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CERTAIN ANATOMICALAND FUNCTIONAL INTERRELATIONS BETWEEN

THE TEGMENTUM O F THE MIDBRAINAND THE BASAL GANGLIAs2

JOSHUA H. CAREY3Laboratory of Comparat ive Neurology , Depar tment of A n a t o m y ,

Universi ty of MichiganNINE FIGURES

INTRODUCTIONThis paper is an anatomical and experimental study of the

location and the connections of certain selected areas of themacaque midbrain and forebrain. Lesions of the comparableareas in man produce involuntary movements (including tre-mor), loathness to move, rigidity and other disabilities whichcharacterize the symptomatology of patients with a Parkin-sonian syndrome.

CONSIDERATION O F PERTINENT LITERATUREThe areas and fiber systems which may show involvement

in patients with the Parkinsonian syndrome are so numerousand so widespread that presentation of the pertinent literatureadequately would imply writing an account of the anatomy,physiology and neuropathology of the midbrain, considerable

Accepted in partial fulfillment of the requirement for the degree of Doctorof Philosophy at the University of Michigan.Some of the monkeys used in this experiment were made available through thekindness of Parke, Davis and Company, Detroit , Michigan. The necessary technicalassistance was made possible by a grant given by the University of MichiganMedical School from the Hill Experimental Trust Fund. The author is verygrateful for the assistance given him by Parke, Davis and Company and theUniversity of Michigan Medical School.

Authors present address is the Childrens Hospital, 219 Bryant Street, Buffalo22 , New York.

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58 J O S H U A H. CAREYparts of the dorsal thalamus, the basal ganglia and the efferentparts of the cerebral cortex. Reviews of earlier literature(none of them complete) are to be found in volume 21 of theResearch Publication for the Association of Nervous andMental Diseases, which is devoted to a consideration of thediseases of the basal ganglia, and in the accounts by Wilson( '12, '14)' Kodama ('26, '29), Aring and Fulton ('36)'Ariens Kappers, Huber and Crosby ('36) Woodburne,Crosby and McCotter ( '46)' Carpenter, Whittier and Mettler('50) and Carrea and M et t l e r ('54, '55). The necessaryclinical background for this study is provided in such neuro-logical texts as those by Wilson ( '41), Denny-Brown ( '46),Grinker and Bucy ( '49) and De Jong ( '50).

I n the present account certain papers which provide arelatively adequate background for placing the lesions orinterpreting the results will be quoted. Those accounts whichpresent corroborative material or points of view contrary tothe present writer's interpretation will receive particularattention.

Wilson presented his historical account of lenticular de-generation in 1912 and two years later ('14), to provideanatomical and experimental evidence for his clinical work,studied experimentally the connections of the corpus striatumin the macaque. His results presented evidence f o r striato-thalamic and thalamostriate fibers. He found no evidencefor corticos triate connections.

Morgan ( '27) based his conclusions on pathological materialfrom human cases having basal ganglion involvements andon the results following experimental lesions in the corpusstriatum of cats. His report deals with efferent fibers only.In addition to the usually described connections with the rednucleus and the subthalamic nucleus, Morgan traced fibers tothe hypothalamus, to the interstitial nucleus of the mediallongitudinal fasciculus and the nucleus of Darkschewitsch,to the oculomotor and Edinger-Westphal nuclei and, by astriatobulbar system, to practically all of the motor nucleiof the brainstem and the reticular formation. Such striato-


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M A C A Q U E MIDBRAIN AND BASAL GANGLIA 59bulbar connections have not been confirmed by later observers.Morgan reported that the operated cats showed athetosis,occasional tremor', homolateral hypertonicity and circus move-ments to the side of the lesion.

