Complete About Caudate and Putamen

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$hapter 1

Striatum, Basal Ganglia, ThalamusCaudate, Putamen, Globus Pallidus, Limbic Striatumn's Disease, Alzheimer's Psychosis, Catatonia, bsessi!e"Com#ulsions $ Disorders o% &o!ement rom( )euro#sychia

)euro#sychology, Clinical )euroscience*rd +dition,

by ha-n .ose#h, Ph/D/0Academic Press, 1222/ )e- 3ork4

The Basal Gangliaglia, 8hose subdi7isions include the brainstem, cerebellum, thalamus, and striatum, guide all aspects o. gross muscular acti7ity, such as kicking, hitng, s8imming, and e7en smiling! 9hen in'ured, mo7ement may become labored, sti.., clumsy, or e7en .ro en as 8ell as marked by uncontrollableith Parkinson<s disease!



along 8ith the thalamus, are part o. the .orebrain, and in many respects, act as a ne=us, or inter.ace, bet8een the more recently e7ol7ed neocorticalrontal lobes, and the more ancient motor areas located in the brainstem! Important components o. the striatum, include the caudate, putamen, globuhe amygdala

e course o. 7ertebrate e7olution, motor .unctioning 8as the pro7ince o. the spinal cord, brainstem, cerebellum, and limic striatum, 'ust as it is in mmuch o. e7olution the .orebrain consisted o. the ol.actory system and the amygdala, hypothalamus, and hippocampus! The striatum 8as dominated

8as originally part o. the amygdala! &oreo7er, the entire .orebrain including the amygdala, hypothalamus, and hippocampus, 8as greatly in.luencm, reacting to ol.actory impulses by .eeding, .ighting, .leeing, or engaging in se=ual beha7ior! Thus this part o. the brain is sometimes re.erred to a

on> or, >nose brain!>



?striatal system became almost completely separate structures once 7ertebrates cra8led .rom the ocean onto dry land! @%loor, +552, &acLean, +55; Alinsky, +556 ! o8e7er, e7en in modern humans, the tail o. the striatum becomes the amygdala, or con7esely, the nose o. the amygdala becom

his reason portions o. the striatum is also re.erred to as the >limbic striatum> and the >e=tended amygdala!>



nt motor centers go7erning mo7ement include the thalamus, and the primary, secondary and supplementary motor areas o. the .rontal lobes! The lihe basal ganglia motor circuit, including the .rontal motor areas are tightly linked and .unction as an integrated system 8hich go7erns all aspects o.ggered gross motor beha7ior,in con'unction 8ith the brainstem, cerebellum, spinal cord and cranial ner7e nuclei!



unction as an integrated system in the production o. mo7ement! For e=ample, the basal ganglia pro7ides input to the brainstem @7ia the >e=tra?py as 8ell as to the motor thalamus and motor neocorte= 8hich also pro'ects to the brainstem and spinal cord @Parent C a rati +550 ! I. in'ured, or

de7elop secondary to e=cessi7e or diminished le7els o. neurotransmitters such as dopamine @e!g! Fahn, +555; Tur'anski et al, +555; 9olters, +555cti7e, and motor disturbances may ensue, including Parkinson<s and #l heimer<s diseases, chorea, hemiballismus @uncontrolled kicking, punchingcatatonia, schi ophrenia, obsessi7e?compulsions, or depression @e!g! #yl8ard et al! +55/; $astellanos et al! +55/; $hakos et al! +55/; (eicken et al!

arrison, +555; *oseph, +555a; Tur'anski et al, +555 ! o8e7er, the nature o. the symptoms depends on the nature, degree, e=tent, and laterality o.

is not thought o. as a disorder o. mo7ement, but as a disorder o. mind! o8e7er, subtypes o. schi ophrenia, such as catatonia, are typi.ied by .ro euch that patients may stay in the same positions .or hours, days, and e7en 8eeks at a time!

asal ganglia acts as an inter.ace bet8een the neocorte= and the limbic system, disturbances in this system can e..ect the .unctioning o. both areas! Tecome emotionally abnormal, lose control o7er their thoughts, or e7en control o7er their mo7ements, as is the case 8ith obsessi7e compulsi7e diso not a .orm o. schi ophrenia; ho8e7er, some .olks su..ering .rom schi ophrenia may de7elop obsessi7e thoughts and beha7iors; and in these cases,licated!



ome subgroups diagnosed 8ith schi ophrenia ha7e been .ound to ha7e reduced striatal acti7ity and reduced blood .lo8 and metabolism @Buchsbauet al! +533; 9iesel et al! +532 ! # schi ophrenia?striatal association has also been demonstrated based on &)I, such that the limbic @7entral striatueduced in si e @Shihabuddin et al! +553 8hereas the corpus @dorsal striatum has been .ound to be increased in si e @ eckers et al! +55+; Shihably the le.t striatum @Breier et al! +55 ; Buchanan et al! +55-; S8ay e et al! +55 ! Le.t or bilateral caudate in'uries are also associated 8ith apatheti

ntaneous acti7ity, slo8ed and delayed dysarthric and emotionally .lat speech, 8ith some patients responding to Duestions only a.ter a 6?-6 second+556; )ich.ield et al! +532 ! By contrast, in'uries or abnormalities restricted to the right caudate are more likely to result in a manic?like psychosisal! +55/; )obinson and (o8nhill +550 ??similar to right .rontal lobe in'uries @*oseph +531a, +533a, +555a; Lishman +52- !

Structural 47er7ie8glia is composed o. se7eral ma'or nuclei 8hich subser7e di..erent .unctions @(eLong +550; Parent +550; Parent C a rati +550 ! These include theatum @>striped bodies> i!e!, the caudate and putamen 8hich are e=tensi7ely interconnected and 8hich pro'ect to a 7ariety o. brain areas including

d'acent globus pallidus @>pale globe> ! The dorsal globus pallidus although related to the hypothalamus and midbrain, is in many respects coe=tege 8ith the putamen gi7ing the entire structure the appearance o. a camera lens! ence the globus pallidus and the putamen are re.erred to as the le> ! The dorsal striatum also continues to be intimately related to the amgydala, recei7ing massi7e input .rom this structure but pro7iding little in re



mydalostriatal gray consisted o. both dorsal and 7entral components, and so too does the human striatum??also re.erred to as the limbic @7entral sinnominata, nucleus accumbens, ol.actory tubercle constitute the limbic striatum! The in.erior 7entral globus pallidus @also re.erred to as the 7ent

bstantia innominata is also part o. the limbic @7entral striatum and in .act e7entually merges 8ith the centro?medial amygdala and recei7es e=tenm the lateral amygdala, the ol.actory tubercle, and nucleus accumbens!

e >motor thalamus,> the orbital and medial .rontal lobes and medial supplementary motor area, hippocampus @as 8ell as the central and medial amconnected 8ith and constitute ma'or components o. the basal ganglia! o8e7er, as noted in chapter + , the basal ganglia @i!e! the corpus and limbiclidus e7ol7ed out o. the ol.actory?amygdala and in many respects it could be considered part o. the limbic system @ eimer C #lheid, +55+; &acL



ed and thus part o. the basal ganglia is the substantia nigra, reticular .ormation, and the midbrain tegmentum, 8hich .eed dopamine to the corpus ai.ically, the nigrostriatal (# @#?5 cell group pro'ects .rom the substantia nigra to the dorsal caudate and putamen and the medial .rontal lobes @ElliC Phillips, +531; Parent C a rati +550 , although some .ibers also inner7ate the limbic striatum! It is the nigro?@dorsal ?striatal system 8hich is thotor .unctions including the production o. stereotyped and routine actions!



ic (# systems originates in the 7entral midbrain tegmentum @#+6 (# cell group and sends .ibers to the amygdala, septal area, hippocampus, .rontincluding the 7entral caudate?putamen, nucleus accumbens and substantia innominata @Le &oal C Simon +55+; 4lton et al! +55+; abors ky et al.ibers also inner7ate the dorsal striatum! The mesolimbic (# system is belie7ed to be related to emotion, mood, memory, and re8ard, including lo

d acti7ities such as running and e7en >galloping> @Ellison, +55/; Fibiger C Phillips, +531; Le &oal C Simon +55+ !



glia> @striatum, subthalamic nucleus recei7es much o. its input .rom the neocorte= @*ones C Po8ell, +526; Pandya C "ignolo, +52+ , and the ammal e=tent the hippocampus! The ma'ority o. these incoming .ibers are e=citatory and terminate in the corpus striatum and subthalamic nucleus! Sprtion o. the .rontal lobes pro'ects to the head o. the caudate 8hereas the more posterior putamen recei7es con7erging and o7erlapping input .rom thcondary motor and somesthetic cortices @*ones C Po8ell, +526; Pandya C "ignolo, +52+ ! This structure does not recei7e any direct input .rom th

sory or motor systems!

ue o. output is 7ia the globus pallidus @and in the brainstem, the substantia nigra 8hich pro'ects to the thalamus and the brainstem 7ia the >e=tra?asal ganglia does not pro'ect directly to the spinal cord! The ma'ority o. these outgoing a=ons arise .rom >spiny> neurons, and these are responsiblriatal impulses to the globus pallidus @%P ! These are predominantly inhibitory and employ %#B# @and 7arious peptides, e!g! substance P asers!



mits to the brainstem and to the motor thalamus and subthalamic nucleus @&ink C Thach, +55+; Parent C a rati +550 ! The motor thalamus in turnmotor areas i!e! the primary, secondary, supplementary motor areas and .rontal eye .ields, including the anterior .rontal lobe!

ic nucleus, is directly linked 8ith the hypothalamus and midbrain, and recei7es e=citatory input .rom all .rontal motor areas; Anlike the globus palle subthalamic nucleus is e=citatory, and it in .act pro'ects back to the globus pallidus!

ore, recei7es di..use e=itatory input .rom the subthalamic nucleus, and con7erging inhibitory input .rom the striatum, and the transmits the bulk o. iulses to the motor thalamus 8hich acts on the .rontal neocortical motor areas! Thus a comple= .eedback loop in7ol7ing inhibitory and e=citatory cithis area??.eedback 8hich presumably assists in the guidance o. mo7ements directly controlled by the .rontal motor areas, as 8ell as those initiated=ternally @Schult C )omo, +55 !



sturbances in this .eedback loop, or in the neurotransmitters 8hich maintain it, can result in a host o. motor disturbances, ranging .rom the rigiditysease and catatonia to chorea, hemiballismus, or >restless leg syndrome!> )estless leg syndrome, .or e=ample, is a chronic condition 8hich presum o. the population, and is characteri ed by a constant, sometimes pain.ul urge to mo7e the limbs 8hich is only relie7ed by 8alking @e!g! Tergau,

i, et al!, +555 ! Functional imaging indicates that this disorder is directly related to disturbances in striatal dopamine binding and uptake, particular

utamen @Tur'anski, et al!, +555 ! Presumably, this disturbances is thus a .unction o. abnormal acti7ity in these structures 8hich begin to .ire in the amo7e, thus inducing an urge to mo7e, coupled 8ith e=cessi7e acti7ity in the .rontal motor areas @e!g!, Tergau, et al!, +555

t is note8orthy that neurons in the striatum begin .iring prior to mo7ement, 6 ms on a7erage! They increase their rate o. .iring at the start o. specind cease to .ire .ollo8ing mo7ement @&ontgomery C Buchol , +55+; Schult C )omo, +55 ! &oreo7er, neurons related to mo7ement are somatoth that those that represent the leg, .ace or arm, cluster together 8ithin the striatum, and increase their acti7ity prior to and during mo7ements o. the l



iatum, %P, and subthalamic nucleus, ho8e7er, represent only the dorsal aspect o. the >basal ganglia!> "entral to and intimately associated 8ith thelimbic striatum, portions o. 8hich ha7e also been re.erred to as the >e=tended amygdala!> Indeed, the amygdala is a ma'or component o. the >basahese structures .unction as a cohesi7e interacting unit .or the purposes o. de.ensi7e and other a..ecti7e beha7iors regarding gross body mo7ements,g, running, and kicking!

