 of Brodmann). I t comprises t he area adjacent t o Heschl's gyri in t he superior t emporal gyrus, including t he post erior port ion of t he f loor of t he sylvian f issure (t he planum t emporale). This area is concerned w it h t he comprehension of spoken sound. Area 22 in t he dominant hemisphere is know n as Wernicke's area. Lesions of t his area are associat ed w it h a recept ive t ype of aphasia, a disorder of communicat ion charact erized by t he inabilit y of t he pat ient t o comprehend spoken w ords. The primary audit ory associat ion cort ex in t he nondominant (right ) hemisphere is specialized f or nonspeech audit ory inf ormat ion, such as environment al sounds, musical melodies, and t onal qualit ies of sound (prosody). Bilat eral lesions in t he primary audit ory associat ion cort ices result in t he inabilit y t o recognize sounds (audit ory agnosia) in t he presence of normal hearing, alert ness, and int elligence. Disconnect ion of t he primary audit ory associat ion cort ex (area 22) f rom t he primary audit ory cort ex (areas 41 and 42) result s in a condit ion know n as pure w ord deaf ness, charact erized by poor comprehension of spoken language and poor repet it ion w it h int act comprehension of w rit t en language. The audit ory associat ion cort ex is connect ed via t he ant erior commissure w it h t he pref ront al cort ex and via t he corpus callosum w it h t he pref ront al, premot or, pariet al, and cingulat e cort ices.
Primary Gustatory Cortex The cort ical recept ive area f or t ast e is locat ed in t he pariet al operculum, vent ral t o t he primary somest het ic area and in close proximit y t o t he cort ical areas
receiving sensory aff erent s f rom t he t ongue and pharynx. I t corresponds t o area 43 of Brodmann. I rrit at ive lesions in t his area in humans have been show n t o give rise t o hallucinat ions of t ast e, usually preceding t he onset of an epilept ic at t ack. Such a prodromal sympt om preceding an epilept ic f it f ocuses at t ent ion on t he sit e of t he irrit at ive lesion. Conversely, ablat ion of t his area produces impairment of t ast e cont ralat eral t o t he sit e of t he lesion. The gust at ory cort ex receives f ibers f rom t he post erovent ral medial nucleus of t he t halamus, upon w hich converge sensory f ibers f rom t he f ace and mout h, including t ast e f ibers. Alt hough crude t ast e sensat ions can be perceived at t he t halamic level, discriminat ion among diff erent t ast e sensat ions is a cort ical f unct ion.
Primary Olfactory Cortex The primary olf act ory cort ex is locat ed in t he t ip of t he t emporal lobe and consist s of t he pirif orm cort ex and t he periamygdaloid area. The primary olf act ory cort ex receives f ibers f rom t he lat eral olf act ory st ria and has an int imat e relat ionship w it h adjacent cort ical regions comprising part of t he limbic syst em. Such relat ionships, as w ell as t he role of olf act ion in emot ion and behavior, are discussed in t he chapt er on t he limbic syst em (Chapt er 21). Adjacent t o t he primary olf act ory cort ex is t he ent orhinal cort ex (area 28), w hich is considered t he associat ion or secondary olf act ory cort ical area. I rrit at ive lesions in t he region of t he olf act ory cort ex give rise t o olf act ory hallucinat ions t hat are usually disagreeable. As in t he case of t ast e, such hallucinat ions f requent ly precede an epilept ic f it . Since olf act ory hallucinat ions f requent ly occur in associat ion w it h lesions in t he uncus of t he t emporal lobe (including t he olf act ory cort ex), t hey are ref erred t o clinically as uncinat e f it s. The olf act ory syst em is t he only sensory syst em in w hich f ibers reach t he cort ex w it hout passing t hrough t he t halamus. Basic olf act ory f unct ions needed f or ref lex act ion reside in subcort ical st ruct ures. The discriminat ion of diff erent odors, how ever, is a f unct ion of t he olf act ory cort ex.
Primary Vestibular Cortex Dat a are scant about t he anat omic locat ion as w ell as t he physiologic propert ies of t he primary vest ibular cort ex. Many cort ical areas have been ident if ied in humans as possibly involved in vest ibular processing. How ever, t he various met hods used provide variable degrees of accuracy and do not provide precise localizat ion. Recent st udies using cort ical st imulat ion in pat ient s undergoing brain surgery f or t reat ment of epilepsy have ident if ied a lat eral cort ical t emporopariet al area (t he t emporoperisylvian vest ibular cort ex) f rom w hich vest ibular sympt oms, including rot at ory sensat ions, w ere easily elicit ed. The area ext ended above and below t he sylvian f issure, mainly inside Brodmann areas 40 (supramarginal gyrus), 21 (middle t emporal gyrus), and 22 (primary audit ory associat ion area in t he superior t emporal gyrus). I t included t he pariet al operculum. Lesions in t his area in humans impair percept ual judgment s about
body orient at ion and movement . Such lesions, how ever, do not impair brain st em vest ibular ref lexes such as t he vest ibuloocular ref lex.
CORTICAL M OTOR AREAS There are t hree major cerebral cort ical areas involved in mot or cont rol: 1. Primary mot or area (MI ) 2. Supplement ary mot or area (MI I ) 3. Premot or area The primary mot or area is coext ensive w it h area 4 of Brodmann, and t he supplement ary mot or and premot or areas are coext ensive w it h area 6 of Brodmann. The supplement ary mot or and premot or areas t oget her represent t he nonprimary mot or cort ex. The t hree mot or areas diff er in t heir elect rical excit abilit y, f unct ional neuronal propert ies, and connect ivit y. They receive input s f rom diff erent t halamic nuclei and have diff erent cort icocort ical connect ions and diff erent out put project ions.
Primary Motor Area (MI) The primary mot or area (Figure 17-18) corresponds t o t he precent ral gyrus (area 4 of Brodmann). O n t he medial surf ace of t he hemisphere, t he primary mot or area comprises t he ant erior part of t he paracent ral lobule. The cont ralat eral half of t he body is represent ed in t he primary mot or area in a precise but disproport ionat e manner, giving rise t o t he mot or homunculus in t he same w ay as t hat described f or t he primary somest het ic cort ex. St imulat ion of t he mot or cort ex in conscious humans gives rise t o discret e and isolat ed cont ralat eral movement limit ed t o a single joint or a single muscle. Bilat eral responses are seen in ext raocular muscles and muscles of t he f ace, t ongue, jaw, larynx, and pharynx. The primary mot or cort ex t hus f unct ions in t he init iat ion of highly skilled f ine movement s, such as but t oning one's shirt or sew ing. The represent at ion of bodily regions in t he cont ralat eral mot or cort ex does not seem t o be rigidly f ixed. Thus repet it ive st imulat ion of t he t humb area w ill produce movement of t he t humb, f ollow ed af t er a w hile by immobilit y of t he t humb and movement at t he index f inger or even t he w rist . This has been int erpret ed t o mean t hat in t he t humb area of t he cort ex t he mot or unit s cont rolling t he index f inger and w rist have a higher t hresh-old f or st imulat ion t han t hose cont rolling t he t humb.
Fi gure 17-18. Schemat ic diagram of t he primary mot or area (area 4), premot or area (area 6), and t he f ront al eye f ield (area 8).
The mot or area receives f ibers f rom t he vent rolat eral nucleus of t he t halamus, t he main project ion area of t he cerebellum. The mot or area also receives f ibers f rom t he somest het ic cort ex (areas 1, 2, and 5) and t he supplement ary mot or cort ex. The connect ions bet w een t he primary mot or and somest het ic cort ices are reciprocal. The out put cont ribut es t o t he associat ion, commissural, and cort icof ugal f iber syst ems discussed earlier. The primary mot or cort ex is t he sit e of origin of about 30% t o 40% of t he f ibers in t he pyramidal t ract . Furt hermore, all t he large-diamet er axons (approximat ely 3% of t he pyramidal f ibers) originat e f rom t he giant mot or neurons (of Bet z) in t he primary mot or cort ex. Most of t he neurons cont ribut ing f ibers t o t he cort icospinal t ract have glut amat e or aspart at e as t heir excit at ory neurot ransmit t er. Ablat ion of t he primary mot or cort ex result s in f laccid (hypot onic) paralysis in t he cont ralat eral half of t he body associat ed w it h loss of all ref lexes. Wit h t ime, t here is recovery of st ereot yped movement at proximal joint s, but t he f unct ion of dist al muscles concerned w it h skilled movement remains impaired. Exaggerat ed myot at ic ref lexes and a Babinski sign also appear. Alt hough t he primary mot or cort ex is not t he sole area f rom w hich movement can be elicit ed, it is nevert heless charact erized by init iat ing highly skilled movement at a low er t hreshold of st imulat ion t han t he ot her mot or areas. Epilept ic pat ient s w it h a lesion in t he primary mot or cort ex f requent ly manif est a seizure (epilept ic) pat t ern t hat consist s of progression of t he epilept ic movement f rom one part of t he body t o anot her in a charact erist ic sequence corresponding t o body represent at ion in t he mot or cort ex. Such a phenomenon is know n clinically as a Jacksonian march, af t er t he English neurologist John Hughlings-Jackson. Neurophysiologic st udies of mot or cort ex neurons reveal t hat act ion pot ent ials can be recorded f rom mot or neurons in t he cort ex about 60 t o 80 ms bef ore
muscle movement . Furt hermore, t w o t ypes of neurons in t he mot or cort ex have been ident if ied. These are a larger neuron w it h a phasic pat t ern of f iring and a smaller neuron t hat f ires in a t onic pat t ern. From experiment s on conscious animals perf orming specif ic t asks, it has been show n t hat t he f requency of f iring is highly correlat ed w it h t he f orce exert ed t o perf orm a specif ic movement . Mot or neurons supplying a given muscle are usually grouped t oget her in a columnar f ashion. Alt hough some mot or neurons can be st imulat ed f rom a w ide area, each has a so-called best point f rom w hich it can be st imulat ed most easily. Such best point s usually are conf ined t o a cylindric area of cort ex about 1 mm in diamet er.
Supplementary Motor Area (MII) The supplement ary mot or area is locat ed on t he medial surf ace of t he f ront al lobe, ant erior t o t he medial ext ension of t he primary mot or cort ex (area 4). I t corresponds roughly t o t he medial ext ensions of area 6 of Brodmann. Alt hough t he exist ence of a mot or area in t he medial aspect of t he f ront al cort ex rost ral t o t he precent ral leg area of primat es has long been know n, Penf ield and Welch w ere t he f irst t o call t his port ion of t he cort ex t he supplement ary mot or area in 1949 and 1951. A homunculus has been def ined f or t he supplement ary mot or area in w hich f ace and upper limbs are represent ed rost ral t o t he low er limbs and t runk. St imulat ion in humans gives rise t o complex movement in preparat ion f or t he assumpt ion of charact erist ic post ures. Alt hough simple mot or t asks are elicit ed f rom st imulat ion of t he supplement ary mot or area, t he role of t his area in simple mot or t asks is much less signif icant and is likely t o be subsidiary t o t hat of t he primary mot or area. O n t he ot her hand, t he supplement ary mot or area assumes more signif icance in execut ing simple mot or t asks as a compensat ory mechanism w hen t he primary mot or area is dest royed. The supplement ary mot or area seems crucial in t he t emporal organizat ion of movement , especially in sequent ial perf ormance of mult iple movement s, and in mot or t asks t hat demand ret rieval of mot or memory. Cells w ere ident if ied in t he supplement ary mot or area in response t o movement s of bot h proximal and dist al ext remit y muscles, ipsilat eral and cont ralat eral. Supplement ary mot or area neurons diff er f rom primary mot or area neurons in t hat only a small percent age (5%) of supplement ary mot or area neurons cont ribut e axons t o t he pyramidal t ract and t hese neurons have insignif icant input f rom t he periphery and are act ivat ed bilat erally. The supplement ary mot or cort ex is connect ed reciprocally w it h t he ipsilat eral primary mot or (area 4), premot or (area 6), and somat osensory (areas 5, 7) cort ices and t he cont ralat eral supplement ary mot or cort ex. Subcort ical project ions t o t he supplement ary mot or area are predominant ly f rom t he basal ganglia via t he t halamus. An input f rom t he cerebellum via t he basal ganglia also has been show n t o exist . Subcort ical project ions of t he supplement ary mot or
cort ex are prof use t o part s of t he caudat e nucleus and put amen and t o t he vent ral ant erior, vent ral lat eral, and dorsomedial t halamic nuclei. Approximat ely 5% of neurons in t he supplement ary mot or cort ex cont ribut e f ibers t o t he cort icospinal t ract . Available anat omic and physiologic dat a suggest t hat t he supplement ary mot or area could be t he sit e w here ext ernal input s and commands are mat ched w it h int ernal needs and drives t o f acilit at e f ormulat ion (programming) of a st rat egy of volunt ary movement . The t hreshold of st imulat ion of t he supplement ary mot or area is higher t han t hat of t he primary mot or cort ex and t he responses elicit ed are ipsilat eral or bilat eral. I n cont rast t o t he evidence f rom physiologic st udies, f ew clinical case report s have described persist ent eff ect s on mot or behavior of damage t o t he supplement ary mot or area. I n t he acut e phase, pat ient s have global reduct ion in movement (akinesia) t hat is part icularly pronounced on t he side cont ralat eral t o t he lesion and a grasp ref lex. Lesions in t he supplement ary mot or area of t he dominant hemisphere are associat ed w it h severe impairment of spont aneous speech w it h preserved repet it ion. These manif est at ions are most ly t ransient and resolve w it hin a f ew w eeks. The last ing disorder of mot or behavior report ed t o occur in humans af t er supplement ary mot or area lesions has been a dist urbance of alt ernat ing movement s of t he t w o hands. O t her clinical manif est at ions, of uncert ain et iology, associat ed w it h lesions in t he supplement ary mot or area include hypert onia, increase in myot at ic ref lexes, clonus, and t he Babinski sign. The t radit ionally def ined supplement ary mot or area includes t w o separat e regions: a caudal region (supplement ary mot or area proper) t hat has reciprocal connect ions w it h t he primary mot or area and project s t o t he spinal cord and a rost ral region (presupplement ary mot or area) t hat receives project ions f rom t he pref ront al and cingulat e cort ices. Basal ganglia input reaches t he caudal region, w hereas cerebellar input reaches t he rost ral region. Neuronal responses t o visual st imuli prevail in t he rost ral region, w hereas somat osensory responses prevail in t he caudal region. The urge t o init iat e movement in humans is elicit ed only f rom t he rost ral region.
Premotor Area The concept of a premot or cort ex w as f irst proposed in 1905 by Campbell, w ho called it t he int ermediat e precent ral cort ex. The t erm premot or cort ex w as f irst used by Hines in 1929. The premot or cort ex has undergone a st rong phylogenet ic development . Whereas in monkeys t he premot or area is equally large as t he primary mot or area, in humans t he premot or area is about six t imes larger t han t he primary mot or area. The premot or area (Figure 17-18) is locat ed in t he f ront al lobe just ant erior t o t he primary mot or area. I t corresponds t o area 6 of Brodmann. The premot or area is concerned w it h volunt ary mot or f unct ion dependent on sensory input s (visual, audit ory, somat osensory). St imulat ion of t he premot or area elicit s a st ereot yped gross movement t hat requires coordinat ion among many muscles,
such as t urning movement s of t he head, eyes, and t runk t ow ard t he opposit e side, elevat ion of t he arm, elbow f lexion, and pronat ion of t he hand. The t hreshold of st imuli t hat elicit responses f rom t his area is higher t han t hat required f or t he primary mot or cort ex. I n normal subject s, t he premot or area show s increased act ivit y w hen mot or rout ines are run in response t o visual, audit ory, or somat osensory cues such as reaching f or an object in space, obeying a spoken command, or ident if ying an object by manipulat ion. The premot or area exert s inf luence on movement via t he primary mot or area or direct ly t hrough it s project ions t o t he pyramidal and ext rapyramidal syst ems. Approximat ely 30% of pyramidal f ibers originat e f rom t he premot or area. The premot or area is act ivat ed w hen a new mot or program is est ablished or w hen t he mot or program is changed on t he basis of sensory inf ormat ion received, f or example, w hen t he subject is exploring t he environment or object s. Ablat ion of t he premot or cort ex in humans may produce a def icit in t he execut ion of skilled, sequent ial, and complex movement such as w alking. Such a def icit is know n clinically as idiomot or apraxia. I n such a syndrome, t he pat ient has diff icult y in w alking, alt hough t here is no volunt ary mot or paralysis. The grasp ref lex at t ribut ed t o lesions of t he premot or area in t he older lit erat ure is now believed t o be due t o involvement of t he supplement ary mot or cort ex. Some neuroscient ist s consider t he separat ion of t he mot or cort ex int o primary mot or and nonprimary mot or areas somew hat art if icial. How ever, closer considerat ion of t his issue just if ies t his separat ion on t he basis of t he t hreshold of st imuli t hat elicit mot or responses (much low er in t he primary mot or area) as w ell as t he t ype of movement elicit ed f rom st imulat ion (simple f rom t he primary mot or area versus coordinat ed, complex movement f rom t he nonprimary areas). Alt hough neural act ivit y in relat ion t o each of many aspect s of mot or cont rol seems t o be dist ribut ed in mult iple cort ical areas, an individual mot or area (primary mot or, premot or, supplement ary mot or) is used pref erent ially under specif ic circumst ances requiring a cert ain variet y of mot or behavior. I n clinical sit uat ions, how ever, all areas are more of t en t han not involved t oget her in disease processes, be it vascular occlusion or hemorrhage leading t o st roke or a t umor invading t his region of t he cort ex. I n such sit uat ions, t he clinical manif est at ions can be classif ied int o t hose seen immediat ely af t er t he onset of t he pat hology and t hose w hich f ollow af t er a f ew days or w eeks. The f ormer consist of loss of all ref lexes and hypot onia of aff ect ed muscles. Wit hin hours or days, how ever, st ereot yped movement , part icularly in proximal muscles, ret urns, hypot onia changes t o hypert onia and aref lexia t o hyperact ive myot at ic ref lexes, and a Babinski sign appears. The discret e movement s in dist al muscles, how ever, remain impaired. Such a clinical pict ure is seen of t en f ollow ing a st roke involving t his region of t he cort ex.
Cortical Eye Fields
A. SACCADIC EYE M OVEM ENTS Saccadic movement s are f ast eye movement s w it h rapid ref ixat ion of vision f rom point t o point w it h no int erest in t he point s in bet w een. Posit ron emission t omography (PET) scans and lesion st udies indicat e t hat t he cerebral areas most import ant f or saccadic cont rol are: (1) post erior pariet al cort ex and (2) f ront al premot or cort ex. The post erior pariet al cort ex (cort ex in t he post erior region of t he int rapariet al sulcus and t he adjacent superior pariet al lobule) is act ivat ed by t he primary visual cort ex during saccades f or w hich t here is a visual goal. Three areas in t he f ront al lobe part icipat e in saccadic processing: (1) t he f ront al eye f ield (area 8 of Brodmann), (2) t he dorsolat eral pref ront al cort ex (area 46 of Brodmann), and (3) t he supplement ary eye f ield (ant erior part of t he supplement ary mot or area). The f ront al and supplement ary eye f ields are act ivat ed during all t ypes of saccadic movement s. The dorsolat eral pref ront al cort ex is act ivat ed during f ixat ion.
1. Frontal Eye Field. The f ront al eye f ield (Figure 17-18) is locat ed in t he middle f ront al gyrus ant erior t o or in t he ant erior port ion of t he mot or st rip. I t corresponds t o area 8 of Brodmann and t he immediat ely adjacent cort ex. The f ront al eye f ield t riggers int ent ional (volunt ary) saccades t o visible t arget s in t he visual environment , t o remembered t arget locat ions, or t o t he locat ion w here it is predict ed t hat t he t arget w ill appear. These movement s subserve int ent ional explorat ion of t he visual environment . The f ront al eye f ield receives mult iple cort ical input s, in part icular f rom t he pariet ooccipit al cort ex, supplement ary eye f ield, and t he pref ront al cort ex (area 46 of Brodmann). The f ront al eye f ield elicit s int ent ional (volunt ary) saccades t hrough connect ions t o nuclei of ext raocular muscles in t he brain st em. The pat hw ay f rom t he f ront al eye f ield t o t he nuclei of ext raocular movement is not direct but involves mult iple brain st em ret icular nuclei, including t he superior colliculus, t he int erst it ial nucleus of t he medial longit udinal f asciculus (RiMLF), and t he paramedian pont ine ret icular f ormat ion (PPRF). I rrit at ing lesions in t he f ront al eye f ield, as in an epilept ic f ocus, w ill deviat e bot h eyes in a direct ion cont ralat eral t o t he irrit at ive lesion (Figure 17-19). Conversely, ablat ion of t he f ront al eye f ield w ill result in deviat ion of t he eyes t o t he side of ablat ion (Figure 17-19) as a result of t he unopposed act ion of t he int act f ront al eye f ield. Such a condit ion is encount ered in pat ient s w it h occlusion of t he middle cerebral art ery, w hich supplies t he bulk of t he lat eral surf ace of t he hemisphere, including t he f ront al eye f ield. As a result of t he art erial occlusion, inf arct ion (deat h) of cort ical t issue w ill ensue. Such pat ient s manif est paralysis of f ace and limbs (upper limbs more t han low er) cont ralat eral t o t he side of art erial occlusion and conjugat e deviat ion of t he eyes t ow ard t he cort ical lesion.
Fi gure 17-19. Schemat ic diagram of t he eff ect s of st imulat ion and lesions in t he f ront al eye f ields on conjugat e eye movement s.
I n humans, conjugat e eye deviat ions occur more f requent ly af t er lesions in t he right hemisphere t han af t er lesions in t he lef t hemisphere. There is no explanat ion f or t his ot her t han t hat it may be relat ed t o t he neglect syndrome associat ed more f requent ly w it h right hemisphere lesions. Conjugat e eye deviat ions also have been observed w it h lesions t hat spare t he f ront al eye f ield but t hat int errupt t he connect ions bet w een t he post erior pariet al and f ront al eye f ields or t heir subcort ical project ions.
2. Supplementary Eye Field. An oculomot or area in t he f ront al cort ex, separat e f rom t he f ront al eye f ield, w as f irst def ined by Schlag in 1985. I t is locat ed rost ral t o t he supplement ary mot or area (MI I ) on t he medial surf ace of t he hemisphere. The supplement ary eye f ield receives mult iple cort ical input s, in part icular f rom t he pref ront al cort ex and t he post erior part of t he cerebral hemisphere. The supplement ary eye f ield project s t o t he f ront al eye f ield and t o subcort ical nuclei involved in eye movement s (superior colliculus and ret icular f ormat ion). The supplement ary eye f ield plays a role in t riggering sequences of saccades and in t he cont rol of saccades concerned w it h complex mot or programming such as t hose made during head or body movement s (spat iot opic saccades).
3. Posterior Parietal Eye Field. The post erior pariet al eye f ield corresponds t o areas 39, 40, and 19 of Brodmann. This area t riggers ref lexive, visually guided saccades. I t exert s it s inf luence on saccadic eye movement s via it s connect ions t o t he f ront al eye f ield or direct ly t o t he superior colliculus. Pat ient s w it h lesions in t he post erior
pariet al eye f ield lose ref lexive visually guided saccades but are able t o move t heir eyes in response t o command (int ent ional saccades).
B. CORTICAL AREAS PREPARING SACCADES Three cort ical areas not involved direct ly in t riggering of saccades play import ant roles in planning, int egrat ion, and chronologic ordering of saccades. The pref ront al cort ex (area 46 of Brodmann) plays a role in planning saccades t o remembered t arget locat ions. The inf erior pariet al lobule is involved in visuospat ial int egrat ion. Bilat eral lesions in t his area result in Balint syndrome, named af t er t he Hungarian neurologist Rudolph Balint (opt ic at axia, ocular apraxia, psychic paralysis of visual f ixat ion), a rare syndrome charact erized by t he inabilit y t o direct t he eyes t o a cert ain point in t he visual f ield despit e ret ent ion of int act vision and eye movement s. The hippocampus appears t o cont rol t he t emporal w orking memory required f or chronologic order of saccade sequences.
C. SM OOTH-PURSUIT EYE M OVEM ENTS Smoot h-pursuit movement s are slow eye movement s init iat ed by a moving object . The goal of t he pursuit syst em is t o produce eye velocit y t hat mat ches t he velocit y of t he moving object . Unlike saccades, smoot h-pursuit movement s cannot occur in darkness. They require a visual st imulus t o occur. Cort ical areas involved in smoot h pursuit include t he t emporooccipit al region and t he f ront al eye f ield. Each of t hese areas has direct project ions t o brain st em neurons t hat drive pursuit . The t emporooccipit al region is driven by input f rom t he primary visual cort ex. Tw o ot her cort ical areas (t he post erior pariet al and t he superior t emporal cort ices) may cont ribut e t o smoot h pursuit indirect ly t hrough visual at t ent ion. Specif ic lesions in t he t emporooccipit opariet al cort ex in humans associat ed w it h smoot h-pursuit def icit s correspond t o Brodmann areas 19, 37, and 39. Lesions in t he f ront al eye f ield also have been associat ed w it h def icit s in smoot h pursuit . The cort icof ugal pat hw ays f or smoot h-pursuit movement s f ollow t w o rout es. The f irst courses f rom t he t emporooccipit opariet al cort ex t hrough t he post erior limb of t he int ernal capsule t o t he dorsolat eral pont ine nucleus in t he midpons. The second courses f rom t he f ront al eye f ield t o t he dorsolat eral pont ine nucleus and nucleus ret icularis t egment i pont is. Cort ical areas f or smoot h pursuit also project t o t he f locculus of t he cerebellum af t er relays in t he dorsolat eral pont ine nucleus. The f locculus, in t urn, project s on t he vest ibular nuclei, w hich project t o cranial nerve nuclei of ext raocular movement (CN I I I , I V, VI ). Cerebral hemisphere lesions impair ocular pursuit ipsilat erally or bilat erally, w hereas post erior f ossa lesions impair ocular pursuit eit her cont ralat erally or ipsilat erally. This variabilit y probably ref lect s involvement of a presumed pursuit pat hw ay t hat crosses f rom t he pont ine nuclei t o t he cerebellum and t hen consist s
of a unilat eral project ion f rom t he cerebellum t o vest ibular nuclei.
CORTICAL LANGUAGE AREAS Language is an arbit rary and abst ract w ay t o represent t hought processes by means of sent ences and t o present concept s or ideas by means of w ords. The neural syst em f or language is made up of many component s in several areas of t he brain. Most component s of t he language syst em are locat ed in t he lef t hemisphere. The lef t hemisphere is t he dominant hemisphere f or language in approximat ely 95% of humans as det ermined by f unct ional imaging and cort ical st imulat ion st udies. Nearly all right -handers and about t w o-t hirds of lef t -handers have such dominance. A disorder in language f unct ion (aphasia or dysphasia) includes dist urbances in t he abilit y t o comprehend (decoding) and/ or program (coding) t he symbols necessary f or communicat ion. The cort ical area of t he lef t hemisphere invariably involved in aphasia is a cent ral core surrounding t he sylvian f issure, w hich includes Wernicke's area, t he arcuat e f asciculus, t he angular gyrus, and Broca's area. This perisylvian core area is surrounded by a larger region in w hich aphasia occurs less f requent ly. Tradit ionally, a dist inct ion has been made bet w een t w o major cort ical language areas: (1) Wernicke's area and (2) Broca's area. The t w o areas are connect ed via a long associat ion f iber bundle, t he arcuat e f asciculus.
Wernicke's Area Wernicke's area, named af t er t he G erman neurologist Karl Wernicke, comprises an ext ensive region t hat includes t he post erior part of t he superior t emporal gyrus (Brodmann area 22) including t he planum t emporale in t he f loor of t he sylvian f issure, and t he pariet ooccipit ot emporal junct ion area including t he angular gyrus (Brodmann area 39). The lat t er component is a recent addit ion t o Wernicke's area not included in t he area originally described by Wernicke. The upper surf ace of area 22, t he planum t emporale, is dist inct ly longer on t he lef t side (dominant hemisphere f or language) in most people. Wernicke's area is concerned w it h t he comprehension of language. The superior t emporal gyrus component of Wernicke's area (area 22) is concerned w it h comprehension of spoken language, w hereas t he angular gyrus (area 39) and adjacent regions are concerned w it h comprehension of w rit t en language. Spoken language is perceived in t he primary audit ory area (Heschl's gyrus, areas 41 and 42) in t he superior t emporal gyrus and t ransmit t ed t o t he adjacent ly locat ed Wernicke's area w here it is comprehended (Figure 17-20). Lesions in Wernicke's area are associat ed w it h a t ype of aphasia (sensory, recept ive, post erior, f luent ) in w hich pat ient s have diff icult y comprehending spoken language.
Fi gure 17-20. Schemat ic diagram show ing t ransmission of audit ory symbols f rom t he primary audit ory cort ex t o Wernicke's area f or comprehension, and via t he arcuat e f asciculus, t o Broca's area of speech.
Broca's Area Broca's area, named af t er t he French pat hologist Pierre Paul Broca w ho def ined t his area in 1861, comprises t he post erior part of t he t riangular gyrus (Brodmann area 45) and t he adjacent opercular gyrus (Brodmann area 44) in t he inf erior f ront al gyrus of t he dominant hemisphere (Figure 17-21). Broca's area receives input s f rom Wernicke's area via t he arcuat e f asciculus (Figure 17-20). Wit hin Broca's area, a coordinat ion program f or vocalizat ion is f ormulat ed. The element s of t he program are t ransmit t ed t o t he f ace, t ongue, vocal cords, and pharynx areas of t he mot or cort ex f or execut ion of speech. Broca's area is also connect ed t o t he supplement ary mot or area, w hich is concerned w it h t he init iat ion of speech. Lesions in Broca's area are associat ed w it h a t ype of aphasia (mot or, ant erior, expressive, nonf luent ) charact erized by inabilit y of t he pat ient t o express himself or herself by speech. Such pat ient s are able t o comprehend language (int act Wernicke's area).
Fi gure 17-21. Schemat ic diagram of Broca's area of speech.
Elect rophysiologic st udies and cerebral blood f low st udies have conf irmed t he role of Broca's area in speech expression. Records made f rom scalp elect rodes placed over Broca's area have revealed a slow negat ive pot ent ial of several seconds in durat ion appearing over Broca's area 1 t o 2 s prior t o ut t ering of w ords. St imulat ion of Broca's area in conscious pat ient s may inhibit speech or may result in ut t erance of vow el sounds. St udies on cerebral blood f low have show n a marked increase in f low in Broca's area during speech. Recent dat a f rom f unct ional imaging st udies of t he human brain reveal t hat , in addit ion t o a role in language, Broca's area is also act ivat ed during nonlinguist ic t asks, such as observat ion of f inger movement and recognit ion of manual gest ures.
The Arcuate Fasciculus The arcuat e f asciculus (Figure 17-20) is a long associat ion f iber bundle t hat links Wernicke's and Broca's areas of speech. Damage t o t he arcuat e f asciculus is associat ed w it h impairment of repet it ion of spoken language.
Sequence of Cortical Activities during Language Processing The sequence of t he complex cort ical act ivit ies during t he product ion of language may be summarized as f ollow s: When a w ord is heard, t he out put f rom t he primary audit ory area (Heschl's gyrus) is conveyed t o t he adjacent Wernicke's area, w here t he w ord is comprehended (Figure 17-20). I f t he w ord is t o be spoken, t he comprehended pat t ern is t ransmit t ed via t he arcuat e f asciculus f rom Wernicke's area t o Broca's area in t he inf erior f ront al gyrus (Figure 17-20). I f t he w ord is t o be read, represent at ions visualized as w ords or images are conveyed f rom t he visual cort ex (areas 17, 18, and 19) t o t he angular gyrus (area 39), w hich in t urn arouses t he corresponding audit ory f orm of t he w ord in Wernicke's area (Figure 17-22). From Wernicke's area, t he inf ormat ion is relayed via t he arcuat e f asciculus t o Broca's area.
Fi gure 17-22. Schemat ic diagram show ing t ransmission of out put f rom t he primary visual area t o t he angular gyrus w here t he audit ory f orm of t he w ord is elicit ed f rom Wernicke's area.
The Right Hemisphere and Language Alt hough several areas in t he lef t hemisphere are dominant in t he recept ion,
programming, and product ion of language f unct ion, corresponding areas in t he right hemisphere are met abolically act ive during speech. These areas are believed t o be concerned w it h melodic f unct ion of speech (prosody). Lesions in such areas of t he right hemisphere render speech amelodic (aprosodic). Lesions in area 44 on t he right side, f or example, result in a dull monot onic speech. Lesions in area 22 on t he right side, on t he ot her hand, may lead t o inabilit y of t he pat ient t o det ect inf lect ion of speech. Such pat ient s may be unable t o diff erent iat e w het her a part icular remark is int ended as a st at ement of f act or as a quest ion.
CORTICAL LOCALIZATION OF M USIC Wit h t he allocat ion of specif ic f unct ions t o each hemisphere, t he quest ion has arisen as t o w hich hemisphere is specialized f or music. I n t his cont ext , one should separat e musical percept ion f rom musical execut ion by t he naive, casual list ener and t he music prof essional. Whereas a naive list ener perceives music in it s overall melodic cont our, t he prof essional perceives music as a relat ion bet w een musical element s and symbols (language). Wit h t his t ype of analysis, it is conceivable t hat t he naive list ener perceives music in t he right hemisphere, w hereas t he prof essional perceives music in t he lef t hemisphere. Musical execut ion (singing), on t he ot her hand, seems t o be a f unct ion of t he right hemisphere irrespect ive of musical know ledge and t raining.
OTHER CORTICAL AREAS I n addit ion t o t he previously discussed cort ical areas, t he cerebral cort ex cont ains ot her f unct ionally import ant areas. These include t he mult imodal (het eromodal) pref ront al cort ex and t he post erolat eral pariet al (major associat ion) cort ex. Mult imodal cort ices are relat ed t o more t han one sensorimot or modalit y. They have undergone major expansion in humans relat ive t o animals.
Prefrontal Cortex The pref ront al cort ex (Figure 17-23) comprises t he bulk of t he f ront al lobe rost ral t o t he premot or cort ex (area 6). I t includes Brodmann areas 9, 10, 11, 12, and 46, locat ed on t he medial, lat eral and orbit al surf aces of t he f ront al lobe. Mot or responses are as a rule not elicit ed by st imulat ion of t his area of t he f ront al lobe. The pref ront al cort ex is w ell developed only in primat es and especially so in humans. I t is believed t o play a role in aff ect ive behavior and judgment . Clues about t he f unct ions of t he pref ront al cort ex have been gained by st udying pat ient s w it h f ront al lobe damage, such as Phineas G age, t he New England railroad w orker w ho w as st ruck by a t hick iron bar t hat penet rat ed his pref ront al cort ex. Miraculously, he survived but w it h a st riking change in his personalit y. Whereas prior t o t he injury he w as an eff icient and capable supervisor, f ollow ing t he accident he w as unf it t o perf orm such w ork. He became
f it f ul and engaged in prof anit y. Lesions in t he pref ront al cort ex lead t o impairment in execut ive f unct ions such as decision making, priorit izat ion, and planning. These usually occur in associat ion w it h alt erat ions in emot ion and of social behavior. Such pat ient s usually neglect t heir appearance, laugh or cry inappropriat ely, and have no appreciat ion of norms of social behavior and conduct . They are uninhibit ed and highly dist ract ible. The pref ront al cort ex can be t hought of in t erms of t hree divisions: (1) dorsolat eral pref ront al (areas 9, 10, 46), (2) vent romedial (areas 11 and 12), and (3) superior mesial (mesial 6 and part s of 9 and 32 areas). Damage t o t he dorsolat eral pref ront al area result s in impairment of w orking (short -t erm) memory, allocat ion of at t ent ion, and speed of processing. Damage t o t he vent romedial area result s in severe impairment of decision making and emot ion. Damage t o t he superior mesial area impact s emot ion, mot ivat ion, and init iat ion of behavior. Bilat eral damage t ends t o produce great er impairment s t han does unilat eral damage. Pat ient s w it h pref ront al cort ex lesion t hus exhibit one or more of t he f ollow ing signs: impaired decision making, dist ract ibilit y, emot ional labilit y, social disinhibit ion, impulsiveness, hyperphagia, lack of planning, rest rict ed emot ion, def icient empat hy, f ailure t o complet e t asks, and lack of aw areness or concern. A charact erist ic sympt om in humans w it h pref ront al lobe lesions is perseverat ion, t he inappropriat e repet it ion of behavior (speech or mot or behavior). Surgical ablat ion of t he pref ront al cort ex (pref ront al lobot omy) w as resort ed t o in t he past t o t reat pat ient s w it h ment al disorders such as schizophrenia and int ract able pain. I n t he lat t er group, t he eff ect of t he operat ion w as not t o relieve t he sensat ion of pain but rat her t o alt er t he aff ect ive react ion (suff ering) of t he pat ient t o pain. Such pat ient s cont inue t o f eel pain but become indiff erent t o it . The ablat ion of t he pref ront al area in pat ient s w it h ment al illness has been replaced largely by administ rat ion of psychopharmacologic drugs. Through it s int erconnect ions w it h associat ion cort ices of ot her lobes and w it h t he hypot halamus, medial t halamus, and amygdala, t he pref ront al cort ex receives inf ormat ion about all sensory modalit ies as w ell as about mot ivat ional and emot ional st at es.
Fi gure 17-23. Schemat ic diagram of t he pref ront al cort ex.
Major Association Cortex The major associat ion cort ex (Figure 17-24) ref ers t o t he supramarginal and angular gyri in t he inf erior pariet al lobule. I t corresponds t o areas 39 and 40 of Brodmann. The major associat ion cort ex in Einst ein's brain w as f ound t o be 15% w ider t han in cont rols, suggest ing a role in mat hemat ical and visual reasoning. The major associat ion cort ex is connect ed w it h all t he sensory cort ical areas and t hus f unct ions in higher-order and complex mult isensory percept ion. I t s relat ion t o t he speech areas in t he t emporal and f ront al lobes gives it an import ant role in communicat ion skills. Pat ient s w it h lesions in t he major associat ion cort ex of t he dominant hemisphere present a conglomerat e of manif est at ions t hat include recept ive and expressive aphasia, inabilit y t o w rit e (agraphia), inabilit y t o synt hesize, correlat e, and recognize mult isensory percept ions (agnosia), lef t -right conf usion, diff icult y in recognizing t he diff erent f ingers (f inger agnosia), and inabilit y t o calculat e (acalculia). These sympt oms and signs are grouped t oget her under t he t erm G erst mann's syndrome. I nvolvement of t he major associat ion cort ex in t he nondominant hemisphere is usually manif est ed by dist urbances in draw ing (const ruct ional apraxia) and in t he aw areness of body image. Such pat ient s have diff icult y in draw ing a square or circle or copying a complex f igure. They of t en are unaw are of a body part and t hus neglect t o shave half t he f ace or dress half t he body.