Ranson and his associates studied both the midbrain teg-mentum and the basal ganglia with a view to establishingexperimentally their connections and certain of their functions.Davenport and Ranson ( '30) reported the nuclear configura-tion of the red nucleus, the subthalamic nucleus and adjacenttegmental areas in the rabbit and the cat. I n 1932 Ingram,Ranson, Hannett, Zeiss and Terwilliger stimulated the teg-mental areas in cats and monkeys. By use of the Horsley-Clarke stereotaxic apparatus they obtained a turning of theanimal's head, neck and trunk toward the side stimulated,o r a flexion of the ipsilateral and an extension of the contra-lateral forelimb, or various movements of the hindlimb.Two years later, Ingram and Ranson ( '34) placed lesionsin the red nucleus of the cat. Following the operation thecat showed transient ataxia and incoordination of movementsdue undoubtedly to involvement of the superior cerebellarpeduncles. There was a mild permanent hypertonicity of theextensor muscles but no tremor appeared. Keller and Hare('34) described the effects of section of the rubrospinal tractin the region of the red nucleus. I n addition to incoordinationand ataxia they obtained an intention tremor which lasted onlya few weeks. I n 1942 Ranson and Ranson placed lesions inthe head of the caudate, the putamen, the globus pallidus andthe hypothalamus of macaques. They checked the position ofthe lesion in Marchi material. Those animals in which the ansalenticularis and the lenticular f asciculus were involved athypothalamic levels exhibited, postoperatively, a slownessand poverty of movement. Bilateral involvement of the globuspallidus produced no tremor, no ridigity, no slowness orpoverty of movement and no masklike facies.

Later Ranson and his associates ( '41) made isolated lesionsin the corpus stria tum of monkeys. The microscopic materialprepared from the brain of these operated monkeys revealed


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60 JOSHUA H. CAREYoiily the pallidohypothalamic connections, distribution of fi-bers to the dorsal thalamus and some fascicles to the subthal-amic nucleus. The connection described from globus pallidusto the habenula was probably not striatohabenular but thelateral corticohabenular fibers from the amygdala and thegyrus hippocampi.

Aring and Fulton ( ' 3 6 ) elicited action tremor-such aswas obtained by the present observcr in stimulation of themidbrain tegmentum- y removal of the cerebellum in twobaboons and 14 macaques. Fe rr ar o and Barrera, in the sameyear, obtained a resting tremor by large lesions in the teg-mentum of the macaque.

Kennard ( '44) placed lesions in the basal ganglia of variousprimates by sucking out portions of the area following a directapproach through the cortex. Bilateral injuries to the caudateand to the putamen produced bilateral tremor often morein the head than in the arms. Lesion of one globus pallidusalone gave no results but addition of lesions in area 8 resultedi n tremor (sometimes bilateral) and in spasticity. Choreoath-etoid movements appeared contralateral to the destructionsi n these experiments ; uch destructions involved considerableportions of the cortex so that it is difficult to evaluate theresults.

Several studies on the functions and connections of thebasal ganglia have been presented by Mettler and his as-sociates ('42, '47). Mettler and Whittier ( '47) placed lesionsin and around the subthalamic nucleus in 71 monkeys. In19 monkeys in which the subthalamic nucleus was involved,persistent choreiform, athetoid or choreoathetoid movementswere present. Tremor, ipsi lateral to the subthalamic involve-ment, also appeared. The animals with basal ganglion lesionshad hyperkinesia. In a later paper ( '49) Whittier and Mettlerdescribed the paths involved in the subthalamic lesions. Theyobtained evidence for connections of the subthalamic nucleuswith globus pallidus, substantia nigra and the dorsal thalamus- pparently nucleus ventralis lateralis. In 1950 Carpenter,Whittier and Mettler gave a graphic method of studying


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MACAQUE MIDBRAIN AND BASAL GANGLIA 61the tremor produced in monkey by diencephalic lesions. Adetailed account of the distribution of the superior cerebellarpeduncles in the monkey is to be found in the 1954 paperby Carrea and Mettler. I n a later recent paper ('55) theauthors presented an extensive study of the results of lesionsin and around the brachium conjunctivum, before, duringand after its decussation. The lesions of the brachium con-junctivum in the midbrain tegmentum produced, on the sideof the lesion, an ataxic tremor, a hypokinesia and a circlingtoward that side. Lesions in the decussation of the brachiaconjunctiva, or rostral to the decussation, or in the magno-cellular pa rt of the red nucleus, produced like results. Tremoralone resulted when only the ventral part of the brachiumwas sectioned.