T E #&G%(#L#, E&4TI4N, &E&4)G, PSG$ 4SIS, C T E B#S#L %#N%LI#chapter +-, early in the course o. animal e7olution, the amydala and striatum .ormed a composite dorsalH7entral amygdala?striatum, these structurnd become distinct one animals began to li7e on land! For e=ample, it can be surmised, based on the brain o. a >li7ing .ossil> the shark, that /06 m

ma'ority o. the .orebrain in cartilaginous animals, consisted o. a dorsal and 7entral amygdala?striatum, the striatoamygdaloid gray, such that the amere enmeshed .orming a dorsal lateralH7entral lobe, an organi ation pattern that is also e7ident in cyclostromes, .ish, and @to a much lesser degreeurodela ! The dorsalH7entral amygdalaHstriatum .ormed a composite allocortical structure that 8as dominated by the ol.actory system @ aberly, ++556 !

ygdaloid gray @or >dorsal pallium> per.ormed motor .unctions that in some respects mirrored those o. the brainstem 8hich 8as dominated by the 7a lesser e=tent, the 7isual system; one o. the ma'or di..erences being that the ol.actory?.orebrain 8as pro7ided 8ith a crucial >pregnant inter7al> be8hich enabled it to beocme a thinking machine 8hereas the brainstem remained re.le=i7e!

erged .rom the sea and began to li7e on dry land, the amygdala and striatum 8ere pushed apart due to the increased important o. motor .unctioningulb e=panded as did its .orebrain path8ays, so as to adapt to li7ing in a 8orld o. smell! 9ith the e7olution o. amphibians @the tailless anura the amm @and much later the hippocampus and striatum became semi?separate structures @ errick, +5 0; Nieu8enhuys C &eek, +556ab; Stephan C #nd8hich ne7ertheless remained tightly linked, the striatum responding to amygdala impulses 8hich 8ere directed to the brainstem! #s these structure8ere pushed .urther apart, the dorsal aspect became a rudimentary dorsal striatum, and the 7entral aspect became the 7entral @limbic striatum!

n replicates phylogeny and this amygdala?striatal separation is also repeated o7er the course o. embrylogical de7elopment! For e=ample, around the7elopment immature neuroblasts migrate in massi7e numbers .rom the 7entricular lining, and congregate in the more caudal portion o. the emergi.orming an arc shaped >striatal ridge> .rom 8hich the primordial amygdala 8ill emerge @%illes et al! , +53-; umphrey, +513 ! #ppro=imately onetion o. the amygdala, this primordial striatum begins to di..erentiate and balloon out8ard! Thus both the striatum and amygdala are deri7ed .rom tl ridge,> the caudal portion gi7ing rise to the primordial amgydala at about the 1th 8eek o. gestation, and the basal portion later gi7ing rise to the pinitially o7erlies and is contiguous 8ith the amygdala @%illes et al!, +53-; umphrey, +513 ! 47er the ensuing 8eeks, these structures are pushedn, replicating phylogeny!



hey do not completely separate, and the medial amygdala remains e=tensi7ely interconnected 8ith the limbic @7entral striatum! #s noted, the sub7entral globus pallidusHnucleus basalis merges 8ith the centro?medial amygdala and recei7es e=tension pro'ections .rom the lateral amygdala! In aala id directly connected 8ith the corpus striatum, 7ia the so called >tail o. the caudate!> o8e7er, as these connnections are predominantly .rom the striatum and not 7ice 7ersa, the caudate could be considered the bulbous >tail> end o. the amygdala!





eurons also respond 8hen making tongue and lip mo7ements @e!g! licking and during arm mo7ements to8ard a .ood item @)olls C 9illiams, +53

suggest the striatum is in7ol7ed in orienting and guiding mo7ements to8ard the mouth presumably so that a desired ob'ect can be licked, sucked oonsumed! In this regard the striatum could be considered a primary motor center 8hich enables 7arious limbic desires, needs, and impulses such as

atum @e!g! the nucleus accumbens and the mesolimbic (# system 8hich pro'ects to these nuclei also appear to be highly in7ol7ed in mediating .eding the re8arding e..ects o. amphetamine, cocaine and opiates @see Ellison, +55/; akan et al! +55/; oob et al! +55+ ! These e..ects @including th. opiate 8ithdra8al are probably due not only to the presence o. opiate, (#, and related receptors, but the rich interconnections maintained 8ith tell as the lateral hypothalamus @ elsey C #rnold +55/; 4lton et al! +55+; abors ky et al! +55+ 8hich constitute part o. the >pleasure circuit> maiorebrain bundle @4lds C Forbes, +53+; see also chapter +- !



mals 8ill also 8ork in order to sel.?administer opiates directly into the accumbens @ oob et al! +55+; 4lds C Forbes +53+ ! $on7ersely, lesions to thy disrupt the capacity to e=perience pleasure or the re8arding e..ects o. opiates and cocaine @ oob et al! +55+ ; or to engage in comple= coordinat@see belo8 !

$atatonia, Parkinson<s (isease, C Psychosis!corpus striatum and lenticular nucleus @putamen and globus pallidus can attenuate one<s capacity to motorically e=press their emotions 7ia the may become .ro en and mask?like! These latter motor disturbances are 8ell kno8n symptoms associated 8ith Parkinson<s disease, a disturbance diremine de.iciency @Fahn, +555 and neuronal degeneration not only in the putamen @%oto, et al! +556; ish, et al! +533; see also auser et al!, +555bic striatum, i!e! the nucleus accumbens @see )olls C 9illiams, +532 , as 8ell as in the supplementary motor areas and medial .rontal lobe ?8hichections 8ith the striatum!

n chemical or structural lesions e=tend beyond the basal ganglia and come to include the medial .rontal lobe, not only might an indi7idual su..er m

may become catatonic and e=perience e=treme di..iculty responding to e=ternal or internally mediated impulses @*oseph, +555a ! "arious aspects ople= also characteri e those 8ith Parkinson<s disease @see belo8 !

nces associated 8ith striatal abnormalities include untington<s chorea, ballismus, restless leg syndrome, catatonia, sensory neglect and apathy, obssorders, mania, depression, >schi ophrenia> and related psychotic states @#yl8ard et al! +55/; Ba=ter et al! +55 ; $aplan, et al! +556; $astellanos et+55/; (a7is, +503; (eicken et al! +550; Ellison, +55/; )auch et al! +55/; )ich.ield, et al! +532; Tur'anski, et al!, +555 !





y loss and social?emotional agnosia and an inability to recongi e .riends or lo7ed ones is also characteristic o. striatal abnormalities, particularlyn7ol7ing the limbic striatum!

the basal ganglia is o.ten 7ie8ed and described as a ma'or motor center @detailed belo8 , the .unctional capacities and symptoms associated 8ith tuite di7erse, and 7ary depending on the nuclei and chemical neurotransmitters in7ol7ed as 8ell as the laterality, location, and e=tent o. any lesion!

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nd putamen are tightly interlinked and in some respects are indistinguishable and possess a similar internal compartmental structure o. patches and1; %er.en, +53/ ! This is 8hy a gross analysis o. the the mammalian caudate and putamen re7eals a striated @patchlike appearance!



nd matri= are biochemically distinct and recei7e pro'ections .rom di..erent regions o. the neuroa=is @%er.en, +53/, +532; %raybiel +531 ! For e=amn dense concentration o. opiate receptors @%raybiel, +531 and recei7e pro'ections .rom the amygdala, hippocampus, and other limbic tissue and mns 8ith the (# neurons in the substantia nigra! The patches in .act .orm a continuous labyrinth 8hich snakes throughout the striatum!

ng matri= also recei7es pro'ections .rom the cingulate gyrus, the motor thalamus, and .rom throughout the neocorte= and maintains interconnectionneurons in the substantia nigra @%er.en, +532 ! The matri= also contains large amounts o. acetylcholinesterase!

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ly linked and similar in structural organi ation, the caudate appears to e=ert more in.luence and pro7ide more input to the putamen, than 7ice 7ersathe caudate, the putamen also recei7es considerable input .rom the medial .rontal, supplementary, secondary and primary motor corte=, as 8ell asrietal lobe @*ones C Po8ell, +526; Pandya C "ignolo, +52+ !



unctioning, presumably the putamen, in con'unction 8ith the caudate, transmits this in.ormation to the globus pallidus 8hich in turn pro'ects to thenstem reticular .ormation, as 8ell as to the motor neocorte=, thus creating a 7ery elaborate .eedback loop @see &ink C Thach, +55+; Parent C a r may begin in the medial .rontal lobes @#le=ander C $rutcher, +556; $rutcher C #le=ander, +556 or perhaps the limbic system, e!g! anterior cingul

8hen anticipating or preparing to make a mo7ement, but prior to the actual mo7ement, neuronal acti7ity 8ill .irst begin and then dramatically incrementary motor areas @S&# , as 8ell as in the striatum @&ontgomery C Buchhol , +55+; Schult C )omo, +55 .ollo8ed by acti7ity in the secondry motor area @see chapter +5 , and then again in the caudate, putamen and globus pallidus 8hich become increasingly acti7e prior to and then durceasing their acti7ity once the mo7ement is completed @#le=ander C $rutcher, +556; &ink C Thach, +55+; Schult C )omo, +55 !



reas, including the >motor> thalamus, in many respects act in a coordinated .ashion so as to mediate purpose.ul mo7ement! #s noted in chapter + ,e o. the basal ganglia long be.ore the e7olution o. the neocorte= and .rontal motor areas!

mportant to point out that some in7estigators ha7e argued there are at least .i7e di..erent motor circuits in7ol7ing the basal ganglia 8hich are segreges @#le=ander et al! +556 ! The dorsal striatal motor circuit also consists o. at least t8o separate systems in7ol7ing the putamen and medial @internhe putamen and lateral @e=ternal globus pallidus @re7ie8ed in &arsden C 4beso, +55/; Parent C a rati +550 !

(IFFE)ENTI#TI4N 4F T E $#A(#TE C PAT#&EN

e o. e7olutionary metamorphosis, the corpus striatum and the motor thalamus began to de7elop in tandem and became increasingly interlinked in oric and related acti7ities, including the processing and analysis o. sensory in.ormation and the e=pression o. .eeling states 7ia speci.ic motor acti7ittriatum initially ser7ed not only the motor .unctions and related in.ormation reDuirements o. the limbic system but in many respects per.ormed @a7els some o. the same >analytical> and perceptual .unctions that 8ould later be subsumed by the neocorte=!



nued e=pansion o. the the neocorte= and the e=ponential increase in the capacity to analy e and respond to di7ergent sensory in.ormation, the corptially 8as split in t8o by the tremendous proli.eration o. thalamic a=ons @i!e! the internal capsule, or rather, the thalamic radiations that not only tedrites, but 8hich s8ept .or8ard and radiated out8ard to inner7ate the .rontal lobes @ emp C Po8ell, +526 ! Thus the putamen and caudate nucleusgan to recei7e di..erential input .rom the thalamus as 8ell as .rom the neocorte= and there.ore began to subser7e some8hat di..erent .unctions!



although both nuclei contain signi.icant amounts o. (#, 0 T, #$ , and %#B# @re7ie8ed in Ellison, +55/; Parent C a rati +550; Stoo. et al! +55rom the amygdala, hippocampus, and motor and somatosensory perceptual data @ aber et al! +530; "an oesen, et al! +53+; 9hitlock C Nauta, +5recipient o. considerable bilateral and topographical input, such that a motor and sensory map o. the body @particularly the .ace, mouth, leg, and

this region @(elong et al! +53-; Parent C a rati +550 ! #=onal pro'ections .rom the motor and sensory neocorte= 8hich are concerned 8ith the ar

e area o. the putamen, 8hereas those concerned 8ith the leg con7erge in another!