Fi gure 17-24. Schemat ic diagram of t he major associat ion cort ex.
THE INSULA (ISLAND OF REIL) Vicq d'Azyr w as t he f irst , in 1786, t o express int erest in t he insula. He ref erred t o it as t he c onvolut ions sit uat ed bet w een t he sylvian f issure and t he corpus callosum. I n 1809, Reil w as t he f irst t o describe t he insula. I n humans, t he insula is a highly developed st ruct ure in t he dept h of t he sylvian f issure, covered by t he f ront al, pariet al, and t emporal opercula. The sulcus separat ing t he insula f rom t he operculae is ref erred t o by diff erent aut hors as t he periinsular sulcus, limit ing sulcus, circuminsular sulcus, or insular sulcus. I t is one of t he paralimbic st ruct ures comprised of mesocort ex, int erposed anat omically and f unct ionally bet w een allocort ex and neocort ex. A variet y of f unct ions have been at t ribut ed t o t he insula, including olf act ion, t ast e, visceral cont rol, memory, aff ect , and drive. The insula is shaped like a pyramid. The summit of t he pyramid is t he insular apex (ref erred t o by some as insular pole or limen insula). The insula is t raversed by an obliquely direct ed cent ral insular sulcus w hich divides t he insula int o t w o zones. The ant erior zone is larger and exhibit s more gyri t han t he post erior zone. The ant erior zone exhibit s t ransverse and accessory insular gyri and t hree short insular gyri (ant erior, middle, and post erior). The t ransverse and accessory insular gyri f orm t he insular pole locat ed at t he most ant erior inf erior aspect of t he insula. The post erior zone, locat ed caudal t o t he cent ral insular sulcus, is composed of t he ant erior and post erior long gyri, separat ed by t he post cent ral insular sulcus. The ant erior insular zone connect s w it h t he f ront al lobe. The post erior zone connect s w it h t he pariet al and t emporal lobes. Lesion-
based analysis has show n t hat dest ruct ion of t he lef t ant erior zone impairs coordinat ion of art iculat ion and speech product ion. The insula is surrounded by t he superior longit udinal (arcuat e) f asciculus, a long associat ion bundle t hat int erconnect s t he t emporal, pariet al, and f ront al lobes. The uncinat e f asciculus int erconnect s t he insula w it h ot her para-limbic st ruct ures (t emporal pole, orbit al gyri). The occipit of ront al f asciculus, anot her long associat ion bundle, passes beneat h t he inf erior port ion of t he insular cort ex t o connect t he f ront al, insular, t emporal, and occipit al regions.
CORTICAL ELECTROPHYSIOLOGY Evoked Potentials Evoked pot ent ials represent t he elect rical responses recorded f rom a populat ion of neurons in a part icular cort ical area f ollow ing st imulat ion of t he input t o t hat area. The most st udied of t he evoked pot ent ials is t he primary response recorded f rom t he cort ical surf ace and elicit ed by a single shock t o a major t halamocort ical pat hw ay. This response is charact erized by a diphasic, posit ivenegat ive w ave and is generat ed primarily by synapt ic current s in cort ical neurons. Evoked pot ent ials elicit ed by a volley of impulses in t halamocort ical pat hw ays are of t w o variet ies, recruit ing responses and augment ing responses. Recruit ing responses are recorded f ollow ing 6- t o 12-cps (cycles per second) st imulat ion of a nonspecif ic t halamocort ical pat hw ay (e. g. , f rom int ralaminar nuclei). They are charact erized by a long lat ency (mult isynapt ic pat hw ay), a predominant ly surf ace negat ive response t hat increases in amplit ude t o a maximum by t he f ourt h t o t he sixt h st imulus of a repet it ive t rain. This is f ollow ed by a decrease in amplit ude (w axing and w aning). Such a response has a diff use cort ical dist ribut ion. This pat t ern of response is generally at t ribut ed t o an oscillat or net w ork at cort ical as w ell as t halamic levels in w hich cort ical and t halamic element s provide bot h posit ive and negat ive f eedback. Augment ing responses are recorded f ollow ing low -f requency (6 1 2 cps) st imulat ion of a specif ic t halamocort ical pat hw ay (e. g. , f rom vent rolat eral t halamic nucleus). They are charact erized by a short lat ency (monosynapt ic pat hw ay), a diphasic, posit ive-negat ive conf igurat ion t hat increases in amplit ude and lat ency during t he init ial f our t o six st imuli of t he t rain. The response t o subsequent st imuli remains augment ed but w axes and w anes in amplit ude. This t ype of response is localized in t he primary cort ical area t o w hich t he st imulat ed specif ic t halamocort ical pat hw ay project s.
Fi gure 17-25. Elect roencephalograms show ing t he normal alpha pat t ern A, slow delt a pat t ern B, and spike pot ent ials C.
Somatosensory, Visual, and Auditory Evoked
Responses Recording of cort ical evoked pot ent ials f ollow ing somat osensory (skin), visual (f lashes or pat t erns of light ), and audit ory (sound) st imuli has been used t o st udy pat hology along each of t hese pat hw ays in humans. The det erminat ion of lat ency and amplit ude of t he evoked pot ent ial f requent ly can aid in localizing t he sit e of pat hology in t he respect ive pat hw ay.
ELECTROENCEPHALOGRAPHY Elect roencephalography (Figure 17-25) is t he recording of spont aneous cort ical act ivit y f rom t he surf ace of t he scalp. This procedure is used very commonly in t he invest igat ion of diseases of t he brain. I t s usef ulness is mainly in t he diagnoses of epilepsy and localized (f ocal) brain pat hology (e. g. , brain t umors). I n recent years and w it h t he advent of t he concept of brain deat h, t he elect roencephalogram (EEG ) has been used t o conf irm a st at e of elect rical brain silence (brain deat h). I n such a condit ion, elect roencephalographic t racings w ill show no evidence of cort ical pot ent ials (f lat EEG ). The spont aneous rhyt hmic act ivit y of t he cort ex is classif ied int o f our t ypes: 1. Alpha rhyt hm w it h a range of f requency f rom 8 t o 13 cps. This t ype is most developed over t he post erior part of t he hemisphere. 2. Bet a rhyt hm w it h a range of f requency f ast er t han 13 cps (17 t o 30 cps). This act ivit y can be seen over w ide regions of t he cort ex and is especially apparent in records f rom pat ient s receiving sedat ive drugs. 3. Thet a rhyt hm w it h a range of f requency f rom 3 t o 7 cps. 4. Delt a rhyt hm w it h a range of f requency f rom 0. 5 t o 3 cps. The EEG pat t ern varies in diff erent age groups. The EEG is dominat ed by slow act ivit y (t het a and delt a) in childhood. The alpha rhyt hm increases in amount w it h t he advent of pubert y. I n t he adult , delt a act ivit y and excessive t het a act ivit y usually denot e cerebral abnormalit y. The EEG of unconscious pat ient s is dominat ed by generalized slow f requencies. The EEG in epilept ic pat ient s is charact erized by t he presence of spike pot ent ials. Tw o EEG pat t erns have been associat ed w it h sleep. The f irst is a slow pat t ern (delt a and t het a) associat ed w it h t he early phase of sleep. The second is a f ast pat t ern (bet a) associat ed w it h a lat er and deeper st age of sleep. This second pat t ern is associat ed w it h rapid eye movement s (REM) and dreaming; hence t his st age of sleep has been called REM sleep or D-sleep (dreaming).
BLOOD SUPPLY
Arterial Supply The blood supply t o t he cerebral cort ex is provided by t he ant erior and middle cerebral art eries (branches of t he int ernal carot id art ery) and t he post erior cerebral art ery (branch of t he basilar art ery). The ant erior cerebral art ery runs t hrough t he int erhemispheric f issure, giving off f ive major branches: orbit of ront al, f ront opolar, pericallosal, callosomarginal, and paracent ral. These branches supply t he medial surf ace of t he f ront al and pariet al lobes as f ar back as t he pariet ooccipit al f issure (Figure 17-26). All branches cross t he convexit y of t he f ront al and pariet al lobes t o supply a st rip of marginal cort ex on t he lat eral surf ace of t he hemisphere. O cclusion of t he ant erior cerebral art ery result s in paralysis and sensory def icit s in t he cont ralat eral low er limb due t o int errupt ion of blood supply t o t he low er limb area in t he medial surf ace of t he mot or and sensory cort ices. The middle cerebral art ery is a cont inuat ion of t he main branch of t he int ernal carot id art ery. I t courses w it hin t he lat eral (sylvian) f issure and divides int o a number of branches (f ront al, rolandic, t emporal, pariet al) t hat supply most of t he lat eral surf ace of t he hemisphere (Figure 17-27). The post erior cerebral art ery const it ut es t he t erminal branch of t he basilar art ery. Several branches (t emporal, occipit al, pariet ooccipit al) supply t he medial surf aces of t he occipit al lobe, t emporal lobe, and caudal pariet al lobe (Figure 17-26).
Venous Drainage Three groups of cerebral veins drain t he lat eral and inf erior surf aces of t he cerebral hemisphere: superior, middle, and inf erior (Figure 17-28). The superior cerebral group drains t he dorsolat eral and dorsomedial surf aces of t he hemisphere and opens int o t he superior sagit t al sinus. Convent ionally, t he most prominent of t hese veins in t he cent ral sulcus is called t he superior anast omot ic vein of Trolard, w hich connect s t he superior and middle groups of veins.
Fi gure 17-26. Schemat ic diagram of t he major branches of t he ant erior cerebral and post erior cerebral art eries and t he areas t hey supply.
Fi gure 17-27. Schemat ic diagram of t he major branches of t he middle cerebral art ery and t he areas t hey supply.
The middle cerebral group runs along t he sylvian f issure, drains t he inf erolat eral surf ace of t he hemisphere, and opens int o t he cavernous sinus. The inf erior cerebral group drains t he inf erior surf ace of t he hemisphere and opens int o t he cavernous and t ransverse sinuses. The anast omic vein of Labbé int erconnect s
t he middle and inf erior groups of cerebral veins. The medial surf ace of t he hemisphere is drained by a number of veins t hat open int o t he superior and inf erior sagit t al sinuses, as w ell as int o t he basal vein and t he great cerebral vein of G alen.
Fi gure 17-28. Schemat ic diagram of t he superf icial syst em of venous drainage of t he brain.
TERM INOLOGY Acalculia (G reek a, n egative ; Latin cal cul are, t o reckon ). Diff icult y in calculat ing. Usually associat ed w it h inabilit y t o copy (acopia). The condit ion w as described and named by Henschen in 1919. Agnosia (G reek a, n egative gnosi s, k nowledge ) . I nabilit y t o recognize and int erpret sensory inf ormat ion. Agraphia (G reek a, n egative graphei n, t o write ). I nabilit y t o express t hought s in w rit ing. The f irst modern descript ions w ere t hose of Albert Pitres in 1884 and Dejerine in 1891. Agyria (G reek a, n egative ; gyros, r ing ) . A malf ormat ion in w hich t he convolut ions of t he cerebral cort ex are not normally developed. Also called lissencephaly (smoot h brain). Akinesia (G reek a, n egative ; ki nesi s, m otion ) . Absence or povert y of movement . Akinetopsia. Cerebral mot ion blindness, a syndrome in w hich a pat ient loses specif ically t he
abilit y t o perceive visual mot ion as a result of cort ical lesions out side t he st riat e cort ex. Allocortex (G reek al l os, o ther Latin cortex, b ark ) . Phylogenet ically old, t hree-layered cerebral cort ex, divided int o paleocort ex and archicort ex. Aphasia (G reek a, n egative ; phasi s, s peech ) . I mpairment of language f unct ion; inabilit y eit her t o speak (mot or aphasia) or t o comprehend (sensory aphasia). Apraxia (G reek a, n egative ; pratto, t o do ). I nabilit y t o perf orm complex purposef ul movement s, alt hough muscles are not paralyzed. Aprosodia (G reek a, n egative ; prosodos, a solemn procession ). The variat ion in st ress, pit ch, and rhyt hm of speech by w hich diff erent shades of meaning are conveyed; t he aff ect ive component of language. Archicortex (G reek arche, b eginning Latin cortex, b ark ) . Phylogenet ically old, t hree-layered cort ex seen in t he hippocampal f ormat ion. A variet y of paleocort ex or allocort ex. Arcuate (Latin arcuatus, b ow-shaped ) . Shaped like an arc. The arcuat e f asciculus arches around t he sylvian f issure t o connect Wernicke's area in t he t emporal lobe w it h Broca's area in t he f ront al lobe. Asymbolia (G reek a, n egative ; symbol on, s ymbol ) . Loss of pow er t o comprehend symbols as w ords, f igures, gest ures, and signs. Asymbolia of pain is t he absence of psychic react ion t o painf ul sensat ions. The t erm asymbolia f or pain w as f irst described by Schilder and St engel in 1938. Badal, Jules (1840 1 929). French neuroopht halmologist w ho, in 1888, published t he case of a post eclampt ic w oman (Valerie) w ho developed G erst mann syndrome. Baillarger, Jules-G abriel-Franéois (1809 1 890). French psychiat rist w ho described t he lines of Baillarger in t he cerebral cort ex. Balint syndrome. Also know n as Bal i nt-Hol mes syndrome, ocul ar apraxi a, opti c ataxi a. A rare syndrome result ing f rom bilat eral pariet ooccipit al disease and charact erized by inabilit y t o direct t he eyes t o a cert ain point in t he visual f ield despit e int act eye movement s. Named af t er Rudolph Balint (1874 1 929), a Hungarian neurologist . Betz, Vladimir A. (1834 1 894). Russian anat omist w ho described t he giant pyramidal cells in t he mot or area of t he cerebral cort ex in 1874. Bravais, Louis.
French physician w ho described spread of epilept ic seizure (Jacksonian march) in his graduat ion t hesis in 1827. Broca, Pierre Paul (1824 1 880). French pat hologist and ant hropologist . Broca localized t he cort ical mot or speech area in t he inf erior f ront al gyrus. He also described t he diagonal band of Broca in t he ant erior perf orat ed subst ance. He is also credit ed w it h descript ion of muscular dyst rophy bef ore Duchenne. Brodmann, Korbinian (1868 1 918). G erman physicist w ho divided t he cerebral cort ex int o 52 areas on t he basis of disposit ion of t he cellular (cyt oarchit ect onics) bet w een 1903 and 1908. Campbell, Alfred Walter (1868 1 937). Aust ralian neurologist and psychiat rist . Know n f or his elegant w ork on t he archit ect onics of t he cerebral cort ex. He and Brodmann are considered t he f at hers of cerebral archit ect onics. Cingulum (Latin a girdle ). A bundle of associat ion f ibers w it hin t he cingulat e gyrus. Cortex (Latin b ark ). Ext ernal gray layer of t he cerebrum. Cushing, Harvey Williams (1869 1 939). American neurosurgeon, regarded as t he f at her of modern neurosurgery. He t rained w it h William O sler w ho t aught him about neurology and w hose lif e became t he basis f or Cushing's w rit ings and subsequent Pulit zer Prize. Cytoarchitectonic. The design of t he cellular charact erist ics of t he cort ex, w hich varies in diff erent regions of t he brain and allow s mapping of t he brain. Dejerine, Joseph-Jules (1849 1 917). French neurologist w ho cont ribut ed signif icant ly t o know ledge about t he anat omy of t he nervous syst em, cerebral localizat ion, agraphia, and alexia. Dysphasia (G reek dys, d i ffi cul t phasi s, s peech ) . Diff icult y in t he underst anding or expression of language. Ferrier, David (1843 1 928). Scot t ish neurophysiologist and neurologist w ho is credit ed w it h localizat ion of t he primary audit ory cort ex in t he superior t emporal gyrus. Fusiform (Latin fusus, s pindle ; forma, s hape ) . A cell t hat is w idest in t he middle and t apering at bot h ends. G ennari, Francesco. I t alian physician w ho, as a medical st udent , described t he lines of G ennari (out er band of Baillarger) t hat charact erize lamina I V of t he visual cort ex. He
ref erred t o it as lineola albidor. G erstmann, Josef (1887 1 969). Aust rian neuropsychiat rist w ho described f inger agnosia in 1924 and t he f ull G erst mann syndrome in 1930. Badal's earlier descript ion of t he syndrome, in 1888, w as less complet e and w as at t ribut ed t o psychic blindness. G erstmann syndrome. A clinical syndrome charact erized by right l ef t disorient at ion, acalculia, agraphia, and f inger agnosia due t o a lesion in t he lef t angular gyrus. Josef G erst mann, Aust rian neuropsychiat rist , developed t he concept of a body image w it h visual, t act ile, and somest het ic component s in 1924 and considered cort ical represent at ion f or t hese in t he angular gyrus. The syndrome is also know n as angular gyrus syndrome and t he Badal-G erstmann syndrome. Jules Badal's descript ion of t he syndrome in 1888 w as less complet e. G ustatory (Latin gustatori us, p ertaining to the sense of taste ). Head, Sir Henry (1861 1 940). English neurologist and neurophysiologist . Among his many cont ribut ions is t he mapping of dermat omes (Head's zones), w hich w as t he subject of his graduat ion t hesis at Cambridge. He sect ioned his ow n nerves in order t o delineat e t he result ing sensory loss. He described t he anat omy and variat ions of major peripheral nerves and t he brachial plexus, and he localized t he sit e of herpes zost er inf lammat ion t o t he dorsal root ganglia. He also w rot e on aphasia and published a book of poet ry. He w as aff lict ed w it h Parkinson's disease. Hemiachromatopsia. Loss of color vision in one-half t he visual f ield. Henschen, Solomon Eberhard (1847 1 930). Sw edish int ernist and neurologist w ho is credit ed w it h describing t he st riat e and ext rast riat e cort ex in addit ion t o t he acalculia. He w as one of t he physicians w ho at t ended Lenin w hen st ricken w it h aphasia. Heschl, Richard (1824 1 881). Aust rian anat omist and pat hologist w ho described t he ant erior t ransverse t emporal gyri (Heschl's convolut ions), w hich serve as t he primary audit ory area. Heterotopia (G reek heteros, o ther, different ; topos, p lace ) . The presence of cort ical t issue in an abnormal locat ion during development . Heterotypical cortex (G reek heteros, d ifferent ; typos, p attern ) . The isocort ex (neocort ex) in w hich some of t he six layers are obscured, as in mot or cort ex and visual cort ex. Holmes, Sir G ordon Morgan (1876 1 965). I rish neurologist and f at her of Brit ish neurology (along w it h John HughlingsJackson). Made signif icant cont ribut ions t o sensat ion (w it h Head), spinal cord injury, cerebellar disease, neuroopht halmology, and neurological localizat ion.
Many of his cont ribut ions emanat ed f rom observat ions he made in army f ield hospit als in nort hern France. Homotypical cortex (G reek homos, s ame ; typos, p attern ) . Associat ion areas of t he neocort ex all have a similar (same) pat t ern six-layered st ruct ure. They are t hus examples of homot ypical cort ex. Hughlings-Jackson, John (1835 1 911). Brit ish neurologist and one of t he great est f igures in neurology's hist ory. Made major cont ribut ions, including hierarchical organizat ion of t he nervous syst em, organizat ion of movement , mind b rain relat ionship, speech, and epilepsy. He int roduced t he t erm uncinat e f it s in 1899 and t he rout ine use of t he opht halmoscope. Isocortex (G reek i sos, e qual ; Latin cortex, b ark ) . Six-layered cerebral cort ex. Jacksonian march (Jacksonian epilepsy, Bravais-Jackson epilepsy). The spread of t onic-clonic epilept ic act ivit y t hrough cont iguous body part s on one side of t he body due t o spread of epilept ic act ivit y in t he corresponding mot or areas of t he cort ex. Named af t er John Hughlings-Jackson (1835 1 911), one of t he great est f igures in t he hist ory of neurology. Bravais described t he same pat t ern of epilept ic spread in his graduat ion t hesis in 1827 but did not elaborat e on t he et iology. Koniocortex (G reek koni s, d ust Latin cortex, b ark ) . Areas of cerebral cort ex w it h large number of small neurons. Lamina (Latin a thin plate or layer ). Lorente de Nó, Rafael. American neurobiologist w ho described columnar organizat ion w it hin t he cerebral cort ex. I n addit ion, he is credit ed w it h descript ion of t he CA1 4 regions of t he hippocampus. Martinotti, G iovanni. I t alian physician w ho described t he Mart inot t i neuron in t he cerebral cort ex. Mesocortex. I nt ermediat e cort ex (in hist ology) bet w een t he isocort ex and allocort ex. Also know n as periallocort ex and periarchicort ex. Micropolygyria (polymicrogyria) (G reek mi kros, s mall ; gyros, c onvolutions ) . A malf ormat ion of t he brain charact erized by t he development of numerous small convolut ions. Myeloarchitectonics. The arrangement of nerve f ibers in t he cerebral and cerebellar cort ex t hat varies in diff erent regions and allow s mapping of t he brain.
Neocortex (G reek neos, n ew Latin cortex, b ark ) . The most recent phylogenet ic development of t he cerebral cort ex. O perculum (Latin opertum, c overed ) . The f ront al, t emporal, and pariet al opercula cover t he insular cort ex. O ptic ataxia. The inabilit y t o reach f or object s under visual guidance. I solat ed opt ic at axia result s f rom bilat eral lesions in t he post erior pariet al cort ex (Brodmann area 7). When combined w it h bilat eral lesions in unimodal (primary) visual associat ion area (Brodmann area 19), it const it ut es Balint syndrome. O pt ic at axia w as f irst described by Balint in 1909. Pachygyria (G reek pachys, t hick ; gyros, c onvolutions ) . A development al disorder of neuronal migrat ion in w hich t here are f ew, t hickened, and w ide cerebral gyri. Paleocortex (G reek pal ai os, a ncient Latin cortex, b ark ) . Phylogenet ically old, t hree-layered cort ex f ound in rost ral insular cort ex, pirif orm cort ex, and primary olf act ory cort ex. Penfield, Wilder (1891 1 973). American-Canadian neurosurgeon w ho direct ed t he Mont real Neurological I nst it ut e. Cont ribut ed signif icant ly t o neuroscience and especially t o t reat ment of epilepsy and cort ical localizat ion. Piriform (Latin pyrum, p ear ; forma, f orm ) . Pear-shaped. The pirif orm cort ex is a region of t he olf act ory cort ex. Pitres, Albert (1848 1 928). French neurologist w ho cont ribut ed t o cerebral localizat ion and aphasia. His descript ion of agraphia is considered t he f irst modern narrat ive on t he subject . Prosody (G reek prosodos, a solemn procession ). Variat ion in st ress, pit ch, and rhyt hm of speech by w hich diff erent shades of meaning are conveyed. Prosopagnosia (G reek prosopon, f ace ; gnosi s, t o know ). I nabilit y t o recognize f amiliar f aces. Prosopagnosia pat ient s have no problem in recognizing t hat a f ace is a f ace, in discriminat ing f aces according t o sex or race, or in decoding t heir emot ional expression. Errors occur only in ident if ying w hose f ace it is. The severit y of t he disorder ranges f rom pat ient s w ho f ail t o recognize t heir ow n f aces in t he mirror t o t hose w ho f ail only t o recognize f aces of ot her persons t hey have know n. Q uadrantanopsia. Loss of vision in one-quart er of t he visual f ield. This occurs w it h pariet al (inf erior quadrant loss) or t emporal (superior quadrant loss) lobe lesions.
Reil, Johann Christian (1759 1 813). Danish physiologist , anat omist , and psychiat rist w ho w as t he f irst t o describe t he insula or island of Reil in 1796. He is also credit ed w it h t he use of t he t erm veget at ive nervous syst em t o ref er t o t he aut onomic nervous syst em. Rolando, Luigi. I t alian anat omist . The cent ral sulcus of t he cerebral hemisphere is named af t er him and so is t he subst ant ia gelat inosa of t he spinal cord. Saccadic (French saccader, t o jerk ). Q uick movement s of t he eyes. Somesthetic (G reek soma, b ody ; ai sthesi s, p erception ) . Somest het ic sensat ions are t hose of pain, t emperat ure, t ouch, pressure, posit ion, movement , and vibrat ion. Stellate (Latin stel l a, s tar ) . St ellat e neurons have many short dendrit es t hat radiat e in all direct ions like a st ar. Stereopsis (G reek stereos, s olid, having three dimensions ; opsi s, v ision ) . The abilit y t o discriminat e dept h; st ereoscopic vision. Sylvius, Franéois de la Boe (1614 1 672). French anat omist w ho gave t he f irst descript ion of t he lat eral sulcus of t he cerebral hemisphere. Uncinate (Latin h ook-shaped ) fasciculus. Connect s t he cort ex of t he vent ral surf ace of t he f ront al lobe w it h t hat of t he t emporal pole. Uncinate fits. Complex part ial seizures in w hich olf act ory hallucinat ions occur as part of t he seizure. The t erm w as int roduced by Hughlings-Jackson in 1899. Vogt, Césile (1875 1 931). French neuroanat omist w ho, w it h her Danish-G erman neuroanat omist husband, O skar Vogt (1870 1 959), developed t he myeloarchit ect onic organizat ion of t he cerebral cort ex. The Vogt s also assist ed Brodmann in developing t he cyt oarchit ect onic organizat ion of t he cerebral cort ex. Wernicke, Karl (1848 1 905). G erman neuropsychiat rist w ho, in 1874, conceived t hat sensory aphasia w as due t o damage t o t he lef t t emporal lobe. He also conceived t hat mot or aphasia w as due t o lesion in Broca's area, conduct ion aphasia t o lesion of t he pat hw ay bet w een Wernicke's and Broca's areas, and global aphasia t o lesion in bot h speech areas.
SUGGESTED READINGS
Baizer JS: Serot onergic innervat ion of t he primat e claust rum. Brai n Res Bul l 2001; 55: 431 4 34. Bechara A et al: The somat ic marker hypot hesis and decision making. I n G raf man J (ed): Handbook of Neuropsychol ogy 1, vol 7, 2d ed. Amst erdam, Elsevier, 2002; 117-143. Brandt TH et al: Vest ibular cort ex lesions aff ect t he percept ion of vert icalit y. Ann Neurol 1994; 35: 403 4 12. Brinkman C, Port er R: Supplement ary mot or area in t he monkey: Act ivit y of neurons during perf ormance of a learned mot or t ask. J Neurophysi ol 1979; 42: 681 7 09. Brodal P: The cort icopont ine project ion in t he rhesus monkey: O rigin and principles of organizat ion. Brai n 1978; 101: 251 2 83. Brouw er B, Ashby P: Alt ered cort icospinal project ions t o low er limb mot oneurons in subject s w it h cerebral palsy. Brai n 1991; 114: 1395 1 407. Buchel C: Cort ical hierarchy t urned on it s head. Nature Neurosci ence 2003; 6: 657 6 58. Caselli RJ: Vent rolat eral and dorsomedial somat osensory associat ion cort ex damage produces dist inct somest het ic syndromes in humans. Neurol ogy 1993; 43: 762 7 71. Cherubini E et al: Caudat e neuronal responses evoked by cort ical st imulat ion: Cont ribut ion of an indirect cort icot halamic pat hw ay. Brai n Res 1979; 173: 331 3 36. Damasio A et al: Cent ral achromat osia: Behavioral, anat omic and physiologic aspect s. Neurol ogy 1980; 30: 1064 1 071. Damasio H et al: The ret urn of Phineas G age: Clues about t he brain f rom t he skull of a f amous pat ient . Sci ence 1994; 264: 1102 1105. De Renzi E: Disorders of visual recognit ion. Sem Neurol 2000; 20: 479 4 85. Divac I et al: Vert ical ascending connect ions in t he isocort ex. Anat Embryol 1987; 175: 443 4 55.
Eccles JC: The modular operat ion of t he cerebral neocort ex considered as t he mat erial basis of ment al event s. Neurosci ence 1981; 6: 1839 1 856. Fallon JH, Ziegler BTS: The crossed cort ico-caudat e project ion in t he rhesus monkey. Neurosci Lett 1979; 15: 29 3 2. Foot e SL: Ext rat halamic modulat ion of cort ical f unct ion. Ann Rev Neurosci 1987; 10: 67 9 5. Freund H-J, Hummelsheim H: Lesions of premot or cort ex in man. Brai n 1985; 108: 697 7 33. G allese V et al: Act ion recognit ion in t he premot or cort ex. Brai n 1996; 119: 593 6 09. G aymard B et al: Role of t he lef t and right supplement ary mot or areas in memory-guided saccade sequences. Ann Neurol 1993; 34: 404 4 06. G odoy J et al: Versive eye movement s elicit ed by cort ical st imulat ion of t he human brain. Neurol ogy 1990; 40: 296 2 99. G orman DG , Unüt zer J: Brodmann's m issing numbers. Neurol ogy 1993; 43: 226 2 27.
G orno-Tempini ML et al: Explicit and incident al f acial expression processing: An f MRI st udy. Neuroi mage 2001; 14: 465 4 73. G rabow ski T et al: Disorders of cognit ive f unct ion. Conti nuum 2002; 8: 1 2 96. G reen JR: The beginning of cerebral localizat ion and neurological surgery. BNI Q uart 1985; 1: 12 2 8. G uldin WO , G rüsser O -J: I s t here a vest ibular cort ex? TINS 1998; 21: 254 2 58. Haymaker W: The Founders of Neurol ogy. Springf ield, Charles Thomas, 1953. Heff ner HE: Ferrier and t he st udy of audit ory cort ex. Arch Neurol 1987; 44: 218 2 21.
Hocherman S, Yirmiya R: Neuronal act ivit y in t he medial geniculat e nucleus and in t he audit ory cort ex of t he rhesus monkey ref lect s signal ant icipat ion. Brai n 1990; 113: 1707 1 720. Hubl D et al: Funct ional imbalance of visual pat hw ays indicat e alt ernat ive f ace processing st rat egies in aut ism. Neurol ogy 2003; 61: 1232 1 237. I w at subo T et al: Cort icof ugal project ions t o t he mot or nuclei of t he brain st em and spinal cord in humans. Neurol ogy 1990; 40: 309 3 12. Jinnai K, Mat suda Y: Neurons of t he mot or cort ex project ing commonly on t he caudat e nucleus and t he low er brain st em in t he cat . Neurosci Lett 1979; 13: 121 1 26. Kahane P et al: Reappraisal of t he human vest ibular cort ex by cort ical elect rical st imulat ion st udy. Ann Neurol 2003; 54: 615 6 24. Karbe H et al: Planum t emporale and Brodmann's area 22: Magnet ic resonance imaging and high resolut ion posit ron emission t omography demonst rat e f unct ional lef t r ight asymmet ry. Arch Neurol 1995; 52: 869 8 74. Lee HW et al: Mapping of f unct ional organizat ion in human visual cort ex. Elect rical cort ical st imulat ion. Neurol ogy 2000; 54: 849 8 54. Leichnet z G R et al: The pref ront al cort icot ect al project ion in t he monkey: An ant erograde and ret rograde horseradish peroxidase st udy. Neurosci ence 1981; 6: 1023 1 041. Leigh RJ: Human vest ibular cort ex. Ann Neurol 1994; 35: 383 3 84. Lekw uw a G U, Barnes G R: Cerebral cont rol of eye movement s: I . The relat ionship bet w een cerebral lesion sit es and smoot h pursuit def icit s. Brai n 1996; 119: 473 4 90. Liegeois-Chauvel C et al: Localizat ion of t he primary audit ory area in man. Brai n 1994; 114: 139 1 53. Lüders H et al: The second sensory area in humans: Evoked pot ent ial and elect rical st imulat ion st udies. Ann Neurol 1985; 17: 177 1 84. Markow it sch HJ et al: Cort ical aff erent s t o t he pref ront al cort ex of t he cat : A
st udy w it h t he horseradish peroxidase t echnique. Neurosci Lett 1979; 11: 115 1 20. Meyer BU et al: I nhibit ory and excit at ory int erhemispheric t ransf ers bet w een mot or cort ical areas in normal humans and pat ient s w it h abnormalit ies of t he corpus callosum. Brai n 1995; 118: 429 4 40. Morecraf t RJ, Yet erian E: Pref ront al cort ex. Encycl opedi a of Human Brai n 2000; 4: 11 2 6. Morecraf t RJ et al: Cort ical innervat ion of t he f acial nucleus in t he non-human primat e. A new int erpret at ion of t he eff ect s of st roke and relat ed subt ot al brain t rauma on t he muscles of f acial expression. Brai n 2001; 124: 176 2 08. Morrow MJ, Sharpe JA: Cerebral hemispheric localizat ion of smoot h pursuit asymmet ry. Neurol ogy 1990; 40: 284 2 92. O rgogozo JM, Larsen B: Act ivat ion of supplement ary mot or area during volunt ary movement s in man suggest s it w orks as a supramot or area. Sci ence 1979; 206: 847 8 50. Parnavelas JG : The origin and migrat ion of cort ical neurons: New vist as. TINS 2000; 23: 126 1 31. Pierrot -Deseilligny C, G aymard B: Eye movement disorders and ocular mot or organizat ion. Curr O pi n Neurol Neurosurg 1990; 3: 796 8 01. Pierrot -Deseilligny C et al: Cort ical cont rol of saccades. Ann Neurol 1995; 37: 557 5 67. Pryse-Phillips W: Compani on to Cl i ni cal Neurol ogy, 2nd ed. O xf ord, O xf ord Universit y Press, 2003. Rabinow icz T et al: G ender diff erence in t he human cerebral cort ex: More neurons in males; more processes in f emales. J Chi l d Neurol 1999; 14: 98 1 07. Roland PE et al: Diff erent cort ical areas in man in organizat ion of volunt ary movement in ext rapersonal space. J Neurophysi ol 1980; 43: 137 1 50. Romansky KV et al: Cort icosubt halamic project ion in t he cat : An elect ron microscopic st udy. Brai n Res 1979; 163: 319 3 22.
Rumeau C et al: Locat ion of hand f unct ion in t he sensorimot or cort ex: MR and f unct ional correlat ion. AJNR 1994; 15: 567 5 72. Schmahmann JD, Leif er D: Pariet al pseudot halamic pain syndrome: Clinical f eat ures and anat omic correlat es. Arch Neurol 1992; 49: 1032 1 037. Sharp J et al: Dist urbances of ocular mot ilit y. Conti nuum 1995; 1: 41 9 1. Shat z CJ: Dividing up t he neocort ex. Sci ence 1992; 258: 237 2 38. Sherw ood CC et al: Variabilit y of Broca's area homologue in Af rican great apes: I mplicat ions f or language evolut ion. Anat Rec Part A 2003; 271A: 276 2 85. Sut herling WW et al: Cort ical sensory represent at ion of t he human hand: Size of f inger regions and nonoverlapping digit somat ot opy. Neurol ogy 1992; 42: 1020 1 028. Tanji J: The supplement ary mot or area in t he cerebral cort ex. Neurosci Res 1994; 19: 251 2 68. Tanji J, Kurat a K: Changing concept s of mot or areas of t he cerebral cort ex. Brai n Dev 1989; 11: 374 3 77. Tijssen CC et al: Conjugat e eye deviat ion: Side, sit e, and size of hemispheric lesion. Neurol ogy 1991; 41: 846 8 50. Ture U et al: Topographic anat omy of t he insular region. J Neurosurg 1999; 90: 720 7 33. Tusa RJ, Ungerleider LG : The inf erior longit udinal f asciculus: A reexaminat ion in humans and monkeys. Ann Neurol 1985; 18: 583 5 91. Urasaki E et al: Cort ical t ongue area st udied by chronically implant ed subdural elect rodes: Wit h special ref erence t o pariet al mot or and f ront al sensory responses. Brai n 1994; 117: 117-132. Van Hoesen G W et al: Widespread cort icost riat e project ions f rom t emporal cort ex of t he rhesus monkey. J Comp Neurol 1981; 199: 205 2 19. Verf aellie M, Heilman KM: Response preparat ion and response inhibit ion af t er
lesions of t he medial f ront al lobe. Arch Neurol 1987; 44: 1265 1 271. Wise RJ et al: Brain regions involved in art iculat ion. Lancet 1999; 353: 1057 1 061. Wise SP: The primat e premot or cort ex: Past , present , and preparat ory. Ann Rev Neurosci 1985; 8: 1 1 9. Yamashit a M, Yamamot o T: Aberrant pyramidal t ract in t he medial lemniscus of t he human brainst em: Normal dist ribut ion and pat hological changes. Eur Neurol 2001; 45: 75-82. Yet erian EH, Van Hoesen G W: Cort ico-st riat e project ions in t he rhesus monkey: The organizat ion of cert ain cort ico-caudat e connect ions. Brai n Res 1978; 139: 43 6 3. Zeki S, Lamb M: The neurology of kinet ic art . Brai n 1994; 117: 607 6 36.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 18 - C er ebr al C or tex: C linic al C or r elates
18 Cerebral Cortex: Clinical Correlates
Epileptic Seizures Hem isphere Specialization Aphasia Apraxia Ideomotor Apraxia Ideational Apraxia Visuoconstructive Apraxia Alexia (Dyslexia) Agnosia Callosal Syndrom e Visual Effects Hemialexia Unilateral (Left) Ideomotor Apraxia Unilateral (Left) Agraphia Unilateral (Left) Tactile Anomia Left Ear Extinction Prefrontal Lobe Syndrom e T he Grasp Reflex Forced Collectionism Alzheim er's Disease Balint's Syndrom e Gerstm ann's Syndrom e Anosognosia (Denial Syndrom e, Anton-Babinski Syndrom e)
Anton's Syndrom e Kluver-Bucy Syndrom e Sim ultanagnosia T he Alien Hand (Lim b) Syndrom e KEY CONCEPTS Epileptic seizures are manifestations of synchronized discharges of groups of neurons. The left hemisphere is specialized or dominant for comprehension and expression of language, arithmetic, and analytic functions. The right hemisphere is specialized or dominant for complex nonverbal perceptual tasks, emotion, and some aspects of visual and spatial perception. Aphasias are classified into two major categories based on whether repetition is intact or not. Apraxia is the inability to perform skilled, learned, purposeful motor acts correctly. Alexia pertains to the inability to comprehend written language (reading disability). It can be developmental or acquired. Two forms of acquired alexia are recognized: pure alexia (without agraphia) and alexia with agraphia. Agnosia pertains to the inability to recognize stimuli that were recognized formerly. Agnosia is modality specific: visual, auditory, and tactile. Callosal syndromes include hemialexia, unilateral (left) ideomotor apraxia, unilateral (left) agraphia, unilateral (left) tactile anomia, and left ear extinction. Prefrontal lobe syndrome pertains to a conglomerate set of signs and symptoms that
includes impairments in decision making, ability to plan, social judgment, conduct, modulation of affect and of emotional response, and creativity. Alzheimer's disease is the example par excellence of cortical dementia.