The neuroanatomy group at Michigan also have contributedto the anatomical relations of the areas under consideration.The nuclear pattern on the midbrain tegmetum was describedby them (Huber et al., '43) for a series of mammals includingmonkey and man (see particularly paper by Crosby andWoodburne, '51). The interrelations between the basal gang-lia and the tegmentum of the midbrain (Woodburne, Crosbyand McCotter, '46) and the liypothalamotegmental pathways(Crosby and Woodburne, '51) were described in some detail,and the results obtained checked with the literature. A paperby Rand ( '54), contains a detailed account of the distributionof the superior cerebellar peduncle to the midbrain teg-mentum and the dorsal thalamus. Laursen ( '55) reported onthe effect of lesions in the globus pallidus of the monkey.Two of his results are of particular interest. He demonstratedsome direct fibers from the globus pallidus to the capsule ofthe red nucleus by way of the lenticular fasciculus. He alsoproduced a monkey which exhibited marked loathness tomove. I n this monkey the lesion involved the subpallidalregion as well as the globus pallidus.

In a series of experimental stimulations of the macaquetegmentum in midbrain and pons, beginning in front of thered nucleus and continuing spinalward to a plane just rostral


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62 JOSHUA H. CAREYto the level of the abducens nucleus, Jenker and Ward ( 5 3 )obtained, rostrocaudally and successively, a tremor of thefollowing regions: (a ) the contralateral fingers and toes; (b )the contralateral cheek, chin and lower lip; (c) the contra-lateral hand; (d ) the upper and lower lips. The tremorpersisted for a short time after the stimulation ceased. Theexact points of stimulation were not indicated although thewhole area stimulated was figured.

On the clinical side innumerable articles have dealt with theIarkinsonian syndrome since the original article was writtenby Parkinson (1817) entitled An Essay on Shaking Palsy.This paper by Parkinson presented so completely the clinicalpicture that succeeding accounts, as Vilson (41) pointed out,have added little to this early description.

Gordon Holmes (04) escribed 9 cases of Parkinsonism(two with autopsy reports) seen in his own practice and anumber of similar cases reported in the literature. He con-cluded that the action tremor was associated with a lesionin the cerebellorubral system.

M A T E R I A L S A N D M E T H O D SThe animals uscd fo r these experiments were part ly Macaca

mulatta and part ly Macaca cynmologus. The weight rangedfrom about 2.2 kg to 5.5 kg. Their ages were approximatelyone to three and one half years. Five were male and 4werefemale.

Great care was taken to select monkeys which were in goodgeneral condition fo r the experiments. They were tested pre-operatively and found to have normal voluntary movements,normal deep reflexes, and absence of Babinski reflexes andmuscle tone within the normal range. They showed no ob-servable signs of cortical, basal ganglia or cerebellar involve-ment, and no involuntary movements or tremor. They mereactive and alert. Their behavior was recorded in movingpictures.The animals were operated on f o r survival and so steriletechnique was employed. The deep stimulations and lesions


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M A C A Q U E M I D B R A I N A N D B A S A L G A NG L IA 63were placed by use of a sterotaxic instrument (McCullochmodification). The lesions on the surface were made bytrephining the skull over the area to be operated upon, openingthe dura, identifying the area and then removing it by suction.The dura was carefully sutured, and the muscle, fascia andskin closed in layers. Most of these monkeys were given asubcutaneous dose of l m g of morphine sulfate and 0.1mgof atropine sulfate about 45 minutes before the operationbegan. The monkey w a s anesthetized throughout the operationby ether given by the open cone method. This permittedvarying the depth of anesthesia a t will.In all experiments where the stereotaxic instrument wasused, stimulation was employed before any lesions were made.Stimulation was provided by a Grass stimulator, Model C, andthe details of the voltages are given in the individual protocols.The frequency of the current for stimulation was 40 witha duration of l/ms. Monopolar electrodes and rectal plugwere used in stimulation. The lesions were placed with thesame Grass instrument using the amperage of 400 micro-amperes usually for 60 seconds. During the operation therespiration was checked for changes in rate, depth and regular-ity.