8ith the symptoms and e=periments describes belo8, it is suspected that the putamen is concerned 8ith integrating sensory 8ith intended motor ache mo7ement o. the limbs and body in 7isual space 7ia pro'ections maintained 8ith the medial and lateral globus pallidus as 8ell as the parietal lob



caudate nucleus is dominated by a=ons .rom association cortices including the in.erior temporal lobe and anterior cingulate @Percheron, et al! +5mmaral et al! +55 ; eimer C #heid, +55+ and the .rontal motor areas! The caudate appears to be more in7ol7ed in multi?modal motor, emotional aation, analysis and inhibitory .unctions! $onseDuently lesions to the caudate can produce sensory neglect and unresponsi7eness, or con7ersely, losstrol o7er the musculature; depending on the e=tent and laterality o. the lesion!

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e caudate nucleus is concerned 8ith multi?modal in.ormation processing and inhibition! "ia inhibition the caudate is able to e=ert modulatory e..ecand .acial?gestural posture and e=pression, and aids in the maintenance o. selecti7e motoric attention, e!g! standing still and obser7ing! In conseDumans, lesions, destruction, or shrinkage o. the head o. the caudate can result in sensory neglect, agitation, hyperacti7ity, distractibility and in somo be a manic or >schi o?a..ecti7e> psychosis @#yl8ard et al! +55/; $aplan, et al! +556; $astellanos et al! +55/; $hakos et al! +55/; (a7is, +503; )inding on the e=tent and laterality o. the destruction!



ich.ield et al! @+532, p! 213 report a 0 year old .emale honor student @soon to be married 8ho a.ter complaining o. headaches and nausea disaphen .ound, she had undergone a dramatic personality change mani.ested by alterations in a..ect, moti7ation, cognition, and sel.?care!> These changnent! > er abnormal beha7iors included 7ulgarity, impulsi7eness, 7iolent outbursts, enuresis, indi..erence, hyperse=uality, shopli.ting and e=posingnti7e and uninterested in her surroundings but could be encouraged to concentrate .or short periods o. time! She 8ould .reDuently lie do8n to sleep> $T?scan indicated bilateral damage to the head o. the caudate nuclei!



8ill alternate bet8een hyperacti7ity and apathy? a .unction perhaps, o. the laterality and e=tent o. the lesion as 8ell as associated biochemical alter n'uries or abnormalities restricted to the right caudate are more likely to result in a manic?like psychosis @$astellanos et al! +55/ ??Duite similar t

ght .rontal lobe in'ury @chapter +5 ! Similarly, right caudate hypermetabolism and blood .lo8 has also been associated 8ith obsessi7e compulsi7e d+55 ; )auch et al! +55/ 8hereas .rontal abnormalities may induce perse7erati7e disturbances @chapter +5 as 8ell as obsessi7e? compulsions @)auc

t caudate in'uries @particularly those 8hich e=tend to the mesial and le.t .rontal lobe may induce se7ere apathy as 8ell as speech disturbances! #sries are associated 8ith similar abnormalties @chapter +5 !



e le.t or bilateral caudate in'uries it is not uncommon .or patients to appear agitated, apathetic, 8ith decreased spontaneous acti7ity and slo8ed andr stuttering and emotionally .lat speech, 8ith some patients responding to Duestions only a.ter a 6?-6 second delay @$aplan et al! +556 ! This condely i. the medial .rontal lobes ha7e been compromised as 8ell!

rhaps to it<s e=tensi7e interconnections 8ith the medial .rontal lobes and S&# ?a region 8hich 8hen destroyed can gi7e rise to catatonia @*oseph +ral lesions to the anterior caudate and anterior putamen and surrounding tissue has been sho8n to produce catatonic or >.ro en> states, 8here animaaintain a single posture or simply stand unmo7ing .or 8eeks at a time @(enny?Bro8n, +51 !

mically lesions o. the caudate can produce complete catatonia, posturing and a cessation o. all mo7ement @Spiegel C S ekely, +51+ ! o8e7er, i. thatal path8ay andHor the amygdala is destroyed prior to lesioning the caudate, these .ro en catatonic states can no longer be induced @Spiegel C S e

C T E F)4NT#L?$#A(#TE?#&G%(#L# NEA)#L NET94)

head o. the caudate is e=tensi7ely interconnected 8ith the .rontal lobes! Thus, some o. the symptoms associated 8ith caudate destruction @e!g! man

llels those associated 8ith .rontal lobe in'ury @chapter +5 ! For e=ample, 8hereas lesions to the .rontal lobe may produce perse7erati7e abnormalitis andHor increased metabolism or regional blood .lo8 may induce obsessi7e?compulsi7e beha7iors @Ba=ter et al! +55 ; )auch et al! +55/ ! In part s o. .rontal lobe control o7er the caudate, andHor the loss o. striatal inhibitory in.luences o7er the .rontal lobe!



caudate and .rontal lobes are also intimately linked to the amygdala @#mmaral et al! +55 ; a stucture that under conditions o. e=treme .ear and arolete cessation o. mo7ement; i!e! catatonic?like .ro en panic states @chapter -6 ! The amygdala is able to accomplish this 7ia interconnections 8ith ttem, as 8ell as the medial .rontal lobes!

&ENT#)G &4T4) #)E#S

ontal lobes are damaged or e=perimentally electrically stimulated, there sometimes results in a inability to initiate a 7oluntary mo7ement, and the >may be completely attenuated and abolished @ asslet, +536; Laplane et al! +522; Luria, +536; Pen.ield C *asper, +50/; Pen.ield C 9elch, +50+ !

medial .rontal lobes can cause sub'ects to simply sit or stand motionless, as i. .ro en, and display 8a=y .le=ibility, or >gegenhalten> or counterpull ?sistance to mo7ement o. the e=temities @Brutko8ski, +510; asslet, +536; Laplane et al!, +522; Luria, +536; &ishkin, +51/ ! Posturing is also noteremain in odd and uncom.ortable positions .or e=ceedingly long time periods and make no e..ort to correct the situation @Freeman C 9atts, +5/ ;y 8ere dead and in the .irst stages o. rigor mortise!

ns @see belo8 occur a.ter disasters and in instances o. e=treme .ear and terror! #..ected indi7iduals may display all the classical symptoms o. cataty respects, could be likened to death .eigning or >playing possum>!



response to e=treme .ear the amygdala acts on the striatum and S&# @as 8ell as the brainstem , thereby inducing not only rigidity and a .ro en paatatonic state accompanied by 8a=y .le=ibility, and a complete paralysis o. the 8ill! The S&#, in .act, is 7ery susceptible to the disrupti7e in.luencC #bercrombie +55+ !

#L#, ST)I#TA&, S&#, C LIFE T )E#TENIN% FE#) C #)4AS#L

7ol7ing e=ceedingly high le7els o. arousal coupled 8ith e=treme .ear, the indi7idual may simply .ree e and attentional .unctioning may become soarro8 that little or nothing is percei7ed and cogniti7e acti7ity may be almost completely @albeit temporarily abolished @see chapter -6 ! These beder the control o. the amygdala 8hich can trigger a >.ree ing> reaction and a complete arrest o. ongoing beha7ior @%loor, +516; app et al! +55 ; A7ia these brainstemHstriatal interconnections! This is part o. the amygdala attention response, 8hich at lo8er le7els o. e=citation may be .ollo8ed b, an increase in respiration and heart rate, pupil dilation, and perhaps cringing and co8ering or .light @%loor, +516; Arsin C aada, +516 !



ns, the .ear response is one o. the most common mani.estations o. amygdaloid stimulation @%loor, +556; algren, +55 ; 9illiams, +501 ! o8e7er,continue to increase, sub'ects do not merely .ree e in response to increased .ear, they may become catatonic; a condition 8hich may be secondary tserotonin depletion and amygdaloid in.luences on the S&# as 8ell as the striatum; nuclei 8hich are intimately interconnected!

n response to e=treme .ear, >one tendency is to remain motionless, 8hich reaches its e=treme .orm in death?.eigning in certain animals and sometia=y .le=ibility o. catatonics> @&iller, +50+ ! The a..ected indi7idual becomes psychologically and emotionally numb and unresponsi7e 8hich is co

e blocking o.. o. cognition! &oreo7er, the indi7idual may resist and .ail to respond to attempts at assistance @ rystal, +533; &iller, +50+; Stern, +5

ustry has re.erred to this as >.ro en panic states> @ rystal, +533 , a condition sometimes seen in air and sea disasters! For e=ample, in mass disastetims 8ill become .ro en, stunned, and immobile, and 8ill .ail to take any action to sa7e their li7es, such as attempting to e7acuate a burning or siney ha7e been unin'ured @see rystal, +533 !

rystal @+533 8ith increasing .ear >there is also a progressi7e loss o. the ability to ad'ust, to take the initiati7e or de.ensi7e action, or act on one<s oarts 8ith a 7irtual complete blocking o. the ability to .eel emotions and pain, and progresses to inhibition o. other mental .unctions> @ rystal, +533

Signi.icance o. )igidity!

c states are pre7alent in the animal kingdom, and constitute a li.e preser7ing reaction that is apparently mediated by the amygdala and striatum! Thot mo7ing, predators may .ail to take note o. their presence, or con7ersely, re.use to eat them, belie7ing them already dead; also kno8n as >playing



pled 8ith emotional and >psychological> numbing, also represents a total surrender reaction, usually as a prelude @and hope.ul guarantee o. a paiby predators or in7aders! That is, the prey may cease to run or .ight and simply stand still or lie do8n and allo8 predators to literally eat them ali7

mans as sometimes occurs during 8ar and genocidal mass murders, passi7ely allo8 themsel7es to be marched into a ditch and shot!

rystal @+533, p! +// , >thousands o. European *e8s obeyed orders in an automatonlike .ashion, took o.. their clothes, and together 8ith their childa pit, lay do8n on top o. the last layers o. corpses, and 8aited to be machine?gunned,> all the 8hile seemingly almost petri.ied 8ith .ear andHor coat 8as going on around them!





is numbing is made possible 7ia the massi7e secretion o. opiates 8ithin the amygdala and basal ganglia, 8hereas the rigidity and loss o. the 8ill to. o7er8helming .ear and hyper?amygdala in.luences on the medial .rontal lobe and corpus and limbic striatum!

e sighted a predator, some animals, ho8e7er, instead o. running in .ear, 8ill simply >.ree e,> .all to the ground, and lie sti.., rigid, and motionless aingly hungry, many predators 8ill a7oid eating creatures 8hich appear to be already dead @i!e! unresponsi7e !

occurs to potential 7ictims during mass killings @e!g! the +55/ )8anda ci7il 8ar bet8een the utus and the Tutus humans too, 8ill sometimes .ally remain .ro en, sti.. and and unmo7ing .or long time periods e7en though they may not ha7e been harmed @ rystal +533 ! Indeed, sometimes thes



belie7ed to be dead e7en by rescuers or those 8ho are clearing a8ay and burying bodies!

is 7ia connections 8ith the basal ganglia and medial .rontal lobes that the amygdala is able to induce these catatonic states, 8hich in part is also deFor e=ample, it has been demonstrated that under e=tremely stress.ul conditions the striatal and .rontal lobe (# system is ad7ersely a..ected @see L

NS )E%#)(IN% P#) INS4N<S (ISE#SE

y o. the .unctions originally associated 8ith the basal ganglia ha7e been subsumed by the neocorte=, and damage to the .rontal lobes can produce ems as seen .ollo8ing caudate destruction; including sti..ness, rigidity, and di..iculty initiating mo7ement @see chapter +5 !

medial .rontal lobes, corpus and limbic striatum, and amygdala are e=tensi7ely interconnected, and gi7en the po8er.ul in.luences o. the limbic syseha7ior, it thus appears that 8hen e=ceedingly aroused or emotionally stressed, the amygdala is able to inhibit @or o7eracti7ate the .rontal?striatal@in addition to the amygdala are simultaneously undergoing (# depletion @8hich in turn results in hyperacti7ation o. these nuclei including the aSimon +55+ ! 9hen this occurs, the organism may .all and cease to mo7e, blink or e7en breathe @or breathe only shallo8ly and slo8ly ! The creat

ars to be in a state o. rigor mortis and thus dead @i!e! catatonic !

amygdala?basal ganglia?medial .rontal lobe?.ear induced .ro en and catatonic states are e=ceedingly adapti7e; that is, unless the hapless 7ictim is ine or sinking ship!

as dramatic or se7ere, similar states occur 8ith biochemical abnormalities in7ol7ing the dopamine path8ays .rom the substantia nigra 8hich not onlut the medial .rontal lobes and the amygdala! Speci.ically, loss o. (# @or e=cessi7e amygdaloid arousal results in motor neuron hyperacti7ity and tand thus limb and .acial rigidity; conditions 8hich also a..lict those 8ith Parkinson<s disease!

these same e=act >semi?.ro en> and akinetic states are present in many o. those 8ith Parkinson<s disease, and gi7en that a..ected indi7iduals are s=cessi7ely aroused andHor unable to rela=, and to su..er .rom heightened autonomic ner7ous system acti7ity @Stacy C *anko7ic, +55 this raises t

the amygdala and related limbic nuclei may signi.icantly contribute to the de7elopment o. this disorder! Indeed, as noted, destruction o. the amygesioning the corpus striatum pre7ents the de7elopment o. Parkinsonian symptoms!