EPILEPTIC SEIZURES Epilepsy is a common clinical condit ion charact erized by recurrent paroxysmal at t acks of mot or, sensory, aut onomic, or psychic sympt oms and signs depending on t he area of t he brain involved. Epilept ic seizures are t riggered by synchronized discharges of a group of neurons in t he cerebral cort ex as a result of development al abnormalit y, inf ect ion, t rauma, t umor, met abolic derangement , or st roke. Epilept ic seizures may be f ocal or generalized. When generalized, t hey are usually associat ed w it h loss of consciousness. The most common generalized seizure t ype is t he t onic-clonic seizure t ype know n as grand mal seizure. Focal seizures are manif est at ions of t he f unct ion of t he cort ical area f rom w hich epilept ic discharges emanat e. Epilept ic discharges in t he region of t he cent ral sulcus may give rise t o mot or and sensory sympt oms. Spreading of t he epilept ic discharge along t he mot or or sensory homunculus produces t he so-called Jacksonian seizures or Jacksonian march. I n such a pat ient , a f ocal mot or seizure may st art by shaking of t he side of t he f ace cont ralat eral t o t he cort ical lesion in t he precent ral gyrus and spread t o involve t he t humb, hand, arm, and leg in t his order in a pat t ern consist ent w it h t he locat ion of t hese body part s in t he mot or homunculus. A similar pat t ern of sensory march is associat ed w it h lesions in t he post cent ral gyrus. An epilept ic discharge in t he f ront al eye f ield produces at t acks consist ing of cont ralat eral t urning of eyes and head (adversive seizures). O ccipit al discharges are associat ed w it h visual hallucinat ions. Discharges in t he primary visual cort ex produce cont ralat eral f lashes of light , w hereas discharges in t he associat ion visual cort ex produce w ell-f ormed images. Epilept ic discharges f rom t he uncus and adjacent regions of t he t emporal lobe (uncinat e f it s) produce a combinat ion of complex mot or and aut onomic sympt oms (psychomot or seizures). The epilept ic at t ack in such pat ient s consist s of a dreamy st at e, olf act ory hallucinat ions (usually of b ad odors), gust at ory hallucinat ions, oral movement s of chew ing, sw allow ing, or smacking of lips, visual hallucinat ions (déjá vu experiences), and possibly aggressive behavior. Complex act s and movement s such as w alking and f ast ening or unf ast ening
but t ons may occur.
HEM ISPHERE SPECIALIZATION The concept of cerebral dominance has undergone signif icant modif icat ion in recent years, primarily because of st udies on pat ient s w it h unilat eral brain damage. The older concept , int roduced by G ust av Dax and Paul Broca in 1865, w hich assigned t o t he lef t hemisphere a dominant role in higher cerebral f unct ion, w it h t he right hemisphere being subordinat e t o t he dominant hemisphere, has been replaced by a new concept of hemisphere specializat ion t hat implies t hat each hemisphere is in some w ay dominant f or t he execut ion of specif ic t asks. According t o t his concept , t he lef t hemisphere is dominant or specialized f or comprehension and expression of language, arit hmet ic, and analyt ic f unct ions, w hereas t he right hemisphere is specialized f or complex nonverbal percept ual t asks and f or some aspect s of visual (e. g. , f ace) and spat ial percept ion. The right side of t he brain is also dedicat ed t o mapping f eelings, bodily sensat ions linked t o emot ions of happiness, anger, and f ear. Language is localized t o t he lef t hemisphere in more t han 90% of right -handed people and t w o-t hirds of lef t -handers. Thus lesions of t he lef t hemisphere are associat ed w it h disorders of language (aphasia or dysphasia), w hereas lesions of t he right hemisphere are associat ed w it h impairment of visuospat ial and visuoconst ruct ive skills. Pat ient s w it h right hemisphere lesions are more likely t o show such manif est at ions as const ruct ional apraxia (inabilit y t o const ruct or t o draw f igures and shapes), dressing apraxia, denial of t he lef t side of t he body (denial t hat t heir lef t side is part of t heir body), and hemineglect (visual and spat ial neglect of t he lef t side of t heir space, including t heir ow n body part s). I diographic(pict ographic) language (Japanese Kanji) may be processed by t he right hemisphere because of it s pict orial f eat ures.
APHASIA The t erm aphasia ref ers t o an acquired dist urbance in comprehension, f ormulat ion of verbal messages (language), or bot h. I t can aff ect t he grammat ical st ruct ure of sent ences (synt ax), t he dict ionary of w ords (cont ained in language) t hat denot e meanings (lexicon), or t he combinat ion of phonemes t hat result s in w ord st ruct ure (w ord morphology). Aphasia, as a specif ic impairment of language, should not be conf used w it h mut ism, dysart hria, aphemia, and speech apraxia. Mut ism is a nonvolit ional st at e in w hich t he pat ient does not at t empt t o init iat e speech. Dysart hria is a speech art iculat ion due t o dist urbance in t he muscular cont rol of t he speech mechanism associat ed w it h damage t o t he cent ral or peripheral nervous syst em. Aphemia is a condit ion in w hich no art iculat ion occurs due t o a cent ral mot or def icit . Speech apraxia is an imprecisely def ined condit ion of impaired art iculat ion of speech in w hich speech is phonet ically and prosodically aw kw ard compared t o dysart hric speech. Aphasia is encount ered most f requent ly in cort ical lesions in t he lef t
hemisphere, alt hough it may occur in subcort ical lesions. The cort ical area of t he lef t hemisphere invariably involved in aphasia is a cent ral core surrounding t he sylvian f issure. The perisylvian core area is surrounded by a larger region in w hich aphasia occurs less f requent ly. The sequence of complex cort ical act ivit ies during t he product ion of language may be simplif ied as f ollow s: When a w ord is heard, t he out put f rom t he primary audit ory area (Heschl's gyrus) is conveyed t o an adjacent cort ical area (Wernicke's area), w here t he speech sounds are processed int o w ord f orm and t he w ord is comprehended (see Figure 17-20). I f t he w ord is t o be spoken, t he comprehended pat t ern is t ransmit t ed via t he arcuat e f asciculus f rom Wernicke's area t o Broca's area of speech in t he inf erior f ront al gyrus (see Figure 17-20). I f t he w ord is t o be read, t he out put f rom t he primary visual area in t he occipit al cort ex is t ransmit t ed t o t he angular gyrus, w hich in t urn arouses t he corresponding audit ory f orm of t he w ord in Wernicke's area (see Figure 17-22). For didact ic purposes, aphasia is classif ied int o Broca's, Wernicke's, conduct ion, t ranscort ical, anomic, and global. The diff erent variet ies of aphasia can be classif ied int o t hose w it h impaired repet it ion (Broca's, Wernicke's, conduct ion, and global aphasias) and t hose in w hich repet it ion is preserved (t ranscort ical and anomic aphasias) (Table 181). Broca's aphasi a is also know n as nonf luent , ant erior, mot or, or expressive aphasia. This t ype of aphasia is charact erized by a diff icult y in init iat ing speech and a decreased and labored language out put of 10 w ords or less per minut e, during w hich t he pat ient ut ilizes f acial grimaces, body post uring, deep breat hs, and hand gest ures t o aid out put ; charact erist ically, small grammat ical w ords and t he endings of nouns and verbs are omit t ed, result ing in t elegraphic speech. The speech out put is t hus unmelodic and dysrhyt hmic (dysprosody). Despit e t he preceding limit at ions in verbal out put , t he speech of t en conveys considerable inf ormat ion. These pat ient s are unable t o repeat w hat has been said t o t hem. Paraphasias are common and usually involve omission of phonemes or subst it ut ion of incorrect phonemes ( ha f or hall, p em f or p en ) . Writ ing and conf ront at ion naming are impaired. Alt hough Broca's aphasia is usually at t ribut ed t o a lesion in Broca's area of t he f ront al lobe, recent correlat ions of aphasic speech w it h lesions seen on imaging st udies have show n t hat t he lesion is f requent ly larger t han Broca's area and involves t he ant erior insula, f ront al operculum and t he underlying w hit e mat t er. Pure damage t o Broca's area (Brodmann areas 44 and 45) produces mild t ransient speech def icit . Since t he t emporal lobe is int act in t hese pat ient s, comprehension of language in aural and w rit t en f orms is usually int act . Most pat ient s w it h Broca's aphasia can sing. Tabl e 18-1. Aphasias
Type
Broca's
W ernicke's
Conduction
Global
Repetition Fluency
X
X
Auditory Lo Com prehension
Po an su tem gy pla tem low pa co
X
X
Br are an ins fro op un wh
Po pe reg
Ma pe or Br W
are
Transcortical motor
Sensory
Mixed
Anomic
X
X
X
X
X
X
X
An su Br are inv of are
Su W are
Bo zo wa are mi an ce art
X
Inf an tem
Broca's aphasia occurs of t en as a result of st roke (inf arct s) most commonly aff ect ing t he middle cerebral art ery t errit ory. Such inf arct s of t en involve t he mot or cort ex; t hus pat ient s w it h Broca's aphasia are of t en hemiplegic w it h t he arm (middle cerebral art ery t errit ory) more aff ect ed t han t he leg (ant erior cerebral art ery t errit ory). Broca's aphasia is named af t er Paul Broca, t he French ant hropologist -physician w ho st udied t he pat ient Leborgne (nicknamed Tan because t he only w ord he could ut t er w as t an) w it h aphasia and localized t he lesion t o t he post erior part of t he lef t inf erior f ront al convolut ions. Pierre Marie,
in 1906, examined Leborgne's brain and f ound t hat t he lesion w as more ext ensive. Werni cke's aphasi a is also know n as f luent , post erior, sensory, or recept ive aphasia. I n cont rast t o Broca's aphasia, t he quant it y of out put in t his t ype ranges f rom low normal t o supernormal, w it h an out put in most pat ient s of 100 t o 150 w ords per minut e. Speech is produced w it h lit t le or no eff ort , art iculat ion and phrase lengt h are normal, and t he out put is melodic. Pauses t o search f or a meaningf ul w ord are f requent , and subst it ut ion w it hout language (paraphasia) is common; t his may be subst it ut ion of a syllable (lit eral paraphasia) (w ellow f or yellow ), phonemic subst it ut ion of a w ord (kench f or w rench) (verbal paraphasia), semant ic subst it ut ion (knif e f or f ork), or subst it ut ion of a meaningless nonsense w ord (neologism). I f a w ord is not readily available, t he pat ient may at t empt t o describe it , and t he descript ion may necessit at e yet anot her descript ion, result ing in a meaningless out put (circumlocut ion). Very highly paraphasic f luent speech is t ermed jargon aphasia. Paraphasias also may occur in Broca's aphasia, but t hese are art iculat ory errors, in cont rast t o t hose in Wernicke's aphasia, w hich are t rue subst it ut ions. Despit e t he f luent nat ure of speech out put in Wernicke's aphasia, lit t le inf ormat ion is conveyed (empt y speech). As in Broca's aphasia, pat ient s w it h Wernicke's aphasia are unable t o repeat w hat is said t o t hem. I n cont rast t o Broca's aphasia, comprehension of bot h aural and w rit t en f orms of language is severely impaired in Wernicke's aphasia. As in Broca's aphasia, naming is impaired. Wernicke's aphasia is at t ribut ed t o a lesion in Wernicke's area in t he post erior part of t he superior t emporal gyrus and adjacent areas in post erior t emporal (including t he planum t emporale) and low er pariet al cort ex of t he lef t hemisphere. Wernicke's aphasia is named af t er Karl Wernicke, a G erman neurologist w ho in 1874 designat ed t he post erior part of t he superior t emporal gyrus (area 22) of t he lef t hemisphere as an area concerned w it h t he underst anding of t he spoken w ord. Wernicke's aphasia is also know n as Bast ian aphasia, af t er Henry Charlt on Bast ian, t he English neurologist w ho described it in 1869, f ive years bef ore Wernicke. Conducti on aphasi a is charact erized by f luent paraphasic speech, int act comprehension, poor naming, and repet it ion. Classically, pat ient s w it h conduct ion aphasia cannot read out loud because of paraphasic int ervent ion. Pat ient s w it h conduct ion aphasia cannot w rit e t o dict at ion, but w rit e bet t er w hen copying t ext and in spont aneous composit ion. Pat hology in t hese pat ient s is usually locat ed in t he post erior perisylvian region and int errupt s t he out put f rom Wernicke's area t o Broca's area via t he arcuat e f asciculus. G l obal aphasi a is a severe f orm of aphasia in w hich all t he major f unct ions of language (verbal out put , comprehension, repet it ion, naming, reading, and w rit ing) are severely impaired. G lobal aphasics ret ain limit ed capacit y f or singing. G lobal aphasics are diff erent iat ed f rom pat ient s w it h mut ism in t hat t he f ormer make an at t empt t o speak and communicat e w it h ot her means, w hereas
t he lat t er do not make such an at t empt . Pat hol-ogy is invariably ext ensive, involving most of t he lef t perisylvian area including Broca's area, Wernicke's area, t he inf erior pariet al cort ex, and underlying w hit e mat t er. I n rare cases, t w o separat e lesions in Broca's and Wernicke's area are f ound. Transcorti cal aphasi a has been subdivided int o mot or, sensory, and mixed t ypes. All are charact erized by preserved repet it ion. I n t ranscort ical mot or aphasia, verbal out put is nonf luent and comprehension is int act , but w rit ing and reading are invariably abnormal. Pat hology in t his t ype of aphasia is locat ed in t he dominant f ront al lobe in t he neighborhood of Broca's area. I t involves t he premot or region or a limit ed part of t he inf erior f ront al gyrus in t he lef t hemisphere. This t ype of aphasia has been also report ed w it h a lesion in t he lef t basal ganglia. I n t ranscort ical sensory aphasia, speech out put is f luent and paraphasic, comprehension is poor, and t here are associat ed diff icult ies in reading, naming, and w rit ing. Pat hology in such cases is usually in t he border zone bet w een t he t emporal and pariet al lobes in t he neighborhood of Wernicke's area. Mixed t ranscort ical aphasia, also know n as isolat ion of t he speech area, is charact erized by nonf luent speech out put , poor comprehension, and inabilit y t o name, read, or w rit e. Pat hology in t hese pat ient s usually spares t he perisylvian core region but involves t he surrounding border zone or w at ershed area, w hich is supplied by t he most dist al t ribut aries of t he middle cerebral art ery. Anomic aphasi a, also know n as amnest ic or nominal aphasia, is charact erized primarily by w ord-f inding diff icult y. Alt hough naming def ect s are common in almost all aphasic syndromes, anomic aphasia ref ers t o an isolat ed severe impairment of conf ront at ion naming w it hout concomit ant ot her speech impairment s. This t ype of aphasia is most commonly encount ered w it h lesions in t he lef t inf erior or ant erior t emporal cort ex. Diff erent t ypes of naming impairment s have been associat ed w it h damage t o diff erent cort ical areas. Select ive noun ret rieval def icit s have been associat ed w it h damage t o t he lef t inf erior and lef t ant erolat eral t emporal cort ex. Disproport ionat e diff icult y in verb ret rieval, on t he ot her hand, has been associat ed w it h damage t o t he lef t premot or-pref ront al cort ex. Wit hin t he t emporal lobe, lesions in t he vent ral inf erot emporal cort ex have been associat ed w it h disproport ionat e diff icult y in naming nat ural ent it ies (like animals), w hereas damage in t he lef t t emporal pole has been associat ed w it h disproport ionat e diff icult y in naming specif ic persons. Crossed aphasi a ref ers t o t he rare development of aphasia in right -handed persons, w it h right (inst ead of lef t ) hemisphere lesion. The aphasic syndrome in crossed aphasia may f ollow t he classical pat t ern (Broca, Wernicke, et c) w it h lesions in t he corresponding area in t he right hemisphere, or be anomalous. I n t he lat t er, Broca's area lesion may present w it h Wernicke's aphasia and Wernicke's area lesion w it h Broca's aphasia. Subcorti cal aphasi a. Aphasia has been report ed in lef t basal ganglia and
t halamic lesions. Wit hin t he basal ganglia, t he lef t caudat e nucleus is especially involved. Wit hin t he t halamus, t he lef t vent rolat eral and ant erovent ral t halamic nuclei are invariably involved. Aphasia associat ed w it h lef t basal ganglia lesions is charact erized by relat ively f luent , paraphasic, and dysart hric speech. Comprehension and repet it ion are of t en impaired. Thalamic aphasia has t he prof ile of Broca's or t ranscort ical mot or aphasia. Pure word deaf ness, also know n as verbal audit ory agnosia, is charact erized by poor comprehension of spoken language and by poor repet it ion w it h int act comprehension of w rit t en language, naming, w rit ing, and spont aneous speech. The lesion in t his t ype of disorder eit her aff ect s t he primary audit ory area or disconnect s t his area f rom Wernicke's area. This syndrome is p ure in t he sense t hat it is not associat ed w it h ot her aphasic sympt oms.
APRAXIA Apraxia is t he inabilit y t o perf orm skilled, learned, purposef ul mot or act s correct ly despit e int act relevant mot or and sensory neural st ruct ures, at t ent ion, and comprehension. The concept of apraxia and t he f irst classif icat ion of apraxia are credit ed t o Hugo Karl Liepmann, t he G erman neurologist . There are several t ypes of apraxia: ideomot or, ideat ional, and visuoconst ruct ive.
Ideomotor Apraxia I deomot or apraxia is t he inabilit y t o carry out , on verbal command, an act ivit y t hat can be perf ormed perf ect ly w ell spont aneously. I t is implied t hat t his i nabilit y is not due t o compre hension, mot or, or sensory def ect s. Thus a pat ient w it h ideomot or apraxia w ill not be able t o carry out a verbal command t o w alk, st op, salut e, open a door, st ick out t he t ongue, et c. To appreciat e t he pat hophysiology of ideomot or apraxia, it should be underst ood t hat f or a skilled t ask t o be perf ormed, several event s must t ake place. For example, t he command t o w alk, if oral, reaches t he primary audit ory area and is relayed t o t he lef t audit ory associat ion cort ex (Wernicke's area) f or comprehension. Wernicke's area is connect ed t o t he ipsilat eral premot or area (mot or associat ion cort ex, area 6) via t he arcuat e f asciculus. The mot or associat ion area on t he lef t side is connect ed t o t he primary mot or cort ex (area 4) on t he lef t side. When t he person is asked t o carry out a command w it h t he lef t hand, t he inf ormat ion is relayed f rom t he lef t premot or area t o t he right premot or area (via t he ant erior part of t he corpus callosum) and f rom t here t o t he right primary mot or area, w hich cont rols movement s of t he lef t side of t he body (Figure 18-1). Based on t he preceding anat omic connect ions, t hree clinical variet ies of ideomot or apraxia have been recognized: pariet al, in w hich t he lesion is in t he ant eroinf erior pariet al lobe of t he dominant hemisphere; sympat het ic, in w hich t he lesion is in t he lef t premot or area; and callosal, in w hich t he lesion is in t he ant erior part of t he corpus callosum.
Ideational Apraxia I deat ional apraxia is an abnormalit y in t he concept ion of movement so t hat t he pat ient may have diff icult y sequencing t he diff erent component s of a complex mot or act . To mail a let t er, f or example, one must seal it , st amp it , and place it in t he mailbox. The lesion in ideat ional apraxia is in t he dominant t emporopariet ooccipit al area.
Visuoconstructive Apraxia Visuoconst ruct ive apraxia, also know n as const ruct ional apraxia, is t he inabilit y of t he individual t o put t oget her or art iculat e component part s t o f orm a single shape or f igure, such as assembling blocks t o f orm a design or draw ing f our lines t o f orm a shape. I t implies a def ect in perceiving spat ial relat ionships among t he component part s. Visuoconst ruct ive apraxia w as described originally in lesions of t he lef t (dominant ) post erior pariet al area. Subsequent ly, it w as show n t hat t his t ype of apraxia is more prevalent and severe in right hemisphere pariet al lesions.
Fi gure 18-1. Schemat ic diagram show ing t he pat hw ays in-volved in carrying out a mot or skill in response t o an oral command.
The t erm const ruct ional apraxia w as suggest ed by Kleist in 1923 and f ully described by Mayer-G ross in 1935. Lord Brain proposed t he t erm apract agnosia.
ALEXIA (DYSLEXIA) Alexia (dyslexia) is t he inabilit y t o comprehend w rit t en language (reading disabilit y). I t may be acquired (acquired alexia or dyslexia), as in st roke pat ient s w ho lose t he abilit y t o read, or development al (development al dyslexia),
in w hich t here is an inabilit y t o learn t o read normally f rom childhood. Acquired alexia is of t w o t ypes: pure alexia (alexia w it hout agraphia, pure w ord blindness) and alexia w it h agraphia (pariet al alexia). I n pure alexia, t he def ect in comprehension may manif est as an inabilit y t o read let t ers (lit eral alexia) or w ords (verbal alexia) or may be global w it h a t ot al inabilit y t o read eit her let t ers or w ords (global alexia). The anat omic subst rat e of pure alexia is usually a lesion in t he lef t primary visual area coupled w it h an ot her lesion in t he splenium of t he corpus callosum (Figure 18-2). The lesion in t he lef t visual area prevent s visual st imuli ent ering t he lef t hemisphere f rom reaching t he lef t (dominant ) angular gyrus, w hich is necessary f or comprehension of w rit t en language. The lesion in t he splenium of t he corpus callosum prevent s visual st imuli ent ering t he int act right visual area f rom reaching t he lef t angular gyrus. Writ ing is normal in t his t ype of alexia, but t he pat ient cannot read w hat he or she w rit es. Cases have been described of pure alexia w it hout a splenial lesion. I n such cases, one deep lesion in t he lef t occipit ot emporal region isolat es bot h occipit al cort ices f rom t he lef t speech area in t he angular gyrus. Most commonly, alexia w it hout agraphia occurs as a result of inf arct ion in t he t errit ory of t he lef t post erior cerebral art ery t hat supplies neural st ruct ures involved. Usually, a right homonymous visual f ield def ect is present . I n alexia w it h agraphia, t here is a def ect in bot h reading comprehension and w rit ing. The reading disorder is usually verbal (inabilit y t o read w ords). The w rit ing diff icult y is usually severe. The anat omic subst rat e of t his t ype of alexia is a lesion in t he dominant angular gyrus, hence t he name pariet al alexia. The concept of alexia as separat e f rom ot her language disorders w as developed in 1885 by t he G erman neurologist Ludw ig Licht heim. The t w o t ypes of acquired alexia (w it hout and w it h agraphia) w ere int roduced by Dejerine in 1891 and 1892.
AGNOSIA Agnosia is t he inabilit y of t he individual t o recognize perceived sensory inf ormat ion. I mplied in t his def init ion is an int act sensory processing of t he input , clear ment al st at e, and int act naming abilit y. Agnosia is of t en modalit y specif ic: visual, audit ory, and t act ile. Visual agnosias include visual object agnosia (inabilit y t o recognize object s present ed visually), visual color agnosia (inabilit y t o recognize colors), prosopagnosia (i. e. , inabilit y t o recognize f aces, including one's ow n f ace, cars, t ypes of t rees), pict ure agnosia, and simult anagnosia (inabilit y t o recognize t he w hole, alt hough part s of t he w hole are appreciat ed correct ly).
Fi gure 18-2. Schemat ic diagram show ing t he neural subst rat e of t he syndrome of pure alexia w it hout agraphia A and of hemialexiaB.
Audit ory agnosia is t he inabilit y t o recognize sounds in t he presence of ot herw ise adequat e hearing. I t includes audit ory verbal agnosia (inabilit y t o recognize spoken language or pure w ord deaf ness), audit ory sound agnosia (i. e. , inabilit y t o recognize nonverbal sounds such as animal sounds, sound of running w at er, sound of a bell), and sensory amusia (inabilit y t o recognize music). Tact ile agnosia is t he inabilit y t o recognize object s by t ouch. I t is usually associat ed w it h pariet al lobe lesions of t he cont ralat eral hemisphere. Ast ereognosis is t he loss of abilit y t o judge t he f orm of an object by t ouch. I t includes amorphognosia (impaired recognit ion of size and shape of object s), ahylognosia (impaired discriminat ion of qualit y of object s, such as w eight , t ext ure, densit y), and asymbolia (impaired recognit ion of t he ident it y of an object in t he absence of amorphognosia and ahylognosia). Asymbolia is used by some aut hors t o ref er t o t act ile agnosia.
CALLOSAL SYNDROM E The disconnect ion of t he right f rom t he lef t hemisphere by lesions in t he corpus callosum result s in t he isolat ion of each hemisphere in such a w ay t hat each has it s ow n learning processes and memories t hat are inaccessible t o t he ot her hemisphere. The f ollow ing are some of t he eff ect s of callosal disconnect ion. The eff ect s of callosal t ransect ion are considerably less in younger children compared w it h adult s because of t he cont inued reliance in t his age group on ipsilat eral pat hw ays.
Visual Effects Each hemisphere ret ains it s ow n visual images and memories, but only t he lef t hemisphere is able t o communicat e, because of t he callosal disconnect ion, w hat it sees t hrough speech or w rit ing.
Hemialexia Pat ient s are unable t o read mat erial present ed in t he lef t hemif ield. This occurs w hen t he splenium of t he corpus callosum is involved in t he lesion. Such visually present ed mat erial reaches t he right occipit al cort ex but cannot be comprehended because t he splenial lesion int erf eres w it h t ransmission of t he visual image t o t he lef t (dominant ) angular gyrus (Figure 18-2).
Unilateral (Left) Ideomotor Apraxia I n response t o verbal commands, pat ient s are unable t o carry out w it h t he lef t hand some behavior t hat is readily carried out w it h t he right hand. The verbal command is adequat ely received by t he lef t (dominant ) hemisphere but , because of t he callosal disconnect ion, cannot reach t he right hemisphere, w hich cont rols lef t hand movement (Figure 18-3).
Unilateral (Left) Agraphia Pat ient s w it h callosal lesions are unable t o w rit e using t heir lef t hand (Figure 183).
Unilateral (Left) Tactile Anomia Pat ient s w it h callosal disconnect ion are unable, w it h eyes closed, t o name or describe an object placed in t he lef t hand, alt hough t hey readily name t he same object in t he right hand. The object placed in t he lef t hand is perceived correct ly in t he right somat osensory cort ex but cannot be ident if ied because of t he callosal lesion t hat disconnect s t he right pariet al cort ex f rom t he lef t (dominant ) hemisphere (Figure 18-3).
Left Ear Extinction Pat ient s w it h callosal lesions show lef t ear ext inct ion w hen sounds are present ed simult aneously t o bot h ears (dichot ic list ening). Sounds present ed t o t he lef t ear reach t he right t emporal cort ex but , because of t he callosal disconnect ion, are not relat ed t o t he lef t t emporal cort ex (dominant ) f or comprehension. There is evidence t o suggest f unct ional specializat ion of diff erent segment s of t he corpus callosum. Thus lesions in t he post erior part of t he corpus callosum (splenium) are associat ed w it h hemialexia, lesions in t he ant erior part are associat ed w it h lef t ideomot or apraxia, and lesions in t he middle part are
associat ed w it h lef t -hand agraphia; lesions in t he middle and post erior part s result in lef t -hand t act ile anomia.
PREFRONTAL LOBE SYNDROM E The pref ront al lobe syndrome occurs in associat ion w it h t umors, t rauma, or degenerat ive disease in t he pref ront al and or bit of ront al cort ices. The syndrome is charact erized by a conglomerat e of signs and sympt oms t hat include impairment s in decision making, abilit y t o plan, social judgment , conduct , modulat ion of aff ect and of emot ional response, and creat ivit y. Such pat ient s lose spont aneit y in mot or as w ell as ment al act ivit ies. They do not appear t o realize t hat t hey are neglect ing t hemselves and t heir responsibilit ies at home and w ork. Aff ect ed pat ient s may sit f or hours looking at object s in f ront of t hem or st aring out a w indow. They manif est loss of inhibit ion in social behavior and are usually euphoric and unconcerned. They may become incont inent of st ools and urine because of t he lack of spont aneit y. Pat ient s w it h pref ront al lobe syndrome exhibit inappropriat e repet it ive mot or or speech behavior (perseverat ion) because of t heir inabilit y t o disengage f rom a behavior t hat is no longer usef ul.
Fi gure 18-3. Schemat ic diagram illust rat ing t he mechanism of unilat eral (l ef t) ideomot or apraxia A and of unilat eral (l ef t) t act ile anomia B.
THE GRASP REFLEX Some brain-damaged pat ient s show, in response t o t act ile st imulat ion of t heir hands or t o t he mere present at ion of an object , a t endency t o grasp at t he object w it hout any apparent int ent ion t o use it in a purposef ul manner. Tw o t ypes of grasp phenomena have been described: (1) t he grasp ref lex and (2) t he inst inct ive grasp react ion. The grasp ref lex is generally considered an index of f ront al lobe pat hology,
alt hough t he evidence in support of t his localizat ion is not so compelling. The grasp ref lex has been report ed w it h pat hology in t he basal ganglia, t emporal lobe, pariet al lobe, and pariet ooccipit al region. I n t he majorit y of cases, how ever, pat hology is eit her in t he f ront al lobe or in subcort ical st ruct ures. Unilat eral lesions usually result in bilat eral grasping. I n cont rast , t he inst inct ive grasp react ion (f orced groping) is usually ipsilat eral t o t he f ocal cerebral lesion and is seen more of t en w it h ret rorolandic lesions of t he right hemisphere, suggest ing t hat it is one of t he right hemisphere behavioral syndromes caused by dist urbances of select ive at t ent ion.
FORCED COLLECTIONISM Forced collect ionism is a rare pref ront al lobe syndrome charact erized by involunt ary, irrepressible behavior of searching, collect ing, and st oring t hat is goal-direct ed and it em-select ive. I t result s f rom ineff icient or loss of f ront al lobe inhibit ion. I t is associat ed w it h bilat eral damage t o t he orbit of ront al and polar pref ront al cort ices. Pat hologic pat t erns of collect ing have been observed f ollow ing f ront al lobe injury. They range f rom a t endency t o grasp t o t he irrepressible seizure and st orage of surrounding object s (hoarding behavior). I n cont rast t o f orced collect ionism, t hese behaviors are not planned and not select ive.
ALZHEIM ER'S DISEASE Alzheimer's disease is t he example par excellence of cort ical dement ia. I t w as f irst described by Alois Alzheimer, t he G erman psychiat rist , in 1906 1 907, based on pat hological f indings in t he brain of a pat ient (August e D) w it h memory impairment . I t is charact erized by relent lessly progressive memory loss. Early on in t he disease, pat ient s lose recent memory (t elephone numbers, appoint ment s). As t he disease progresses, remot e memory is impaired. I n t he end st age, memory loss is nearly t ot al. Wit h advance in t he disease, pat ient s w ill be unable t o recognize t heir f amily members or t heir f amiliar surroundings. The pat hologic hallmarks are neurof ibrillary t angles and senile plaques. The f ormer are int racellular aggregat es of t w ist ed cyt oskelet al f ilament s and abnormally phosphorylat ed t au prot ein. The lat t er are abnormal neurit es surrounding an aggregat ed B-amyloid core in t he neuropil bet w een nerve cells. The limbic cort ex is most aff ect ed, t he associat ion cort ices are heavily aff ect ed, t he primary sensory areas are minimally aff ect ed, and t he mot or cort ex is least aff ect ed. Wit hin t he limbic cort ex, t he ent orhinal cort ex (Brodmann area 28) is t he most heavily aff ect ed, t hus disconnect ing t he hippocampus f rom associat ion areas of t he cort ex. I n Alzheimer's disease, about 50% of neurons are lost . Ninet y percent of Alzheimer's disease is sporadic. The f amilial cases comprise 10% of cases and are relat ed t o abnormal mut at ions in chromosomes 21, 14, and 1. Chromosome 21 mut at ion is in t he amyloid precursor prot ein and has
been associat ed w it h abnormal quant it ies of amyloid product ion. Mut at ions in chromosomes 14 and 1, on t he ot her hand, are associat ed w it h prot ein presenilins t hat are possibly responsible f or build up of amyloid. Risk f act ors f or Alzheimer's disease have been associat ed w it h chromosome 19, w hich encodes apolipoprot ein, and chromosome 12, w hich encodes alpha 2 macroglobulin.
BALINT'S SYNDROM E This rare syndrome is named af t er t he Hungarian neurologist Rudolph Balint . The syndrome is also know n as Balint -Holmes syndrome, opt ic at axia, ocular apraxia, and psychic paralysis of visual f ixat ion. I t is charact erized by a t riad of (1) simult anagnosia, (2) opt ic at axia, and (3) ocular apraxia. Simult anagnosia, also know n as visual disorient at ion, is t he inabilit y of t he pat ient t o perceive t he visual f ield as a w hole. O pt ic at axia is t he inabilit y t o reach f or object s under visual guidance. O cular apraxia is t he inabilit y t o direct gaze volunt arily t o visual t arget s. The associat ed cort ical lesion is bilat eral pariet ooccipit al junct ion (Brodmann areas 7 and 19).
GERSTM ANN'S SYNDROM E This syndrome is named af t er Josef G erst mann, an Aust rian neuro-psychiat rist w ho described t he syndrome in 1930. The syndrome is also know n as t he BadalG erst mann syndrome and t he angular gyrus syndrome. Ant oine-Jules Badal, a French opht halmologist , had report ed some f eat ures of t he syndrome in 1888. The syndrome consist s of t he combinat ion of right -lef t disorient at ion, acalculia (reduced abilit y t o perf orm simple calculat ions), agraphia (inabilit y t o w rit e), and f inger agnosia (inabilit y t o recognize various f ingers) due t o a lesion in t he lef t angular gyrus. Asymbolia f or pain and const ruct ional apraxia are added f eat ures in some cases.
ANOSOGNOSIA (DENIAL SYNDROM E, ANTON-BABINSKI SYNDROM E) The t erm anosognosia w as int roduced by Josef -Franéois-Felix Babinski in 1912 f or unaw areness of physical def icit s or disease. This is seen most of t en w it h lesions of t he nondominant (right ) pariet al lobe, w it h unaw areness of def icit s of t he lef t side of t he body. The denial syndrome may include denial t hat t he paret ic limbs belong t o t he pat ient . Hemispat ial neglect of t en co-occurs w it h anosognosia. I n hemispat ial neglect , t he cont ralat eral side of t he body and visual space are ignored but can be used if at t ent ion is draw n t o t hem. Hemispat ial neglect occurs af t er damage t o eit her hemisphere but is t ypically more common and severe af t er right pariet al lesions. The precise locat ion of t he lesion in t he pariet al lobe has not been
det ermined, but most likely is in t he inf erior pariet al lobule and t he adjacent int rapariet al sulcus.
ANTON'S SYNDROM E Ant on's syndrome t radit ionally ref ers t o t he clinical phenomenon of denial of blindness (anosognosia f or blindness) in a pat ient w ho has suff ered acquired cort ical blindness. The most common set t ing is acut e bilat eral occipit al cort ex ischemia secondary t o post erior circulat ion insuff iciency. Alt hough classically a manif est at ion of cort ical blindness, Ant on's syndrome has been report ed in pat ient s w it h blindness f rom peripheral visual pat hw ay lesions (opt ic nerve, chiasm). The syndrome is named af t er G abriel Ant on, an Aust rian neurologist w ho described t he syndrome in 1899.
KLUVER-BUCY SYNDROM E The Kluver-Bucy syndrome w as f irst described in 1939 in monkeys af t er bilat eral t emporal lobect omy. The human count erpart w as described by Terzian and Dalle O re in 1955 af t er bilat eral removal of t he t emporal lobes. The syndrome consist s of six main element s: (1) blunt ed aff ect w it h apat hy, (2) psychic blindness or visual agnosia w it h inabilit y t o dist inguish bet w een f riends, relat ives, and st rangers, (3) hypermet amorphosis w it h a marked t endency t o t ake not ice and at t end t o f ine and minut e visual st imuli, (4) hyperoralit y, placing all it ems in t he mout h, (5) bulimia or unusual diet ary habit s, and (6) alt erat ion in sexual behavior (hypersexualit y, sexual libert arianism).
SIM ULTANAGNOSIA Simult anagnosia is t he inabilit y t o appreciat e more t han one aspect of t he visual panorama at any single t ime. Aff ect ed pat ient s cannot experience a spat ially coherent visual f ield because of an inabilit y t o volunt arily cont rol t he shif t ing of at t ent ion or t o disengage f rom a f ixed t arget . O bject s in t he visual f ield of aff ect ed pat ient s appear and disappear errat ically. Aff ect ed pat ient s f ail t o see a mat ch f lame held several inches aw ay w hen t heir at t ent ion is f ocused on t he t ip of a cigaret t e held bet w een t heir lips. The t erm simult anagnosia w as int roduced by Wolpert in 1924 t o ref er t o a condit ion in w hich t he pat ient is unable t o recognize or abst ract t he meaning of t he w hole (pict ures or series of pict ures) even t hough t he det ails are appreciat ed correct ly. Simult anag-nosia is f requent ly a component of Balint 's syndrome. I solat ed simult anagnosia is associat ed w it h lesions in t he unimodal visual associat ion cort ex (Brodmann area 19).