Before stimulation or the placing of destructive lesionsthe drapes were so arranged that the face, trunk and ex-tremities of the animal were exposed t o view. The head wasfixed in the stereotaxic instrument. Careful observationswere made with respect to movements of any type includingthose of athetoid character or tremor. Any such movementswhich appeared to the observer to be significant were photo-graphed with the moving picture camera.

Tests made immediately at the end of the operation werefound not to be valid because of the influence of the anesthetic.Detailed testing was not attempted until the first postopera-tive day. From then on the testing was done frequentlyduring the survival period of the animal or until anotheroperation was performed. The postoperative observationsconsisted of checking for the appearance of pyramidal tract


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64 JOSHUA H. CAREYsigns (such as a Babiiiski and changes in deep reflexes), thepossible appearance of ataxias or other changes in locomotion,variations in muscle tonus and the possible occurrence ofirivoluntary movements or tremor. The animals were alsowatched closely to determine any deviation from normalbehavior, especially in respect to alertness arid amount ofactivity. Moving pictures were taken to record any significantchanges in behavior from that shown preoperatively.

All the animals mere operated on more than once. In somecases (see protocols) comparable lesions were placed bilater-ally. I n other cases a succession of different lesions wereplaced in the same animal to accentuate o r modify the resultsfirst obtained.When the animal was sacrificed the bra in was perfused withneutral formal (10-15F). It was then removed from theskull, examined grossly and prepared by the Swank-Davenportmodification of the Marchi technique. Microscopic checking ofthe location of the lesions and the degenerating fiber pathsn-as carried out .

R E P O R T O F E X P E R I M E N T SMonkey h 'o . 1

This was an alert female Macaea cynmologus weighing 1.9 kg andwith no neurological signs.F i r s t o p er a t i o n (1 0 -9 -5 3 ) a n d p o s to p era t i ve t e s t i n g . The animalwas operated upon after being anesthetized in a stereotaxic machine.The needle was iiiserted in the left substantia nigra in accordancewith previously determined readings. The stimulation was madeat 4 volts. There was 110 evident response. Lesions were placedat three levels of the substantia nigra.O n t h e third postoperative day the animal was sluggish, lethargic,weak and hypotonic. The rig ht pup il w as smaller than the leftbut both reacted to light. There was no change on the 4th postopera-tive day; on the 5th day the animal still showed some hypotonicityand lethargy. 1Jsing thesame readings as in the preceding operation but to thp right of themidline, the stereotaxic needle was again placed in the substantianigra. Neither stimulation nor the lesions placed immediately aft er

Second o p cr a t i o n (1 0 -1 6 -5 3 ) a n d p o s t o p er a t i ve t e s t i n g .


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MACAQUE MIDBRAIN AND B A S A L GANGLIA 65such st imula t ion p roduced a ny neuro log ical changes. O n remova lf rom the mach ine the an imal showed a t en d e nc y t o t u r n t o t h e l ef t.O n t h e first p o s to p e r a ti v e d a y t h e a n i m a l h a d a mild weaknes s andhypo ton ic i ty in the l e f t uppe r an d l e f t lower ex t remi t ie s . The re wassome le tha rgy b u t no pup i l l a ry changes. Th e weaknes s pe r s i s ted un t i lthe an im al was sac ri fi ced . O n the 4 th pos topera t ive da y the monkeyexhibi ted a few myoclonic movements .Microscopic report . The monkey was sacr i f iced on 11-13-53. T h ebra in was prepared by the March i techn ique . The mic roscop ic p repara -t ions ma de f ro m the b ra in of m onkey no . 1 showed a v e r y s m a l ll e s ion in the cauda te nuc leus on the r igh t s ide ( f ig . 1, r i g h t ) . T h i slesion has a n anteropos ter ior extent of abo ut 1mm . A few f ibers inth e pos ter ior l imb of the in t erna l capsule ( fig. 1, r i g h t ) a r e a ls odamaged . There is a smal l l e sion i n the r ig h t op t ic t r ac t . an d , atth e same level, a s l ight involvement of th e r ig ht su bthalam ic nucleus .Th is las t les ion increases somew hat cauda l ly . Sm al l area s of des t ruc-t io n a r e p r e s e n t i n t h e r i g h t g l ob u s p a l li d u s (fig. 1) a n d t h e r i g h tr e d n u c l e u s a n d a n e e d l e t r a c k t h r o u g h t h e l e f t g l o b u s p a l l i d u s