P#) INS4N<S (ISE#SEglia plays a ma'or role in controlling and .acilitating speci.ic mo7ements, as 8ell as inhibiting un8anted mo7ements @&arsden C 4besco +55/; Tur

basal ganglia is also directly implicated in the generation o. a 7ariety o. mo7ement disorders, including chorea, ballismus, restless leg syndrome, rParkinson<s disease!



sease is a progressi7e degenerati7e disorder characteri ed by rigidity and shu..ling gait, stooped posture, generali ed slo8ness and sti..ness o. mo7cial emotional e=pression, as 8ell as a loss o. spontaneity and .le=ibility in making postural ad'ustments 8hen eating, going to the toilet, or ha7ing

ny Parkinson<s patients e=perience not only rigidity and akinesia, but su..er .rom episodic .ree ing o. mo7ement @(iet , et al! +556; Pascual?Leonency to easily .all @Stacy C *anko7ic +55 an impairment o. >righting re.le=es> @$alne +55/ , and a reduced capacity to blink @Freedman +55 aC *anko7ic, +55 ; similar to the .ro en panic states and induced catatonia!

@reduced 7oice 7olume dysarthria and a tendency to speak in a monotone, micrographia @small hand8riting , and a /?3 cHsec! @>pill rolling> rey stress in7ol7ing antagonistic muscles are common @Freedman, +55 ; Stacy C *anko7ic, +55 ! (epression, changes in personality and slo8ed thlso not unusual among Parkinson<s patients @9alters, +555 ! Parkinsonism can result .ollo8ing neurological trauma or 7ascular abnormalities @ o+556 or isolated lesions to the substantia nigra @Stern, +511 and can there.ore arise .rom a number o. di..erent causes including in.ection and to=

kinson<s disease may also o7erlap 8ith other striatal disturbances such as #l heimers disease @$alne +55/ ! Indeed, sigi.icant cogniti7e de.icits areg those 8ith Parkinson<s disease @Freedman, +55 ; )a'put +55 ; i!e! subcortical dementia!

sease usually begins a.ter age 16 @though the .irst signs may appear during the early /6<s , e..ects about o. the population @ oller, +532 and isy a massi7e loss o. up to 36?30 o. the dopamine neurons in the substantia nigra and an 36 decrease in striatal (#, 8ith (# depletion greatest ito, et al! +556; ish, et al! +533 ! In .act, transplanting .etal nigral tissue into the putamen, can result in increased dlurodopa intake and some long?t

7ement @ auser et al!, +555 !



s the substantia nigra (# system is directly implicated, the mesolimbic path8ays and limbic striatum are only a mild .actor and are only mildly e..

&B#L#N$E C P#) INS4N<S (ISE#SE

l in7ol7ement o. the nigrostriatal 7s mesolimbic (# system raises the possibility that 8hereas the corpus striatum and medial .rontal lobes are negamygdala and limbic striatum may continue to .unction normally ?due to preser7ation o. the mesolimbic (# system! o8e7er, because the normal7arious nuclei is disrupted, amygdala in.luences recei7ed 8ithin the S&# and corpus striatum may in .act o7er8helm and massi7ely inhibit @or o7nuclei thereby gi7ing rise to Parkinsonian symptoms @see Le &oal C Simon +55+ .or related discussion ; i!e! rigidity, a tendency to .all coupled 8ng and disturbed righting re.le=es, etc!



# in the genesis o. Parkinsonian symptoms, signi.icant reductions in opiate receptors 8ithin the putamen as 8ell as the globus pallidus ha7e alsoto et al! +556 , such that neurons in7ol7ed in the e=perience o. >re8ard> are e..ected! This selecti7e loss o. >re8ard> neurons suggests a a reductionbasal ganglia to recei7e pleasurable or positi7e emotional input as might be pro7ided not only by opiates, but 7ia the lateral amygdala and lateral

use striatal neurons associated 8ith negati7e .eelings states may be selecti7ely preser7ed in Parkinson<s disease, the basal ganglia @but not the amor neocorte= may respond as i. in a highly aroused negati7e state @e!g! .ear.ul, stressed e7en 8hen that is not the case! #dding to this imbalanceser7ation o. the mesolimbic (# system, and the continued input .rom the medial amygdala into the corpus and limbic striatum ?the medial amygdin the generation o. unpleasant including .ear.ul mood states @chapter +-

corpus striatal (# andHor e=cessi7e amygdaloid arousal is directly associated 8ith the de7elopment o. tonic E&% acti7ity, motor neuron hyperactitonic e=citation o. the musculature and limb rigidity; i!e! Parkinson<s symptoms! $on7ersely, e=cess striatal (# can result in chorea and e=cessi7e

8ell as psychosis!

#) INS4N<S (ISE#SE

orted that many patients 8ith Parkinson<s disease display reductions in norepinephrine @NE as 8ell as (# throughout the upper layers o. the motomedial .rontal lobes @%asper et al! +55+; ornykieci , +53 ! NE is produced by the Locus coeruleus in the brainstem and NE path8ays inner7ate t

mbic system, striatum, and the neocorte=!



epletion also occurs .ollo8ing heightened emotional states, including e=treme .ear, prolonged stress and heightened arousal, and 8ith amygdalan! #s noted, indi7iduals 8ith Parkinson<s disease are also sometimes described as e=cessi7ely aroused andHor unable to rela=, and to su..er .rom he7ous system acti7ity and gastrointestinal disturbances @Stacy C *anko7ic, +55 ??disturbances 8hich also implicate the amygdala and e=cessi7e l! $on7ersely, the autonomic ner7ous sytem o. those 8ho su..er .rom #l heimer<s disease ha7e been characteri ed has hypoacti7e @Borson et al! +5

m being implicated in #l heimer<s disease!

cally becomes .unctionally acti7ated prior to mo7ement @chapter +5 and 8ell be.ore the caudate or putamen 8ith 8hich it is interconnected! 9henatients attempt to make repetiti7e mo7ements, S&# .unctional acti7ity is abnormally reduced as is putamen acti7ity @Play.ord et al! +55 ! This sughe corpus striatum one o. the ma'or regions o. the neuroa=is in7ol7ed in the >8ill> to mo7e and the capacity to prepare to mo7e; i!e! the S&#, isn those su..ering .rom Parkinson<s disease! Thus the S&# and medial .rontal lobes as 8ell as the corpus striatum, (# system, and amygdala, are i

o. this disorder @e!g! Play.ord et al! +55 !

=ample, that Parkinson<s patient<s ha7e di..iculty using both hands to per.orm t8o di..erent mo7ements @e!g! sDuee e a ball 8ith one hand, dra8 a! )ather, they tend to per.orm one action, then s8itch to the other @$aligiuri et al! +55 ! S&# dys.unction can result in similar disturbances @see cthe ability o. Parkinson<s patients to engage in seDuential and repetiti7e mo7ements @Play.ord et al! +55 , or to simultaneously engage in separach as 8alking, turning, and talking @Stacy C *anko7ic +55 is se7erely e..ected; a disorder 8hich is also associated 8ith .rontal lobe abnormalities

&PAS C S&#

triatum is also inner7ated by the hippocampus 8hich is in7ol7ed not only in memory, but spatial and cogniti7e mapping o. the en7ironment @chaporpus striatum presumably relies on hippocampal @as 8ell as parietal lobe input in order to coordinate mo7ement in 7isual?space!



y that Parkinson<s patients .ind it easier to per.orm mo7ements that are cued or guided by e=ternal 7isual stimuli, 8hereas those 8hich are internallmore se7erely e..ected @(iet , et al! +556 ! ence, perhaps those striatal neurons 8hich normally recei7e and integrate hippocampal input may also

ole o. the hippocampus appears to be minimal in the de7elopment o. Parkinson<s disease, at least in those cases 8ithout memory loss or dementia!e..ect o. e=ternal cues again raises the specter o. signi.icant medial .rontal lobe and S&# in7ol7ement!

esions to the medial .rontal lobes can result in an inability to internally generate mo7ements 8hereas e=ternal en7ironmental and 7isual cues can e=etic> e..ect on limb acti7ation and patients may in7oluntarily respond and react to e=ternal stimuli by reaching, grasping, or utili ing 8hate7er ob'ecapter +5 ! In contrast, the lateral .rontal lobes are in7ol7ed in e=ternally dri7en mo7ements @chapter +5 !

son<s patients are possibly better able to >mo7e> in response to 7isual stimuli presumably because o. preser7ed lateral .rontal lobe .unctioning and# control ?8hich @in part accounts .or their di..iculty internally >8illing> purpose.ul and .luid mo7ements!

T)I#T#L I&B#L#N$E!

holinergic, #$h system appear to e=ert counterbalancing in.luences! For e=ample, loss o. nigrostriatal (# results in increased #$h, neuron hyperacan C Bunney, +522; Bloom et al! +510 and tonic E&% acti7ity and thus limb rigidity 8hich can be re7ersed by anti?cholinergic drugs @ lockgethdrugs 8hich decrease #$h and those 8hich increase (#, can ameliorate Parkinsons symptoms @Fahn, +555 , 8hich suggests these t8o transmitter

nd balancing roles @see Stoo. et al! +55 ! &oreo7er, #$h can be inceased by drugs that decrease (#, and can be decreased by drugs 8hich increasStoo. et al! +55 !



nhibits #$h release and increases %#B# acti7ity! The (# system appears to e=ert an controlling in.luences not only on %#B# but #$h neurons in&oal C Simon +55+ ! ence, reductions in (# result in decreased %#B# acti7ity and increased limbic striatal arousal and #$h acti7ity, and reduceand reduced %#B# acti7ity @see Stoo. et al! +55 ! Ander these latter conditions the sub'ect becomes rigid!

er conditions 8here striatal (# is depleted, the e=cessi7e release o. #$h creates e=cessi7e neural acti7ity @#ghan'anian C Bunney, +522; Bloom, etmay be mani.ested in the .orm o. e=cessi7e motor actions; i!e! ballismus, chorea, i. the medial and 7entral globus pallidus?subthalamic circuit is e..t and Parkinson<s symptoms i. the corpus striatum and dorsal globus pallidus is e..ected!

luctuations in (# le7els can either act to e=cite or inhibit motor and related cogniti7e?memory acti7ity 8ithin the limbic striatum @Le &oal C SimoGang +55+ ! o8e7er, 8ith high le7els o. l imbic striatal (# @andHor amygdala acti7ity, coupled 8ith reduced %#B#, animals may appear hyperac

ing, >galloping,> and biting, and related mo7ements!

ese latter actions are due to inhibitory release @a conseDuence o. striatal dys.unction or hyperacti7ation , and thus the triggering o. brainstem motosubser7e these speci.ic beha7ioral acts! These same stimulus @predator released actions, across e7olution, and across most animal species, are dirunctional integrity o. the limbic system and striatum, and the capacity to sur7i7e 8hen li7ing in close pro=imity to predators, the elements, and cosut thought are in .act the pro7ince not o. the basal ganglia, but the brainstem, 8hich is 8hy these and related motor programs are stored 8ithin braipter +2 !