THE ALIEN HAND (LIM B) SYNDROM E The alien hand (limb) syndrome is charact erized by t he unw illed and uncont rolled act ions of an upper limb on eit her t he dominant or nondominant side. The alien hand perf orms aut on-omous act ivit y t hat t he subject cannot inhibit and t hen of t en
cont rast s w it h volunt ary act ions perf ormed by t he ot her hand. Pat ient s of t en f ail t o recognize ow nership of t he limb and st at e t hat t he alien hand has a mind of it s ow n. The alien hand syndrome w as f irst described in 1908 by G oldst ein. Tw o f orms of alien hand exist : (1) an acut e, t ransient condit ion in t he non-dominant hand due t o callosal lesion and (2) a chronic condit ion result ing f rom addit ional medial f ront al lesions involving t he supplement ary mot or area. The combined callosal and medial f ront al lesions presumably release t he lat eral f ront al mot or syst em responsible f or environment ally driven act ivit y. A sensory alien hand syndrome has also been described in w hich t he right arm involunt arily at t acks t he lef t side of t he body, including choking movement .
TERM INOLOGY Adversive seizures. A variet y of seizures in w hich t here is deviat ion of eyes and/ or head t o one side secondary t o a st imulat ing lesion in t he cont ralat eral f ront al eye f ield region. Agnosia (G reek a, n egative gnosi s, k nowledge ) . I mpairment of t he abilit y t o recognize st imuli t hat w ere recognized f ormerly despit e int act percept ion, int ellect , and language. The t erm w as coined by Sigmund Freud in 1891. The lesion is usually in t he post erior pariet al region. Agraphia (G reek a, n egative grapho, t o write ). I nabilit y t o express t hought s in w rit ing due t o a cerebral lesion. The f irst modern descript ions of agraphia are t hose of Jean Pit res in 1884 and of Joseph-Jules Dejerine in 1891. Alzheimer, Alois (1864 1 915). G erman neuropsychiat rist and pat hologist . He described Alzheimer's disease in a lect ure in 1906 and a publicat ion in 1907. The t erm A lzheimer's disease w as coined in 1910 by Ernst Kraepelin, a G erman psychiat rist and co-w orker of Alzheimer. Anomia (G reek a, n egative onoma, n ame ) . I nabilit y t o name object s or of recognizing and recalling t heir names. Anton, G abriel (1858 1 933). Aust rian neurologist w ho described visual anosognosia (anosognosia f or blindness) in 1899. The t erm anosognosi a w as coined by Babinski in 1912. Aphasia (dysphasia) (G reek a, n egative phasi s, s peech ) . Language impairment f ollow ing cort ical lesion in t he lef t hemisphere. Eit her inabilit y t o speak or t o comprehend language or bot h. Apraxia (G reek a, n egative praxi s, a ction ) . I nabilit y t o carry out learned skilled movement s on command despit e int act mot or and sensory syst ems and good comprehension.
Babinski, Josef-Franéois-Felix (1857 1 932). French neurologist of Polish descent . Described t he p henomenon of t he t oes in 1896, w hich became know n as t he Babinski sign. Coined t he t erms anosognosi a, dysdi adochoki nesi s, and asynergi a, among ot hers. Bastian, Henry Charlton (1837 1 915). English neurologist , w ho described Wernicke's aphasia in 1869, f ive years bef ore Karl Wernicke. Circumlocution. Convolut ed, meaningless speech out put , providing inf ormat ion rat her t han def ining t he object s t o be communicat ed. Charact erist ic of Wernicke's aphasia. Dax, G ustav. French physician, w ho, in 1865, published t he observat ion of his f at her, Marc Dax, about lef t hemisphere dominance f or language, w hich w as not ed, but not published, by his f at her in 1836. Déjá vu (French, a lready seen ). An illusion in w hich a new sit uat ion is incorrect ly view ed as a repet it ion of a previous sit uat ion. Usually an aura of a t emporal lobe seizure. Dysphasia (G reek dys, d ifficult phasi s, s peech ) . Dist ur-bance in communicat ion involving language. Dysprosody (G reek dys, d ifficult prosodos, a solemn procession ). Dist urbance in st ress, pit ch, and rhyt hm of speech. A f eat ure of all t ypes of aphasia, but especially of Broca's aphasia. G oldstein, Kurt (1878 1 965). G erman-American physician. Described t he alien hand (limb) syndrome (la main et rangere, anarchic hand). Idiographic language. Pict ographic language such as Japanese Kanji. Jacksonian seizures. The spread of t onic-clonic seizure act ivit y t hrough cont iguous body part s on one side of t he body secondary t o excit at ion of adjacent cort ical areas w it hin t he mot or or sensory homunculus. Also know n as Jacksoni an march and Bravai sJackson epi l epsy. L. Bravais described t his phenomenon in his graduat ion t hesis in 1827 f rom t he Universit y of Paris but did not analyze t he et iology, w hich John Hughlings-Jackson did. Lichtheim, Ludwig (1845 1 928). G erman neurologist and pat hologist . Recognized alexia as a dist inct condit ion separat e f rom ot her language disorders. He is credit ed w it h describing subcort ical aphasia in 1885 and subacut e combined degenerat ion of t he spinal
cord in vit amin B12 def iciency (Licht eim syndrome). Liepmann, Hugo Karl (1863 1 925). G erman neurologist and psychiat rist , w ho int roduced t he concept of apraxia and proposed it s classif icat ion in 1900. Marie, Pierre (1853 1 940). French neurologist w ho, in 1906, disagreed w it h Broca on t he ext ent of t he lesion t hat produced aphasia in pat ient Leborgne. He and Charcot are credit ed w it h describing peroneal muscular at rophy in 1886 (Charcot -Marie-Toot h disease). Mayer-G ross, Willi. G erman psychiat rist w ho provided f ull descript ion of const ruct ional apraxia in 1935. Neologism (G reek neos, n ew l ogos, w ord ) . A new ly coined w ord eit her in response t o a communicat ive need or as a result of brain disorder. I n t he lat t er case, t he new ly coined w ord is a replacement of a desired w ord but w it hout meaning. Paraphasia (G reek para, t o, at, from the side of phasi s, s peech ) . An aphasic phenomenon in w hich t he pat ient employs w rong w ords or uses w ords in w rong combinat ions. Prosopagnosia (G reek prosopon, f ace gnosi s, k nowledge ) . I nabilit y t o recognize f amiliar f aces. The w ord w as coined by Bodamer in 1947, alt hough t he phenomenon had been recognized by Jackson and Charcot at t he end of t he ninet eent h cent ury. Simultanagnosia. The inabilit y t o comprehend more t han one element of a visual scene at t he same t ime or t o int egrat e t he part s int o a w hole. Uncinate (Latin unci nus, h ook-shaped ) . Pert aining t o t he uncus of t he t emporal lobe. Uncinat e seizures are t emporal lobe seizures in w hich olf act ory and gust at ory hallucinat ions occur as part of t he seizure. The name unci nate f i ts w as applied by Jackson in 1899.
SUGGESTED READINGS Absher RR, Benson DF: Disconnect ion syndromes: An overview of G eschw ind's cont ribut ions. Neurol ogy 1993; 43: 862 8 67. Albert ML: Alexia. I n Heilman KM, Valenst ein E (eds): Cl i ni cal Neuropsychol ogy. New York, O xf ord Universit y Press, 1979: 59. Alexander MP et al: Broca's area aphasias: Aphasia af t er lesions including t he
f ront al operculum. Neurol ogy 1990; 40: 353 3 62. Banks G et al: The alien hand syndrome: Clinical and post mort em f indings. Arch Neurol 1989; 46: 456 4 59. Benson DF: Aphasia. I n Heilman KM, Valenst ein E (eds): Cl i ni cal Neuropsychol ogy. New York, O xf ord Universit y Press, 1979: 22. Benson DF: Aphasia, alexia, and agraphia. I n G laser G H (ed): Cl i ni cal Neurol ogy and Neurosurgery Monographs, vol 1. New York, ChurchillLivingst one, 1979: 1 2 05. Bent on A: Visuopercept ive, visuospat ial, and visuoconst ruct ive disorders. I n Heilman KM, Valenst ein E (eds): Cl i ni cal Neuropsychol ogy. New York, O xf ord Universit y Press, 1979: 186. Bent on A: G erst mann's syndrome. Arch Neurol 1992; 49: 445 4 47. Boeri R, Salmaggi A: Prosopagnosia (comment ary). Curr O pi n Neurol 1994; 7: 61 6 4. Boegn JE: The callosal syndrome. I n Heilman KM, Valenst ein E (eds): Cl i ni cal Neuropsychol ogy. New York, O xf ord Universit y Press, 1979: 308. Branch Coslet t H et al: Pure w ord deaf ness af t er bilat eral primary audit ory cort ex inf arct s. Neurol ogy 1984; 34: 347 3 52. But t ers N: Amnesic disorders. I n Heilman KM, Valenst ein E (eds): Cl i ni cal Neuropsychol ogy. New York, O xf ord Universit y Press, 1979: 439. Damasio AR: Not es on t he anat omical basis of pure alexia and of color anomia. I n Taylor M, Höök S (eds): Aphasi a: Assessment and Treatment. St ockholm, Almqvist & Wiksell, 1978: 126. Damasio AR: The neural basis of language. Ann Rev Neurosci 1984; 7: 127 1 47. Damasio AR: Prosopagnosia. TINS 1985; 8: 132 1 35. Damasio AR: The nat ure of aphasias: Signs and syndromes. I n Taylor Sarno M (ed): Acqui red Aphasi a. New York, Academic Press, 1981: 51.
Damasio H: Cerebral localizat ion of t he aphasias. I n Taylor Sarno M (ed): Acqui red Aphasi a. New York, Academic Press, 1981: 27. Damasio AR, Damasio H: The anat omic basis of pure alexia. Neurol ogy 1983; 33: 1573 1 583. Damasio AR, Damasio H: Brain and language: A large set of neural st ruct ures serves t o represent concept s; a smaller set f orms w ords and sent ences; bet w een t he t w o lies a crucial layer of mediat ion. Sci Am Sept 1992; 89 9 5. Damasio H, Damasio AR: Lesi on Anal ysi s i n Neuropsychol ogy. New York, O xf ord Universit y Press, 1989. Damasio H, Damasio AR: The anat omical basis of conduct ion aphasia. Brai n 1980; 103: 337 3 50. Damasio AR et al: Face agnosia and t he neural subst rat es of memory. Annu Rev Neurosci 1990; 13: 89 1 09. DeRenzi E, Barbieri C: The incidence of t he grasp ref lex f ollow ing hemispheric lesions and it s relat ion t o f ront al damage. Brai n 1992; 115: 293 3 13. Feinberg TE et al: Tw o alien hand syndromes. Neurol ogy 1992; 42: 19 2 4. Feinberg TE et al: Anosognosia and visuoverbal conf abulat ion. Arch Neurol 1994; 51: 468 4 73. Finger S, Roe D: G ust ave Dax and t he early hist ory of cerebral dominance. Arch Neurol 1996; 53: 806 8 13. Funkenst ein HH: Approaches t o hemispheric asymmet ries. I n Tyler HR, Daw son DM (eds): Current Neurol ogy, vol 1. Bost on, Hought on Miff lin Medical Division, 1978: 336. G oet z CG : Bat t le of t he t it ans. Charcot and Brow n-Sequard on cerebral localizat ion. Neurol ogy 2000; 54: 1840 1 847. G rabow ski TJ et al: Disorders of cognit ive f unct ion. Conti nuum 2002; 8: 1 2 96. Heilman KM: Apraxia. I n Heilman KM, Valenst ein E (eds): Cl i ni cal
Neuropsychol ogy. New York, O xf ord Universit y Press, 1979: 159. Kert esz A et al: Comput er t omographic localizat ion, lesion size and prognosis in aphasia and nonverbal impairment . Brai n Language 1979; 8: 34 5 0. Kreisler A et al: The anat omy of aphasia revisit ed. Neurol ogy 2000; 54: 1117 1123. Lassonde M et al: Eff ect s of early and lat e t ransect ion of t he corpus callosum in children: A st udy of t act ile and t act omot or t ransf er and int egrat ion. Brai n 1986; 109: 953 9 67. Mazzochi F, Vignolo LA: Localizat ion of lesions in aphasia: Clinical C T scan correlat ions in st roke pat ient s. Cortex 1979; 15: 627 6 54. McDaniel KD, McDaniel LD: Ant on's syndrome in a pat ient w it h post -t raumat ic opt ic neuropat hy and bif ront al cont usions. Arch Neurol 1991; 48: 101 1 05. Mori E, Yamadori A: Unilat eral hemispheric injury and ipsilat eral inst inct ive grasp react ion. Arch Neurol 1985; 42: 485 4 88. Pryse-Phillips W: Compani on to cl i ni cal neurol ogy, 2d ed. O xf ord Universit y Press, O xf ord, 2003.
Rizzo M, Hurt ig R: Looking but not seeing: At t ent ion, percept ion, and eye movement s in simult anagnosia. Neurol ogy 1987; 37: 1642 1 648. Rizzo M, Robin DA: Simult anagnosia: A def ect of sust ained at t ent ion yields insight s on visual inf ormat ion processing. Neurol ogy 1990; 40: 447 4 55. Rubens AB: Agnosia. I n Heilman KM, Valenst ein E (eds): Cl i ni cal Neuropsychol ogy. New York, O xf ord Universit y Press, 1979: 233. Saff ran EM: Aphasia and t he relat ionship of language and brain. Sem Neurol 2000; 20: 409 4 18. Schäff ler L et al: Comprehension def icit s elicit ed by elect rical st imulat ion of Broca's area. Brai n 1993; 116: 695 7 15. Schlaug G et al: I n vivo evidence of st ruct ural brain asymmet ry in musicians.
Sci ence 1995; 267: 699 7 01. Smit h Doody R, Jankovic J: The alien hand and relat ed signs. J Neurol Neurosurg Psychi atry 1992; 55: 806 8 10. Trojano L et al: How many alien hand syndromes&quest ; Follow -up of a case. Neurol ogy 1993; 43: 2710 2 712. Vallar G : Ext rapersonal visual unilat eral spat ial neglect and it s neuroanat omy. Neuroi mage 2001; 14: S52 S 58. Volle E et al: Forced collect ionism af t er orbit of ront al damage. Neurol ogy 2002; 58: 488 4 90. Warringt on EK, Shallice T: Word-f orm dyslexia. Brai n 1980; 103: 99 112. Wat son RT et al: Post erior neocort ical syst ems subserving aw areness and neglect : Neglect associat ed w it h superior t emporal sulcus but not area 7 lesions. Arch Neurol 1994; 51: 1014 1 021. Weint raub S, Mesulam M-M: Right cerebral dominance in spat ial at t ent ion: Furt her evidence based on ipsilat eral neglect . Arch Neurol 1987; 44: 621 6 25. Yamadori A et al: Lef t unilat eral agraphia and t act ile anomia: Dist urbances seen af t er occlusion of t he ant erior cerebral art ery. Arch Neurol 1980; 37: 88 9 1.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 19 - Hypothalam us
19 Hypothalamus
Boundaries and Divisions Preoptic Region Suprachiasmatic (Supraoptic) Region Tuberal Region Mamillary Region Connections Local Connections Extrinsic Connections Functions of the Hypothalam us Control of Posterior Pituitary (Neurohypophysis) Control of Anterior Pituitary Autonomic Regulation Temperature Regulation Emotional Behavior Feeding Behavior Drinking and Thirst Sleep and W akefulness Circadian Rhythm Memory Sexual Arousal Blood Supply KEY CONCEPTS
The hypothalamus is divided by the fornix into medial and lateral zones. The hypothalamus contains the following nuclear groupings: preoptic, suprachiasmatic (supraoptic), tuberal, and mamillary. Hypothalamic connections are divided into local (efferent) and extrinsic (afferent and efferent). Local hypothalamic connections consist of the hypotha-lamohypophyseal tract and the tuberohypophyseal (tuberoinfundibular) tract. Afferent extrinsic connections include the retinohypothalamic, fornix, amygdalohypothalamic, thalamohypothalamic, medial forebrain bundle, inferior mamillary peduncle, dorsal longitudinal fasciculus (of Schütz), pallidohypothalamic, cerebello-, spino-, and prefrontal hypothalamic. Efferent extrinsic connections include the mamillotha-l amic, mamillotegmental, fornix, medial forebrain bundle, dorsal longitudinal fasciculus (of Schütz), hypoth-alamoamygdaloid, descending autonomic, hypothalamocerebellar and hypothalamoprefrontal. The hypothalamus is involved in a variety of functions that include (1) control of water reabsorption in the kidney through secretion of the antidiuretic hormone (ADH) or vasopressin, (2) contraction of uterine smooth muscle and ejection of milk from the lactating nipple through secretion of oxytocin, (3) control of anterior pituitary function through secretion of hypothalamic releasing factors, (4) control of brain stem and spinal cord autonomic centers related to cardiovascular, respiratory, and
gastrointestinal functions, (5) control of body temperature through thermoreceptors that are sensitive to changes in temperature of blood perfusing the hypothalamus, (6) emotional behavior and the f ight or flight reaction, (7) regulation of feeding behavior through the hypothalamic satiety and feeding centers, (8) regulation of drinking and thirst, (9) wakefulness and sleep through the hypothalamic centers for wakefulness and sleep, (10) circadian rhythm through the connections of the suprachiasmatic nucleus, and (11) memory through connections to the anterior thalamic nucleus and hippocampal formation. The blood supply of the hypothalamus is derived from perforating branches of the anterior cerebral, anterior communicating, posterior communicating, and posterior cerebral arteries.
BOUNDARIES AND DIVISIONS The hypot halamus is t he area of t he diencephalon vent ral t o t he hypot halamic sulcus (see Figure 11-1). I t w eighs about 4 g and comprises 0. 3 t o 0. 5 percent of brain volume. I t is limit ed ant eriorly by t he lamina t erminalis and is cont inuous post eriorly w it h t he mesencephalon. O n it s vent ral surf ace, caudal t o t he opt ic chiasma, t he hypot halamus narrow s t o a small neck, t he t uber cinereum. The vent ral-most port ion of t he t uber cinereum const it ut es t he median eminence. The median eminence blends int o t he inf undibular st alk, w hich is cont inuous w it h t he post erior lobe of t he pit uit ary gland (hypophysis). I n coronal sect ions, t he hypot halamus is bordered medially by t he t hird vent ricle and lat erally by t he subt halamus (see Figure 11-2). The f ornix divides t he hypot halamus int o medial and lat eral regions. The lat eral region cont ains mainly longit udinally orient ed f ibers of t he medial f orebrain bundle (w hich connect s t he sept al area, hypot halamus, and midbrain t egment um), among w hich are scat t ered neurons of t he lat eral hypot halamic nucleus. The medial region has a clust er of nuclei organized int o f our major groups. I n a rost rocaudal orient at ion (Figure 19-1), t hese nuclear groups are as f ollow s:
1. Preopt ic 2.
Suprachiasmat ic (supraopt ic)
3. Tuberal 4. Mamillary
Preoptic Region (Figure 19-2) The gray mat t er in t he most rost ral part of t he hypot halamus, just caudal t o t he lamina t erminalis, is t he preopt ic region. The preopt ic region receives many f ibers t hat carry neuromediat ors, such as angiot ensin I I , sleep-inducing pept ides, enkephalin, and endorphin, among ot hers. I t cont ains medial and lat eral preopt ic nuclei and t he preopt ic perivent ricular nucleus.
Fi gure 19-1. Schemat ic diagram show ing t he f our regions of t he medial hypot halamus.
The medial preopt ic nucleus cont ains neurons t hat elaborat e gonadot ropic releasing hormone w hich reaches t he ant erior pit uit ary gland via t he t uberoinf undibular t ract . I t is relat ed t o reproduct ion, eat ing, locomot ion, and
sexual arousal. The medial preopt ic nucleus is ref erred t o as t he sexually dimorphic nucleus. I t is t w ice as large in young males compared t o f emales, probably because gonadot ropin release in males is const ant , w hereas it is cyclic in f emales. The diff erence in size may also explain t he report ed great er sexual arousal t o erot ic st imuli experienced by men. Funct ional magnet ic resonance imaging (f MRI ) st udies have show n great er act ivat ion in t he preopt ic region in men compared t o w omen w hen view ing erot ic f ilms.
Suprachiasmatic (Supraoptic) Region (Figure 19-2) Locat ed above t he opt ic chiasma, t his nuclear group cont ains t he supraopt ic, paravent ricular, ant erior hypot halamic, and suprachiasmat ic nuclei. The supraopt ic nucleus is locat ed above t he opt ic t ract , w hereas t he paravent ricular nucleus is dorsal t o it , lat eral t o t he t hird vent ricle (Figure 19-3). Bot h nuclei cont ain magnocellular secret ory neurons. Axons of bot h nuclei course in t he pit uit ary st alk t o reach t he post erior lobe of t he pit uit ary (hypot halamoneurohypophyseal syst em), t ransport ing neurosecret ory mat erial elaborat ed in t hese nuclei and st ored in axonal sw ellings w it hin t he post erior lobe. The neurosecret ory mat erial consist s of vasopressin ADH and oxyt ocin. There is evidence t o suggest t hat t he supraopt ic nucleus elaborat es mainly ADH, w hereas t he paravent ricular nucleus elaborat es mainly oxyt ocin. ADH act s on t he dist al convolut ed t ubules of t he kidney t o increase reabsorpt ion of w at er. Lesions of t he supraopt ic nucleus, t he hypot halamoneurohypophyseal syst em, or t he post erior lobe of t he pit uit ary result in excessive excret ion of urine (polyuria) of low specif ic gravit y. This condit ion is know n as diabet es insipidus. Anot her sympt om of t his condit ion is excessive int ake of w at er (polydipsia). Unlike diabet es mellit us diabet es insipidus is not associat ed w it h alt erat ions in t he sugar cont ent of blood or of urine. Product ion of ADH is cont rolled by t he osmolarit y of t he blood t hat bat hes t he supraopt ic nucleus. An increase in blood osmolarit y, as occurs in dehydrat ion, increases ADH product ion, w hereas t he reverse occurs in st at es of low ered blood osmolarit y, such as excessive hydrat ion. ADH secret ion is increased by pain, st ress, and such drugs as morphine, nicot ine, and barbit urat es; it is decreased by alcohol int ake, w hich explains t he increase in urinat ion w it h alcohol consumpt ion.
Fi gure 19-2. Schemat ic diagram show ing nuclei w it hin each of t he regions of t he medial hypot halamus.
O xyt ocin causes cont ract ion of ut erine smoot h musculat ure and promot es milk eject ion f rom t he lact at ing mammary glands by st imulat ing cont ract ion of it s myoepit helial cells. Commercially produced oxyt ocin (Pit ocin) is used t o induce labor. The f unct ion of oxyt ocin in males is not yet know n. The ant erior nucleus merges w it h t he preopt ic region. St imulat ion of t he ant erior part of t he hypot halamus in animals result s in excessive int ake of w at er, suggest ing t hat a cent er f or t hirst is locat ed in t his region. Tumors in t his region in children are associat ed w it h ref usal of pat ient s t o drink despit e severe dehydrat ion.
Fi gure 19-3. Schemat ic diagram show ing t he hypot halamo-neurohypophyseal syst em.
The suprachiasmat ic nucleus, poorly developed in humans, overlies t he opt ic chiasma. I t is involved in regulat ion of sleep-w ake cycle, body t emperat ure, and day-night cycle (circadian rhyt hm). I t receives bilat eral input s f rom ganglion cells of t he ret ina. I t project s t o t he paravent ricular, t uberal, and vent romedial nuclei of t he hypot halamus. Lesions of t he nucleus in experiment al animals w ill dist urb t he cyclic variat ions of a number of bodily f unct ions (e. g. , t emperat ure cycle, sleep-w ake cycle, circadian changes of hormones).
Tuberal Region (Figure 19-2) This is t he w idest region of t he hypot halamus and t he one in w hich t he division of t he hypot halamus int o medial and lat eral areas by t he f ornix is best illust rat ed. I t ext ends f rom t he inf undibulum ant eriorly t o t he mamillary body post eriorly. The t uberal region cont ains t he vent romedial hypot halamic, dorsomedial hypot halamic, and arcuat e (inf undibular) nuclei. The vent romedial nucleus, a poorly delineat ed area of small neurons, is concerned w it h sat iet y. Bilat eral lesions in t he vent romedial nucleus in animals produce a voracious appet it e, obesit y, and savage behavior. Lesions in t he lat eral hypot halamus at t his level produce loss of appet it e. Thus a cent er f or sat iet y is believed t o be associat ed w it h t he vent romedial nucleus and a f eeding cent er w it h t he lat eral hypot halamus. The dorsomedial nucleus is a poorly delineat ed mass of small neurons dorsal t o t he vent romedial nucleus. The arcuat e nucleus consist s of small neurons locat ed vent ral t o t he t hird vent ricle near t he inf undibular recess. The arcuat e nucleus
cont ains dopamine, w hich cont rols prolact in and grow t h hormone secret ions. I n addit ion, neurons of t he arcuat e nucleus st ain posit ively f or adrenocort icot ropic hormone (ACTH), bet a-lipot ropic pit uit ary hormone (β -LPH), and bet a-endorphin (β -END). These sub-st ances are t ransmit t ed t o t he ant erior pit uit ary via t he t ubero-inf undibular t ract and t he hypophyseal port al syst em. The arcuat e nucleus is believed t o play a role in emot ional behavior and endocrine f unct ion. The arcuat e nucleus is a major t arget in t he hypot halamus f or lept in act ion t o suppress f ood int ake. Bot h f ood promot ing (orexinergic) and f ood inhibit ing (anorexinergic) neurons exist in t he arcuat e nucleus and are t arget s f or lept in act ion. The arcuat e orexinergic neurons are t he neuropept ide Y neurons.
Mamillary Region (Figure 19-2) The most caudal region of t he hypot halamus is t he mamillary region; it cont ains mamillary and post erior hypot halamic nuclei. The mamillary nuclei (bodies) are t w o spherical masses prot ruding f rom t he vent ral surf ace of t he hypot halamus caudal t o t he t uber cinereum and rost ral t o t he int erpeduncular f ossa and t he ant erior perf orat ed subst ance. Each mamillary body cont ains t w o nuclei, medial and lat eral. The medial nucleus is especially w ell developed in man. I t is t he main t arget of t he f ornix and t he source of t he mamillot halamic t ract . The post erior hypot halamic nucleus is a mass of large neurons locat ed dorsal t o t he mamillary bodies. I t is t he main source of descending hypot halamic f ibers t o t he brain st em.
A. LATERAL REGION The lat eral region of t he hypot halamus lies lat eral t o t he f ornix and mamillot halamic t ract . I t cont ains t he medial f orebrain bundle and t he lat eral hypot halamic nucleus. The medial f orebrain bundle connect s t he hypot halamus w it h t he sept al area rost rally and brain st em ret icular f ormat ion caudally. The lat eral hypot halamus is specif ically responsible f or f eeding. O rexin (hypocret in) pept ide cont aining neurons are exclusively locat ed in t he lat -eral hypot halamic region. Cent ral administ rat ion of hypocret in-1 st imulat es f ood int ake. Hypocret in neurons in t he lat eral region send a dense project ion t o t he hypot halamic arcuat e nucleus. Hypocret in inhibit s anorexinergic and excit es orexinergic arcuat e neurons. Hypocret in neurons also project t o t he paravent ricular and vent romedial hypot halamic nuclei, st ruct ures know n t o int egrat e f eeding. The orexin/ hypocret in syst em is also t he major excit at ory neuromodulat ory syst em t hat cont rols act ivit ies of monoaminergic and cholinergic syst ems t o cont rol vigilance st at es. Dest ruct ion of orexin/ hypocret in neurons is associat ed w it h t he sleep disorder of narcolepsy.
CONNECTIONS (Figure 19-3)
The hypot halamus has ext ensive connect ions ref lect ing it s roles in endocrine, aut onomic, and somat ic int egrat ion.
Local Connections The hypot halamus inf luences pit uit ary f unct ion via t w o pat h w ays: t he hypot halamohypophyseal (supraopt ic-hypophyseal) t ract and t he t uberohypophyseal (t ubero-inf undibular) t ract .
A. THE HYPOTHALAM OHYPOPHYSEAL (SUPRAOPTICHYPOPHYSEAL) TRACT (Figure 19-3) This t ract arises f rom t he large magnocellular neurons of t he supraopt ic and paravent ricularnuclei of t he hypot halamus and t erminat es in t he post erior lobe of t he pit uit ary gland (neurohypophysis). Axons in t his t ract t ransport vasopressin (ADH) f rom t he supraopt ic nucleus and oxyt ocin f rom t he paravent ricular nucleus t o t he f enest rat ed capillary bed in t he neurohypophysis. I nt errupt ion of t his t ract result s in diabet es insipidus, a condit ion charact erized by excessive urine excret ion (poly-uria) of low specif ic gravit y and excessive int ake of w at er (polydipsia) w it hout alt erat ions in t he glucose cont ent of blood or urine.
B. THE TUBEROHYPOPHYSEAL (TUBEROINFUNDIBULAR) TRACT This t ract arises f rom t he small parvicellular neurons of t he arcuat e and perivent ricular nuclei and t erminat es on capillaries in t he median eminence and inf undibular st em. Fibers in t his t ract t rans-mit hypot halamic releasing f act ors (hypophysiot ropic agent s) t o t he ant erior lobe of t he pit uit ary gland via t he hypophyseal port al syst em. Hypophysiot ropic agent s st imulat e or inhibit secret ion of ant erior lobe of t he pit uit ary hormones.
Extrinsic Connections A. AFFERENT EXTRINSIC CONNECTIONS The f ollow ing hypot halamic ext rinsic input s have been report ed: 1.
Reti nohypothal ami c tract. Fibers f rom ganglion cells of t he ret ina project bilat erally t o t he suprachiasmat ic nuclei of t he hypot halamus via t he opt ic nerve and opt ic chiasma. They reach t he nucleus as direct f ibers f rom t he opt ic chiasm or as collat erals f rom ret inogeniculat e f ibers. This t ract t ransmit s light periodicit y inf ormat ion t o t he suprachiasmat ic nucleus, w hich plays a role in t he circadian rhyt hm.
2. Forni x. The f ornix comprises t he major input t o t he hypot halamus. Arising f rom t he hippocampal f ormat ion and subiculum, t he f ornix f ollow s a C-shaped
course underneat h t he corpus callosum as f ar f orw ard as t he int ervent ricular f oramen of Monro, w here it disappears in t he subst ance of t he diencephalon t o reach t he mamillary bodies. Alt hough t he major component of t he f ornix comes f rom t he hippocampal f ormat ion and subiculum, it also carries f ibers f rom t he sept al area t o t he mamillary bodies. I t s major t arget w it hin t he mamillary body is t he medial nucleus. 3. Amygdal ohypothal ami c tract. I nput s t o t he hypot halamus f rom t he amygdala f ollow t w o pat hw ays. O ne is via t he phylogenet ically older st ria t erminalis, w hich links t he amygdala w it h t he preopt ic, ant erior hypot halamic, vent romedial, and arcuat e nuclei of t he hypot halamus. The ot her is via t he phylogenet ically more recent vent ral amygdalof ugal f iber syst em, w hich links t he amygdala w it h t he lat eral hypot halamic nucleus. 4. Thal amohypothal ami c f i bers. These f ibers run f rom dorsomedial and midline t halamic nuclei t o t he lat eral and post erior hypot halamus and are sparse. Fibers f rom t he ant erior t ha-lamic nuclei reach t he mamillary bodies via t he mamillo-t halamic t ract and provide a f eedback mechanism t o t he mamillary bodies. 5. Medi al f orebrai n bundl e. This f iber bundle runs in t he lat eral hypot halamus. I t conveys t o t he hypot halamus input s f rom a variet y of sources, including t he basal f orebrain (olf act ory cort ex, sept al area, nucleus accumbens sept i), amygdala, premot or f ront al cort ex, brain st em ret icular f ormat ion, and spinal cord. 6. Inf eri or mami l l ary peduncl e. This f iber bundle links t he dorsal and vent ral t egment al nuclei of t he midbrain w it h t he mamillary body. I t also cont ains indirect input s f rom ascending sensory pat hw ays. 7. Dorsal l ongi tudi nal f asci cul us of Schütz. Aff erent f ibers in t his f asciculus link t he periaqueduct al (cent ral) gray mat t er of t he midbrain w it h t he hypot halamus. 8. Pal l i dohypothal ami c f i bers. This f iber bundle originat es f rom t he lent if orm nucleus and project s on neurons in t he vent romedial hypot halamic nucleus. 9. Cerebel l ohypothal ami c f i bers. This f iber bundle originat es f rom all deep cerebellar nuclei and relat es t he cerebellum t o aut onomic f unct ion. 10. O ther i nputs. O t her aff erent s t o t he hypot halamus f rom t he brain st em include t hose f rom t he raphe nuclei (serot oninergic), locus ceruleus (noradrenergic), and nucleus solit arius. These f ibers ent er t he hypot halamus via t he medial f orebrain bundle. I nput f rom t he spinal cord reaches t he hypot halamus via t he ret icular f ormat ion of t he brain st em. 11. Pref rontal -hypothal ami c f i bers. Reciprocal connect ions bet w een t he hypot halamus and pref ront al cort ex have been demonst rat ed. Pref ront alhypot halamic f ibers originat e primarily f rom t he orbit al and medial pref ront al
areas and t erminat e primarily in t he post erior hypot halamus, w it h some t erminat ions in t he t uberal and ant erior hypot halamus. The origin of pref ront al-hypot halamic f ibers f rom limbic pref ront al cort ex and t heir t arget s in t he hypot halamus suggest t hat t hey are import ant links f or aut onomic response t o emot ion.
B. EFFERENT EXTRINSIC CONNECTIONS The hypot halamus sends f ibers t o most areas f rom w hich it receives input s. The f ollow ing hypot halamic ext rinsic eff erent connect ions have been report ed: 1.
Mami l l othal ami c tract (t ract of Vicq d'Azyr) (see Figure 11-4). This is a t w o-w ay f iber syst em connect ing t he mamillary bodies w it h t he ant erior t halamic nucleus.
2. Mami l l otegmental tract. Fibers f rom t he mamillary bodies course caudally t o t erminat e on dorsal and vent ral t egment al nuclei and secondarily on aut onomic cranial (dorsal mot or nucleus of vagus, nucleus solit arius, nucleus ambiguus) and spinal nuclei (int ermediolat eral cell column). 3. Forni x. Reciprocal f ibers t ravel in t he f ornix f rom t he mamillary body t o t he hippocampal f ormat ion. 4. Medi al f orebrai n bundl e. This bundle conveys impulses f rom t he lat eral hypot halamus rost rally t o t he sept al nuclei and caudally t o t egment al nuclei and periaqueduct al (cent ral) gray of t he midbrain. 5. Dorsal l ongi tudi nal f asci cul us of Schütz. Fibers in t his f asciculus link t he medial hypot halamus w it h t he periaqueduct al gray mat t er of t he midbrain, t he accessory oculomot or nuclei, and salivary nuclei. 6. Hypothal amoamygdal oi d f i bers. These f ibers t ravel via t he st ria t erminalis and vent ral amygdalof ugal f iber syst em and provide f eedback inf ormat ion t o t he amygdaloid nucleus. 7. Descendi ng autonomi c f i bers ( Figure 19-4). Axons of neurons in t he paravent ricular nucleus, t he lat eral hypot halamic area, and t he post erior hypot halamus project int o aut onomic cranial nerve nuclei in t he brain st em (dorsal mot or nucleus of t he vagus, nucleus ambiguus, nucleus solit arius) and aut onomic spinal cord nuclei in t he int ermediolat eral cell column and t he sacral aut onomic cell column. Via t hese connect ions, t he hypot halamus exert s cont rol over cent ral aut onomic processes relat ed t o blood pressure, heart rat e, t emperat ure regulat ion, and digest ion. Many of t hese f ibers are component s of t he dorsal longit udinal f asciculus of Schüt z.
Fi gure 19-4. Schemat ic diagram show ing descending aut onomic project ions of t he hypot halamus.
8. Hypothal amocerebel l ar f i bers. I n t he past f ew years, a series of invest igat ions has revealed t he exist ence of a complex net -w ork of direct and indirect pat hw ays bet w een t he hypot halamus and cerebellum. The project ions are bilat eral w it h ipsilat eral preponderance. They originat e f rom various hypot halamic nuclei and areas but principally f rom t he lat eral and post erior hypot halamic areas. The direct pat hw ay reaches t he cerebellum via t he superior cerebellar peduncle. The indirect pat hw ay reaches t he cerebellum af t er relays in a number of brain st em nuclei. The hypot halamocerebellar pat hw ay may provide t he neuroanat omic subst rat e f or t he aut onomic responses elicit ed f rom cerebellar st imulat ion. 9. Hypothal amothal ami c f i bers: This f iber syst em connect s t he preopt ic hypot halamic area w it h t he dorsomedial t halamic nucleus. 10. Hypothal amopref rontal f i bers: These f ibers originat e principally f rom t he post erior hypot halamus w it h some cont ribu-t ions f rom t he ant erior and t uberal hypot halamus. I n con-t rast t o t he pref ront al hypot halamic connect ion w hich originat es select ively f rom limbic pref ront al cort ex, t he hypot halamus pref ront al project ion is w idespread t o all sect ors of t he pref ront al cort ex. Table 19-1 is a summary of t he aff erent and eff erent connect ions of t he hypot halamus.
FUNCTIONS OF THE HYPOTHALAM US The f unct ions of t he hypot halamus, mediat ed t hrough it s varied and complex connect ions, involve several import ant bodily act ivit ies. The f ollow ing is a list ing of some of t he most import ant and best know n.
Control of Posterior Pituitary (Neurohypophysis) This is served t hrough t he hypot halamoneurohypophyseal sys-t em discussed
earlier. Approximat ely 100, 000 unmyelinat ed f ibers ext end f rom t he supraopt ic and paravent ricular nuclei of t he hypot halamus t o t he f enest rat ed capillary bed of t he neurohy-pophysis. These f ibers convey t w o pept ide hormones: vasopressin (ADH) and oxyt ocin. Vasopressin promot es reabsorpt ion of w at er f rom t he kidney. I n lesions of t he neurohypophysis, urine out put of low specif ic gravit y reaches 10 t o 15 lit ers per day, a condit ion know n as di abetes i nsi pi dus. O xyt ocin st imulat es cont ract ion of smoot h muscles of t he ut erus and promot es eject ion of milk f rom t he lact at ing mammary gland.
Tabl e 19-1. Connections of the Hypothalamus
Pathway Hypothalamohypophyseal tract
Tuberohypophyseal tract
Afferent Efferent
Retinohypothalamic tract
X
Fornix
Stria terminalis
X
X
Supraoptic and paraventric nuclei
X
Arcuate an periventricu nuclei
Ganglion ce of retina
Hippocamp formation, subiculum
X
X
Origin
Mamillary body
Amygdaloid nucleus
Ventral amygdalofugal tract
X
X
Thalamohypothalamic
Amygdaloid nucleus
X
X
X
Lateral hypothalam nucleus
Dorsomedia and midline thalamic nu
Basal forebrain, amygdala, premotor frontal cort brain stem reticular formation (raphe nucl locus ceruleus, nucleus solitarius), spinal cord
Medial forebrain bundle
Preoptic an arcuate nuc
X
Lateral
hypothalam
Inferior mamillary peduncle
X
Dorsal longitudinal fasciculus(of Schütz)
X
Tegmental nuclei of midbrain, ascending sensory pathways
Periaquedu gray matter midbrain
X
Medial hypothalam
Pallidohyphothalamic
X
Lentiform nucleus
Cerebellohypothalamic fibers
X
Deep nucle cerebellum
Hypothalamocerebellar fibers
X
Lateral and posterior hypothalam
Mamillothalamic tract
X
Mamillary body
Mamillotegmental tract
Descending autonomic fibers
Prefrontal-hypothalamic
Hypothalamic-prefrontal
X
X
Mamillary body
X
Paraventric nucleus, lateral hypothalam area, poste hypothalam
Orbitofronta cortex Med prefrontal cortex
X
Posterior hypothalam Tuberal hypothalam Anterior hypothalam
Control of Anterior Pituitary Several t rophic f act ors (hypophysiot ropins, hypot halamic releasing f act ors) are produced in t he hypot halamus and inf luence product ion of hormones in t he ant erior pit uit ary. Trophic f act ors are released int o capillaries of t he median eminence, f rom w hich t hey reach t he ant erior pit uit ary via t he hypophyseal port al circulat ion. I n t he ant erior lobe, t rophic f act ors act on t he appropriat e chromophil cell t o release or inhibit t he appropriat e t rophic hormone. The ant erior pit uit ary t rophic hormones t hen act on t he appropriat e t arget gland. The serum hormone level of t he t arget gland has a f eedback eff ect on hypot halamic t rophic f act ors.
The know n hypot halamic t rophic f act ors include cort icot ropin-releasing f act or (CRF), w hich inf luences product ion of ACTH and bet a-lipot ropin (precursor of ACTH and of endorphins) by t he pit uit ary basophils; t hyrot ropin-releasing f act or (TRF), w hich inf luences secret ion of t hyroid-st imulat ing hormone (TSH) f rom t he basophils; gonadot ropin-releasing f act or (G nRF), w hich inf luences product ion of f ollicle-st imulat ing (FSH)- and lut einizing hormones (LH) f rom t he basophils; grow t h hormone r eleasing f act or (G HRF), w hich inf luences grow t h hormone (somat ost at in, G H) secret ion f rom t he acidophils; melanocyt e-st imulat ing hormone r eleasing f act or (MSHRF), w hich inf luences melanocyt e-st imulat ing hormone (MSH) product ion; prolact in-inhibit ing f act or (PI F), w hich inhibit s product ion of prolact in f rom t he acidophils; somat ic inhibit ing r eleasing f act or (SI RF), also know n as somat ost at in (SS); grow t h hormone i nhibit ing f act or (G HI F) or somat ot ropin release i nhibit ing f act or (SRI F), w hich inhibit s release of G H and t hyrot ropin (TSH); and melanocyt e-st imulat ing hormone release-inhibit ing f act or (MI F), w hich inhibit s t he release of MSH. Secret ion of G HRF and G HI F is st imulat ed by dopamine, norepinephrine, and serot onin. The PI F is dopamine.
Autonomic Regulation The hypot halamus is know n t o cont rol brain st em and spinal cord aut onomic cent ers. St imulat ion or ablat ion of t he hypot halamus inf luences cardiovascular, respirat ory, and gast roint est inal f unct ions. Aut onomic inf luences are mediat ed via t he dorsal longit udinal f asciculus (of Schüt z) and t he mamillot egment al t ract . Alt hough def init e delineat ion w it hin t he hypot halamus of sympat het ic and parasympat het ic cent ers is not f easible, it is generally held t hat t he rost ral and medial hypot halamus is concerned w it h parasympat het ic cont rol, w hereas t he caudal and lat eral hypot halamus is concerned w it h sympat het ic cont rol mechanisms. St imulat ion of t he rost ral and medial hypot halamus (preopt ic and supraopt ic areas) result s in parasympat het ic act ivat ion, charact erized by a slow ing of heart rat e, decrease in blood pressure, vasodilat at ion, pupillary const rict ion, increased sw eat ing, and in creased mot ilit y and secret ions of t he aliment ary t ract . I n cont rast , st imulat ion of t he post erior and lat eral hypot halamus (part icularly t he post erior) result s in sympat het ic act ivat ion, charact erized by an increase in heart rat e and blood pressure, vasoconst rict ion, pupillary dilat at ion, piloerect ion, decreased mot ilit y and secret ion of t he aliment ary t ract , bladder inhibit ion, and height ened somat ic react ions of shivering and running.
Temperature Regulation Some regions of t he hypot halamus cont ain t hermal recept ors t hat are sensit ive t o changes in t he t emperat ure of blood perf using t hese regions. Ant erior regions of t he hypot halamus are sensit ive t o a rise in blood t emperat ure and t rigger
mechanisms f or heat dissipat ion, w hich include sw eat ing and cut aneous vascular dilat at ion in humans. Bilat eral damage t o t his region, t hrough surgery or by t umors or vascular lesions, result s in elevat ion of body t emperat ure (hypert hermia). I n cont rast , t he post erior hypot halamic region is sensit ive t o t he low ering of blood t emperat ure and t riggers t he mechanisms f or heat conservat ion, w hich include cessat ion of sw eat ing, shivering, and vascular const rict ion. Bilat eral damage t o t his region result s in poikilot hermia, in w hich body t emperat ure f luct uat es w it h environment al t emperat ure.
Emotional Behavior The hypot halamus is a major component of t he cent ral aut onomic nervous syst em and as such plays a role in emot ional behavior. Lesions of t he vent romedial hypot halamic nuclei in animals are associat ed w it h a rage react ion, charact erized by hissing, snarling, bit ing, piloerect ion, arching of t he back, and pupillary dilat at ion. I n cont rast , st imulat ion of lat eral regions of t he ant erior hypot halamus elicit s a f light response. St imulat ion of some hypot halamic regions elicit s a pleasurable response. St imulat ion of ot her regions produces unpleasant responses. The role of t he hypot halamus in behavior and emot ion is int imat ely relat ed t o t hat of t he limbic syst em. The connect ion bet w een limbic pref ront al cort ex and post erior hypot halamus is an import ant link f or aut onomic response t o emot ion.
Feeding Behavior As det ailed earlier, bilat eral lesions in t he vent romedial nucleus elicit hyperphagia (excessive f eeding), w hereas similar lesions in t he lat eral hypot halamic nucleus produce loss of hunger, suggest ing t he presence of a sat iet y cent er and f eeding cent er, respect ively, in t hese regions. The lat eral hypot halamus has recent ly been f ound t o cont ain orexin/ hypocret in pept ide cont aining neurons. Cent ral administ rat ion of orexin/ hypocret in st imulat es f ood int ake. O rexin/ hypocret in neurons in t he lat eral hypot halamus inhibit anorexinergic and excit e orexinergic neurons in t he arcuat e nucleus of t he hypot halamus. O rexin/ hypocret in neu-rons also project t o vent romedial and paravent ricular nuclei of t he hypot halamus, st ruct ures know n t o int egrat e f eeding.
Drinking and Thirst I n addit ion t o t he cont rol of body w at er by ADH, st imulat ion of t he lat eral and ant erior regions of t he hypot halamus elicit s drinking behavior t hat persist s despit e overhydrat ion. Lesions of t he same area abolish t hirst .
Sleep and Wakefulness The hypot halamus is believed t o play a role in t he daily sleep-w akef ulness cycle.
A sleep cent er is proposed t o be in t he ant erior part of t he hypot halamus and a w aking cent er in t he post erior part . The orexin/ hypocret in syst em in t he lat eral hypot halamus is t he major excit at ory neuromodulat ory syst em t hat cont rols act ivit ies of monoaminergic (dopamine, norepinephrine, serot onin, hist amine) and cholinergic syst ems t hat cont rol vigilance st at es. Lesions in t he orexin/ hypocret in syst em are associat ed w it h a st at e of irresist ible sleep (narcolepsy).
Circadian Rhythm Through t he connect ions of t he suprachiasmat ic nucleus w it h t he ret ina and brain regions relat ed t o circadian rhyt hm, t he hypot halamus plays an import ant role as an int ernal clock regulat ing cyclic variat ions of a number of bodily f unct ions such as t emperat ure cycle, sleep-w ake cycle, and hormonal cyclic variat ions. The suprachiasmat ic nucleus serves t he f unct ion of an endogenous pacemaker. I t regulat es secret ion of melat onin by t he pineal gland. Disrupt ion of release of melat onin is part ially responsible f or t he phenomenon of jet lag.
Memory Through it s connect ions w it h t he hippocampal f ormat ion and ant erior t halamic nucleus, t he mamillary body of t he hypot halamus plays a role in memory.
Sexual Arousal Several brain areas have been show n by f MRI t o be associat ed w it h sexual arousal in humans. These include t he ant erior cingulat e, medial pref ront al, orbit of ront al, insular and occipit ot emporal cort ices, as w ell as t he amygdala, vent ral st riat um, t halamus, and hypot halamus. All of t hese areas have reciprocal connect ions w it h t he hypot halamus. f MRI act ivat ion during sexual arousal is similar in all areas except t he preopt ic region of t he hypot halamus w here act ivat ion is signif icant ly great er in males. This gender diff erence in act ivat ion of t he hypot halamus has been correlat ed w it h t he great er sexual arousal generally experienced by men in response t o erot ic st imuli, and w it h t he larger volume of t he medial preopt ic nucleus (t he sexually dimorphic nucleus) in young males compared t o young f emales. Lesions in t he medial preopt ic area have delet erious eff ect on copulat ion in males, w hile elect rical st imulat ion of t his area has f acilit at ory eff ect on t his biological f unct ion.
BLOOD SUPPLY The preopt ic and supraopt ic regions, as w ell as t he rost ral part of t he lat eral hypot halamus, are supplied by perf orat ing branches f rom t he ant erior communicat ing and ant erior cerebral (A-1 segment ) art eries. The t uberal and mamillary regions, as w ell as t he middle and post erior part s of t he lat eral hypot halamus, are
supplied by perf orat ing branches f rom t he post erior communicat ing and post erior cerebral (P-1 segment ) art eries.
TERM INOLOGY WArcuate (Latin arcuatus, b ow-shaped ) . The arcuat e nucleus of t he hypot halamus has an arcuat e shape in coronal sect ions. Diabetes insipidus (G reek di abetes, a syphon ). A condit ion of excessive product ion of urine f rom def iciency of t he ant idiuret ic hormone. The condit ion w as dist inguished f rom diabet es mellit us by Thomas Willis, t he English physician in 1674. The relat ion of t he condit ion t o lesions in t he neurohypophysis is at t ribut ed t o t he G erman physiologist Alf red Frank. Diabetes mellitus (G reek di abetes, a syphon Latin mel l i tus, h oney sweet ). A disorder of carbohydrat e met abolism w it h high levels of glucose in blood and urine. Thomas Willis in 1674 diff erent iat ed sw eet urine (diabet es mellit us) f rom clear, insipid urine (diabet es insipidus). Fornix (Latin a rch ). The f ornix is an archlike cerebral st ruct ure t hat connect s t he hippocampal f ormat ion w it h t he mamillary body. The f ornix w as not ed by G alen and described by Andreas Vesalius, t he sixt eent h-cent ury Belgian anat omist . Thomas Willis int roduced t he name f orni x cerebri . Hypocretin. A hypot halamic neuropept ide discovered in 1998. Like orexin, it increases f ood int ake. The name hypocret in derives f rom it s hypot halamic origin and it s similarit y t o t he gut hormone secret in. Hypophysis (G reek hypo, u nder phyei n, t o grow ). Anyt hing grow ing under or beneat h. The hypophysis (pit uit ary gland) is under t he brain. Infundibulum (Latin f unnel ). Andreas Vesalius, t he Belgian anat omist , used t his t erm t o describe t he at t achment of t he pit uit ary gland t o t he brain. O rexin (G reek, orexi s a ppetite ) . A hypot halamic neuropept ide discovered in 1998. Cent ral administ rat ion of orexin pot ent ly increases f ood int ake. Pituitary (Latin pi tui ta, p hlegm or mucus ). Pit uit ary gland. Jacob Berengarius, t he I t alian anat omist and surgeon, not ed t he presence of t he pit uit ary gland in 1524. Andreas Vesalius, t he Belgian anat omist , called it g landula pit uit am cerebri excipiens and t hought t hat t he gland secret ed mucus int o t he nose, an opinion held unt il t he sevent eent h cent ury.
Poikilothermia (G reek poi ki l os, v aried therme, h eat ) . Variat ion of body t emperat ure w it h environment al t emperat ure. Polydipsia (G reek pol ys, m any ; di psa, t hi rst ) . Chronic excessive t hirst as in diabet es insipidus and mellit us. Polyuria (G reek pol ys, m any ouron, u rine ) . The passage of a very large volume of urine, charact erist ic of diabet es. Satiety (Latin sati s, s ufficient ety, state or condi ti on of ). Suff iciency or sat isf act ion or grat if icat ion of t hirst or appet it e. Vicq d'Azyr, Felix (1748 1 794). French anat omist and physician t o Q ueen Marie Ant oinet t e w ho described t he mamillot halamic t ract (t ract of Vicq d'Azyr) in 1781, alt hough his observat ion w as not published unt il 1805.
SUGGESTED READINGS Braak H, Braak E: The hypot halamus of t he human adult : Chiasmat ic region. Anat Embryol 1987; 175: 315 3 30. Diet richs E et al: Hypot halamocerebellar and cerebellohypot halamic project ion circuit s f or regulat ing nonsomat ic cerebellar act ivit y? Hi stol Hi stopathol 1994; 9: 603 6 14. Hat t on G L: Emerging concept s of st ruct ure-f unct ion dynamics in adult brain: The hypot halamo-neurohypophyseal syst em. Prog Neurobi ol 1990; 34: 337 5 04. Holst ege G : Some anat omical observat ions on t he project ions f rom t he hypot halamus t o brain st em and spinal cord: An HRP and aut oradiographic t racing st udy in t he cat . J Comp Neurol 1987; 260: 98 1 26. Hungs M, Mignot E: Hypocret in/ orexin, sleep and narcolepsy. Bi oessays 2001; 23: 397 4 08. Karama S et al: Areas of brain act ivat ion in males and f emales during view ing of erot ic f ilm excerpt s. Hum Brai n Mappi ng 2002; 16: 1 1 3. Kordon C: Neural mechanisms involved in pit uit ary cont rol. Neurochem Int 1985; 7: 917 9 25. Meist er B, Hakansson ML: Lept in recept ors in hypot halamus and
circumvent ricular organ. Cl i n Expt Pharmac Physi ol 2001; 28: 610 6 17. Naut a WJH, Haymaker W: Hypot halamic nuclei and f iber connect ions. I n Haymaker W et al (eds): The Hypothal amus. Springf ield, I L, Charles C Thomas, 1969: 136. Nishino S: The hypocret in/ orexin syst em in healt h and disease. Bi ol Psychi atry 2003; 54: 87 9 5. Pickard G E, Silverman AJ: Direct ret inal project ions t o t he hypot halamus, pirif orm cort ex, and accessory opt ic nuclei in t he golden hamst er as demonst rat ed by a sensit ive ant erograde horseradish peroxidase t echnique. J Comp Neurol 1981; 196: 155 1 72. Raf ols JA et al: A G olgi st udy of t he monkey paravent ricular nucleus: Neuronal t ypes, aff erent and eff erent f ibers. J Comp Neurol 1987; 257: 595 6 13. Remple-Clow er NL, Barbas H: Topographic organizat ion of connect ions bet w een t he hypot halamus and pref ront al cort ex in t he rhesus monkey. J Comp Neurol 1998; 398: 393 4 19. Saper CB et al: Direct hypot halamo-aut onomic connect ions. Brai n Res 1976: 117: 305 3 12. Sw aab DF et al: St ruct ural and f unct ional sex diff erences in t he human hypot halamus. Horm Behav 2001; 40: 93 9 8. Sw anson LW: The neuroanat omy revolut ion of t he 1970s and t he hypot halamus. Brai n Res Bul l 1999; 50: 397.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 20 - Hypothalam us : C linic al C or r elates
20 Hypothalamus: Clinical Correlates
Disorders of Water Balance Diabetes Insipidus Syndrome of Inappropriate Secretion of Adh (Siadh) Disorders of T herm oregulation Hypothermia Hyperthermia Poikilothermia Disorders of Caloric Balance Diencephalic Syndrome of Infancy (Russell Syndrome, Batten-Russell-Collier Disease) Fröhlich Syndrome (Babinski-Fröhlich Syndrome, Dystrophia-Adiposogenitalis) Disorders of Em otional Behavior Disorders of Sleep Kleine-Levin Syndrome Disorders of Mem ory KEY CONCEPTS A number of clinical signs and symptoms have been associated with lesions of the hypothalamus. They are related to disorders of water balance, temperature regulation, caloric balance, alertness and sleep, memory, and emotional behavior.
Two syndromes are related to disorders of water balance: diabetes insipidus and the syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH). The lesion in the former is in the supraoptic and paraventricular nuclei or the supraopticohypophyseal tract. The lesion in SIADH involves hypothalamic osmoreceptors in the re-gion of the supraoptic and paraventricular nuclei. Disturbances in hypothalamic thermoregulation may result in hypothermia, hyperthermia, or poikilothermia related to pathology in different regions of the hypothalamus. In general, chronic hypothermia and poikilothermia are related to posterior hypothalamic pathology, whereas sustained hyperthermia is related to pathology in the anterior hypothalamus. Disturbances in hypothalamic caloric balance are associated with two syndromes: emaciation (diencephalic syndrome) and obesity (Fröhlich syndrome). The former is related to pathology in the anterior hypothalamus or its connections; the latter is related to pathology in the ventromedial nucleus. Disturbances in sleep are associated with hypersomnolence (posterior hypothalamus), insomnia (anterior hypothalamus), and the Kleine-Levin syndrome. Disturbances in episodic memory are associated with lesions in the mamillary body or fornix.
A large number of clinical signs and sympt oms have been report ed in associat ion w it h hypot halamic dysf unct ion. They include dist urbances in (1)
w at er balance, (2) t hermoregulat ion, (3) caloric balance, (4) emot ional behavior, (5) sleep, and (6) memory.
DISORDERS OF WATER BALANCE Diabetes Insipidus Diabet es insipidus result s f rom lesions t hat dest roy t he majorit y of neurons of t he supraopt ic and paravent ricular nuclei (sit es of ADH secret ion) or t hat int errupt t he supraopt ic-neurohypophyseal t ract . Aff ect ed pat ient s pass large volumes of dilut e urine (polyuria). Because t he t hirst mechanism is int act , pat ient s drink large amount s of f luid (polydipsia). Such pat ient s drink over 10 lit ers of w at er per day and excret e a similar amount of urine. I n cont rast t o diabet es mellit us, values f or glucose in blood and urine are normal in diabet es insipidus. The t w o t ypes of diabet es w ere diff erent iat ed by Thomas Willis in 1674. The relat ion of diabet es insipidus t o t he neurohypophysis w as recognized by t he G erman physiologist Alf red Frank. Diabet es insipidus can be caused by a variet y of disease processes, including hypot halamic t umors, t rauma, st orage diseases, and inf ect ion. A f amilial variet y of diabet es insipidus may be due t o a def ect in t he neurophysin gene precluding normal product ion of ADH. Treat ment of diabet es insipidus consist s of int ranasal administ rat ion of a long-act ing vasopressin analogue, desmopressin acet at e (des-amino-D-arginine vasopressin, DDAVP).
Syndrome of Inappropriate Secretion of ADH (SIADH) This syndrome is due t o lesions in t he region of t he supraopt ic and paravent ricular nuclei t hat impair hypot halamic osmorecept ors and t hat result in elevat ed ADH release. The syndrome is charact erized by (1) hyponat remia, (2) low serum osmolarit y, (3) normal renal excret ion of sodium, (4) elevat ed urine osmolarit y, and (5) absence of volume deplet ion.
DISORDERS OF THERM OREGULATION Hypothermia Hypot hermia of hypot halamic origin may be chronic or periodic (episodic). Chronic hypot hermia is associat ed w it h post erior hypot halamic injury f rom t rauma, t umor, inf ect ion, or met abolic or vascular disease. Episodic hypot hermia (Shapiro syndrome, diencephalic epilepsy) is charact erized by spont aneous episodic hypot hermia last ing minut es t o days occurring at variable int ervals (daily or decades). The hypot hermia is usually associat ed w it h polydipsia, polyuria, hypona-t remia, and aut onomic paroxysms charact erized by hypert ension, t achycardia, and diaphoresis. The condit ion may respond t o ant iepilept ic drug t herapy. The lesion in t he hypot halamus may involve t he arcuat e nucleus and t he premamillary area. Agenesis of t he corpus callosum is
of t en present .
Hyperthermia Hypert hermia of hypot halamic origin may be sust ained or episodic (periodic). Sust ained hypert hermia usually is associat ed w it h head t rauma or w it h surgery adjacent t o t he ant erior hypot halamus. I t usually last s 1 t o 2 days but may last up t o 2 w eeks. Episodic hypert hermia has been associat ed w it h lesions in t he vent romedial hypot halamus. A reverse Shapiro syndrome has been described, charact erized by periodic hypert hermia and agenesis of t he corpus callosum.
Poikilothermia Fluct uat ions in body t emperat ure w it h changes in environmen-t al t emperat ure are associat ed w it h bilat eral post erior hypot halamic lesions.
DISORDERS OF CALORIC BALANCE Diencephalic Syndrome of Infancy (Russell Syndrome, Batten-Russell-Collier Disease) This condit ion is charact erized by progressive emaciat ion during t he f irst year of lif e despit e a reasonable f ood int ake. Despit e t heir emaciat ion, such children are charact erist ically happy and act ive. O t her associat ed clinical signs include poor t emperat ure regulat ion, vomit ing, and nyst agmus. G row t h hormone may be normal or elevat ed. The et iology of t his syndrome is usually a slow ly grow ing t umor of t he ant erior hypot halamus. O t her lesions int errupt ing project ions f rom or t o t he ant erior hypot halamus can produce t he syndrome. The syndrome w as best described by A. Russell in 1951.
Fröhlich Syndrome (Babinski-Fröhlich Syndrome, Dystrophia-Adiposogenitalis) Fröhlich syndrome is charact erized by obesit y, genit al hypoplasia, and st unt ed grow t h as a result of hypot halamic or pit uit ary lesion. O besit y in t his syndrome is at t ribut ed t o damage t o t he vent romedial nucleus of t he hypot halamus (sat iet y cent er) and hypogonadism t o t he involvement of t he adjacent inf undibulum. Alt hough t he syndrome is at t ribut ed t o a report by Fröhlich in 1901, t he main f eat ures of t he syndrome had been described in 1900 by Babinski and in 1840 by t he G erman physician Berhard Mohr.
DISORDERS OF EM OTIONAL BEHAVIOR Lesions in t he vent romedial region of t he hypot halamus have been associat ed w it h rage, w hereas lesions in t he post erior hypot halamus have been associat ed w it h f ear and apat hy. St imulat ion of t he lat eral regions of t he ant erior
hypot halamus elicit s a f light response. Pleasurable as w ell as unpleasant responses have been elicit ed f rom hypot halamic st imulat ion. The reciprocal connect ions bet w een t he limbic pref ront al cort ex and t he hypot halamus are an import ant link f or aut onomic response t o emot ion.
DISORDERS OF SLEEP Sleep dist urbances associat ed w it h hypot halamic lesions w ere at t ribut ed previously t o concomit ant involvement of t he ascending ret icular pat hw ays. Accumulat ing evidence, how ever, point s t o t he exist ence of a w aking cent er in t he post erior hypot halamus and a sleep cent er in t he ant erior hypot halamus. Lesions of t he post erior hypot halamus provoke let hargy and hypersomnia, w hereas lesions in t he ant erior hypot halamus cause insomnia. The lat eral hypot halamus cont ains a major excit at ory neuromodulat ory syst em (orexin/ hypocret in) w hich cont rols act ivit ies of monoaminergic and cholinergic syst ems t hat cont rol vigilance. Lesions in t he orexin/ hypocret in syst em are associat ed w it h a st at e of irresist ible sleep know n as narcolepsy. Tabl e 20-1. Hypothalamic Disorder
Hypothalam ic function
Hypothalam ic disorders
Site of pathology
W ater balance
Diabetes insipidus
Supraoptic and paraventricular nuclei
Syndrome of inappropriate secretion of antidiuretic hormone
Supraoptic and paraventricular nuclei or neighborhood
Hypothermia Chronic
Posterior hypothalamus
Episodic
Arcuate nucleus, premamillary area
Thermoregulation Hyperthermia
Caloric balance
Emotional behavior
Sleep
Sustained
Anterior hypothalamus
Episodic
Ventromedial hypothalamus
Poikilothermia
Posterior hypothalamus
Diencephalic syndrome of infancy Fröhlich syndrome
Anterior hypothalamus Ventromedial nucleus, infundibulum
Rage Fear, apathy
Ventromedial nucleus Posterior hypothalamus
Hypersomnolence Insomnia
Posterior hypothalamus Anterior hypothalamus
Loss of episodic
Mamillary
Memory
memory
bodies, fornix
Kleine-Levin Syndrome Hypot halamic lesions have been associat ed w it h Kleine-Levin syndrome w hich is charact erized by episodic compulsive eat ing (bulimia), hypersomnolence, and hypersexualit y in adolescent males and, rarely, in f emales. A similar syndrome occurs w it h lesions in t he medial t halamus. Each episode last s days t o w eeks at int ervals of 3 t o 6 mont hs bet w een episodes. The episodes decrease in f requency w it h age and usually disappear by t he f ourt h decade. Some evidence indicat es t hat t he dopaminergic t one of t he hypot halamus is reduced during t he sympt omat ic phase of t he syndrome. Alt hough credit is given t o t he G erman neuropsychiat rist Kleine and t he American neurologist Levin f or describing t he syndrome in 1925 and 1929, a similar syndrome of episodic hypersomnolence and morbid hunger w as described by Ant imoff in 1898.
DISORDERS OF M EM ORY Hypot halamic lesions in t he post erior hypot halamus involving t he mamillary bodies or t he f ornix are associat ed w it h inabilit y t o est ablish (encode) new memories f or personally experienced, cont ext - and t ime-specif ic event s (episodic memory) such as t he memory of eat ing a specif ic dish at a specif ic rest aurant . The connect ions of t he mamillary bodies w it h t he hippocampus (via t he f ornix) and w it h t he ant erior t halamic nucleus (via t he mamillot halamic t ract ) make t hem crucial t o t he process of acquisit ion of recent memory. The diff erent hypot halamic disorders discussed herein and corresponding sit es of hypot halamic pat hology are summarized in Table 20-1.
TERM INOLOGY Bulimia (G reek bous, o x ; l i mos, h unger ) . A disorder of eat ing occurring predominant ly in adolescent f emales, charact erized by morbid hunger and binge eat ing t hat cont inue unt il t erminat ed by abdominal pain, vomit ing, or sleep. Diabetes insipidus (G reek di abetes, a syphon ). A condit ion of excessive product ion of urine f rom def iciency of t he ant idiuret ic hormone. The condit ion w as dist inguished f rom diabet es mellit us by Thomas Willis, t he English physician in 1674. The relat ion of t he condit ion t o lesions in t he neurohypophysis is at t ribut ed t o t he G erman physiologist Alf red Frank. Fröhlich syndrome.
A hypot halamic syndrome charact erized by obesit y, genit al hypoplasia, and st unt ed grow t h. Named af t er Alf red Fröhlich (1871 1 953), t he Viennese neurologist and pharmacologist . Also know n as Babi nski -Fröhl i ch syndrome. Kleine-Levin syndrome. A hypot halamic syndrome occurring in adolescent males and, less f requent ly, in f emales, charact erized by episodic hypersomnolence, hypersexualit y, and compulsive eat ing. The syndrome w as described by Willi Kleine, t he G erman neuropsychiat rist , in 1925. Max Levin, t he American neurologist , report ed anot her case in 1929 and summarized t he f eat ures of t he syndrome in 1936. Poikilothermia (G reek poi ki l os, v aried ; therme, h eat ) . Variat ion of body t emperat ure w it h environment al t emperat ure. Polydipsia (G reek pol ys, m any ; di psa, t hirst ) . Chronic excessive t hirst as in diabet es insipidus and mellit us. Polyuria (G reek pol ys, m any ; ouron, u rine ) . The passage of a very large volume of urine, charact erist ic of diabet es. Shapiro syndrome. A hypot halamic syndrome charact erized by recurrent hypot hermia and agenesis of t he corpus callosum. Named af t er W. R. Shapiro, w ho described t he syndrome in 1969.
SUGGESTED READINGS Arroyo HA et al: A syndrome of hyperhidrosis, hypot hermia, and bradycardia possibly due t o cent ral monoaminergic dysf unct ion. Neurol ogy 1990; 40: 556 5 57. Bart t er FC, Schw art z WB: The syndrome of inappropriat e secret ion of ant idiuret ic hormone. Am J Med 1967; 42: 790 8 06. Bauer HG : Endocrine and ot her clinical manif est at ions of hypot halamic disease. J Cl i n Endocri nol Metab 1954; 14: 13 3 1. Burr I M et al: Diencephalic syndrome revisit ed. J Pedi atr 1976; 88: 439 4 44. Chesson AL et al: Neuroendocrine evaluat ion in Kleine-Levin syndrome: Evidence of reduced dopaminergic t one during periods of hypersomnolence. Sl eep 1991; 14: 226 2 32.
Culebras A: Neuroanat omic and neurologic correlat es of sleep dist urbances. Neurol ogy 1992; 42(suppl 6): 19 2 7.
G aff an EA et al: Amnesia f ollow ing damage t o t he lef t f ornix and t o ot her sit es. Brai n 1991; 114: 1297 1 313. G amst orp I et al: Diencephalic syndrome of inf ancy. J Pedi atr 1967; 70: 383 3 90. G illberg C: Kleine-Levin syndrome: Unrecognized diagnosis in adolescent psychiat ry. J Am Acad Chi l d Adol esc Psychi atry 1987; 26: 793 7 94. Harris AS: Clinical experience w it h desmopressin: Eff icacy and saf et y in cent ral diabet es insipidus and ot her condit ions. J Pedi atr 1989; 114: 711 7 18. Hirayama K et al: Reverse Shapiro's syndrome. A case of agenesis of corpus callosum associat ed w it h periodic hypert hermia. Arch Neurol 1994; 51: 494 4 96. LeWit t PA et al: Episodic hyperhidrosis, hypot hermia, and agenesis of t he corpus callosum. Neurol ogy 1983; 33: 1122 1129. Maghnie M et al: Correlat ion bet w een magnet ic resonance imaging of post erior pit uit ary and neurohypophyseal f unct ion in children w it h diabet es insipidus. J Cl i n Endocri nol Metab 1992; 74: 795 8 00. Perry RJ, Hodges JR: Spect rum of memory dysf unct ion in degenerat ive disease. Curr O pi n Neurol 1996; 9: 281 2 85. Reeves AG , Plum F: Hyperphagia, rage, and dement ia accompanying a vent romedial hypot halamic neoplasm. Arch Neurol 1969; 20: 616 6 24. Russell A: A diencephalic syndrome of emaciat ion in inf ancy and childhood. Arch Di s Chi l d 1951; 26: 274. Shapiro WR et al: Spont aneous recurrent hypot hermia accompanying agenesis of t he corpus callosum. Brai n 1969; 92: 423 4 36. Shapiro WR et al: Spont aneous recurrent hypot hermia accompanying agenesis of t he corpus callosumk Brai n 1969; 92: 423 4 36.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 21 - Lim bic S ys tem
21 Limbic System
Definition of Term s: Lim bic Lobe, Lim bic System , and Rhinencephalon Rhinencephalon (Sm ell Brain) Olfactory Nerve Rootlets Olfactory Bulb Olfactory Tract Olfactory Striae Olfactory Cortex Lim bic Lobe T he Papez Circuit Lim bic System Hippocampal Formation Fornix Entorhinal-Hippocampal Circuitry Amygdala Septal Area Overview of the Lim bic System KEY CONCEPTS The term limbic lobe refers to the structures that form a limbus (ring or border) around the brain stem. These structures include the subcallosal gyrus,
cingulate gyrus, isthmus, parahippocampal gyrus, and uncus. The term limbic system refers to the limbic lobe and the structures connected to it. Limbic system structures play important roles in emotional behavior, memory, homeostatic responses, sexual behavior, and motivation. The term hippocampal formation refers to the hippocampus, dentate gyrus, and subiculum. The bulk of extrinsic input to the hippocampal formation comes from the entorhinal area and the septal area. The major targets of the hippocampal formation's output are the entorhinal cortex, the hypothalamus, and the septal area. The entorhinal area is reciprocally connected with the hippocampus and serves as a gateway between the cerebral cortex and the hippocampus. The hippocampus plays a role in declarative or associative memory, attention and alertness, and behavioral, endocrine, and visceral functions. Output from the amygdala is carried in two pathways: the stria terminalis (dorsal amygdalofugal pathway) and the ventral amygdalofugal pathway (ventrofugal bundle). The amygdala plays an important role in a variety of functions, including autonomic and orienting responses, emotional behavior, food intake, arousal, sexual activity, and motor activity. The term septal area refers to the septum pellucidum and the septum verum. The septum pellucidum is a thin glial partition between the lateral
ventricles; the septum verum is a group of basal nuclei that includes the septal nuclei. Reciprocal connections with the hippocampus (via the fornix) constitute the major connection of the septal area. Other connections include those with the amygdala, hypothalamus, thalamus, brain stem, and cingulate gyrus. The septal area plays an important role in emotional behavior, learning, reward, autonomic responses, drinking and feeding, and sexual behavior. The limbic system plays a major role in integrating exteroceptive and interoceptive information by serving as a link between cortical sensory association areas, the subcortical autonomic and endocrine centers, and the prefrontal association cortex. It thus mediates the effects of emotion on motor function.
DEFINITION OF TERM S: LIM BIC LOBE, LIM BIC SYSTEM , AND RHINENCEPHALON The concept of t he limbic syst em is derived f rom t he limbic lobe. The t erm l e grande l obe l i mbi que (limbic lobe), coined by t he French ant hropologist , anat omist , and surgeon Pierre-Paul Broca in 1878, ref ers t o a number of st ruct ures on t he medial and basal surf aces of t he hemisphere t hat f orm a limbus (border or ring) around t he brain st em. Broca w as possibly unaw are t hat Thomas Willis (of Circle of Willis f ame) had designat ed t he cort ical border encircling t he brain st em as t he cerebri limbus in 1664, 200 years earlier. The limbic lobe and all t he st ruct ures connect ed t o it const it ut e t he limbic syst em, w hich plays a major role in visceral f unct ion, emot ional behavior, and memory. Because of t he large size of t he limbic lobe in phylogenet ically low er animals, Broca post ulat ed t hat it might have an olf act ory f unct ion; hence, t he t erms l i mbi c l obe and smel l brai n (rhinencephalon) w ere used synonymously. I n humans, t he
limbic lobe has very lit t le if any primary olf act ory f unct ion. The rhinencephalon, by cont rast , is primarily concerned w it h olf act ion but has some reciprocal relat ionships w it h part s of ot her limbic syst em regions.
RHINENCEPHALON (SM ELL BRAIN) The rhinencephalon (Figures 21-1 and 21-2) consist s of t he f ollow ing st ruct ures: 1. O lf act ory nerve root let s 2. O lf act ory bulb 3. O lf act ory t ract 4. O lf act ory st riae 5. Primary olf act ory cort ex
Olfactory Nerve Rootlets The olf act ory nerve is composed of unmyelinat ed t hin processes (root let s) of t he olf act ory hair cells (recept ors) in t he nasal mucosa. Fascicles of t he olf act ory nerve pierce t he cribrif orm plat e of t he et hmoid bone, ent er t he cranial cavit y, and t erminat e on neurons in t he olf act ory bulb.
Olfactory Bulb The olf act ory bulb is t he main relay st at ion in t he olf act ory pat hw ays.
Fi gure 21-1. Vent ral view of t he brain show ing component s of t he rhinencephalon.
Fi gure 21-2. Schemat ic diagram of olf act ory pat hw ays.
A. LAM INATION AND CELL TYPES I n hist ologic sect ions (Figure 21-3), t he olf act ory bulb appears t o be laminat ed int o t he f ollow ing layers: 1. The olf act ory nerve layer is composed of incoming olf act ory nerve f ibers. 2. I n t he glomerular layer synapt ic f ormat ions occur bet w een t he olf act ory nerve axons and t he dendrit es of olf act ory bulb neurons (mit ral and t uf t ed neurons). 3. The ext ernal plexif orm layer consist s of t uf t ed neurons, some granule cells, and a f ew mit ral cells w it h t heir processes. 4. The mit ral cell layer is composed of large neurons (mit ral neurons). 5. The granule layer is composed of small granule neurons and processes of granule and mit ral cells; it also cont ains incoming f ibers f rom ot her cort ical regions. The mit ral cells and t uf t ed cells are t he principal neurons of t he olf act ory bulb.
Their dendrit es est ablish synapt ic relat ion-ships w it h olf act ory nerve f ibers w it hin t he glomeruli. The granule cells are t he int rinsic neurons of t he olf act ory bulb. These cells have vert ically orient ed dendrit es but no axon and exert t heir act ion on ot her cells solely by means of dendrit es. Anot her t ype of int rinsic neuron, t he short axon neuron, is f ound in t he glomerular layer (periglomerular short axon neu-ron) and t he granular layer. The olf act ory bulb receives f ibers (input ) f rom t he f ollow ing sources: 1. O lf act ory hair cells in t he nasal mucosa 2. Cont ralat eral olf act ory bulb 3. Primary olf act ory cort ex 4. Diagonal band of Broca 5. Ant erior olf act ory nucleus The out put f rom t he olf act ory bulb is composed of axons of mit ral cells and t uf t ed cells (principal neurons), w hich project t o t he f ollow ing areas: 1. Cont ralat eral olf act ory bulb 2. Subcallosal gyrus 3. Ant erior perf orat ed subst ance 4. Primary olf act ory cort ex 5. Ant erior ent orhinal cort ex
Olfactory Tract The olf act ory t ract is t he out f low pat hw ay of t he olf act ory bulb. I t is composed of t he axons of principal neurons (mit ral and t uf t ed cells) of t he olf act ory bulb and cent rif ugal axons originat ing f rom cent ral brain regions. The olf act ory t ract also cont ains t he scat t ered neurons of t he ant erior olf act ory nucleus, t he axons of w hich t ravel in t he olf act ory t ract , cross in t he ant erior commissure, and project on t he cont ralat eral ant erior olf act ory nucleus and t he olf act ory bulb. At it s caudal ext remit y, just ant erior t o t he ant erior perf orat ed subst ance, t he olf act ory t ract divides int o t he olf act ory st riae.