PSG$ 4SIS!on o. the head o. the caudate @particularly the caudate nucleus o. the right hemisphere appears to be inhibition! Similarly, the principle e..ect o. stEllison, +55/; Le &oal C Simon +55+; &ercuri, et al! +530 ! ence, e=cessi7e and abnormal amounts o. corpus striatal (# can result in increased len acti7ity such that limbic striatal, and the reception o. amygdaloidHemotional input may be se7erely diminished andHor abnormally processed! us striatal acti7ity might also result in emotional blunting or distortion as 8ell as cogniti7e abnormalities! $on7ersely, because ben odia ipine recehout the striatum, anti?psychotic agents, due to their dopamine properties, can reduce this abnormal acti7ation!





mal le7els o. corpus striatal (# acti7ity can inter.ere 8ith selecti7e attention and the reception o. neocortical and limbic impulses 8ithin the striatuesolimbic (# acti7ity @Le &oal C Simon +55+ ! o8e7er, 8ith increases in striatal (#, cogniti7e, social, and emotional integrati7e .unctions maydistorted and the indi7idual may become psychotic @see $astellanos et al! +55/; $hakos et al! +55/; )ing et al! +55/; Snyder, +52 !

8n, indi7iduals diagnosed as paranoid and schi ophrenic 8ith psychomotor retardation ha7e been .ound to ha7e ele7ated (# le7els and increasedng @$ro8, +525; Ellison, +55/; &atthyse, +53+; )ing et al! +55/ ! Presumably this is 8hy dopamine blockers such as the phenothia ines are e..ectihotic beha7ior; i!e! they reduce e=cessi7e (# binding and e=cessi7e striatal acti7ity 8hich in turn restores the capability o. the striatum @and relatedogniti7e?emotional integrati7e acti7ities!

, Temporal Lobe C (#!

urbances, including >schi ophrenia> need not in7ol7e the basal ganglia or (# dys.unction, as disorders o. thought and mood may also appear .ollooral lobe damage @chapter +5, + ! o8e7er, 8ith .rontal lobe damage the basal ganglia and S&# are o.ten e..ected, 8hereas the amygdala is implrelated psychotic states!



mal (# as 8ell as norepinephrine @NE and serotonin @0 T ha7e been reported in the amygdala o. those diagnosed as psychotic @Spoont +55-; Steion, a gross asymmetry in the post?mortem le7els o. mesolimbic (# has been noted in the brains o. those diagnosed as schi ophrenic @re7ie8ed in

+ ! Speci.ically, an increase in (# has been noted in the central amygdala and in the striatum o. the le.t hemisphere, 8hereas (# le7els 8ithin the rimilar to normals!

amygdala and le.t temporal lobe @Flor? enry, +515; Pere , et al! +530; Ste7ens, +55 ha7e long been thought to be a ma'or component in thegy o. psychosis and schi ophrenia @ eath, +50/; Ste7ens, +52-; Torey C Peterson, +52/ ! For e=ample, abnormal acti7ity as 8ell as si e decrementhe le.t amygdala @Flor? enry, +515; Pere , et al! +530 as 8ell as the le.t in.erior temporal lobe in schi ophrenic patients @see Ste7ens, +55 ! Spik r7ed in the amygdala o. psychotic indi7iduals 8ho are e=periencing emotional and psychological stress @see algren, +55 !

t has been suggested that stress, particularly 8hen e=perienced prenatally may be responsible, in some cases, .or the de7elopment o. (# abnormalimon +55+ , 8hereas ad7erse early en7ironmental e=periences and trauma may contribute to the de7elopment o. kindling, spiking and abnormal amsee chapters 3, -6 ! #s noted, Parkinson<s symptoms in some respects also resemble the e..ects o. chronic stress and an inability to rela=!

4BSESSI"E?$4&PALSI"E (IS4)(E)Sotional turmoil can be induced 7ia e=ternal agents, as 8ell as 7ia one<s personal and pri7ate thoughts and inclinations ??particularly i. at a >conscioinds these impulses ob'ectionable! o8e7er, i. internally or e=ternally generated, the amygdala @and hypothalamus , as 8ell as the .rontal?striataled andHor a..ected 8hich in turn can in.luence motor .unctioning in a number o. 8ays! This includes the de7elopment o. obsessi7e compulsi7e dist

mpulsi7e disorders are characteri ed by the repetiti7e e=perience o. un8anted and recurrent, perse7erati7e thoughts @obsessions andHor a compulsr.orm certain acts! The 8orld 8ide pre7alance rate is about !- @see 4kasha et al! +55/ ! o8e7er, some patients tend to su..er .rom compulsions



nce obsessions, 8ith the ma'ority e=periencing both @(S& I" !

t uncommonly tend to be religious or concerned 8ith contamination coupled 8ith cleaning and 8ashing rituals! The e=perience o. intrusi7e and unndHor se=ual images is not uncommon @Lipinsk C Pope +55/ !

ces obsessi7e compulsions ser7e as a means o. coping 8ith un8anted or troubling impulses; i!e! by perse7erating in thinking certain thoughts or en, the indi7idual is able to a7oid .ocusing on and recogni ing thoughts, actions, or impulses 8hich he or she .inds disturbing!

onsider >Bob> a -6 year old socially inept, single male 8ith a B# degree in English, 8ho .or se7eral years 7oiced >homophobic> and >right 8ing>e=perienced and engaged in a compulsion to 8ork on his car andHor 8ash and dust the engine late in the e7ening and e7en a.ter midnight! o8e7eatedly complained about the noise, he 8as .orced to cease these acts, under8ent a noticeable personality change and 8as soon .reDuenting bars lat

ht dri7es and ha7ing se= 8ith men he met 8hile into=icated!

basal ganglia is intimately associated 8ith the hypothalamus, amygdala, and orbital .rontal lobes; nuclei 8hich are also associated 8ith se=ual acti7io. emotional .unctioning, 8ith the orbital areas acting to gate and inhibit limbic system acti7ity @*oseph, +555a ! ence, the orbital .rontal lobes arehe de7elopment o. obsessi7e compulsi7e disorders @Ba=ter et al! +533; )appoport +55+; )auch et al! +55/ !

7e?compulsi7e disorders are also associated 8ith hyper?metabolism 8ithin the caudate nucleus @Ba=ter et al! +55 ; )appoport +55+; )auch et al! +5d 0 T @serotonin acti7ity @%oodman et al! +556; ohar C Insel +532 8hich in turn results in disinhibition? this raises the possibility that the inhibned by the orbital .rontal lobes and basal ganglia, in some instances, may be deacti7ated or o7er8helmed!

7ia the .rontal lobes that thoughts and emotions come to be integrated and in.used 8ith emotion, andHor inhibited and suppressed, this also suggesdys.unction may result in the inability to e=tinguish certain thoughts and actions, e7en in the absence o. an underlying emotional problem @see B

h et al! +55/, .or a di..erent albeit related e=planation ! The indi7idual may perse7erate on a single thought or action, 8hich in turn may inter.eregage in alternati7e modes o. response due to neurological dys.unction in7ol7ing this circuit!

is suggested by the actions o. >Bob> re.erred to abo7e, it is possible that this same .rontal?inhibitory circuit may be employed so as to pre7ent an iin certain beha7ioral acts 8hich the >conscious> mind .inds ob'ectionable or >dirty!> They perse7erate on a certain theme, thought, or action to thhers! There.ore, 8hen >Bob> 8as .eeling homose=ually aroused, rather than >cruising> .or se= partners, a di..erent @albeit related motor program

e 8ould 8ash and dust his car and e7en its engine @8hich simultaneously and symbolically cleansed him o. his dirty thoughts andHor at least pre7eand acting on them ! #s noted, the .rontal lobes are instrumental in memory search and acti7ation as 8ell as impulse inhibition and memory a7oida

T E LI&BI$ ST)I#TA&, &E&4)G C #L EI&E)<S (ISE#SE

ST)I#TA&, (#, 0 T, #$ , NE, C &E&4)G

atum consists o. the nucleus accumbens, ol.actory tubericle, the e=tended @centro?medial amygdala, as 8ell as the 7entral aspects o. the caudate, lidus @?substantia innomminata !

cumbens is located immediately beneath the anterior portion o. the caudate and .rom a microscopic le7el appears to be part o. the 7entral caudate @s ky et al! +55+ ! o8e7er, it maintains e=tensi7e interconnections 8ith the amygdala as 8ell as the hippocampus 7ia the .imbria?.orni= .iber bunl! +530 , 8hich implicates this nuclei in memory .unctioning and probably the learning o. 7isual?spatial and perhaps social?a..ecti7e relationships!

dorsal portion o. the substantia innominata @>great unkno8n> merges @dorsally 8ith the 7entral globus pallidus @and 7entrally 8ith the centro?md maintains interconnections 8ith the accumbens, hippocampus, lateral amygdala, and dorsal medial @(& nucleus o. the thalamus @Goung et al! +l! +55+ ?the (& being in7ol7ed in regulating neocortical arousal and in.ormation reception as 8ell as memory @see chapter +5 !

mbens, the substantia innominata @SI is also important in memory .unctioning and has been implicated as one o. the principle sites @along 8ith th



e initial de7elopment o. #l heimers disease @see 4lton et al! +55+; abors ky et al! +55+, .or re7ie8 o. related details !

he limbic striatum are also interconnected 8ith the lateral and medial hypothalamus, brainstem reticular .ormation, and the .rontal and in.erior temC )obbins, +55 ; %roene8egen, et al! +55+; eimer C #lheid, +55+; elly, et al! +53 ; &ogenson C Gang +55+; 4lton et al! +55+; Parent C a r t al! +53+; abors ky et al! +55+ ! The limbic striatum is able, there.ore, to e=ert 8idespread e..ects on neocortical and subcortical structures!

imbic striatum recei7es (# .rom the mesolimbic system as does the amygdala! The amygdala also sends a=ons that terminate in striatal neuronsd'acent to those inner7ated by mesolimbic (# neurons @ elly et al! +53 ; Gim C &ogenson, +53-, +535 ! Thus, a comple= interactional loop is .or nuclei, the integrity o. 8hich, in part is dependent on the mesolimbic (# system 8hich can act on the amygdala, hippocampus and limbic striatum

y so as to modulate striatal reception o. amygdala @&aslo8ski?$obu i C Napier, +55/ and hippocampal e=citatory signals, and regulate the transut into the SI! #lterations in mesolimbic (# acti7ity, there.ore, can signi.icantly in.luence limbic striatal, amygdala and hippocampal acti7ity as 8

ssion o. limbic impulses!

depletions in mesolimbic (# can disrupt motor and social?emotional memory .unctioning; a condition compounded by (# in.luences on acetylchol, and the e..ects o. striatal (# on the reception o. hippocampal, amygala, and neocortical input!

mbic striatum @and limbic system contain high densities o. #$h neurons 8hich are in7ol7ed in memory as 8ell as motor .unctioning @4lton et al! +! +55 ; abors ky et al! +55+ ! In .act, o. all striatal nuclei, densities o. (# @and #$h neurons are highest 8ithin the @SI and nucleus accumbensch in turn greatly in.luences the SI @8hich is a ma'or source o. neocortical #$h , as does the amygdala @Gim C &ogenson +53- and hippocampuon7erge on the SI!

um, the hippocampus @and the amygdala also recei7es meso?limbic (# input and contains (+ and ( receptors @$amps et al! +556 as 8ell as #$neuronal acti7ity can be e=citory or inhibitory depending on the resting membrain potential o. the recei7ing neuron @#'ima et al! +556 as 8ell as cpeci.ically, mesolimbic (# mediated signals are relayed .rom the accumbens to #$h neurons in the SI 8hich in turn pro'ect to (& and the neocortn particular @&ogenson C Gang +55+; 4lton et al! +55+; abors ky et al! +55+ ! o8e7er, the (# and cholinergic, #$h system appear to e=ert



ng in.luences!