Olfactory Striae At it s caudal ext remit y, just rost ral t o t he ant erior perf orat ed subst ance, t he olf act ory t ract divides int o t hree st riae:
1. Lat eral olf act ory st ria 2. Medial olf act ory st ria 3. I nt ermediat e olf act ory st ria. Each st ria is covered by a t hin layer of gray mat t er know n as an olf act ory gyrus.
Fi gure 21-3. Schemat ic diagram of olf act ory bulb show ing laminae and t ypes of cells.
The lat eral olf act ory st ria project s t o t he primary olf act ory cort ex in t he t emporal lobe. The medial olf act ory st ria project s on t he medial olf act ory area, w hich also is know n as t he sept al area, on t he medial surf ace of t he f ront al lobe, vent ral t o t he genu and rost rum of t he corpus callosum and ant erior t o t he lamina t erminalis. The medial olf act ory area is closely relat ed t o t he limbic syst em and t hus is concerned w it h emot ional responses elicit ed by olf act ory st imuli. I t does not play a role in t he percept ion of olf act ory st imuli. The medial and int ermediat e st riae are poorly developed in humans. The int ermediat e st ria blends w it h t he ant erior perf orat ed subst ance. The t hin cort ex at t his sit e is designat ed t he int ermediat e olf act ory area. The t hree areas of olf act ory cort ex are int erconnect ed by t he diagonal band of Broca, a bundle of subcort ical f ibers in f ront of t he opt ic t ract .
Olfactory Cortex
The olf act ory cort ex is locat ed w it hin t he t emporal lobe and is composed of t he pyrif orm cort ex, t he periamygdaloid area, and part of t he ent orhinal area. The pyrif orm cort ex is t he region on each side of and beneat h t he lat eral olf act ory st ria; hence, it is also called t he lat eral olf act ory gyrus. The periamygdaloid area is dorsal and rost ral t o t he amygdaloid nuclear complex. The pyrif orm cort ex and t he periamygdaloid area const it ut e t he primary olf act ory cort ex. The ent orhinal area, w hich is sit uat ed in t he rost ral part of t he parahippocampal gyrus, corresponds t o Brodmann's area 28. I t const it ut es t he secondary olf act ory cort ex. The olf act ory cort ex is relat ively large in some animals, such as t he rabbit , but in humans it occupies a small area. The primary olf act ory cort ex in humans is concerned w it h t he conscious percept ion of olf act ory st imuli. I n cont rast t o all ot her primary sensory cort ices (vision, audit ion, t ast e, and somat ic sensibilit y), t he primary olf act ory cort ex is unique in t hat aff erent f ibers f rom t he recept ors reach it direct ly w it hout passing t hrough a relay in t he t halamus. The primary olf act ory cort ex cont ains t w o t ypes of neurons: (1) principal neurons (pyramidal cells) w it h axons w hich leave t he olf act ory cort ex and project t o nearby or dist ant regions and (2) int rinsic neurons (st ellat e cells) w it h axons w hich remain w it hin t he olf act ory cort ex. The major input t o t he primary olf act ory cort ex is f rom (1) t he olf act ory bulb via t he lat eral olf act ory st ria and (2) ot her cent ral brain regions. The out put f rom t he primary olf act ory cort ex is via axons of principal neurons w hich project t o (1) t he secondary olf act ory cort ex in t he ent orhinal area, (2) t he amygdaloid nucleus, and (3) t he dorsomedial nucleus of t he t halamus. The out put of t he secondary olf act ory cort ex, t he ent orhinal area, is t o t he (1) hippocampal f ormat ion and (2) t he ant erior insular and f ront al cort ices. The connect ions of t he olf act ory cort ex w it h t he t halamus, t he amygdaloid nucleus, t he hippocampal f ormat ion, and t he insular and f ront al cort ices provide t he anat omic basis f or a role of olf act ion in emot ional behavior, visceral f unct ion, and memory. Q uant it at ive st udies of t he primary olf act ory cort ex have revealed t hat (1) t here is a predominance of principal neurons (compared w it h t he int rinsic variet y) and (2) t he number of principal neurons f ar exceeds t he number of f ibers in t he lat eral olf act ory st ria. Thus, in cont rast t o t he olf act ory bulb, in w hich t here is a high convergence rat io, t he rat io of input t o out put in t he primary olf act ory cort ex is low. This is similar t o t he pat t ern in t he neocort ex and t he climbing f iber syst em of t he cerebellar cort ex.
LIM BIC LOBE As described by Broca in 1878, t he limbic lobe ref ers t o t he gray mat t er in t he medial and basal part s of t he hemisphere t hat f orms a limbus (border) around t he brain st em. The limbic lobe is a synt het ic lobe w hose component
part s are derived f rom diff erent lobes of t he brain (f ront al, pariet al, t emporal). There is no general agreement on all t he part s t hat ent er int o t he f ormat ion of t he limbic lobe. The f ollow ing, how ever, are generally accept ed as limbic lobe component s (Figure 21-4): 1. Subcallosal gyrus, inf erior t o t he genu and rost rum of t he corpus callosum, just ant erior t o t he lamina t erminalis 2. Cingulat e gyrus 3. I st hmus of t he cingulat e gyrus, post erior and inf erior t o t he splenium of t he corpus callosum 4. Parahippocampal gyrus (and t he underlying hippocampal f ormat ion and dent at e gyrus) 5. Uncus The limbic lobe is f ormed of archicort ex (hippocampal f ormat ion and dent at e gyrus), paleocort ex (rost ral parahippocampal gyrus and uncus), and juxt allocort ex or mesocort ex (cingulat e gyrus). O riginally, t he limbic lobe w as assigned a purely olf act ory f unct ion. I t has been est ablished t hat only a minor part of t he limbic lobe has an olf act ory f unct ion. The rest of t he limbic lobe, w hich f orms part of t he limbic syst em, plays a role in emot ional behavior and memory.
THE PAPEZ CIRCUIT I n 1937, James Papez, an American neuroanat omist , described a closed circuit of connect ions st art ing and ending in t he hippocampus t hat lat er became know n as t he Papez circuit . I t w as suggest ed t hat t he st ruct ures connect ed by t his circuit play a role in emot ional react ions. The circuit consist ed of out f low of impulses f rom t he hippocampus via t he f ornix t o t he mamillary bodies of t he hypot halamus; f rom t here, via t he mamillot ha-la-mic t ract , t o t he ant erior t halamic nucleus; and, via t he t halamocort ical f iber syst em, t o t he cingulat e gyrus, f rom w hich impulses ret urned t o t he hippocampus via t he ent orhinal area. The circuit w hich has been modif ied since it s int roduct ion, provided t he basis f or t he concept of t he limbic syst em int roduced by McLean in 1952.
LIM BIC SYSTEM The limbic syst em is def ined as t he limbic lobe and all t he cort ical and subcort ical st ruct ures relat ed t o it . These include t he f ollow ing st ruct ures: 1. Sept al nuclei 2. Amygdala
3. Hypot halamus (part icularly t he mamillary body) 4. Thalamus (part icularly t he ant erior and medial t ha-lamic nuclei) 5. Brain st em ret icular f ormat ion 6. Epit halamus 7. Neocort ical areas in t he basal f ront ot emporal region 8. O lf act ory cort ex 9. Vent ral part s of t he st riat um
Fi gure 21-4. Midsagit t al view of brain show ing component s of t he limbic lobe.
This conglomerat e of neural st ruct ures, w hich const it ut e t he old part of t he brain and are highly int erconnect ed, seems t o play a role in t he f ollow ing processes: 1. Emot ional behavior 2. Memory 3. I nt egrat ion of homeost at ic responses such as t hose relat ed t o preservat ion of t he species, securing f ood, and t he f ight or f light response. 4. Sexual behavior
5. Mot ivat ion The underlying mechanisms f or t hese diff erent f unct ions are very complex and are inadequat ely underst ood. Furt hermore, it has become diff icult t o def ine t he ext ent of t he limbic syst em w it h precision and t o at t ribut e common connect ions and f unct ions t o it s individual component s. Some researchers have advocat ed t he t heory t hat t he limbic syst em is not usef ul as a scient if ic or clinical concept . The present at ion of t he limbic syst em in t his chapt er f ocuses on t he f ollow ing component s: hippocampal f ormat ion, amygdala, and sept al area. These are t he regions t hat are most closely relat ed t o t he limbic lobe.
HIPPOCAM PAL FORM ATION The hippocampal f ormat ion (Figures 21-5 and 21-6) is an inf olding of t he parahippocampal gyrus int o t he inf erior (t emporal) horn of t he lat eral vent ricle and consist s of t hree regions: hippocampus dent at e gyrus (f ascia dent at a), and subiculum. The dent at e gyrus occupies t he int erval bet w een t he hippocampus and subiculum part of t he parahippocampal gyrus. The dent at e gyrus and subiculum are separat ed by t he hippocampal sulcus (Fig. 21-7). The name dent at e gyrus is derived f rom it s t oot hed or beaded surf ace. The subiculum is t he part of t he parahippocampal gyrus t hat is in direct cont inuit y w it h t he hippocampus. O f t he t hree component s of t he hippocampal f ormat ion, t he hippocampus is t he largest and t he best st udied in humans. Theref ore, it is present ed in t his chapt er as t he prot ot ype of t his segment of t he limbic syst em.
Hippocampus The hippocampus appears as a C-shaped st ruct ure in coronal sect ions, bulging int o t he inf erior horn of t he lat eral vent ricle. The hippocampus is closely associat ed w it h t he adjacent dent at e gyrus (Figures 21 5 t o 21 7 ), and t oget her t hey f orm an S s haped st ruct ure.
A. HIPPOCAM PAL TERM INOLOGY I n t he lat e 1500s, t he anat o-mist Arant ius exposed a convolut ed st ruct ure in t he f loor of t he t emporal horn of t he lat eral vent ricle. He called t his st ruct ure t he hippocampus because of it s resemblance t o a sea horse. A cent ury lat er t he t erm pes hi ppocampus w as used t o describe t he same st ruct ure, and t w o cent uries lat er anat omist s likened t he st ruct ure t o a ram's horn or t he horns of t he ancient Egypt ian deit y Ammon, w ho had a ram's head, hence t he name Ammon's horn or cornu Ammonis. Terminology over t he years became abundant and of t en conf using. Table 21-1 list s t he pref erred t erminology and synonyms used f or hippocampal st ruct ures.
Fi gure 21-5. Coronal sect ion of t he brain show ing t he hippocampus and dent at e gyrus (component s of t he hippocampal f ormat ion), t he alveus, and f imbria. Adjacent t o t he hippocampal f ormat ion are t he subiculum and ent orhinal cort ex (component s of t he parahippocampal gyrus).
B. LAM INATION AND DIVISIONS Alt hough Ramón y Cajal described seven laminae in t he hippocampus, it is cust omary t o combine t he diff erent laminae int o t hree major layers (Figure 21-7): t he molecular layer, t he pyramidal cell layer, and t he st rat um oriens (polymorphic layer). The pyramidal cell layer is divided int o a zone in w hich t he pyramidal cells are compact and a zone (rost ral t o t he compact zone) in w hich t he pyramidal cells are less compact . The boundary bet w een t he compact and less compact zones of t he pyramidal layer separat es t he t w o divisions of t he hippocampus (Figure 21-7) int o t he superior division (compact zone) and t he inf erior division (less compact zone).
Fi gure 21-6. Schemat ic diagram show ing t he component s of t he hippocampal f ormat ion.
The hippocampus has been subdivided f urt her int o f ields (Figure 21-7) designat ed as cornu Ammonis 1, 2, 3, and 4 (CA1 t hrough CA4 ). CA1 , t he largest hippocampal f ield in humans, is locat ed in t he superior division at t he int erf ace bet w een t he hippocampus and t he subiculum. CA2 and CA3 are in t he inf erior division w it hin t he hippocampus. CA4 const it ut es t he t ransit ion zone bet w een t he hippocampus and t he dent at e gyrus. Field CA1 (also know n as Sommer's sect or and t he vulnerable sect or) is of int erest t o neuropat hologist s because it s pyramidal neurons are highly sensit ive t o anoxia and ischemia and because it is t he t rigger zone f or some f orms of t emporal lobe epilepsy. CA2 and CA3 have been ref erred t o as resist ant sect ors because t hey are less sensit ive t o anoxia. CA 4 (t he Brat z sect or) is also called t he medium vulnerabilit y sect or because of it s medium sensit ivit y t o hypoxia.
C. NEURONAL POPULATION There are basically t w o t ypes of neurons in t he hippocampus: t he principal neurons (pyramidal cell) and t he int rinsic neurons (polymorphic cell, basket cell) (Figure 21-8).
1. Principal Neurons. The pyramidal neurons in t he pyramidal cell layer are t he principal neurons of t he hippocampus. They are t he only neurons w it h axons w hich cont ribut e t o t he out f low t ract f rom t he hippocampus. Pyramidal neurons vary in size and densit y in diff erent regions of t he hippocampus. They are smaller and more densely packed in t he superior region t han in t he inf erior region. The largest neurons in t he inf erior region are ref erred t o as t he giant pyramidal cells of t he hippocampus.
Fi gure 21-7. Schemat ic dia-gram show ing layers of t he hippocampus and t he division of t he hippocampus int o superior and inf erior regions, and f our f ields (CA 1 t o CA4 ).
Basal dendrit es of pyramidal neurons are orient ed t ow ard t he vent ricular surf ace; apical dendrit es are orient ed t ow ard t he molecular layer. Bot h t ypes of dendrit es arborize ext ensively and are rich in dendrit ic spines. Axons of pyramidal cells are direct ed t ow ard t he vent ricular surf ace, w here t hey gat her t o f orm t he alveus and f imbria and f inally join t he f ornix as t he out f low t ract f rom t he hippocampus. Recurrent axon collat erals t erminat e w it hin t he st rat um oriens or reach t he molecular layer. They exert a f acilit at ory inf luence. Tabl e 21-1. Terminology of Hippocampal Structures.
Structure
Preferred term inology
Synonym s Hippocampal formation Ram's horn Ammon's horn
Hippocampus
Hippocampus
Cornu ammonis Pes hippocampus Pes hippocampus major
Cornu ammonis
Ammon's horn Hippocampus proper Hippocampus
Cornu ammonis 1
CA 1
Sommer's sector Vulnerable sector
Cornu ammonis 2
CA 2
Cornu ammonis
CA 3
Resistent sector Spielmeyer sector
Cornu ammonis 4
CA 4
Hilus of fascia dentata End folium Bratz sector
Dentate gyrus
Dentate gyrus
Gyrus dentatus Fascia dentata
Commissure of fornix
Hippocampal commissure
Psalterium Lyre of David
Cornu ammonis 3
I t is est imat ed t hat t he hippocampus of humans cont ains 1. 2 million principal neurons on each side, a f igure close t o t he number of pyramidal t ract f ibers.
2. Intrinsic Neurons. I nt rinsic neurons have axons w hich remain w it hin t he hippocampus. Because of t he irregularit y of t heir perikarya and dendrit es, t hey are ref erred t o as polymorphic neurons. They are sit uat ed in t he st rat um oriens (Figure 21-8). Their irregularly orient ed dendrit es arborize locally, w hile t heir axons ramif y bet w een pyramidal neurons and arborize around t he perikarya of pyramidal neurons in a basket f ormat ion (hence t he t erm basket cells). They are inhibit ory (G ABAergic) t o pyramidal cell act ivit y. There are no est imat es of t he exact number of int rinsic neurons in t he hippocampus. I t has been est imat ed, how ever, t hat one basket cell is relat ed t o about 200 t o 500 pyramidal cells. Thus, it is believed t hat t he int rinsic neurons are much f ew er in number t han are t he principal neurons.
Dentate Gyrus Like t he hippocampus, t he dent at e gyrus is a t hree-layered st ruct ure composed of a molecular layer, a granular cell layer, and a polymorphic layer. The molecular layer is cont inuous w it h t hat of t he hippocampus. The granular layer is made up of small, densely packed granular cells w hose axons f orm t he mossy f iber syst em w hich links t he dent at e gyrus and t he hippocampus. The cells in t he polymorphic layer are varied and include pyramidal and basket cells. Unlike t he hippocampus, t he out put of t he dent at e gyrus does not leave t he hippocampal f ormat ion.
Subiculum Like t he hippocampus and t he dent at e gyrus, t he subiculum is composed of t hree layers: a molecular layer, a pyramidal layer, and a polymorphic layer. The polymorphic layer originat es in t he adjoining ent orhinal cort ex. Axons of pyramidal neurons in t he subiculum, like t hose in t he hippocampus, cont ribut e t o t he out put of t he hippocampal f ormat ion.
Fi gure 21-8. Schemat ic diagram show ing t he major t ypes of neurons in t he hippocampus and t heir int errelat ionships.
Afferent Pathways The bulk of ext rinsic input t o t he hippocampal f ormat ion comes f rom t he ent orhinal area (Brodmann's area 28) of t he parahippocampal gyrus and, t o a lesser ext ent , t he sept al area (Figure 21-9). O t her input s include t hose f rom t he cont ralat eral hippocampus, hypot halamus, amygdala, t halamus, locus ceruleus, raphe nuclei, and vent ral t egment al area of Tsai. Fibers f rom t he parahippocampal gyrus arise mainly f rom it s rost ral part , t he ent orhinal area (Brodmann's area 28). They const it ut e t he major input t o t he hippocampus, dent at e gyrus, and subiculum, w hich t hey reach by t w o rout es. The main input , f irst described by Ramón y Cajal, t ravels t hrough (perf orat es) t he adjacent subicular area en rout e t o t he hippocampus and dent at e gyrus and is t heref ore called t he perf orant pat h. A smaller input arrives in t he hippocampus at t he vent ricular surf ace, w here t he alveus (axons of hippocampal pyramidal neurons) is f ormed, and is t heref ore called t he alvear pat h. The ent orhinal area serves as an import ant gat ew ay bet w een t he cerebral cort ex and t he hippocampus. I nf ormat ion f rom many cort ical areas (limbic, modalit y sensoryspecif ic, and mult imodal associat ion cort ices) in t he f ront al, t emporal, pariet al, and occipit al lobes conveying visual, audit ory, and somat osensory inf ormat ion converges on t he ent orhinal cort ex and t he post erior parahippocampal gyrus. The ent orhinal cort ex in t urn conveys t his cort ical inf ormat ion t o t he hippocampus. Reciprocally, hippocampal out put originat ing in CA1 and t he subiculum is relayed back t o t he ent orhinal cort ex. The ent orhinal cort ex is t he most heavily damaged in Alzheimer's disease and is t he sit e of early onset of t he disease.
Fi gure 21-9. Schemat ic diagram show ing t he major aff erent s t o t he hippocampal f ormat ion.
Fibers f rom t he sept al nuclei reach t he hippocampus via t he f ornix. Compared w it h t he input f rom t he ent orhinal area, t he sept al input is modest . Axons of small pyramidal neurons (granule cells) in t he dent at e gyrus reach t he hippocampus via t he mossy f iber pat hw ay. The t w o hippocampi are in communicat ion via t he hip-pocampal commissure (commissure of t he f ornix). I nt erhippocampal communicat ion in humans is minimal, and t he hippocampal commissure is t hus rudiment ary. Fibers f rom t he hypot halamus originat e f rom cell groups in t he vicinit y of t he mamillary body and exert a st rong inhibit ory inf luence on t he hippocampus. Amygdalohippocampal connect ions t ravel in t he adjacent t emporal lobe w hit e mat t er and may f orm t he anat omic basis f or t he eff ect of emot ion on memory f unct ion. Thalamic input t o t he hippocampus has been show n t o originat e in t he ant erior t halamic nucleus. Noradrenergic f ibers f rom t he locus ceruleus have been t raced t o t he hippocampus and t he dent at e gyrus. Serot onergic f ibers f rom t he raphe nuclei and dopaminergic f ibers f rom t he vent ral t egment al area of Tsai in t he midbrain also have been t raced t o t he hippocampus. The noradrenergic, serot oninergic, and dopaminergic input s exert a modulat ory eff ect on memory f unct ion in t he hippocampus.
Efferent Pathways The out put f rom t he hippocampal f ormat ion consist s of axons of pyramidal neurons in t he hippocampus and subiculum (Figure 21-10). Axons of granule neurons in t he dent at e gyrus have no ext rinsic connect ions but t erminat e locally as mossy f ibers on hippocampal pyramidal neurons. Bot h t he hippocampus and t he subiculum project on t he ent orhinal cort ex. From t here, impulses are mediat ed t o limbic, sensory-specif ic, and mult imodal associat ion cort ical areas. Anot her major out put f rom t he hippocampus is t o t he subiculum. Bot h t he hippocampus and t he subiculum cont ribut e f ibers t o t he f ornix, t he out put t ract of t he hippocampal f ormat ion. Subiculum-originat ing f ibers const it ut e t he major component of t he f ornix and are dist ribut ed, via it s post commissural division, t o t he mamillary bodies of t he hypot halamus and t he ant erior nucleus of t he t halamus. Hippocampal originat ing f ibers in t he f ornix const it ut e it s smaller precommissural division and are dist ribut ed t o t he sept al nuclei, t he medial area of t he f ront al cort ex, t he ant erior and preopt ic hypot halamic nuclei, and t he vent ral st riat um.
FORNIX (FIGURE 21-11) The f ornix is a f iber bundle t hat reciprocally connect s t he hippocampal f ormat ion w it h a number of subcort ical areas, including t he t halamus, t he hypot halamus, and t he sept al region. I t t hus has bot h hippocampof ugal and hippocampopet al f ibers. The hippocampof ugal f ibers are axons of pyramidal neurons in t he subiculum and hippocampus w hich gat her at t he vent ricular surf ace of t he hippocampus as t he alveus. Fibers in t he alveus converge f art her on t o f orm a f lat t ened ribbon of w hit e mat t er, t he f imbria. Traced post eriorly on t he f loor of t he inf erior horn of t he lat eral vent ricle, t he f imbria, at t he post erior limit of t he hippocampus, arches under t he splenium of t he corpus callosum t o f orm t he crus of t he f ornix. The t w o crura converge t o f orm t he body of t he f ornix, w hich is at t ached t o t he inf erior surf ace of t he sept um pellucidum t o t he level of t he rost ral t halamus. As t he crura converge t o f orm t he body, a small number of f ibers cross t o t he ot her side (hippocampal commissure, f ornical commissure, lyra, psalt erium). The hippocampal commissure is rudiment ary in humans. Just above t he int ervent ricular f oramen of Monro, t he body of t he f ornix split s t o f orm t he t w o ant erior columns of t he f ornix, w hich arch vent rally. Most of t he f ibers (75 percent ) in each ant erior column descend caudal t o t he ant erior commissure t o f orm t he post commissural f ornix. The majorit y of f ibers in t his component of t he f ornix t erminat e in t he mamillary body, and t he rest t erminat e in t he ant erior nucleus of t he t halamus and t he midbrain t egment um. A small component (25 percent ) of each ant erior column descends rost ral t o t he ant erior commissure t o f orm t he precommissural f ornix. Fibers in t his component of t he f ornix t erminat e in t he sept al nuclei, medial f ront al cort ex, ant erior hypot halamus, and vent ral st riat um. Fibers in t he post commissural f ornix originat e in t he subiculum,
w hereas t hose in t he precommissural f ornix originat e in bot h t he hippocampus and t he subiculum.
Fi gure 21-10. Schemat ic diagram- show ing t he major eff erent s of t he hippocampus.
Fi gure 21-11. Schemat ic diagram of t he component part s of t he f ornix.
Each f ornix cont ains 1. 2 million axons of pyramidal neurons in humans.
ENTORHINAL-HIPPOCAM PAL CIRCUITRY (FIGURE 2112) Using a variet y of neuroanat omic and neurophysiologic t echniques, t he ent orhinal-hippocampal-ent orhinal circuit of connect ions has been def ined. The circuit st art s in t he ent orhinal area, w hich project s via t he perf orant pat hw ay t o granule cells in t he dent at e gyrus and pyramidal cells in t he hippocampus. Axons of granule cells in t he dent at e gyrus f orm t he mossy f iber syst em, w hich project s on pyramidal neurons in t he CA3 f ield of t he hippocampus. The CA3 pyramidal neurons send Schaff er collat erals t o t he pyramidal cells of t he CA1 hippocampal f ield. Axons of pyramidal neurons in CA1 project on neurons in t he subiculum. The subiculum in t urn project s back t o t he ent orhinal area, t hus closing t he circuit . The synapses in t his circuit are all excit at ory; t he only inhibit ory synapses are t hose f rom hippocampal basket neurons in t he st rat um oriens w hose axons t erminat e on t he perikarya of pyramidal neurons.
Fi gure 21-12. Schemat ic diagram of t he ent orhinal-hippocampal circuit show ing t he perf orant pat hw ay (1) f rom t he ent orhinal cort ex t o t he dent at e gyrus, hippocampus, and subiculum; mossy f ibers (2) connect ing t he dent at e gyrus w it h CA3 neurons of t he hippocampus; Schaff er collat erals (3) linking CA 3 neurons w it h CA1 neurons w it hin t he hippocampus; hippocampalsubiculum pat hw ay (4); and f inally t he circuit is closed by connect ions f rom t he subiculum back t o t he ent orhinal cort ex (5).
FUNCTIONAL CONSIDERATIONS I n considering t he f unct ions of t he hippocampus, it is import ant t o emphasize t he complex relat ionships of t he hippocampus w it h ot her brain regions, as w as out lined above. The eff ect s of st imulat ion or ablat ion of t he hippocampus cannot be evaluat ed in isolat ion f rom t he elaborat e syst ems of hippocampal communicat ion. The hippocampus is no longer believed t o play a role in olf act ion. The hippocampus is very w ell developed in humans, w ho are microsmat ic; it is also present in t he w hale, w hich is anosmat ic. No direct pat hw ays f rom t he primary olf act ory cort ex can be t raced t o t he hippocampus, alt hough a mult isynapt ic pat hw ay t hrough t he primary olf act ory cort ex and t he parahip-pocampal gyrus (ent orhinal area) exist s. O lf act ory bulb st imulat ion result s in excit at ory post synapt ic pot ent ial (EPSP) act ivit y but no ac-t ion pot ent ial f iring in t he hippocampus. This is consist ent w it h a polysynapt ic pat hw ay f rom t he olf act ory bulb t o t he hippocampus. I t has been suggest ed t hat t his subt hreshold EPSP act ivit y may be comparable t o a condit ional st imulus t hat plays a role in memory and learning. Act ion pot ent ials, in cont rast , have been recorded in t he hippocampus af t er st imulat ion of various areas, bot h cent rally and peripherally. Hippocampal responses have been elicit ed af t er visual, acoust ic, gust at ory, and somat osensory st imulat ion as w ell as af t er st imulat ion of various cort ical and subcort ical areas. Such responses are charact erist ically labile and are easily modif ied by a variet y of f act ors. St imulat ion and ablat ion of t he hippocampus give rise t o changes in behavioral, endocrine, and visceral f unct ions. The same eff ect s may f ollow eit her ablat ion or st imulat ion. The hippocampus has been implicat ed in t he processes of at t ent ion and alert ness. St imulat ion of t he hippocampus in ani-mals produces glancing and searching movement s t hat are associat ed w it h bew ilderment and anxiet y. The import ant role of t he hippocampus in memory w as not apparent unt il t he lat e 1950s, w hen Scoville and Milner de-scribed memory loss f ollow ing bilat eral ant erior t emporal lobect omies. Bilat eral ablat ion of t he hippocampus in humans (usually involving adjacent regions as w ell) result s in a loss of recent (60 s) memory and t he inabilit y t o st ore new ly learned f act s (ant erograde amnesia). Remot e or long-t erm memories, how ever, re-main int act . Unilat eral ablat ion of t he hippocampus in humans does not aff ect memory t o a signif icant degree. St udies of humans w it h brain lesions indicat e t hat t he hippocampus is import ant f or declarat ive (explicit ) memory, t he memory of f act s, w ords, and dat a t hat can be brought t o mind and consciously inspect ed. Declarat ive (associat ive) memory
includes episodic, semant ic, and f amiliarit y-based recognit ion, w it h t he addit ional suggest ion t hat t he hippocampus plays a t ime-limit ed role (being needed only f or recent ly acquired inf ormat ion). Episodic memory (recall of past event s w it h a sense of personal f amiliarit y) is usually more severely disrupt ed in hippocampal lesions t han semant ic memory (memory f or general declarat ive inf ormat ion such as f or vocabulary or arit hmet ic f act s). Similar t o hemispheric specializat ion, t he lef t hippocampus is specialized f or verbal memory and t he right hippocampus f or nonverbal memory. The hippocampus has a low t hreshold f or seizure (epilept ic) act ivit y; how ever, t he spread of such epilept ic act ivit y t o t he nonspecif ic t halamic syst em, and hence all over t he cort ex, is not usual. This may explain w hy t emporal lobe epilepsy (psychomot or epilepsy) in humans does not become generalized.
AM YGDALA (FIGURE 21-13) The amygdalar (f rom t he G reek amygdal a, a lmonds ) nuclei, a major component of t he limbic syst em, resemble almonds in shape and are locat ed in t he t ip of t he t emporal lobe beneat h t he cort ex of t he uncus and rost ral t o t he hippocampus and t he inf erior horn of t he lat eral vent ricle. There are t w o main groups of t hese nuclei: t he cort icomedial and cent ral and t he basolat eral. The cort icomedialcent ral group is relat ively small and is phylogenet ically older. I t maint ains connect ions w it h t he phylogenet ically older regions of t he cent ral nervous syst em, such as t he olf act ory bulb, hypot halamus, and brain st em. The basolat eral group is larger and phylogenet ically more recent . I t has ext ensive connect ions w it h t he cerebral cort ex. Several neurot ransmit t ers have been demonst rat ed in t he amygdala, including acet ylcholine, gamma-aminobut yric acid (G ABA), noradrenaline, serot onin, dopamine, subst ance P, and enkephalin. The amygdala w as f irst ident if ied by t he G erman physician Burdach in t he early 19t h cent ury.
Fi gure 21-13. Coronal sect ion of t he brain show ing t he amygdala and adjacent st ruct ures.
Afferent Pathways The amygdala receives a broad range of ext erocept ive aff erent s (olf act ory, somat osensory, audit ory, and visual) f or int egrat ion w it h int erocept ive st imuli f rom a variet y of aut onomic areas (Figure 21-14). Most of t he amygdalar connect ions are reciprocal. The basolat eral nuclear group, t he largest in humans, receives input s f rom t he f ollow ing cort ical and subcort ical sources: (1) cort ical input f rom t he pref ront al, t emporal, occipit al, and insular cort ices, w hich convey t o t he amygdala highly processed somat osensory, audit ory, and visual sensory inf ormat ion f rom modalit y-specif ic and mult imodal associat ion areas as w ell as visceral inf ormat ion, (2) t he t halamus (dorsomedial nucleus), (3) t he olf act ory cort ex, and (4) cholinergic input f rom t he nucleus basalis of Meynert . The basolat eral nuclear group is int imat ely and reciprocally connect ed w it h t he pref ront al cort ex via t he uncinat e f asciculus.
Fi gure 21-14. Schemat ic diagram of t he major aff erent connect ions of t he amygdala.
The cort icomedial and cent ral nuclear complex receives input s f rom t he f ollow ing sources: (1) olf act ory bulb (direct ly via t he lat eral olf act ory st ria and indirect ly via t he olf act ory cort ex), (2) t halamus (dorsomedial nucleus), (3) hypot halamus (vent romedial nucleus and lat eral hypot halamic area), (4) sept al area, and (5) brain st em nuclear groups concerned w it h visceral f unct ion (periaqueduct al gray mat t er, parabrachial nucleus, and nucleus of t he solit ary t ract ).
Efferent Pathways A large number of amygdalar eff erent s t erminat e in nuclei t hat regulat e endocrine and aut onomic f unct ion, and ot hers are direct ed t o t he neocort ex. O ut put f rom t he amygdala is conveyed via t w o main pat hw ays: (1) st ria t erminalis (dorsal amygdalof ugal pat hw ay) and (2) vent ral amygdalof ugal pat hw ay (vent rof ugal bundle).
A. STRIA TERM INALIS The st ria t erminalis (Figure 21-15) is t he main out f low t ract of t he amygdala. I t arises predominant ly f rom t he cort icomedial group of amygdalar nuclei. From it s sit es of origin, it f ollow s a C-shaped course caudally, dorsally, ant eriorly, and vent rally along t he medial surf ace of t he caudat e nucleus t o reach t he region of t he ant erior commissure, w here it branches out t o supply t he f ollow ing areas: (1) sept al nuclei, (2) ant erior, preopt ic, and vent romedial nuclei of t he hypot halamus and t he lat eral hypot halamic area, and (3) bed nucleus of t he st ria t erminalis (a scat t ered group of nuclei at t he rost ral ext remit y of t he st ria t erminalis).
Fi gure 21-15. Schemat ic diagram of t he major eff erent connect ions of t he amygdala.
B. VENTRAL AM YGDALOFUGAL PATHWAY The vent ral amygdalof ugal pat hw ay is a vent ral out f low t ract t hat originat es f rom t he basolat eral and cent ral amygdalar nuclei. I t proceeds along t he base of t he brain beneat h t he lent if orm nucleus and dist ribut es f ibers t o t he f ollow ing areas. Fibers originat ing f rom t he basolat eral amygdalar nucleus project t o t he f ollow ing cort ical and subcort ical areas: (1) pref ront al, inf erior t emporal (ent orhinal area and subiculum), insular, cingulat e, and occipit al cort ices, (2) vent ral st riat um, (3) t halamus (dorsomedial nucleus), (4) hypot halamus (preopt ic and lat eral hypot halamic areas), (5) sept al area, and (6) subst ant ia innominat a (nucleus basalis of Meynert ), f rom w hich a diff use cholinergic syst em act ivat es t he cerebral cort ex in response t o signif icant st imuli. Fibers in t he vent ral amygdalof ugal pat hw ay originat ing in t he cent ral amygdalar nucleus are dist ribut ed t o brain st em nuclei concerned w it h visceral f unct ion (dorsal mot or nucleus of t he vagus, raphe nuclei, locus ceruleus, parabrachial nucleus, and periaqueduct al gray mat t er). The t w o amygdala communicat e w it h each ot her t hrough t he st ria t erminalis and t he ant erior commissure. Fibers leave one amygdaloid nuclear complex and t ravel via t he st ria t erminalis t o t he level of t he ant erior commissure, w here t hey cross and join t he ot her st ria t erminalis and ret urn t o t he cont ralat eral
amygdaloid nuclear complex. Nuclear groups w it hin each amygdaloid nuclear complex communicat e w it h each ot her via short f iber syst ems.
Intra-Amygdaloid Connections Tract t racing st udies have revealed ext ensive int ranuclear and int ernuclear connect ivit y bet w een amygdalar nuclei. Most of t he connect ions are glut amat ergic. These observat ions indicat e t hat t here is ext ensive local processing of inf ormat ion ent ering t he amygdala bef ore it leads t o t he appropriat e behavioral out comes.
Functional Considerations The f unct ions of t he amygdala are somew hat elusive. St imulat ion and ablat ion experiment s usually involve adjacent neural st ruct ures. The int ricat e neural connect ivit y of t he amygdala makes it diff icult t o ascribe an observed behavior purely t o t he amygdala. The f ollow ing manif est at ions, how ever, have been not ed t o occur af t er st imulat ion or ablat ion of t he amygdala.
A. AUTONOM IC EFFECTS Changes in heart rat e, respirat ion, blood pressure, and gast ric mot ilit y have been observed af t er amygdalar st imulat ion. Bot h an increase and a decrease in t hese f unct ions have been observed, depending on t he area t hat is st imulat ed.
B. ORIENTING RESPONSE St imulat ion of t he amygdala enhances t he orient ing response t o novel event s. Such animals arrest ongoing act ivit y and orient t heir bodies t o t he novel sit uat ion. Animals w it h amygdalar lesions manif est reduced responsiveness t o novel event s in t he visual environment . Their responsiveness, how ever, is improved if t hey are rew arded f or t he response.
C. EM OTIONAL BEHAVIOR AND FOOD INTAKE There seem t o be t w o regions in t he amygdala t hat are ant agonist ic t o each ot her w it h regard t o emot ional behavior and eat ing. Lesions in t he cort icomedial nuclear group of t he amygdala result in aphagia, decreased emot ional t one, f ear, sadness, and aggression. Lesions of t he basolat eral nuclear group, by cont rast , produce hyperphagia, happiness, and pleasure react ions. St im-ulat ion of t he basolat eral nuclear group of t he amygdala is associat ed w it h f ear and f light . St imulat ion of t he cort icomedial nuclear group produces a def ensive and aggressive react ion. The at t ack behavior elicit ed by amygdalar st imulat ion diff ers f rom t hat elicit ed by hypot halamic st imulat ion in it s gradual buildup and gradual subsidence upon t he onset and cessat ion of st imulat ion. At t ack behavior elicit ed f rom t he hypot halamus, in cont rast , begins and subsides almost
immediat ely af t er t he onset and cessat ion of t he st imulus. O f int erest also is t he f act t hat prior sept al st imulat ion prevent s t he occurrence of aggressive behavior elicit ed f rom bot h t he amygdala and t he hypot halamus.
D. FACIAL EXPRESSION Several areas in t he brain are specialized f or processing of f aces. Foremost among t hem are t he sect ors of ext rast riat e visual cort ex, not ably in t he f usif orm and superior t emporal gyri, and t he amygdala. Whereas t he ext rast riat e visual cort ices part icipat e primarily in const ruct ing det ailed percept ual represent at ion of f aces, t he amygdala is required t o link t he percept ion of t he f ace t o t he ret rieval of know ledge about it s emot ional and social meaning. Lesions of t he amygdala in monkeys impair t he abilit y t o evaluat e social and emot ional meaning of visual st imuli. Bilat eral amygdalar lesions in humans result in alt erat ion in social behavior and social cognit ion, especially as relat ed t o t he recognit ion of social cues f rom f aces. Bilat eral amygdalar damage in humans is associat ed w it h impaired recognit ion of f acial expressions. Funct ional imaging st udies have demonst rat ed act ivat ion of t he amygdala during present at ion of emot ional f acial expressions. These f indings are most evident f or negat ively valenced emot ions (f ear, anger, and sadness).
E. AROUSAL RESPONSE St imulat ion of t he basolat eral nuclear group of t he amygdala produces an arousal response t hat is similar t o but independent of t he arousal response t hat f ollow s st imulat ion of t he ret icular act ivat ing syst em of t he brain st em. The amygdalar response is independent of t he ret icular act ivat ing syst em response, since it can be elicit ed af t er lesions have been made in t he ret icular f ormat ion of t he brain st em. St imulat ion of t he cort icomedial nuclear group of t he amygdala, by cont rast , produces t he reverse eff ect (a decrease in arousal and sleep). The net t ot al eff ect of t he amygdala, how ever, is f acilit at ory, since ablat ion of t he amygdala result s in a sluggish, hypoact ive animal w hich is placid and t ame. Such animals avoid social int eract ion and may become social isolat es.
F. SEXUAL ACTIVITY The amygdala cont ains t he highest densit y of recept ors f or sex hormones. St imulat ion of t he amygdala has been associat ed w it h a variet y of sexual behaviors, including erect ion, ejaculat ion, copulat ory movement s, and ovulat ion. Bilat eral lesions of t he amygdala produce hypersexualit y and pervert ed sexual behavior.
G. M OTOR ACTIVITY St imulat ion of t he cort icomedial nuclear group of t he amygdala produces complex rhyt hmic movement s relat ed t o eat ing, such as chew ing, smacking of t he lips,
licking, and sw allow ing. Animal experiment s support t he import ance of t he amygdala in t he organizat ion of f ear-relat ed behavior. Bilat eral removal of t he amygdala abolishes nat urally occurring f ear-relat ed responses in animals. Elect ric st imulat ion of t he amygdala elicit s def ensive or f ear-relat ed behavior. The amygdaloid project ions t o t he hypot halamus via t he vent ral amygdalof ugal pat hw ay seem t o be essent ial f or f earrelat ed behavior. St imulat ion of t he amygdala during brain surgery in humans is associat ed w it h a variet y of aut onomic and emot ional react ions and a f eeling of f ear and anxiet y. Some of t hese pat ient s report a memorylike delusion of recognit ion know n as t he déjŕ vu phenomenon (a French t erm meaning a lready seen ) . The déjŕ vu phenomenon, as w ell as olf act ory and gust at ory hallucinat ions, is f requent ly experienced as auras in pat ient s w ho experience t emporal lobe seizures. Dest ruct ion of bot h amygdalas in humans has been done t o relieve int ract able epilepsy and t reat violent behavior. Such pat ient s usually become complacent and sedat e and show signif icant changes in emot ional behavior. I t should be point ed out t hat many, if not all, of t hese f unct ions can be observed af t er st imulat ion or ablat ion of ot her brain regions, not ably t he hypot halamus and t he sept al regions. I t has been proposed t hat t he amygdala plays an int egrat ive role in all t hese f unct ions.
SEPTAL AREA The sept al area (Figures 21-16 and 21-17) has t w o divisions: t he sept um pellucidum and t he sept um verum. The sept um pellucidum is a t hin leaf t hat separat es t he lat eral vent ricles. I t is made up of glia and lined by ependyma.
Fi gure 21-16. Midsagit t al view of t he brain show ing t he sept al area vent ral t o t he sept um pellucidum, bet w een t he subcallosal gyrus rost rally and t he
ant erior commissure, hypot halamus and lamina t erminalis caudally.
Fi gure 21-17. Axial brain sect ion show ing sept al nuclei and sept um pellucidum bet w een t he corpus callosum and f ornix.
Fi gure 21-18. Schemat ic diagram show ing aff erent and eff erent connect ions of t he sept al area.
The sept um verum is vent ral t o t he sept um pellucidum, be-t w een t he subcallosal gyrus rost rally and t he ant erior commissure and t he ant erior hypot halamus caudally. Most aut hors include t he f ollow ing st ruct ures in t he sept um verum: t he sept al nuclei, t he diagonal band of Broca, t he bed nucleus of t he st ria t erminalis, and t he nucleus accumbens sept i. The sept al nuclei are made up of medium-size neurons w hich are grouped int o medial, lat eral, and post erior groups. The lat eral group receives most of t he sept al aff erent s and project s t o t he medial sept al group. The medial group gives rise t o most of t he sept al eff erent s. The post erior group receives input f rom t he hippocampus and direct s it s out put t o t he habenular nuclei. The sept al nuclei are poorly developed in humans.
Connections The sept al area has reciprocal connect ions (Figure 21-18) w it h t he f ollow ing areas: (1) hippocampus, (2) amygdala, (3) hypot halamus, (4) midbrain, (5) habenular nucleus, (6) cingulat e gyrus, and (7) t halamus. The reciprocal connect ions bet w een t he sept al area and t he hippocampus const it ut e t he major connect ion of t he sept al area and t ravel via t he f ornix. The
hippocampal-sept al relat ionship is t opographically organized so t hat specif ic areas of t he hippocampus project on specif ic regions of t he sept um (CA1 of t he hippocampus t o t he medial sept al region; CA3 and CA4 of t he hippocampus t o t he lat eral sept al region, medial sept al region t o CA3 and CA4 ). When one adds t o t his t he int rinsic connect ion bet w een t he medial and lat eral sept al regions and bet w een CA1 and CA3 C A 4 of t he hippocampus, it becomes evident t hat a neural circuit is est ablished connect ing t hese t w o limbic regions. The reciprocal connect ions bet w een t he sept al area and t he amygdala t ravel via t he st ria t erminalis and t he vent ral amygdalof ugal pat hw ay. Reciprocal connect ions w it h t he hypot halamus t ravel in t he medial f orebrain bundle. The hypot halamic nuclei involved include t he preopt ic, ant erior, paravent ricular, and lat eral. The medial f orebrain bundle is an ill-def ined bundle of short nerve f ibers t hat courses t hrough t he lat eral hypot halamus, int erconnect ing nuclei locat ed close t oget her and ext ending f rom t he sept al area int o t he midbrain. Fibers bet w een t he sept al area and t he midbrain t ravel in t he medial f orebrain bundle. The periaqueduct al gray region and t he vent ral t egment al area are t he primary brain st em areas involved in t his connect ion. The st ria medullaris t halami reciprocally connect s t he sept al area and t he habenular nuclei. From t he habenular nuclei, t he habenuloint erpeduncular t ract connect s t he sept al area indirect ly w it h t he int erpeduncular nucleus of t he midbrain. The t halamic nuclei involved in t he sept ot halamic connect ion are t he dorsomedial and t he ant erior nuclei.
Functional Considerations The f unct ional import ance of t he sept al area lies in providing a sit e of int eract ion bet w een limbic and diencephalic st ruct ures. St imulat ion and ablat ion experiment s have provided t he f ollow ing inf ormat ion about t he role of t he sept al region.
A. EM OTIONAL BEHAVIOR Lesions of t he sept al area in animal species such as rat s and mice produce rage react ions and hyper-emot ionalit y. These behavioral alt erat ions usually are t ransit ory and disappear 2 t o 4 w eeks af t er t he lesion.
B. WATER CONSUM PTION Animals w it h lesions in t he sept al area t end t o consume increased amount s of w at er. There is evidence t o suggest t hat t his is a primary eff ect of t he lesion and is caused by disrupt ion of a neural syst em concerned w it h w at er balance in
response t o changes in t ot al f luid volume. Chronic st imulat ion of t he sept al area t ends t o decrease spont aneous drinking even in animals t hat have been deprived of w at er f or a long t ime.
C. ACTIVITY Animals w it h sept al lesions demonst rat e a high init ial st at e of act ivit y in response t o a novel sit uat ion. This height ened act ivit y, how ever, rapidly declines almost t o immobilit y.
D. LEARNING Animals w it h sept al lesions t end t o learn t asks quickly and perf orm t hem eff ect ively once t hey have been learned.
E. REWARD St imulat ion of several regions of t he sept al area gives rise t o pleasure or rew arding eff ect s.
F. AUTONOM IC EFFECTS St imulat ion of t he sept al region has an inhibit ory eff ect on aut onomic f unct ion. Cardiac decelerat ion ensues af t er sept al st imulat ion and is reversed by t he drug at ropine, suggest ing t hat sept al eff ect s are mediat ed via t he cholinergic f ibers of t he vagus nerve.
Fi gure 21-19. Schemat ic diagram show ing t he anat omic subst rat e f or t he int egrat ive f unct ion of t he limbic syst em (t he limbic loop).
G. SEPTAL SYNDROM E Dest ruct ion of t he sept al nuclei gives rise t o behavioral overreact ion t o most
environment al st imuli. Behavioral changes occur in sexual and reproduct ive behavior, f eeding, drinking, and t he rage react ion. Relat ively f ew discret e sept al lesions or st imulat ions have been report ed in humans. Chemical st imulat ion in t he sept al area using acet ylcholine result s in euphoria and sexual orgasm. Recordings f rom t he sept al area during sexual int ercourse have show n spike and w ave act ivit y during orgasm. Markedly increased sexual act ivit y has been report ed in humans af t er sept al damage.
OVERVIEW OF THE LIM BIC SYSTEM I t is evident t hat t he limbic syst em is a highly complex syst em t hat is int erconnect ed by a mult iplicit y of pat hw ays and reciprocal circuit s among it s component part s, not ably t he hypot halamus. The main component s of t he limbic syst em (hippocampal f ormat ion, amygdala, sept al area, and ent orhinal cort ex) are densely int erconnect ed and are connect ed w it h neural syst ems t hat subserve somat osensory, somat omot or, and aut onomic and endocrine f unct ions. They are t hus in a unique posit ion t o int egrat e ext erocept ive and int erocept ive inf ormat ion and are essent ial f or t he maint enance of emot ional st abilit y, learning abilit y, and memory f unct ion. A limbic loop (Figure 21-19) has been proposed as t he anat omic subst rat e f or t he int egrat ive role of t he limbic syst em. The aff erent limb of t he loop consist s of collat erals t o t he limbic syst em f rom t he pat hw ay connect ing neocort ical associat ion cort ices w it h t he pref ont al cort ex. Aut onomic and endocrine cent ers are reciprocally connect ed w it h t he same limbic syst em cent ers t hat receive cort ical collat erals. The eff erent limb of t he loop consist s of project ions f rom t he limbic cent ers t o t he pref ront al associat ion cort ex. The pref ront al cort ex plays a role in guiding behavior and is indirect ly involved in t he init iat ion of movement . The input f rom t he limbic cent ers int o t he pref ront al cort ex subserves t he eff ect s of emot ion on mot or f unct ion. At best , one can def ine t he overall f unct ions of t he limbic syst em in t he most general t erms as subserving t he f ollow ing: 1. Homeost at ic mechanisms f or preservat ion of t he individual (f light or def ensive response, eat ing, drinking) and preservat ion of t he species (sexual and social behavior). I n t his t he limbic syst em serves a prot ect ive f unct ion of assuring graded and considered aut onomic and endocrine responses. 2. Emot ional behavior (including f ear, rage, pleasure, and sadness) and f eeling 3. Memory 4. Mat ching up sensory input w it h aut onomic-endocrine drive-s and put t ing it int o t he cont ext of t he sit uat ion 5. Mot ivat ion Diff erent f unct ions of t he limbic syst em are not dist ribut ed equally among it s
component s. The hippocampus is especially concerned w it h memory, t he amygdala w it h emot ion and sexualit y, t he ant erior cingulat e gyrus w it h mot ivat ion, and t he orbit of ront al cort ex w it h social behavior.
TERM INOLOGY Alveus (Latin, a trough or canal ). The alveus of t he hippocampus is t he t hin layer of w hit e mat t er t hat covers t he vent ricular surf ace of t he hippocampus. Amnesia (G reek, f orgetfulness ) . Lack or loss of memory. Amnesi a w as an old t erm f or loss of memory. The modern use of t he w ord dat es f rom about 1861 and t he w ork of Broca, w ho divided disorders of speech caused by cent ral lesions int o aphemia and verbal amnesia. The t erm f irst appeared in English in 1862. Broca's use of t he t erm verbal amnesi a (impaired w ord f inding) is no longer current . Amygdala (G reek amygdal e, a lmond ) . The amygdaloid nucleus is an almond-shaped nuclear mass in f ront of t he t ail of t he caudat e nucleus. Associative memory. The conscious recollect ion of specif ic event s and f act s. Also know n as declarat ive memory and dat abase memory. Bratz sector. Cornu Ammonis f ield CA4 . Also know n as t he medium vulnerabilit y (t o anoxia) sect or. Broca, Pierre-Paul (1824 1 880). French ant hropologist , anat -omist , and surgeon, and lat er a polit ician. He described hemispheric dominance f or language. He described muscular dyst rophy bef ore Duchenne, and t he use of hypnot ism in surgery. The speech area in t he lef t hemisphere is named af t er him. Burdach, Karl Friedrich (1776 1 847). G erman physician, anat omist and physiologist . He int roduced t he t erms bi ol ogy and morphol ogy. He is credit ed w it h naming many st ruct ures, including t he f asciculus cuneat us (Burdach column), globus pallidus, put amen, int ernal capsule, lent icular nucleus, red nucleus, cingulum, cuneus, and amygdaloid nucleus. He also classif ied t he t halamic nuclei. Cingulate gyrus (Latin, b elt or girdle ). A f our-layered paleo-cort ex above t he corpus callosum. Part of t he limbic lobe. Cornu Ammonis. Ammon's horn. Anat omist s likened t he hippocampus t o a ram's horn or t o t he horns of t he ancient Egypt ian deit y Ammon, w ho had a ram's head.
Crus fornix (Latin, l eg or shin, arch ). The f lat t ened band of w hit e beneat h t he splenium of t he corpus callosum. The t w o crura join t o f orm t he body of t he f ornix. Declarative memory. The conscious recollect ion of specif ic event s and f act s. Also know n as associat ive memory and dat abase memory. Déjŕ vu (French, a lready seen ). An illusion in w hich a new sit uat ion is incorrect ly view ed as a repet it ion of a previous sit uat ion. Usually an aura of a t emporal lobe seizure. Dentate gyrus (Latin dentatus, h aving teeth ; G reek gyros, c ircle ) . The t hree-layered archicort ex of t he t emporal lobe. A component of t he hippocampal f ormat ion. Entorhinal cortex. The rost ral part of t he parahippocampal gyrus in t he t emporal lobe. I t corresponds t o Brodmann's area 28. Fimbria (Latin, f ringe, border, edge ). The band of w hit e mat t er along t he medial edge of t he vent ricular surf ace of t he hippocampus. Part of t he f ornix. Fornix (Latin, a rch ). The out f low t ract of t he hippocampal f ormat ion is archlike. Not ed by G alen and f irst described by Vesalius. Thomas Willis named it t he f ornix cerebri. Hippocampus (G reek, s ea horse ). Part of t he hippocampal f ormat ion. The inf eriomesial part of t he parahippocampal gyrus. So named because of it s resemblance t o a sea horse. The st ruct ure w as f irst observed by Achillini and named by Arant ius. Isthmus (G reek i sthmos, a narrow connection between two larger bodies or parts ) . The ist hmus of t he cingulat e gyrus is it s const rict ed port ion bet w een t he cingulat e and parahippocampal gyri. Limbic (Latin l i mbus, f ringe, border, margin ). The limbic lobe f orms a margin around t he brain st em. Lyra (G reek, l irah ). A st ringed inst rument resembling t he harp. Mitral cells (Latin mi tra, a cap ). Mit ral cells in t he olf act ory bulb have a caplike shape. Papez circuit. A circuit connect ing t he hippocampus w it h t he hypot halamus, t halamus, and
cingulat e gyrus. Described by James Papez, an American neuroanat omist , in 1937. The circuit subsequent ly laid t he basis f or t he concept of t he limbic syst em. Psalterium (G reek psal teri on, h arp ) . The hippocampal commissure or f ornical commissure is called t he psalt erium. Pyriform (Latin pi rum, a pear ; forma shape ). Pear-shaped. The pyrif orm gyrus of t he t emporal lobe is pear-shaped. Rhinencephalon (G reek rhi n, n ose ; enkephal os, b rain ) . The smell brain. The part of t he brain concerned w it h t he olf act ory syst em. Schaffer collaterals. Collat erals of axons of pyramidal neurons in t he CA3 f ield of t he hippocampus t hat project on pyramidal cells in t he CA1 f ield. Sommer's sector. Field CA1 of t he hippocampus. Also know n as t he vulnerable sect or because of it s sensit ivit y t o anoxia and ischemia. Named af t er Wilhelm Sommer, a G erman physician. Subiculum (Latin subi cere, t o raise or lift ). An underlying or support ing st ruct ure. Uncinate (Latin, h ook ). The uncinat e f asciculus is like a hook connect ing t he f ront al and t emporal lobes. Uncus (Latin, h ook ). The medially curved ant erior end of t he parahippocampal gyrus. Willis, T homas (1621 1 675). English physician w ho described t he art erial Circle of Willis in t he base of t he brain in 1664. He described t he 11t h cranial nerve (nerve of Willis), and carot id occlusion headache (Willis headache), among many ot her observat ions.
SUGGESTED READINGS Adolphs R, Tranel D: Amygdala damage impairs emot ion recognit ion f rom scenes only w hen t hey cont ain f acial expression. Neuropsychol ogi a 2003; 41: 1281 1 289. Baleydier C, Mauguiere F: The dualit y of t he cingulat e gyrus in monkey: Neuroanat omical st udy and f unct ional hypot hesis. Brai n 1980; 103: 525 5 54. Ben-Ari Y et al: Regional dist ribut ion of choline acet ylt ransf erase and acet ylcholinest erase w it hin t he amygdaloid complex and st ria t erminalis syst em. Brai n Res 1977; 120: 435 4 45.
Braak H et al: Funct ional anat omy of human hippocampal f ormat ion and relat ed st ruct ures. J Chi l d Neurol 1996; 11: 265 2 75. Brodal P: The Central Nervous System, 5t h ed. New York, O xf ord Universit y Press, 1992: 383 3 97. Bronen RA: Hippocampal and limbic t erminology. AJNR 1992; 13: 943 9 45. Brumback RA, Leech RW: Memories of a sea horse. J Chi l d Neurol 1996; 11: 263 2 64. Burgess N et al: The human hippocampus and spat ial and episodic memory. Neuron 2002; 35: 625 6 41. Emson PC et al: Cont ribut ions of diff erent aff erent pat hw ays t o t he cat echolamine and 5-hydroxyt rypt amine-innervat ion of t he amygdala: A neurochemical and hist ochemical st udy. Neurosci ence 1979; 4: 1347 1 357. G irgis M: Kindling as a model f or limbic epilepsy.Neurosci ence 1981; 6: 1695 1 706. G orman DG , Cummings JL: Hypersexualit y f ollow ing sept al injury. Arch Neurol 1992; 49: 308 3 10. Hopkins DA, Holst ege G : Amygdaloid project ions t o t he mesencephalon, pons and medulla oblongat a in t he cat . Exp Brai n Res 1978; 32: 529 5 47. Horel JA: The neuroanat omy of amnesia: A crit ique of t he hippocampal memory hypot hesis. Brai n 1978; 101: 403 4 45. Kosel KC et al: O lf act ory bulb project ions t o t he parahippocampal area of t he rat . J Comp Neurol 1981; 198: 467 4 82. Lopes da Silva FH, Arnolds DEAT: Physiology of t he hippocampus and relat ed st ruct ures. Annu Rev Physi ol 1978; 40: 185 2 16. Mark LP et al: The f ornix.AJNR 1993; 14: 1355 1 358. Mark LP et al: The hippocampus. AJNR 1993; 14: 709 7 12. Mark LP et al: Hippocampal anat omy and pat hologic alt erat ions on
convent ional MR images. AJNR 1993; 14: 1237 1 240. Mark LP et al: Limbic connect ions. AJNR 1995; 16: 1303 1 306. Mark LP et al: Limbic syst em anat omy: An overview. AJNR 1993; 14: 349 3 52. Mark LP et al: The sept al area. AJNR 1994; 15: 273 2 76. Mega MS et al: The limbic syst em: An anat omic, phylogenet ic, and clinical perspect ive. J Neuropsychi at & Cl i n Neurosci 1997; 9: 315 3 30. Meibach RC, Siegel A: Eff erent connect ions of t he sept al area in t he rat : An analysis ut ilizing ret rograde and ant erograde t ransport met hods. Brai n Res 1977; 119: 1 2 0. Moser MB, Moser EI : Funct ional diff erent iat ion in t he hippocampus. Hi ppocampus 1998; 8: 608 6 19. O t t ersen O P, Ben-Ari Y: Aff erent connect ions t o t he amygdaloid complex of t he rat and cat : I . Project ions f rom t he t halamus. J Comp Neurol 1979; 187: 401 4 24. Sah P et al: The amygdaloid complex: Anat omy and physiology. Physi ol Rev 2003; 83: 803 8 34. Sit oh Y Y et al: The limbic syst em. An overview of t he anat omy and it s development . Neuroi magi ng Cl i ni cs of North Ameri ca 1997; 7: 1 1 0. Sw anson LW, Cow an WM: An aut oradiographic st udy of t he organizat ion of t he eff erent connect ions of t he hippocampal f ormat ion in t he rat . J Comp Neurol 1977; 172: 49 8 4. Tranel D, Hyman BT: Neuropsychological correlat es of bilat eral amygdala damage. Arch Neurol 1990; 47: 349 3 55. Van Hoesen G W: The parahippocampal gyrus: New observat ions regarding it s cort ical connect ions in t he monkey. Trends Neurosci 1982; 5: 345 3 50. Van Hoesen G W: Anat omy of t he medial t emporal lobe. Magn Reson Imagi ng 1995; 13: 1047 1 055.
Van Hoesen G W et al: The parahippocampal gyrus in Alzheimer's disease: Clinical and preclinical neuroanat omical correlat es. Ann NY Acad Sci 2000; 911: 254 2 74. Wit t er MP et al: Anat omical organizat ion of t he parahippocampal-hippocampal net w ork. Ann NY Acad Sci 2000; 911: 1 2 4.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 22 - Lim bic S ys tem : C linic al C or r elates
22 Limbic System: Clinical Correlates
Abnorm alities of Olfaction Mem ory Types of Memory Anatomic Correlates of Memory Types of Memory Loss (Amnesia) Wernicke-Korsakoff Syndrom e Transient Global Am nesia Klüver-Bucy Syndrom e Tem poral Lobe Epilepsy Schizophrenia Alzheim er's Disease Herpes Sim plex Encephalitis KEY CONCEPTS Anosmia may be the earliest clinical sign of a subfrontal meningioma. There are two types of memory: explicit and implicit. Amnesia (memory loss) may be anterograde, retrograde, global, or modality-specific. It may be transient or permanent. Wernicke-Korsakoff's syndrome, a thiamine deficiency syndrome seen in chronic alcoholics, is characterized by amnesia (anterograde and retrograde) and in confabulation.
Transient global amnesia is caused by ischemia in memory structures in the medial temporal lobe. Spreading cortical depression in the medial temporal lobe is another, more recently reported mechanism. Various manifestations of the Klüver-Bucy syndrome can be explained as defects in relating sensory information to past experience or in evaluating sensory stimuli in terms of their biologic significance. Temporal lobe epilepsy is characterized by a combination of psychological and motor manifestations. Schizophrenia is a mental illness with undefined neuropathology. Cortical and subcortical limbic structures are likely sites of the neuropathology. Alzheimer's disease is a degenerative brain disease characterized by severe memory loss, disorientation, and behavioral changes. The brunt of the pathology is in the entorhinal cortex, which isolates the hippocampal formation from the rest of the cerebral cortex.
ABNORM ALITIES OF OLFACTION Rhinencephalic st ruct ures can be aff ect ed in several sit es, result ing in derangement of t he sense of smell. O lf act ory recept ors in t he nose are involved in common colds, result ing in bilat eral diminut ion or loss of smell (anosmia). O lf act ory nerve f ibers may be aff ect ed in t heir course t hrough t he cribrif orm plat e of t he et hmoid bone af t er f ract ures of t he plat e and severe f alls. The anosmia in such cases result s f rom t he shearing of t he f ine olf act ory nerve f ibers as t hey pass t hrough t he cribrif orm plat e. The olf act ory bulb and t ract may be involved in inf lammat ory processes of t he meninges (meningit is) or t umors (meningiomas) in t he inf erior surf ace of t he f ront al lobe or t he ant erior cranial f ossa. Unilat eral loss of smell (anosmia) may
be t he earliest clinical manif est at ion of a subf ront al meningioma. Pat hologic processes in t he region of t he primary olf act ory cort ex (uncus of t he t emporal lobe) usually give rise t o hallucinat ions of smell (uncinat e f it s). The odor experienced in such cases of t en is described as unpleasant . Such hallucinat ions may herald an epilept ic seizure or be part of it .
M EM ORY The t erm memory ref ers t o t he encoding, st orage, and ret rieval of inf ormat ion. A def ect in one or more of t hese processes result s in memory impairment (amnesia). The role of t he nervous syst em in memory has been st udied by using neurosurgical t echniques (ablat ion of select ive areas of t he brain), elect rophysiologic met hods (neural pat hw ays and mechanisms), biochemical st udies (t he role of RNA and ot her prot eins), a neuropharmacologic approach (t he eff ect of drugs on synapt ic t ransmission and int racellular processes), and st udies of humans w it h a memory def icit (amnesia). Memory seems t o depend on t w o dist inct changes: an elect ric membrane event of a t emporary nat ure and a more st able, permanent change in t he chemist ry of t he nervous syst em. The discovery t hat DNA and RNA can act as codes f or synapt ic t ransmission has led t o t he t heory t hat t hose subst ances are responsible f or t ransf orming short -t erm memories int o permanent st ores.
Types of Memory Memories are eit her explicit or implicit .
A. Explicit (Declarative) M emory Explicit memory ref ers t o conscious ret rieval of inf ormat ion. I t support s t he learning and ret ent ion of f act s and t he conscious recollect ion of prior event s (know ing t hat ). Thus, it is consciously accessed. There are t w o subt ypes of explicit memory: (1) episodic and (2) semant ic. Episodic (unique) memory is t he memory of personally experienced f act s and event s w it h special spat ial and t emporal localizat ion, such as t he memory of eat ing a specif ic t ype of f ood in a rest aurant . Semant ic (nonunique, generic) memory ref ers t o t he memory of cult urally and educat ionally acquired encyclopedic know ledge such as t he meaning of w ords, arit hmet ical f act s, and geographic and hist orical inf ormat ion, f or example, t hat Paris is t he capit al of France and t hat bist ro is French f or r est aurant . Episodic memory can be short or long t erm.
1. Short-Term (Immediate, Recent, Working) Memory.
Short -t erm memory ref ers t o t he memory of a limit ed amount of inf ormat ion (e. g. , a seven-digit t elephone number) held cont inuously in consciousness f or a short period (less t han 60 s). This t ype of memory decays in seconds if it is not ref reshed cont inuously.
2. Long-Term (Remote) Memory. Long-t erm memory ref ers t o t he memory ret rieved af t er delays longer t han one minut e, and in t he case of remot e memory, f or more dist ant past .
B. Implicit M emory I mplicit memory support s t he learning and ret ent ion of skills (know ing how ). I t is t he memory of experience-aff ect ed behaviors t hat are perf ormed unconsciously. There are t w o t ypes of implicit memory: (1) procedural memory and (2) priming.
1. Procedural Memory. Procedural memory (skill learning) is t he phenomenon in w hich repeat ed perf ormance of a mot or act , such as driving or riding a bike, enhances and aut omat es f ut ure skill f or t he same act . I t is charact erist ically resist ant t o f orget t ing, hence it s preservat ion in pat ient s w ho are ot herw ise amnesic.
2. Priming. Priming ref ers t o short -lived enhancement of percept ually based perf ormance f ollow ing recent exposure t o visually similar mat erial, such as complet ing a t hree-let t er it em w it h a w ord t hat has been present ed previously or recognizing a w ord or pict ure f ast er or more accurat ely because of prior exposure. Table 22-1 is a summary of t he t ypes of memory. I mmediat e memory may be explained as a t ransient elect ric alt erat ion at t he synapse; longer-last ing memory may be explained as an act ual physical or chemical alt erat ion of t he synapse. Several of t hese alt erat ions have been described in diff erent experiment al sit uat ions, including changes in t he number and size of synapt ic t erminals as w ell as t heir chemical composit ion. Changes in post synapt ic neurons also have been described. Such changes in t he pre- or post synapt ic component s of t he synapse have been t hought t o f acilit at e t he t ransmission of impulses at t he synapse and t hus est ablish a memory code, or ingram. Tabl e 22-1. Memory Types
Explicit
Semantic Episodic Short term Long term Anterograde Retrograde Implicit Procedural Priming Several biochemical st udies have suggest ed a role f or prot ein and RNA in memory mechanisms. Evidence f or t his role has been obt ained f rom (1) experiment s in w hich prot ein and RNA synt heses w ere increased or blocked by drugs, (2) measurement of t he prot ein and RNA cont ent of st imulat ed neuronal syst ems, and (3) experiment s in w hich learned t asks w ere presumably t ransf erred f rom a t rained animal t o an unt rained animal af t er t he inject ion of RNA or prot ein f rom t he brain of t he t rained subject .
Anatomic Correlates of Memory The diff erent t ypes of memory are support ed by diff erent neural syst ems.
A. Episodic M emory The mesial t emporal cort ex (hippocampus, ent orhinal cort ex, perirhinal cort ex, and parahippocampal gyrus) are crit ical f or episodic memory. Pat ient s w it h bilat eral hippocampal resect ion (f or t reat ment of int ract able epilepsy) or acquired lesions (herpes simplex encephalit is) are unable t o acquire new explicit (declarat ive) memory (ant erograde amnesia). I n t hese pat ient s, no new inf ormat ion is ever ret ained beyond t he span of 40 6 0 seconds. Lesions ext ending beyond t he hippocampus t o involve adjacent mesial t emporal regions are associat ed w it h severe ant erograde and/ or ret rograde amnesia. Besides t he mesial t emporal cort ex, t he f ollow ing brain regions are implicat ed in episodic memory: (1) cort ico-cort ical connect ions f rom post erior and ant erior neocort ices t o t he ent orhinal cort ex, (2) hippocampus-mamillary body-ant erior and medial t halamic nuclei via t he f ornix and mamillot halamic t ract , and 3) basal f orebrain
cholinergic nuclei (nucleus basalis of Meynert ).
B. Semantic M emory The t emporal, pariet al, and occipit al lobes, part icularly t he t emporal neocort ex, are associat ed w it h semant ic memory. Semant ic memory impairment is seen in pat ient s w it h bilat eral lesions in t he above cort ices as occurs in herpes simplex encephalit is and Alzheimer's disease. Right hemisphere damage is more import ant t han lef t hemisphere damage.
C. Short-Term (Working) M emory St udies on short -t erm memory point t o t w o separat e neural syst ems t hat handle verbal and nonverbal inf ormat ion. I n pat ient s w it h lef t hemisphere dominance f or language, t he lef t pref ront al cort ex subserves w orking memory f or verbal mat erial, and t he right pref ront al cort ex subserves w orking memory f or nonverbal mat erial. Working memory is unaff ect ed in mesial t emporal lesions.
D. Procedural (Skill Learning) M emory Skill learning memory is a f unct ion of subcort ical circuit s, part icularly in t he basal ganglia and cerebellum, and is t hus unaff ect ed by mesial t emporal pat hology.
E. Priming The neural basis of priming is not cert ain but is most probably relat ed t o unimodal sensory associat ion areas.
Types of Memory Loss (Amnesia) Several t ypes of amnesia are recognized: (1) ret rograde, (2) ant erograde, (3) global, (4) modalit y-specif ic, (5) permanent , and (6) t ransient . Ret rograde amnesia is amnesia f or inf ormat ion learned bef ore t he onset of an illness. Ant erograde amnesia is amnesia f or inf ormat ion t hat should have been acquired af t er t he onset of an illness. Ant erograde amnesia is t he most common t ype of amnesia. I t usually aff ect s verbal and nonverbal (visual) mat erials equally, alt hough unilat eral lef t t emporal lobe damage may select ively aff ect acquisit ion of verbal inf ormat ion, w hereas right t emporal lobe damage may select ively aff ect nonverbal inf ormat ion, such as f aces and locat ion of it ems. Ret rograde amnesia occurs usually in associat ion w it h ant erograde amnesia and is most pronounced f or event s in t he years just preceding t he lesion. G lobal amnesia is an acut e, t ransient (minut es t o hours) severe ant erograde, w it h variable periods of ret rograde amnesia in w hich inf ormat ion cannot be ret rieved
t hrough any sensory channel. Transient global amnesia w as f irst described in 1956 by Morris Bender, and t he t erm w as coined by C. Miller Fisher and Raymond Adams in 1964. Modalit y-specif ic amnesia is t he inabilit y t o ret rieve inf ormat ion t hrough a specif ic channel, such as vision. Amnesia may be permanent , as in Alzheimer's disease, or t ransient , as in post t raumat ic and global amnesia. Much of our know ledge about memory loss has come f rom caref ul observat ions of pat ient s w it h amnesia. Alt hough a relat ionship bet w een t he t emporal lobe and loss of memory w as recognized at around t he t urn of t he cent ury by t he Russian neuropat hologist Vladimir Bekht erev, it w as William Scoville in 1953 w ho est ablished a precise relat ionship bet w een bilat eral ant erior t emporal lobe lesions and ant erograde amnesia. Scoville's pat ient underw ent bilat eral ant erior t emporal lobect omies f or t he t reat ment of int ract able seizures. The lesion included t he ant erior hippocampal f ormat ion and parahippocampal gyrus and t he amygdala. While t he seizures responded f avorably, t he pat ient w as lef t w it h severe declarat ive memory loss and ant erograde memory loss. His ret rograde memory and implicit (procedural) memory w ere not aff ect ed. Pat hologic processes in t he brain may aff ect one t ype of memory and spare ot hers. O lder people lose t he abilit y t o recall w hat t hey at e earlier in t he day but can recall, in t he minut est det ail, experiences t hey had many years earlier. People w ho suff er head t rauma in a car accident are unable t o recall w hat t ranspired f or minut es t o hours bef ore t he accident , but t he recall of older memories remains int act . Severe impairment of episodic memory is t he hallmark of Alzheimer's disease. How ever, ot her t ypes of memory are aff ect ed in t his disease, including semant ic memory, some aspect s of implicit memory, and short -t erm memory.
WERNICKE-KORSAKOFF SYNDROM E The Wernicke-Korsakoff syndrome, w hich w as described by Wernicke in 1881 and Korsakoff in 1887, is charact erized by severe ant erograde and ret rograde amnesia and conf abulat ion. The cause of t his syndrome is vit amin B1 (t hiamine) def iciency result ing f rom malnut rit ion associat ed w it h chronic alcohol int ake. The lesion in Korsakoff 's syndrome involves t he dorsomedial and midline nuclei of t he t halamus, mamillary body, and f ront al cerebral cort ex.
TRANSIENT GLOBAL AM NESIA Transient global amnesia is a short -t erm neurologic condit ion t hat is charact erized by sudden memory loss of recent event s, t ransient inabilit y t o ret ain new inf ormat ion (ant erograde amnesia), and ret rograde amnesia of variable ext ension. I mmediat e and very remot e memories are unaff ect ed. Complet e recovery usually occurs w it hin a f ew hours. The t erm t ransient global amnesia w as coined by Fisher and Adams in 1964. The exact mechanism of
t ransient global amnesia remains cont roversial. This t ype of amnesia has been associat ed w it h epilepsy, migraine headache, and t umor. Most report s emphasize bilat eral t ransient ischemia in t he t errit ory of t he post erior cerebral circulat ion aff ect ing medial t emporal lobe st ruct ures t hat are import ant f or memory. More recent st udies on t ransient global amnesia implicat e spreading cort ical depression in medial t emporal st ruct ures in t he pat hogenesis of t he amnesia. The episodes of t ransient amnesia may be preceded by charact erist ic event s or act ivit ies such as exert ion, int ense emot ion, sexual int ercourse, t emperat ure ext remes, and bat hing.
KLÜVER-BUCY SYNDROM E The Klüver-Bucy syndrome is a clinical syndrome observed in humans and ot her animals af t er bilat eral lesions in t he t emporal lobe t hat involve t he amygdala, hippocampal f ormat ion, and adjacent neural st ruct ures. The syndrome w as f irst described by Klüver and Bucy in 1939 in monkeys af t er bilat eral t emporal lobect omy. The human count erpart w as described by Terzian and Dalle O re in 1955 and by Marlow e in 1975. The syndrome is manif est ed by t he f ollow ing sympt oms: 1. Visual agnosia or psychic blindness (inabilit y t o diff erent iat e bet w een f riends, relat ives, and st rangers). 2. Hyperoralit y (t endency t o examine all object s by mout h). 3. Hypersexualit y (normal as w ell as pervert ed sexual act ivit y). Such pat ient s and animals manif est height ened sexual drives t ow ard eit her sex of t heir ow n or ot her species and even inanimat e object s. 4. Docilit y. 5. Lack of emot ional response, blunt ed aff ect , and apat hy. 6. I ncreased appet it e, bulimia. 7. Memory def icit . The various manif est at ions of t his syndrome ref lect a def ect in relat ing sensory inf ormat ion t o past experience or evaluat ing sensory st imuli in t erms of t heir biologic signif icance.