#$h is usually inhibited by (#! By contrast, (# depletion results increased #$h and neuron hyperacti7ity @see #ghan'anian C Bunney, +522; Bloother, et al!, +532 8hich can greatly disrupt cogniti7e and memory .unctioning as 8ell as motor acti7ities, unless re7ersed by anti?cholinergic drugs(#Hcholinergic system can result in #l heimers disease @4lton et al! +55+; abors ky et al! +55+ !

y .unctioning, it appears that mesolimbic (# modulates the reception o. hippocampal @motor?spatial input into the accumbens 8hich pro'ects to thdistributes these in.luences, perhaps 7ia #$h to the neocorte= ! (# accomplishes this 7ia inhibitory in.luences on #$h and .acilitation o. the %#appears to e=ert inhibitory in.luences 8ithin the striatum and the transmission o. impulses .rom the nucleus accumbens @and amygdalaHhippocami. the inhibitory in.luences o. %#B# and #$h on the SI are dampened, the SI becomes acti7ated and memory .unctioning may be enhanced or disr le7el as this nucleus e=erts 8idespread #$h in.luences on the cerebrum! Thus .luctuations in (# le7els can either act to e=cite or inhibit cogniti7ethe limbic striatum @see &ogenson C Gang +55+ as 8ell as the corpus striatum @Packard C 9hite +55+ and the neocorte=!

o. importance in this memory?striatal neural net8ork is @0 T serotonin @&cLoughlin et al! +55/; &ogenson C Gang +55+ and @NE norepineph $ools, +55/ ! For e=ample, NE le7els ha7e been sho8n to .luctuate 8ithin the amygdala and nucleus accumbens 8hen presented 8ith no7el stim

d during in.ormation acDuisition! Presumably NE le7els 8ithin the accumbens can regulate or in.luence the reception o. amygdala and hippocampan the accumbens and SI 8hich in turn pro'ects to the neocorte= and, in this regard, may act to shunt amygdala?hippocampal impulses to discrete orrebrum!

igh alpha?NE acti7ity is associated 8ith reduced amygdala input, 8hereas lo8 beta NE may reduce hippocampal input into the striatum! $onditions are most likely to result 8hen stressed or traumati ed in 8hich case it is possible .or amygdala @and thus emotional input to be recei7ed in, learn

he striatum in the absence o. hippocampal participation @see )o endaal C $ools +55/ ! It is conditions such as these that can gi7e rise to amnesianing @see chapters +/, -6 !

ome cases, it is also possible .or both the alpha and beta NE system to be e..ected simultaneously such that amygdala and hippocampal input to thehibited in 8hich case pro.ound memory loss may result @see )o endaal C $ools +55/ ! Similar disturbances are associated 8ith the serotonin @0



ughlin et al! +55/ !

T can signi.icantly e..ect the capacity to inhibit irrele7ant sensory input @at the le7el o. the brainstem, amygdala, basal ganglia, and neocorte= ! ities or depletion typically results in con.usion and sensory o7erload and in some instances the production o. hallucinations @see chapter -6 !

n o. the mesolimbic (# system andHor se7ere disruptions in the 0 T system in turn inter.eres 8ith the hippocampal?limbic striatal memory system and can create neuronal hyperacti7ity ?a condition 8hich inter.eres 8ith perceptual and hippocampal? memory?SI?amygdala .unctioning! In this r

at the central 0 T system is se7erely disrupted among those 8ith se7ere memory loss and #l heimer<s disease @&cLoughlin et al! +55/ and thatthe globus pallidusHSI can induce 7isual and auditory hallucinations as 8ell as cogniti7e deterioration @Lauterbach et al! +55/ !

L EI&E)<S (ISE#SE

isease is associated 8ith a pro.ound loss o. memory and cogniti7e and intellectual .unctioning, including, at its later stages, an inability to recogni etheir o8n personal identity! #l hiemer<s disease is estimated to a..lict appro=imately +6 o. those o7er age 10, and 06 o. those o7er 30!

es, #l hiemer<s disease is associated 8ith pro.ound loss o. cerebral .unctional capacity, coupled 8ith neural degeneration and a loss o. neurons and. amyloid @senile plaDue and neuro.ibrillary tangles! Because structures such as the substantia innominata, amygdala, and entorhinal corte= ha7e

son et al! +556; %ome ?Isla, et al!, 666; )apoport +556 it is thought that the destruction o. this tissue and ad'acent tissue accounts .or the loss o.otional, .acial recognition, and related 7isual abnormalities, including 7isual agnosia @%iannakoulos, et al!, +555 !

use there is no single .actor that has been implicated, and due to the number o. associated disturbances, it has been argued that #l heimer<s diseaseniti7e and memory disturbances are due to a >global cortico?cortical disconnection> syndrome @see &orrison et al! +556; )apoport +556 ! Ne7ert. this chapter, the striatal contribution to this disorder 8ill be emphasi ed!



#L EI&E)<S (ISE#SE

chapter +0, the amygdala and hippocampus pro7ide massi7e input to the limbic striatum as 8ell as the dorsal medial nucleus o. the thalamus @(&nd reticular acti7ating system, as does the accumbens and SI @see eimer C #lheid, +55+; oob et al! +55+; &ogenson C Gang +55+; abors ky etd, these nuclei, including the o7erlying entorhinal corte=, play a signi.icant role in memory and the gating o. in.ormation destined .or the neocorteart o. a massi7e neural net8ork designed to control in.ormation processing and to establish memory related neural net8orks @see also chapter +/ !e nucleus accumbens apparently acts to integrate hippocampal and amygdala input, 8hich is then transmitted to the SI 8hich is also the recipient oerned 8ith cogniti7e, memory, and motoric acti7ities @see &ogenson C Gang +55+ !

ars that the accumbens and SI play an inhibitory @.iltering role on in.ormation processing, and may e=ert inhibitory @and counterbalancing in.lu.rontal lobes, the (&, and corpus striatum @see &ogenson C Gang +55+ ! The amygdala e=erts similar in.luences on these nuclei @chapter +0 andthe SI and accumbens!

ole o. the limbic striatum in cogniti7e and memory related acti7ity also includes the learning o. re8ard?related and a7ersion processes, the .acilitati8ithdra8al responses and the memori ation o. 8here a re8ard or a7ersi7e stimulus 8as pre7iously recei7ed @E7eritt et al! +55+; elsey C #rnold +nucleus accumbens and SI are dependent on the medial and lateral amgydala, especially in the learning o. negati7e e=periences @ elsey C #rnold

SI is the primary source o. neocortical cholinergic inner7ation @$arpenter +55+ and appears to be concerned 8ith integrating social?emotional andor memories and then storing them perhaps 8ithin the SI as 8ell as 8ithin the neocorte=! ence, i. the SI is lesioned the cholinergic pro'ection syscogniti7e as 8ell as social?emotional memory .unctioning is negati7ely impacted!

erges 8ith and becomes coe=tensi7e 8ith the centromedial amygdala @ eimer C #lheid +55+ ,and is an amygdala deri7ati7e, not suprisingly, a sigs, neuro.ibrillary changes and senile plaDues ha7e been .ound in the amygdala @and hippocampus, )apoport +556 , as 8ell as in the SI, in patientsisease and those su..ering .rom degenerati7e disorders and memory loss @ er og C emper, +536; &ann, +55 ; Sarter C &arko8itsch, +530 ! (egla 8ould also account .or the social?emotional agnosia and prosopagnosia that is common in the ad7anced states o. #l hiemer<s disease; i!e! .ailuremember lo7ed ones @chapter +- !

NEA)4N#L (E#T C #L EI&E)<S



has also been reported in the entorhinal and parahippocampal areas o. the in.erior temporal lobe @see &orrison et al! +556; )apoport +556 8ithinpocampus and amygdala! Speci.ically, in addition to senile plaDues, neuro.ibrillary tangles, a /6 to 16 loss o. neurons during the early stages o.een .ound in layers / and o. the entorhinal corte= @%ome ?Isla, et al!, 666 ??the gate8ay to the hippocampus! (estruction o. this tissue and ad'acult in memory, social?emotional, .acial recognition, and related 7isual abnormalities, including 7isual agnosia, as recently demonstrated among tho

isease @%iannakoulos, et al!, +555 !

those 8ith #l heimer<s disease, 8idespread atrophy, amyloid plaDues, tangles, and metabolic disturbances ha7e been noted in a 7ariety o. corticalreser7ation o. the motor and primary recei7ing areas @)apoport +556 ! Based on these .indings it has been argued that #l heimer<s disease and assomemory disturbances are due to a >global cortico?cortical disconnection> syndrome @see &orrison et al! +556; )apoport +556 ; i!e!, a loss o. neurns 8ith association neocorte=, 8hich in part 8ould account .or the cogniti7e deterioration!

o. this deteriorati7e process may 8ell be in the SI, and it may be due to an ol.actory borne in.ection due to 7iral or bacterial in7asion! That is, thesemay enter the ol.actory system and in7ade those structures directly inner7ated by the ol.actory ner7es, i!e! the amygdala, entorhinal corte=, and SI

e other hand, or perhaps related to this scenario, are .indings suggesting a genetic .oundation .or this disorder, such that de.ects in at least .our speci

romosomes +, +/, and + may be responsible @Le7y?Lehad et al!, +550; Saunders et al!, +55- !

ihood that the limbic striatum and ol.actory?limbic structures may be selecti7ely in7ol7ed in the early stages o. #l heimers, and gi7en the .act thatnergic input to the neocorte=, then the subseDuent and progressi7e loss o. SI @and amygdala neurons might result in a progressi7e deterioration ahe neocorte= such that other8ise healthy neurons are killed! That is, since the SI contains high concentrations o. cholinergic neurons 8hich in turn peas throughout the neocorte= @re7ie8ed in $arpenter +55+ , perhaps the initial cell loss 8ithin the SI @also re.erred to as the nucleus basalis , may ath in healthy neurons @8hich pro'ect to or recei7e .ibers .rom the a..ected cells 8hich essentially become >pruned> and drop out .orm disuse!



nal Transport!

nce 8hich indicates that perhaps due to head in'ury, drug or to=ic e=posure, or perhaps the loss o. synaptic 'unctions @due to the death o. unhealthyction , a=onal transport becomes de.ecti7e due to the death o. its target neuron! o8e7er, i. a healthy cell cannot discharge and e=change in.ormatieading to a domino e..ect and thus 8idespread cell death @see Burke et al! +55 ! That is, due to the loss o. terminal synaptic 'unctions @due to celcal abnormalties including de.ects in microtubule assembly @8hich participates in neuronal transmission , a=onal transport becomes dys.unctionaland it<s dendrite ha7e died! ence, there is a buildup o. to=ic o=idatati7e metabolites and naturally occurring neuroto=ins in the healthy cell body thl, 8hich causes the normal cell to die as 8ell! This 8ould result in a progressi7e loss o. neurons such that 8idespread areas o. the cerebrum soon b

is 8hat may occur i. the limbic striatum becomes abnormal and cells 8ithin the SI and accumbens begin to die! #s the disturbance and deterioratiotional, memory and related abnormalities including Parkinsonian symptoms begin to appear and become progressi7ely 8orse as neocortical, striata die and drop out!

LI&BI$ C $4)PAS ST)I#T#L $4ANTE)B#L#N$IN% INFLAEN$ES

d corpus striatum are richly interconnected and send pro'ections to many o. the same brain areas! o8e7er, due to di..erential input .rom the amyghese nuclei e=ert tremendous counterbalancing in.luences on each other and their associated neural net8orks! For e=ample, the centro?medial as 8eygdala pro'ects to and e=erts e=citatory in.luences on the the limbic striatum @&aslo8ski?$obu i C Napier, +55/; Gim C &ogenson +53 , 8heresterior?lateral amygdala pro'ects to the corpus striatum and the 7entral and dorsal globus pallidus! "ia these dual interconnections, the amygdala caand e7en oppositional in.luences on these nuclei!



e corpus striatum recei7es the bulk o. its (# .rom the nigrostriatal systems, 8hereas the limbic striatum recei7es (# .rom the mesolimbic (# systlips, +531 .or re7ie8 ?transmitter systems 8hich interact at the le7el o. the brainstem, limbic system, striatum, and neocorte= @&aslo8ski?$obu iFor e=ample, it has been sho8n mesolimbic (# can act on the amygdala and limbic striatum simultaneously so as to modulate striatal reception otatory signals @&aslo8ski?$obu i C Napier, +55/ !

use the corpus and limbic striatum are largely @but not completely inner7ated by di..erent clusters o. midbrain (# neurons, reductions or increasen e=ert pro.ound in.luences on those neurons inner7ated by the others ?.or e=ample, by eliminating inhibitory or counterbalancing in.luences! Thusigrostriatal @but not the mesolimbic path8ays can result in increased acti7ity 8ithin the limbic striatum @see Gim C &ogenson, +53-, +535 and mdeceased acti7ity 8ithin the corpus striatum! I. this occurs, mo7ement programming may be disrupted resulting in rigidity or tremors ?a conseDuenalance in amygdala?(#?striatal acti7ation!

esolimbic (# depletion can result in enhanced corpus striatal acti7ity and decreased limbic striatal and lateral amygdala and hippocampal acti7ity,al?emotional memory .unctioning may be disrupted; a condition compounded by (# in.luences on acetylcholine @#$h neurons and the reception

amygala, and neocortical input 8ithin the striatum! ence, the .unctioning o. the limbic or corpus striatum can be se7erely disrupted e7en 8hen the



grity o. its o8n neurotransmitter systems are other8ise intact; i!e! due to a loss o. counterbalancing in.luences!

NE4$4)TI$#L, T #L#&I$, C ST)I#T#L &4"E&ENT FEE(B#$ L44PS

T E S&#, PAT#&EN, #N( %L4BAS P#LLI(AS

e studies ha7e indicated that those 8ith Parkinson<s disease demonstrate the greatest amounts o. (# depletion and related (# neuronal degeneratioence, many authors ha7e argued that Parkinson<s symptoms are a conseDuence o. damage to this nuclei @e!g! %oto et al!+556 , 8hich in turn canun8anted mo7ements such as tremor! Presumably, in these instances, the medial @internal globus pallidus @8hich recei7es putamen input ceases or acti7ity!

ecei7es much o. it<s input .rom the caudate and in particular the S&#, the secondary and primary motor corte=, as 8ell as areas 0 and 2 o. the parill, +526; Pandya C "ignolo, +52+ ! Presumably the putamen, in con'unction 8ith the caudate, transmits this in.ormation to the medial and lateral to the motor thalamus, and brainstem! o8e7er, like the caudate, the putamen and %P also pro'ect back to the motor neocorte=, thus creating a 7e

back loop @see &ink C Thach, +55+; Parent C a rati +550 8hose origin may begin in the S&# @#le=ander C $rutcher, +556; $rutcher C #le=aps the limbic system @chapter +- !

8hen anticipating or preparing to make a mo7ement, but prior to the actual mo7ement, neuronal acti7ity 8ill .irst begin and then dramatically incred by acti7ity in the secondary and then the primary motor area @see chapter +5 , and then the caudate and last o. all the putamen?%P @#le=ander &ink C Thach, +55+ !

e moment the role o. the limbic system, this indicates that impulses to mo7e .irst appear in the S&# and that other motor regions are temporally?cruited in a step?8ise .ashion; i!e! S&# ? premotor ? primary motor ? caudate ? putamen ? %P ? motor thalamusH.rontal motor areas ? brainstem!!

caudate nucleus also contains neurons 8hich become acti7e prior to, and in anticipation o. making body mo7ements, and in response to associatedironmental cues @)olls, et al! +53-; )olls C 9illiams, +532 ! This caudate neuronal acti7ity precedes, or occurs simultaneously 8ith e=citation in teus, 8hich also results @7ia .eedback in S&# acti7ation! This is because the %P and the putamen not only recei7e caudate and neocortical a..erentck to the .rontal motor areas @as 8ell as to the motor thalamus ! ence, parallel processing also occurs!

y in these regions Duickly begins to o7erlap such that neurons in the motor neocorte= and basal ganglia o.ten remain acti7ated simultaneously @#6 ! &oreo7er, the motor areas all independently send a=ons to the brainstem, 8ith a=ons .rom di..erent areas con7erging on the same motor neuron!

7ity in the motor areas is characteri ed by both temporal?seDuential and parallel processing that in turn is made possible 7ia .eedback neural circuidi..erent net8orks are intimately linked and mutually interacti7e they make coordinated and goal directed mo7ements possible!

le .eedback loops are probably also necessitated by the numerous 7ariables and body? spatial? 7isual? kinesthetic? motor re.erences, etc!, that needrder to make a planned mo7ement! Thus both temporal?seDuential and parallel processing is necessitated as each area is .unctionally speciali ed too. in.ormation and to per.orm certain actions in semi?isolation as 8ell per.orming other .unctions in parallel 8ith yet other motor areas!

N C &E(I#L C L#TE)#L %L4BAS P#LLI(AS

t regions o. the caudate appear to subser7e di..erent .unctions, a 7ariety o. neuronal types also characteri e the lenticular nucleus! For e=ample, pr related neurons are segregated 8ithin the putamen @#le=ander C $rutcher, +556 ! This suggests that the putamen employs t8o di..erent neural netcutes mo7ements, the other 8hich prepares to make the mo7ement; in.ormation 8hich is normally transmitted to the %P as 8ell as back to the mot



ppears to act at the behest o. impulses arising in the neocortical motor areas @as 8ell as the limbic system and then only secondarily acts to prepapate in the guidance o. mo7ement @&ink C Thach, +55+ ! In con'unction 8ith the caudate, the putamen accomplishes this 7ia signals transmitted toeral %P, the motor thalamus, and brainstem reticular .ormation @&arsden C 4beso, +55/ and then back to the motor neocorte= @see also Parent Cated re7ie8 !

putamen and globus pallidus are also coe=tensi7e @the lenticular nucleus and in many respects .unction as a prepatory motor unit in7ol7ed in the 7en the learning o. 7arious motor acti7ities @$rutcher C (eLong, +53/; imura, +532 ! For e=ample, alterations in neuronal acti7ity ha7e been demallidus and the putamen during tasks in7ol7ing learned body mo7ement @$rutcher C (eLong, +53/ ! Lenticular neurons also become highly acti7e

or limb mo7ements are triggered in response to a particular auditory or 7isual stimulus associated 8ith that mo7ement @ imura, +532 !



and %P neurons also .ire in response to re8ard but not to mo7ement and 7ice 7ersa @ imura, et al! +53/ ! o8e7er, these same neurons do not reslearned and re8arded mo7ements are made spontaneously and in the absence o. associated cues, or 8hen they 8ere no longer re8arded! These .in

bility that speci.ic neurons 8ithin these nuclei are responsi7e to moti7ational cues associated 8ith mo7ement and that these neurons utili es these cmake a mo7ement @ imura, +532 !

%P also selecti7ely respond and change their acti7ity 8hen making ballistic mo7ements, particularly those 8hich are 7isually guided @&ink C Thr, acti7ation occurs too late .or these neurons to be in7ol7ed in the initiation or planning o. the mo7ement @&ink C Thach, +55+ ! $on7ersely, desibition o. the %P can result in di..iculty turning o.. a mo7ement @see &ink C Thach, +55+ ?thus gi7ing each mo7ement a ballistic Duality! Similamassi7e inhibition o. the %P can make it e=ceedingly di..iculty to rapidly alternate bet8een mo7ements and thus s8itch .rom an ongoing to a di..e

m @ ore C "ilis, +536 ! This loss o. control o7er motor programming 8ith %P impairment e=tends e7en to attempts to make purpose.ul ballistic reaments @ orak C #nderson, +53/; ore C "ilis, +536 , and the 7elocity and amplitude o. these mo7ements may in .act be signi.icantly slo8ed andh, +55+ !

ernal C L#TE)#LHE=ternal %L4BAS P#LLI(AS

nternal and lateralHe=ternal %P appear to play di..erent and counterbalancing roles in the e=ecution, inhibition and e=citation o. di..erent motor proal! +532; &arsden C 4beso, +55/ ! For e=ample, the medialHinternal %P is belie7ed to pro7ide positi7eHe=citatory .eedback to the neocortical moteralHe=ternal %P pro7ides indirect >negati7e> and inhibitory .eedback so that un8anted mo7ements are pre7ented! &oreo7er, (# inhibits the mediral %P @re7ie8ed in &arsden C 4beso, +55/ !

e @at least in theory , reduced nigrostriatal (# le7els can result in an o7ere=citation o. the medial %P, 8hich inhibits cortically mediated or initiated

ereby producing akinesia @loss o. mo7ement , bradykinesia @reduction in mo7ement and hypokinesis @slo8ness o. mo7ement coupled 8ith trem

and e=cessi7e lateral %P @and limbic striatal acti7ity can also result in gross in7oluntary and e=cessi7e hyperkinetic and ballistic mo7ements usuimbs on the contralateral side o. the body, along 8ith choeri.orm mo7ements and tremors! o8e7er, surgical destruction o. the .ibers tracts leadingl and medial %P can signi.icantly diminish such disturbances, including hemiballismus, tremor, dystonia, chorea and athetosis @see $arpenter C S

e, lesions to the amygdala prior to the de7elopment o. Parkinsonian and related symptoms, can also pre7ent the de7elopment o. these motor abnor



s due to the e=tensi7e interconnections maintained 8ith these regions and the .act that the amygdala becomes coe=tensi7e 8ith the 7entral %P!

cause the putamen pro'ects to the %P, lesions restricted or locali ed to the putamen can also result in abnormal competition bet8een atagonist ando the release o. the %P @and associated neural circuitry .rom putamen control! Patients or primates so e..ected su..er .rom se7ere dystonia as 8ellmuscle tone sometimes accompanied by chorea @Sega8a, et al! +532 ! Similarly, among those 8ith Parkinson<s disease, acti7ity 8ithin the putameeduced @Play.ord et al! +55 , and reduced .unctional acti7ity is also seen in the caudate 8hich merges 8ith the putamen!

T E &4T4) T #L#&AS

motor thalamus e7ol7ed in tandem 8ith the basal ganglia and is richly interconnected 8ith the caudate nucleus and globus pallidus in particular @$Parent C a rati +550; Po8ell C $ohen, +501; )oyce, +532 ! It is an integral aspect o. the motor circuit and becomes acti7ated 8hen making a 7a

mo7ements and in response to kinesthetic and propriocepti7e stimuli @"itek et al! +55/ !



thalamus consists o. the 7entromedial, 7entrolateral, 7entralis intermedius, centromedian and para.ascicular @posterior intralaminar thalamic nuc.rom the brainstem, cerebellum, and neocorte=, and maintains reciprocal pro'ections 8ith the %P and S&# @$arpenter +55+; Brodal, +53+; empabayashi, +532; )oyce, +532; "itek et al! +55/ ! These thalamic >motor> nuclei also recei7e input .rom the .acial, leg, and arm regions o. the motosory corte= @ un le, +521; "itek et al! +55/ and maintains reciprocal interconnections 8ith the amygdala, cingulate gyrus, substantia nigra, and su

colliculus @*ones et al! +525; &esulam et al! +522; )oyce, +532; "ogt et al! +525 !

otor thalamus is intimately associated 8ith limbic and motor nuclei throughout the brain and is able to in.luence as 8ell as recei7e multiple inputsnuclei 8hich in turn are interlinked! For e=ample, some intralaminar thalamic nuclei send collaterali ing a=ons 8hich pro'ect to both the striatum ahereas some motor neocortical a=ons pro'ect to both the striatum and the intralaminar nuclei @)oyce, +532 ! ence, a richly interconnected neural

maintained by these nuclei so as to control and guide motor .unctions!





pects the motor thalamus appears to act as a ne=us 8here multiple .orms o. input are integrated so as to regulate motor acti7ity! There.ore, 8hen thabnormally inhibited or acti7ated, signi.icant motor abnormalities result; e!g!, rigidity, tremor, ballismus, catatonia, and catalepsy! For e=ample, unin.arcts and hemorrhages in7ol7ing the thalamus can induce unilateral thalamic ata=ia and apra=ia @Nadeau et al! +55/; Solomon et al! +55/ !

in'uries or surgical destruction o. the speci.ic thalamic nuclei can in some instances eliminate or reduce the in.luences o. abnormal acti7ity recei7es 8ithin the motor circuit @&arsden C 4beso, +55/; Narabayashi, +532 ! For e=ample, patients su..ering .rom Parkinsonian symptoms appear to det .rom thalamic lesions 8hich abolish contralateral tremor and rigidity @see &arsden C 4beso, +55/ 7ia disruption o. the %P?motor thalamus?.ron

area motor circuit!

y, there is e7idence 8hich indicates that destruction o. the 7entrolateral @"L motor thalamic nuclei can reduced rigidity @i. the lesion is more anterhe lesion is posterior ! Neurosurgical destruction o. the %P to motor thalamus pro'ection .ibers can also signi.icantly decrease rigidity, 8hereas sectioainstemHcerebellum path8ay also reduces tremor @see Narabayashi, +532 ! &oreo7er, "L lesions can signi.icantly reduced choreic and ballistic m



such as secondary to trauma or encephalitis!

eurosurgical destruction or electrical stimulation o. these nuclei @e!g! 7entralis intermedius can eliminate tremors @see Narabayashi, +532 ! Indeor thalamus not only .ire in tandem 8ith tremor, but electrical stimulation o. this nuclei at a .reDuency similar to the tremor, increases the .reDuenc

amplitude o. the tremor! o8e7er, high le7els o. thalamic stimulation reduces or abolishes tremor @Narabayashi, +532 !