TEM PORAL LOBE EPILEPSY Anot her manif est at ion of limbic lesions in humans is t emporal lobe epilepsy, w hich also is know n as psychomot or seizures, uncinat e f it s, and complex part ial seizures. During t he seizure, t he pat ient may manif est one or more of t he f ollow ing sympt oms:
1. O lf act ory hallucinat ions consist ing of t ransient and recurrent episodes of unpleasant olf act ory experiences such as smelling burning rubber. 2. G ust at ory hallucinat ions consist ing of a t ransient unpleasant t ast e sensat ion. 3. Audit ory hallucinat ions. 4. Visual hallucinat ions (déjŕ vu). 5. Rhyt hmic movement s relat ed t o f eeding (chew ing, licking, sw allow ing). 6. Complex mot or act s such as w alking, undressing, and t w ist ing movement s of t runk and ext remit ies. 7. Amnesia, w hich may last several hours or days. 8. Aggressive behavior. During t he seizure, such pat ient s may commit violent or even criminal act s. The pat hology in t emporal lobe seizures involves t he hippocampus, ent orhinal cort ex, and amygdala. Magnet ic resonance imaging (MRI ) is usef ul in ident if ying t emporal lobe pat hology, such as mesial t emporal lobe sclerosis and t umor (Figure 22-1). Unexplained deat h has been report ed in pat ient s w it h t emporal lobe epilepsy. This has been at t ribut ed t o aut onomic changes in cardiovascular f unct ion during a seizure. Aut onomic cardiovascular responses have been elicit ed on st imulat ion of t he insular cort ex in humans. St imulat ion of t he right insular cort ex produces sympat het ic eff ect s on cardiovascular f unct ion (t achycardia and pressor eff ect s). St imulat ion of t he lef t insular cort ex, in cont rast , produces parasympat het ic eff ect s (bradycardia and depressor eff ect s).
Fi gure 22-1. G adolinium-enhanced T1-w eight ed magnet ic resonance image of t he brain show ing an enhancing lesion (t umor) (arrow) in t he t emporal lobe.
SCHIZOPHRENIA Schizophrenia is a severe ment al illness charact erized by disorganized t hought processes, hallucinat ions, delusions, and cognit ive def icit s. Vulnerabilit y t o schizophrenia is 60% genet ic and 40% environment al. Alt hough t he def init ive neuropat hology of schizophrenia has not been def ined, it includes vent riculo-megaly, diff use neuronal loss and disorganizat ion, and decreased f ront al blood f low and met abolism. Neurochemical st udies have st rongly support ed a dysf unct ional dopaminergic neurot ransmission. Thus, t he pat hology involves bot h cort ical and subcort ical st ruct ures. Numerous pat hologic mechanisms have been proposed f or schizophrenia. The current ly predominant hypot hesis is abnormal neurodevelopment t hat becomes manif est in adolescence. The alt ernat ive hypot hesis is a neurodegenerat ive one. Cyt oarchit ect ural st udies in schizophrenic brains point t o abnormal laminar organizat ion in limbic st ruct ures t hat are suggest ive of abnormal neuronal migrat ion during brain development . Findings f rom diff erent st udies suggest a m isw iring of neural connect ions in t he schizophrenic brain.
ALZHEIM ER'S DISEASE Alzheimer's disease is a degenerat ive brain disorder t hat is charact erized by memory loss severe enough t o impair everyday act ivit ies; disorient at ion t o t ime, place, and person; and behavioral changes such as depression, paranoia, and aggressiveness. Memory loss st art s w it h recent (short -t erm) memory such as remembering t o keep appoint ment s, and progresses t o involve remot e (longt erm) memory such as f orget t ing names of children and spouses, and f inally, in t he end st age, t o nearly t ot al loss of memory. The gross neuropat hologic hallmarks of Alzheimer's disease consist of at rophic gyri and w idened sulci (Figure 22-2) most prominent in t he limbic cort ex. The associat ion cort ices are heavily aff ect ed, w hereas primary sensory cort ices are minimally aff ect ed and t he mot or cort ex is least aff ect ed. Microscopically, t he neuropat hologic hallmarks of t he disease consist of neurof ibrillary t angles and senile plaques. Neurochemical st udies have demonst rat ed abnormal accumulat ion in senile plaques of a breakdow n product of amyloid precursor prot ein know n as bet aamyloid or A4 amyloid as w ell as accumulat ion of t au prot ein in neurons dest ined t o have neurof ibrillary t angles. The cognit ive def icit in Alzheimer's disease has been at t ribut ed t o an abnormalit y in t he cholinergic syst em. I n support of t his hypot hesis are t he loss in Alzheimer's brains of cholinergic project ion neurons in
t he nucleus basalis of Meynert and t he loss t hroughout t he cerebral cort ex of choline acet ylt ransf erase act ivit y. Caref ul st udies on t he dist ribut ion of neurof ibrillary t angles in Alzheimer's brains have show n a preponderance of t hese t angles in limbic and mult imodal associat ion cort ices compared w it h primary associat ion, primary sensory, and primary mot or cort ices. The most aff ect ed areas are t he ant erior part s of t he parahippocampal gyrus and part icularly in t he ent orhinal cort ex (area 28). I t is w ell est ablished t hat t he ent orhinal cort ex serves as a link bet w een t he hippocampal f ormat ion (import ant f or memory) and t he rest of t he cerebral cort ex. Severe neuropat hology in t he ent orhinal cort ex, as occurs in Alzheimer's disease, t hus isolat es or disconnect s t he hippocampal f ormat ion f rom t he remainder of t he cort ex and result s in severe memory loss. Alzheimer's disease t hus is a disorder w here t here is a breakdow n of cort ical neural syst ems crit ical f or higher cognit ive behaviors (t hought , reasoning, memory). Alzheimer's disease has been show n t o be a polygenet ic disease. Mut at ions in chromosomes 21, 14, and 1 have been associat ed w it h t he disorder. All t hree chromosomes have been relat ed t o early onset aut osomal dominant Alzheimer's disease. Chromosome 19 has been associat ed w it h lat e onset f amilial and sporadic Alzheimer's disease.
HERPES SIM PLEX ENCEPHALITIS Herpes simplex encephalit is is a viral encephalit is caused by herpesvirus and charact erized by f ocal seizures, f ocal neurologic signs, and progressive det eriorat ion of consciousness. I t is t he single most import ant cause of f at al sporadic encephalit is in t he Unit ed St at es. The neuropat hology consist s of a severe f ocal necrot izing process w it h a predilect ion f or t he limbic syst em. A brain biopsy is diagnost ic in show ing charact erist ic int ranuclear viral inclusions (Figure 22-3) (Cow dry t ype A inclusions) and inf lammat ion. MRI is t he most sensit ive noninvasive t est f or t he early diagnosis of herpes simplex encephalit is and t he demonst rat ion of pat hology in t he limbic syst em (Figure 22-4). Early diagnosis is crucial because t here is an eff ect ive ant iviral t reat ment f or t his t ype of encephalit is.
Fi gure 22-2. Lat eral view of t he brain show ing prominence of sulci (arrows) and at rophy of gyri (stars) in Alzheimer's disease.
Fi gure 22-3. Elect ron micrograph show ing int ranuclear viral inclusions (Cow dry t ype A) (arrow) in brain biopsy of a pat ient w it h herpes simplex encephalit is.
TERM INOLOGY Alzheimer's disease. A progressive degenerat ive brain disorder charact erized by severe loss of memory, disorient at ion, and behavioral changes. Named af t er Alois Alzheimer, a G erman neuropsychiat rist and pat hologist w ho described t he disorder verbally in 1906 and in w rit ing in 1907. Amnesia (G reek, f orgetfulness ) . Lack of or loss of memory. Amnesi a w as an old t erm f or loss of memory. The modern use of t he w ord dat es f rom about 1861 and t he w ork of Broca, w ho divided disorders of speech caused by cent ral lesions int o aphemia and verbal amnesia. The t erm f irst appeared in English in 1862. Broca's use of t he t erm verbal amnesi a (impaired w ord f inding) is no longer current . Anosmia (G reek an, n egative ; osme, s mell ) . Absence of t he sense of smell. The condit ion w as f irst ment ioned by G alen. Bekhterev, Vladimir Mikhailovitch (1857 1 927). Russian neuropat hologist and psychiat rist w hose cont ribut ions include descript ions of t he superior vest ibular nucleus (Bekht erev nucleus), t he relat ionship bet w een t emporal lobe and memory, and spasmodic laught er and w eeping in hemiplegic pat ient s (Bekht erev-Brissaud sign), among ot her f indings. Bulimia (G reek bous, o x ; l i mos, h unger ) . An eat ing disorder charact erized by episodes of binge eat ing t hat cont inue unt il t hey are t erminat ed by abdominal pain, sleep, or self -induced vomit ing. Cribriform (Latin cri brum, s ieve ; forma, f orm ) . The cribrif orm plat e of t he et hmoid bone is perf orat ed w it h small apert ures, resembling a sieve. Ancient anat omist s w ere especially int erest ed in t he perf orat ions of t he et hmoid bone because of t heir t heory t hat pit uit a (mucous brain secret ions) ent ered t he nose t hrough t hese channels. Déjŕ vu (French, a lready seen ) . An illusion in w hich a new sit uat ion is incorrect ly view ed as a repet it ion of a previous sit uat ion. Usually an aura of t emporal lobe seizures. Klüver-Bucy syndrome. A clinical syndrome charact erized by visual agnosia, hyperoralit y, hypersexualit y, docilit y, blunt ed aff ect , bulimia, and memory def icit . First described in monkeys by H. Klüver, and P. C. Bucy in 1937. Korsakoff's syndrome (Wernicke-Korsakoff syndrome). A syndrome of t hiamine def iciency in chronic alcoholics t hat is charact erized by loss of memory and conf abulat ion. The syndrome w as f irst described by Magnus Huss, a Sw edish physician. St rumpell, in 1883, and Charcot , in 1884, called at t ent ion t o t his syndrome. Charles G ayet described t he pat hology in 1875. Karl
Wernicke, a G erman neuropsychiat rist , described t hree cases in 1881 and named t he disorder acut e superior hemorrhagic polioencephalit is. Sergi Korsakoff , a Russian neuropsychiat rist , summarized t he syndrome and described it as an ent it y bet w een 1887 and 1889. The role of vit amin def iciency in t he et iology of t he syndrome w as est ablished by Pet ers in 1936.
Fi gure 22-4. T2-w eight ed magnet ic resonance image of t he brain show ing increased signal int ensit y (arrows) in component s of t he limbic syst em in a pat ient w it h herpes simplex encephalit is.
Nucleus basalis of Meynert. A group of neurons in t he subst ant ia innominat a below t he globus pallidus. This nucleus is t he source of cholinergic innervat ion of t he cerebral cort ex. Loss of neurons in t he nucleus occurs in pat ient s w it h Alzheimer's disease. Named af t er Theodor Hermann Meynert , an Aust rian psychiat rist . Psychic blindness (visual agnosia). A disorder in w hich pat ient s w it h normal vision f ail t o comprehend t he nat ure or meaning of nonverbal visual st imuli. Rhinencephalon (G reek rhi n, n ose ; enkephal os, b rain ) . The smell brain. Uncinate fits (Latin, h ook ) . Uncinat e f it s arise f rom t he area of t he uncus, t he medially curved (like a hook) ant erior end of t he parahippocampal gyrus.
SUGGESTED READINGS
Arnold SE, Trojanow ski JQ : Recent advances in def ining t he neuropat hology of schizophrenia. Acta Neuropathol ( Berl ) 1996; 92: 217 2 31. Blass JP, G ibson G E: Abnormalit y of a t hiamine-requiring enzyme in pat ient s w it h Wernicke-Korsakoff syndrome. N Engl J Med 1977; 297: 1367 1 370. Bossi L et al: Somat omot or manif est at ions of t emporal lobe seizures. Epi l epsi a 1984; 25: 70 7 6. Braak H et al: Funct ional anat omy of human hippocampal f ormat ion and relat ed st ruct ures. J Chi l d Neurol 1996; 11: 265 2 75. D'Esposit o M et al: Amnesia f ollow ing t raumat ic bilat eral f ornix t ransect ion. Neurol ogy 1995; 45: 1546 1 550. Eichenbaum H et al: Select ive olf act ory def icit s in case H. M. Brai n 1983; 106: 459 4 72. Freeman R, Schacht er SC: Aut onomic epilepsy. Semi n Neurol 1995; 15: 158 1 66. G abrieli JDE: Disorders of memory in humans. Curr O pi n Neurol Neurosurg 1993; 6: 93 9 7. G aff an D, G aff an EA: Amnesia in man f ollow ing t ransect ion of t he f ornix. Brai n 1991; 114: 2611 2 618. G aff an EA et al: Amnesia f ollow ing damage t o t he lef t f ornix and t o ot her sit es: A comparat ive st udy. Brai n 1991; 114: 1297 1 313. G rabow ski TJ et al: Cardinal sympt oms of disordered cognit ion. Conti nuum 2002; 8: 41 1 26. Horel JA: The neuroanat omy of amnesia: A crit ique of t he hippocampal memory hypot hesis. Brai n 1978; 101: 403 4 45. Jaf ek BW et al: Post -t raumat ic anosmia: Ult rast ruct ural correlat es. Arch Neurol 1989; 46: 300 3 04. Klüver H, Bucy PC: Preliminary analysis of f unct ions of t he t emporal lobes in monkeys. Arch Neurol Psychi atry 1939; 42: 979 1 000.
Krit chevsky M et al: Transient global amnesia: Charact erizat ion of ant erograde and ret rograde amnesia. Neurol ogy 1988; 38: 213 2 19. Laloux P et al: Technet ium-99m HM-PAO single phot on emission comput ed t omography imaging in t ransient global amnesia. Arch Neurol 1992; 49: 543 5 46. Marlow WB et al: Complet e Klüver Bucy syndrome in man. Cortex 1975; 11: 53 5 9. Mesulam M-M: Large-scale neurocognit ive net w orks and dist ribut ed processing f or at t ent ion, language, and memory. Ann Neurol 1990; 28: 597 6 13. Miller JW et al: Transient global amnesia: Clinical charact erist ics and prognosis. Neurol ogy 1987; 37: 733 7 37. Miller JW et al: Transient global amnesia and epilepsy: Elect roencephalographic dist inct ion. Arch Neurol 1987; 44: 629 6 33. Nissen MJ et al: Neurochemical dissociat ion of memory syst ems. Neurol ogy 1987; 37: 789 7 94. Perani D et al: Evidence of mult iple memory syst ems in t he human brain: A [ 18 F] FDG PET met abolic st udy. Brai n 1993; 116: 903 9 19. Perry RJ, Hodges JR: Spect rum of memory dysf unct ion in degenerat ive disease. Curr O pi n Neurol 1996; 9: 281 2 85. Rapp PR, Heindel WC: Memory syst ems in normal and pat hological aging. Curr O pi n Neurol 1994; 7: 294 2 98. Scoville WB, Milner B: Loss of recent memory af t er bilat eral hippocampal lesions. J Neurol Neurosurg Psychi atry 1957; 20: 11 2 1. Terzian H, Dalle O re G : Syndrome of Klüver and Bucy reproduced in man by bilat eral removal of t he t emporal lobes. Neurol ogy 1955; 5: 373 3 80. Van Hoesen G W, Solodkin A: Cellular and syst ems neuroanat omical changes in Alzheimer's disease. I n Dist enhoff JE et al (eds): Cal ci um Hypothesi s of
Agi ng and Dementi a. Ann NY Acad Sci 1994; 747: 12 3 5. Winocur G et al: Amnesia in a pat ient w it h bilat eral lesions t o t he t halamus. Neuropsychol ogi a 1984; 22: 123 1 43. Yanker B, Mesulam M-M: β -Amyloid and t he pat hogenesis of Alzheimer's disease. N Engl J Med 1991; 325: 1849 1 857.
Editors: Afifi, Adel K. ; Bergman, Ronald A. T itle: Functi onal Neuroanatomy: Text and A tl as, 2nd Edi ti on Copyright Š2005 McG raw -Hill > Table of C ontents > P ar t I - Text > 23 - S pec ial S ens es
23 Special Senses
Olfaction Olfactory Epithelium Olfactory Nerve yOlfactory Bulb Olfactory Tract Olfactory Striae Primary Olfactory Cortex Olfactory Mechanismsy Taste Taste Buds Physiology of Taste Central Transmission of Taste Sensations Vision The Retina Variations in Retinal Structure Synaptic Organization of the Retina Photochemistry and Physiology of the Retina Dark and Light Adaptation Color Vision Visual Pathways Hearing The Ear Sound Transmission Cochlea
Auditory End Organ (Organ of Corti) Auditory Physiology Otoacoustic Emissions Audiometry Deafness Vestibular Sensation KEY CONCEPTS The olfactory sense organ is located in the roof of the nose and the upper part of the lateral wall and septum. Olfactory nerve fibers synapse on mitral and tufted neurons of the olfactory bulb. The olfactory tract subdivides into three striae. The gustatory (taste) sense organs (taste buds) are distributed in the tongue, soft palate, oropharynx, and epiglottis. Taste buds in different locations of the tongue respond best to different tastes. Those at the tip of the tongue respond best to sweet and salty substances; those at the margins and posterior part of the tongue respond best to sour and bitter substances. Taste sensations are transmitted centrally via three cranial nerves: facial, glossopharyngeal, and vagus. Central taste pathways establish synapses in several brain stem nuclei (nucleus solitarius, reticular nuclei, ventral posterior medial) before reaching the primary gustatory cortex in the inferior part of the somesthetic cortex. The visual receptor cells are located in the retina.
Axons of ganglion cells form the optic nerve. Crossed and uncrossed optic nerve fibers join caudal to the optic chiasma to form the optic tract. Axons of neurons in the lateral geniculate nucleus form the geniculocalcarine tract (optic radiation). Geniculocalcarine fibers terminate, in a retinotopic fashion, in the primary visual (striate) cortex in the occipital lobe. The sense organs for hearing and equilibrium are in the inner ear. Efferent nerves originating from the superior olivary complex modulate activity in hair cells.
P.30 Central auditory pathways synapse in several brain stem nuclei before terminating in the primary auditory cortex (transverse gyri of Heschl) in the temporal lobe. Receptors of the vestibular sense organ are located in the inner ear (semicircular canals, utricle, saccule). Central vestibular pathways are directed to several neural structures: spinal cord, cerebellum, thalamus, nuclei of extraocular movement, and the cerebral cortex. The vestibular system is essential for the coordination of motor responses, eye movement, and posture.
The diff erent sensat ions perceived by t he human body are grouped int o t w o major cat egories: t hose concerned w it h general sensat ions (t ouch, pressure, pain, and t emperat ure) and t hose concerned w it h special sensat ions (olf act ion,
t ast e, vision, audit ion, and sense of posit ion and movement ). This chapt er is devot ed t o a considerat ion of t he organs of special senses. Whereas nerve endings concerned w it h general sensibilit y are dist ribut ed w idely, t hose concerned w it h special sensat ions are limit ed t o specif ic areas of t he body.
OLFACTION O lf act ory st imuli are received by recept ors of t he olf act ory epit helium in t he nasal w all and are conveyed via olf act ory nerve f ibers t hrough t he cribrif orm plat e of t he et hmoid bone t o t he olf act ory bulb inside t he cranial cavit y (see Figure 21-2). Wit hin t he olf act ory bulb, axons of t he olf act ory nerve synapse w it h mit ral and t uf t ed cells in a complex st ruct ure know n as t he olf act ory glomerulus (see Figure 21-3). Axons of mit ral and t uf t ed neurons f orm t he olf act ory t ract , w hich lies in t he olf act ory sulcus on t he undersurf ace of t he f ront al lobe. Close t o t he ant erior perf orat ed subst ance, t he olf act ory t ract divides int o t he lat eral, int ermediat e, and medial olf act ory st riae (see Figures 23-1 and 23-2). The lat eral olf act ory st ria t erminat es in t he primary olf act ory cort ex, w here olf act ion is perceived. The medial olf act ory st ria joins t he ant erior commissure t o reach t he cont ralat eral olf act ory t ract and bulb. I t also project s on limbic syst em st ruct ures. The int ermediat e olf act ory st ria blends w it h t he ant erior perf orat ed subst ance. The medial and int ermediat e olf act ory st riae are not w ell developed in humans and do not play a role in percept ion of olf act ory st imuli.
Olfactory Epithelium The olf act ory epit helium is locat ed in t he mucous membrane lining t he roof of t he nasal cavit y on t he inf erior surf ace of t he cribrif orm plat e of t he et hmoid bone. From t he roof , t he olf act ory epit helium ext ends dow n bot h sides of t he nasal cavit y t o cover most of t he superior concha lat erally and 1 cm of nasal sept um medially. Humans are microsmat ic animals in w hom t he surf ace area of olf act ory mucous membrane in bot h nost rils is small (approximat ely 5 cm2 ). Though microsmat ic, humans are able t o dist inguish large numbers of odors, some at very low concent rat ions. The olf act ory epit helium cont ains t hree t ypes of epit helial cells: recept or cells, support ing cells, and basal cells (Figure 23-1). I nt erspersed among epit helial cells are duct s of Bow man's glands.
A. Receptor Cells O lf act ory recept or cells are bipolar sensory neurons. Their perikarya are locat ed in t he low er part of t he olf act ory epit he-lium. Each cell has a single dendrit e t hat reaches t he surf ace of t he epit helium and f orms a knoblike expansion t hat ext ends beyond t he epit helial surf ace. From t his expansion, 10 t o 20 nonmot ile cilia project int o a layer of f luid covering t he epit helium. The olf act ory cilia cont ain recept ors f or odorant molecules. From t he basal part of t he perikaryon,
a nonmyelinat ed axon emerges and joins w it h axons of adjacent recept or cells t o f orm t he olf act ory nerve (f irst cranial nerve). O lf act ory nerve bundles penet rat e t he cribrif orm plat e of t he et hmoid bone t o reach t he olf act ory bulb-. I t is est imat ed t hat t here are more t han 100 million recept or cells in t he olf act ory mucosa. The specialized nerve cells of t he olf act ory epit helium are highly sensit ive t o diff erent odors. O lf act ory neurons are produced cont inuously f rom basal cells of t he olf act ory epit helium and are lost cont inuously by normal w ear and t ear. I t is est imat ed t hat olf act ory recept or cells have an average lif e span of 30 6 0 days. The presence of t hese nerve cells at t he surf ace exposes t hem unduly t o damage; it is est imat ed t hat 1 percent of t he f ibers of t he olf act ory nerves (axons of olf act ory neurons) are lost each year of lif e because of injury t o t he perikarya. The sense of smell t hus diminishes in t he elderly as a result of exposure of t he olf act ory epit helium t o repeat ed inf ect ions and t rauma in lif e. The presence of olf act ory neurons at t he surf ace represent s t he only except ion t o t he evolut ionary rule by w hich nerve cell bodies of aff erent neurons migrat e along t heir axons t o t ake up more cent ral and w ell-prot ect ed posit ions. The surf ace of t he olf act ory epit helium is moist ened const ant ly by secret ions of Bow man's glands. This moist ening helps dissolve t he gaseous subst ances, f acilit at ing st imulat ion of t he olf act ory epit helium. The cont inuous secret ion also cleanses t he recept ors of accumulat ed odorous subst ances and prevent s t heir ret ent ion.
Fi gure 23-1. Schemat ic diagram of t he cellular component s of t he olf act ory mucosa.
I t is believed t hat diff erent basic odors st imulat e diff erent olf act ory neurons. St imulat ion of diff erent combinat ions of recept ors f or basic odors is believed t o be t he basis f or humans' abilit y t o recognize all t he variet ies of odors t o w hich t hey are exposed.
B. Supporting (Sustentacular) Cells Support ing cells are columnar epit helial cells t hat separat e t he olf act ory recept or cells. The surf ace of support ing cells is specialized int o microvilli t hat project int o t he f luid layer covering t he epit helium. As t heir name suggest s, support ing cells provide mechanical support t o t he recept or cells. I n addit ion, t hey con-t ribut e, along w it h Bow man's gland, t o t he elaborat ion of t he overlying mucus. I n cont rast t o t he relat ively short lif e span of olf act ory recept or cells, support ing cells remain st able.
C. Basal Cells Basal cells are polygonal cells limit ed t o t he basal part of t he epit helium. They are t he source of new epit helial cells. Mit ot ic act ivit y persist s in t hese cells t hrough mat urit y.
D. Bow man's Glands Bow man's glands cont ain serous and mucous cells and are locat ed beneat h t he epit helium. They send t heir duct s in bet w een epit helial cells t o pour t heir secret ion ont o t he surf ace of t he epit helium, bat hing t he cilia of recept or cells and t he microvilli of support ing cells. The secret ion of Bow man's glands plays an import ant role in dissolving odorous subst ances and diff using t hem t o recept or cells.
Olfactory Nerve The olf act ory nerve (see Figure 21-2) is composed of unmyelinat ed t hin processes (root let s) of t he olf act ory hair cells in t he nasal mucosa. Fascicles of t he olf act ory nerve pierce t he cribrif orm plat e of t he et hmoid bone, ent er t he cranial cavit y, and t erminat e on neurons in t he olf act ory bulb.
Olfactory Bulb The olf act ory bulb (see Figures 21-1 and 21-2) is t he main relay st at ion in t he olf act ory pat hw ays. I t is locat ed on t he cribrif orm plat e of t he et hmoid and beneat h t he inf erior surf ace of t he f ront al lobe.
A. Lamination and Cell Types (See Figure 21-3) I n hist ologic sect ions, t he olf act ory bulb appears laminat ed int o t he f ollow ing layers (see Figure 21-3): O lfactory nerve layer. This layer is composed of incoming olf act ory nerve f ibers. G lomerular layer. I n t his layer, synapt ic f ormat ions occur bet w een olf act ory
nerve axons and dendrit es of olf act ory bulb neurons (mit ral and t uf t ed neurons). Plexiform layer. This layer consist s of t uf t ed neurons, some granule cells, and a f ew mit ral cells w it h t heir processes. Mitral cell layer. This layer is composed of large neurons (mi-t ral neurons). G ranule layer. Composed of small granule neurons and processes of granule and mit ral cells, t his layer also cont ains incoming f ibers f rom ot her cort ical regions. The mit ral and t uf t ed cells are considered t he principal neurons of t he olf act ory bulb. Their dendrit es est ablish synapt ic relat ionships w it h t he olf act ory nerve f ibers w it hin t he glomeruli. The granule cells (G ABAergic inhibit ory neurons) are considered t o be t he int rinsic neurons of t he olf act ory bulb. These cells have vert ically orient ed dendrit es but no axon and exert t heir act ion on ot her cells solely by dendrit es. The olf act ory bulb cont ains t w o ot her variet ies of int rinsic neurons. These are t he periglomerular short axon cells in close proximit y t o t he glomeruli in t he glomerular layer and t he deep short axon cells locat ed in t he granule layer. Dopamine has been report ed t o be present in t he olf act ory bulb. I t s deplet ion in pat ient s w it h Parkinson's disease may explain t he decrease of t he sense of smell in pat ient s w it h Parkinson's disease. The olf act ory bulb receives f ibers (input ) f rom t he f ollow ing sources: 1. O lf act ory hair c ells in t he nasal mucosa 2. Cont ralat eral olf act ory bulb 3. Primary olf act ory cort ex 4. Diagonal band of Broca 5. Ant erior olf act ory nucleus The out put f rom t he olf act ory bulb is t he olf act ory t ract .
Olfactory Tract The olf act ory t ract (see Figures 21-1 and 21-2) is t he out f low pat hw ay of t he olf act ory bulb. I t is composed of t he axons of principal neurons (mit ral and t uf t ed cells) of t he olf act ory bulb and cent rif ugal axons originat ing f rom t he cont ralat eral olf act ory bulb, as w ell as f rom cent ral brain regions. The olf act ory t ract also cont ains t he scat t ered neurons of t he ant erior olf act ory nucleus, t he axons of w hich cont ribut e t o t he olf act ory t ract . At it s caudal ext remit y, just ant erior t o t he ant erior perf orat ed subst ance, t he olf act ory t ract divides int o t he
olf act ory st riae (see Figures 21-1 and 21-2).
Olfactory Striae At it s caudal ext remit y, just rost ral t o t he ant erior perf orat ed subst ance, t he olf act ory t ract divides int o t hree st riae: 1. Lat eral olf act ory st ria 2.
Medial olf act ory st ria
3. I nt ermediat e olf act ory st ria. Each of t he st riae is covered by a t hin layer of gray mat t er, t he olf act ory gyri. The lat eral olf act ory st ria project s t o t he primary olf act ory cort ex in t he t emporal lobe. The medial olf act ory st ria project s on t he medial olf act ory area, also know n as t he sept al area, locat ed on t he medial surf ace of t he f ront al lobe, vent ral t o t he genu and rost rum of t he corpus callosum (subcallosal gyrus) and ant erior t o t he lamina t erminalis. The medial olf act ory area is closely relat ed t o t he limbic syst em and hence is concerned w it h emot ional responses elicit ed by olf act ory st imuli. I t does not play a role in t he percept ion of olf act ory st imuli. The medial and int ermediat e st riae are poorly developed in humans. The int ermediat e st ria blends w it h t he ant erior perf orat ed subst ance. The t hin cort ex at t his sit e is designat ed t he int ermediat e olf act ory area. The primary t erminal st at ions of t he t hree olf act ory st riae (olf act ory cort ices) are int erconnect ed by t he diagonal band of Broca, a bundle of subcort ical f ibers in f ront of t he opt ic t ract , and w it h a number of cort ical and subcort ical areas concerned w it h visceral f unct ion and emot ion (hippocampus, t halamus, hypot halamus, epit halamus, and brain st em ret icular f ormat ion). Through t hese connect ions, t he olf act ory syst em exert s inf luence on visceral f unct ion (salivat ion, nausea) and behavioral react ions.
Primary Olfactory Cortex The primary olf act ory cort ex is locat ed w it hin t he uncus of t he t emporal lobe and is composed of t he prepirif orm cort ex, periamygdaloid area, and part of t he ent orhinal area. The prepirif orm cort ex is t he region on each side of and beneat h t he lat eral olf act ory st ria; hence it is also called t he lat eral olf act ory gyrus. I t is considered t he major part of t he primary olf act ory cort ex. The primary olf act ory cort ex is relat ively large in some animals, such as t he rabbit , but in humans it occupies a small area. The primary olf act ory cort ex in humans is concerned w it h t he conscious percept ion of olf act ory st imuli. I n cont rast t o all ot her primary sensory cort ices (vision, audit ion, t ast e, and somat ic sensibilit y), t he primary olf act ory cort ex is unique in t hat aff erent f ibers f rom t he recept ors reach it
direct ly w it hout passing t hrough a relay in t he t halamus. The primary olf act ory cort ex cont ains t w o t ypes of neurons. These are (1) principal neurons (pyramidal cells) w it h axons t hat leave t he olf act ory cort ex and project t o nearby or dist ant regions and (2) int rinsic neurons (st ellat e cells) w it h axons t hat remain w it hin t he olf act ory cort ex. The major input t o t he primary olf act ory cort ex is f rom (1) t he olf act ory bulb via t he lat eral olf act ory st ria and (2) ot her cent ral brain regions. The out put f rom t he olf act ory cort ex is via axons of principal neurons t hat project t o nearby areas surrounding t he primary olf act ory cort ex, as w ell as t o more dist ant areas, such as t he t halamus and hypot halamus, w hich play import ant roles in behavior and emot ion.
Olfactory Mechanisms O lf act ion is a chemical sense. For a subst ance t o be det ect ed, it should have t he f ollow ing physical propert ies: Vol ati l i ty, so t hat it can be sniff ed Water sol ubi l i ty, so t hat it can diff use t hrough t he olf act ory epit helium Li pi d sol ubi l i ty, so t hat it w ill int eract w it h t he lipids of t he membranes of olf act ory recept ors Af t er an odorous subst ance is dissolved in t he f luid bat hing t he surf ace of t he olf act ory mucosa, it int eract s w it h recept or sit es locat ed on t he cilia of recept or cells. The binding of a single appropriat e molecule t o one recept or sit e causes a change in membrane permeabilit y. The ion f lux t hat ensues gives rise t o a slow surf ace negat ive w ave (recept or or generat or pot ent ial) t hat can be det ect ed at t he surf ace of t he recept or cell. An all-or-none act ion pot ent ial, how ever, can be det ect ed in t he axons of recept or cells. The olf act ory recept ors show a marked variabilit y in sensit ivit y t o diff erent odors. They can det ect met hyl mercapt an (garlic odor) in a concent rat ion of less t han one-milliont h of a milligram per lit er of air but et hyl et her in a concent rat ion of 5. 8 mg per lit er of air. O lf act ory recept ors adapt rat her quickly t o a cont inuous st imulus. Alt hough t he olf act ory mucosa can discriminat e among a large number of diff erent odors, it s abilit y t o det ect changes in concent rat ion of an odorous subst ance is rat her poor. I t is est imat ed t hat t he concent rat ion of an odorous subst ance must change by 30 percent bef ore it can be det ect ed by recept or cells. The mechanism of discriminat ion is poorly underst ood but is probably relat ed t o a spat ial pat t ern of st imulat ion of t he recept or cells.
TASTE
The gust at ory (t ast e) sense organs in higher vert ebrat es are limit ed t o t he cavit y of t he mout h. Tast e recept ors are locat ed w it hin t ast e buds in t he t ongue (circumvallat e and f ungif orm papillae), as w ell as in t he sof t palat e, oropharynx, and epiglot t is. Circumvallat e papillae are dist ribut ed in t he back of t he t ongue, w hereas f ungif orm papillae are scat t ered on t he ant erior t w o-t hirds of t he t ongue. There are about 2000 t ast e buds in t he human t ongue. This number decreases progressively w it h age. I t is est imat ed t hat t ast e buds are lost at a rat e of 1% per year w it h increased rat e af t er 40 years of age. Tast e sensat ions are conveyed cent rally via t hree cranial nerves: t he f acial (CN VI I ), glossopharyngeal (CN I X), and vagus (CN X) cranial nerves.
Taste Buds (Figure 23-2) Tast e buds are barrel-like st ruct ures dist ribut ed in t he epit helium of t he t ongue, sof t palat e, oropharynx, and epiglot t is. Each t ast e bud is composed of recept or (neuroepit helial), support ing and basal cells, and nerve f ibers.
A. Receptor Cells Tw o t ypes of recept or cells can be ident if ied in t ast e buds, clear recept or cells and dense recept or cells. Clear recept or cells cont ain clear vesicles; dense recept or cells cont ain dense-core vesicles t hat st ore glycosaminoglycans. Bot h cell t ypes presumably f unct ion as recept ors. They are believed t o represent t w o st ages in t he development of recept or element s, t he dense cell being t he more mat ure. The apex of each recept or cell is modif ied int o microvilli, w hich increase t he recept or surf ace area and project int o an opening, t he t ast e pore. Approximat ely 4 t o 20 recept or cells are locat ed in t he cent er of each t ast e bud. Recept or element s decrease in number w it h age. Recept or cells are st imulat ed by subst ances in solut ion.
Fi gure 23-2. Schemat ic diagram of t he cellular component s of t he t ast e bud.
B. Supporting Cells These are spindle-shaped cells t hat surround t he recept or cells. They are locat ed at t he periphery of t he t ast e bud. They have bot h an insulat ing f unct ion and a secret ory f unct ion. They are believed t o secret e t he subst ance t hat bat hes t he microvilli in t he t ast e pore.
C. Basal Cells Basal cells are locat ed at t he base of t he t ast e bud and, by division, replenish t he recept or cells t hat are lost cont inually w it h an average lif e span of 10 1 4 days.
D. Nerve Fibers The nerve f ibers in t he t ast e bud are t erminal nerve f ibers of t he f acial (chorda t ympani branch), glossopharyngeal (lingual-t onsillar branch), and vagus nerves (superior laryngeal branch). They are peripheral processes of sensory neurons in t he geniculat e ganglion of t he f acial nerve and in t he inf erior ganglia of t he glossopharyngeal and vagus nerves (pet rosal and nodose ganglia, respect ively). They ent er t he t ast e bud at it s base and w ind t hemselves around t he recept or cells in close apposit ion t o recept or cell membranes. Synapt ic vesicles clust er on t he inner surf aces of recept or cell membranes at sit es of apposit ion t o nerve t erminals.
Physiology of Taste Alt hough all t ast e buds look alike hist ologically, sensit ivit y t o t he f our basic t ast e modalit ies is diff erent in diff erent regions of t he t ongue. Like olf act ion, t he sense of t ast e is a chemical sense. Alt hough humans can t ast e a large number of subst ances, only f our primary t ast e sensat ions are ident if ied: Sour Salt y Sw eet Bit t er
Fi gure 23-3. Schemat ic diagram of t he gust at ory pat hw ays.
Most t ast e recept ors respond t o all f our primary t ast e modalit ies at varying t hresholds but respond pref erent ially at a very low t hreshold t o only one or t w o. Thus t ast e buds at t he t ip of t he t ongue respond best t o sw eet and salt y subst ances, and t hose at t he lat eral margins and post erior part of t he t ongue respond best t o sour and bit t er subst ances, respect ively. The abilit y of t ast e buds t o det ect changes in concent rat ion of a subst ance is poor, similar t o t he response of olf act ory recept ors. A diff erence in t ast e int ensit y remains undet ect ed unt il t he concent rat ion of a subst ance has changed by 30 percent . Subst ances in solut ion ent er t he pore of t he t ast e bud and come in cont act w it h t he surf ace of t ast e recept ors locat ed on microvilli of t ast e recept or cells. This cont act induces a change in t he elect rical pot ent ial of t he membrane of t he recept or cells (recept or or generat or pot ent ial). The recept or pot ent ial in t urn generat es an act ion pot ent ial in nerve t erminals in apposit ion t o t he recept or cell surf ace.
Central Transmission of Taste Sensations (Figure 23-3) Tast e sensat ions f rom t he ant erior t w o-t hirds of t he t ongue are mediat ed t o t he cent ral nervous syst em via t he chorda t ympani of t he sevent h (f acial) cranial nerve, t hose f rom t he post erior one-t hird of t he t ongue via t he nint h (glossopharyngeal) cranial nerve, and t hose f rom t he epiglot t is and
low er pharynx via t he t ent h (vagus) cranial nerve. These nerves cont ain t he peripheral processes of pseudounipolar sensory nerve cells locat ed in t he geniculat e ganglion (sevent h nerve), pet rous ganglion (nint h nerve), and nodose ganglion (t ent h nerve). These peripheral processes ent er t he deep ends of t he t ast e buds and est ablish int imat e cont act w it h t he neuroepit helial cells of t he buds. The cent ral processes of t hese sensory neurons project t o t he nucleus of t he t ract us solit arius (t he rost ral part of t he nucleus, t he gust at ory subnucleus) in t he brain st em. Axons of neurons in t he nucleus solit arius project on a number of ret icular nuclei (especially t he parabra