T E SABT #L#&I$ NA$LEAS

mic nucleus is a small but densely inner7ated component o. the basal ganglia?thalamocortical?limbic motor circuit! It maintains a 7ery important rd is richly interconnected 8ith the medial and lateral %P @$rossman, et al! +532; Parent C a rati +550; 9ichman et al! +55/ and merges mediallthalamus 8ith 8hich it is intimately linked! The subthalamic nucleus also recei7es e=tensi7e and topographic pro'ections .rom the neocortical motonhibitory a=onal .ibers .rom the .rontal lobes @Parent C a rati +550 ! It also pro'ects to the caduate, putamen, SI and brainstem reticular .ormatio=citatory in.luences to the substantia nigra and other target nuclei @ lockgether, et al! +532; Parent C a rati +550 and thus in.luences the nigrost

dopamine system and a 8ide 7ariety o. brain areas 7ia separate path8ays @9ichman et al! +55/ !

rconnections 8ith so many motor related areas o. the brain @as 8ell as the limbic system , the subthalamic nucleus is able to e=ert signi.icant, albe

ect in.luences on motor e=pression 8hich is accomplished in con'unction 8ith the nigro?striatal (# system and the %P 8hich in turn modulates subts reception o. cortical input @Parent C a rati +550; 9ichman et al! +55/ ! ence, the subthalamic nucleus appears to also e=ert modulating in.lumo7ement @although it also ser7es non?mo7ement .unctions , especially those in7ol7ing the pro=imal limbs!

ubthalamic neurons are somatotopically organi ed, such that those representing the hand, arm, leg, or eyes, are clustered together, and these clustertheir acti7ity during eye, or limb mo7ements @9ichmann, et al!, +55/ ! In .act, they increase their acti7ity 'ust prior to mo7ement!

s locali ed to or in7ol7ing the subthalamic nucleus can there.ore result in signi.icant motor disturbances including chorea and hemiballismus @$roluding sudden and in7oluntary .linging mo7ements o. the arm or leg??mo7ements that might be appropriate i. engaged in de.ensi7e maneu7ers!

patients can still make normal 7oluntary mo7ements!

emiballismus are due presumably to interuption o. the normal %#B#inergic reciprocal relationship it maintains 8ith the caudate, putamen, and in&c%eer C &c%eer, +532; Parent C a rati +550 ! That is, due to loss o. inhibitory %P input, the patient makes sudden and in7oluntary mo7ements,

cti7ity directed, ultimately, the motor neocorte=! ence, again, these are normal mo7ements 8hich are abnormally produced i. the subthalamic nucin'ured or recei7es abnormal signals!

Parent and a rati @+550 argue that inhibitory in.luences e=erted on the motor thalamus, neocorte=, or subthalamic nucleus by the %P can result in7ity is reduced, or hyperkinesia i. enhanced! Similarly, $rossman et al @+532 argue that in hyperkinetic states the medial %P and subthalamic nuc7e and the lateral %P is o7eracti7e! In Parkinsons and akinetic disorders, the medial %P and subthalamic nucleus is o7eracti7e 8hereas the lateral

underacti7e @$rossman, et al! +532 !

y, lesions o. the subthalamic nucleus can result in increased acti7ity 8ithin the %P and motor thalamus, such that the motor thalamus, S&# and braiacti7ated, 8hich results in e=cessi7e mo7ement including ballismus! I. the %P is subseDuently destroyed, hemiballismus disappears! o8e7er, in oreported that a hemorrhage in7ol7ing the subthalamic nucleus, resulted in the amelioration o. a patients Parkinson<s symptoms @9ichmann et al!

(# C %#B# ST)I#T#L INTE)#$TI4NS C &4"E&ENT (IS4)(E)S

es about t8o thirds o. its input .rom the putamen, and one third .rom the caudate @as 8ell as some .ibers .rom the S&# ! Presumably, acti7ation o.tor ?caudate ?putamen loop results in di..erential acti7ation o. the lateral and medial %P, the subthalamus, and the motor thalamus and the brainsteback to the S&# and primary motor areas .rom 8hich arises a massi7e rope o. ner7e .ibers @the corticospinalHpyramidal tract 8hich directly innernd spinal cord! Presumably these comple= .eedback loops insure that coordinated and smooth continuous mo7ements are planned, coordinated, and

carried out! #s noted, these interactions are also dependent on (# acti7ity!





e, Parkinson<s disease, being characteri ed by reduced (#, is associated 8ith a reduction in striatal inhibitory acti7ity and thus increased %P outpuhalamus and brainstem 8hich 8ould produce tonic E&% acti7ity and akinesia and rigidity @ ockgether, et al! +531; Starr C Summerhayes, +53- ;

hypomo7ement due to e=cessi7e tonic e=citation!

e=cessi7e corpus stritatal (# 8ould result in increased striatal %#B# acti7ity and thus inhibition o. the %P 8hich 8ould lead to a disihibition o. thnd subthalamic nucleus and thus increased acti7ation o. brainstem and spinal motor neurons! &o7ements 8ould become hyper, ballistic, and chore

de7elop ?as .reDuently occurs 8ith prolonged neuroleptic treatment!



, %#B# acti7ity 8ithin the %P and subthalamus are signi.icantly e..ected by (# acti7ity 8ithin the corpus striatum! For e=ample, deceases in striaased striatal %#B# neural acti7ity @?8hich is normally inhibitory ! #s these %#B# neurons pro'ect to the %P, the loss o. this %#B# inhibitory inpnic acti7ity 8ithin the %P! 8hich in turn 8ould result in increased inhibitory %P in.luences on the motor thalamus and brainstem thereby decreasine, the modulatory in.luences o. these latter nuclei on motor .unctioning 8ould be eliminated, resulting in heightened acti7ity le7els and thus o7erapect o. the .eedback circuit! Brainstem and spinal motor neurons 8ould become tonically acti7ated thereby creating rigidity and sti..ness o. mo7e

e loss o. %#B# in.luences could induce choreic mo7ements! In this regard it is note8orthy that signi.icant %#B# loss and abnormalities ha7e beetia nigra and basal ganglia o. those 8ith untington<s chorea @Bird C I7ersen, +52/ , along 8ith degeneration o. the nigrostriatal (# pro'ection pat

ANTIN%T4N<S $ 4)E#dance> is characteri ed by 'erky, 8rithing, t8isting, and unpredictable mo7ements o. the e=tremities! The t8o main types are Sydenham<s $horea @ntington<s $horea! Sydenham<s $horea in7ol7es chorei.orm mo7ements o. the .acial, tongue, and e=tremities, and is accompanied by loss o. ner7

the caudate and putamen, as 8ell as 8ithin the cerebral corte=, substantia nigra, and subthalamic nucleus! hodyst!'pg



ton<s chorea is a progressi7e deteriorati7e inherited genetic disorder 8hich is passed on by an autosomal dominant gene located on chromosome /!ed by an insidious onset that may begin during childhood or old age, 8ith the illness beginning earlier in those 8ho ha7e an a..ected .ather @re7ie

Folstein et al! +556; Goung +550 ! $ogniti7e decline, ho8e7er, is gradual!

i7iduals tend to su..er .rom memory and 7isual?spatial de.icits, depression, and reduced .luent output although aphasia is not typical! (i..iculty 8itn, planning skills, decision making, and a reduced capacity to consider alternate problem sol7ing strategies or to shi.t .orm one mental set to anotheuncommon @re7ie8ed in Folstein et al! +556 ! ence, in some respects this disorder is suggesti7e o. .rontal lobe abnormalities @see chapter +5 !

me is also associated 8ith 8idespread neuronal loss in the caudate, putamen, brainstem, spinal cord, cerebellum, and atrophy in the %P @see "onsattung +550 ! (egeneration is predominantly o. small striatal neurons 8hereas larger neurons remain intact! 4piate neurons located in the striatum aree..ected @)einer et al! +533 ! It is belie7ed that the degeneration o. these corpus striatal neurons, as 8ell as the loss o. %#B# in.luences, results in

striatal control o7er the %P @see Narabayashi, +532 , thereby producing e=cessi7e mo7ement!



hy that some reports indicate that the posterior caudate and putamen are more se7erely e..ected than the anterior regions @"onsattel, et al! +532 ! Indate and it<s tail is usually the earliest and most se7erely e..ected part o. the brain ?8hich implicates the amygdala as a .actor in the de7elopment oearly stages o. untingtons chorea, atrophy and degeneration begin in the tail and spreads dorsally and anteriorally thus e..ecting the striatum and

nucleus @Goung +550 !

t is note8orthy that a..ecti7e disorders and personality and mood changes are prominent early signs suggesting amygdala in7ol7ement! Indeed, disy precede any motor or cogniti7e decline by as much as 6 years, 8ith some patients displaying mania, depression as 8ell as antisocial tendencies

in Folstein et al! +556 ! #s noted, neural degeneration tends to begin in the amygdaloid tail o. the corpus striatum @Goung +550 !

rbances o. mo7ement, those 8ith untington<s disease tend to su..er .rom either or both 7oluntary and in7oluntary abnormalities! The in7oluntaryerking and unpredictable mo7ements o. the limbs, trunk and .ace 8hich may occur 8hen at rest, 8alking, or 8hile acti7ely engaged in some task s

they may appear to be into=icated andHor attempting to dance about!

disorders include rigidity, slo8ed, clumsy, or di..iculty initiating mo7ement! Those 8ho su..er .rom 7oluntary mo7ement disorders are the most lik demonstrate cogniti7e decline @Folstein et al! +556 !

$4N$LA(IN% ST#TE&ENT: T E #&G%(#L#

anglia motor circuit, as conceptuali ed and described in this chapter, consists o. multiple neural net8orks in7ol7ing the caudate, putamen, globus plimbic striatum, motor thalamus, subthalamus, brainstem, S&#, pre?motor and primary motor areas, and the amygdala!

y, the role o. the amygdala in mo7ement is o.ten ignored by in7estigators @and almost all te=tbooks although all aspects o. the motor circuit are dnner7ated by this nuclei and respond to amygdala mediated impulses! #lthough the amygdala can be surgically destroyed bilaterally 8ithout signi.irmal motor .unctioning, in many instances the amygdala is implicated in the genesis o. abnormal motor acti7ities and may play a signi.icant role in

dys.unction and the de7elopment o. Parkinson<s and related diseases!

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