i t tonkey No . 2(fig. 2 ) .

This an imal was an ac t ive male Macaca mula t t a we igh ing 4.1 kgan d w i th no neuro log ica l s igns .F i r s t o p e ra t io n (10-27-53) and p o s to p era ti ve t e s t in g . T h e a n i m a lwas anesthe ti zed an d p laced in the s t e reo tax ic mach ine . The need lew a s i n s e r t e d i n t h e r i g h t s u b s t a n t i a n i g r a i n a c c o r d a n c e w i t h p r e -v iously de te rmined r ead ings . Th e s t imula t ion was ma de a t 3-6 volts .Voltages of 4 an d above caused s lowing of resp i r a tion a t a l l r ead ings.Les ions were p laced a t a l l r ead ings .O n t h e first pos topera tive d ay the m onkey showed hyperac t ive l e f tknee j e rk , mi ld weaknes s and hypo ton ic i ty in t h e l e f t l e g, a n d p o o rp lac ing r eac t ions of the l e f t foo t. T h e o p e r a-t ive p rocedure was the s ame as f o r t h e first o p e r a ti o n e x c e pt t h a t t h er e a d i n g s w e r e f o r t h e r i g h t r e d n u c le u s. T h e s t i m u l a t i o n w a s m a d ea t 3-6 vol ts . A t a l l vol tages an d all r e a d i n g s t h e l e f t u p p e r e x t r e m i t yshowed r ig id i ty . This extre m ity a lso showed f ine t rem or b ut f lexedon ly a t the ros t r a l read ings . A t the mos t cauda l r ead ing it showedsome ex tens ion a t bo th wr i s t an d e lbow. A t the h ighest vo l tage the rewas some genera l i zed t r embl ing o f the body , sugges t ing tha t thecombined vol tage and f requency were too great . Les ions were p laceda t a l l r ead ings . W he n the mos t ros t r a l le s ion was p laced , r e sp i r a t ionceased for three seconds . It r e a s u m e d w h e n t h e c u r r e n t w a s t u r n e doff b u t r e m a i n e d s h al lo w t h r o u g h o u t t h e e x p e r im e n t .

lrecond operation (11-10-53) a n d p o s to p era ti ve t e s t in g .


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66 JOSHUA H. CAREYWhen the placing of this rostral lesion was begun there was an

increase in flexion at the left elbow, the left fist was clenched andthe whole extremity became more rigid. Then, as the lesion increased,the extremity relaxed to some extent and a fine alternating tremorappeared which persisted after the current was turned off. Im-mediately after operation there was increased tonus in the left upperextremity with the elbow in flexion and the fist clenched. There wasno cogwheel rigidity. There mas a fine tremor in both left extremities.On the first postoperative day the monkey had mild, jerky, somewhatuncoordinated movements with hypotonicity in both left extremitiesand attacks of action tremor in the left lower extremity. On the 4thpostoperative day t,he tremor had disappeared but there was somereduction of tone in the lower left extremity. On the 7th postopera-tive day there was no change from the previous examination.The opera-tive procedure was the same as for the previous operation exceptthat the readings were for the left red nucleus. On stimulation ofthe most rostral point the left eyelid elevated. Obviously oculomotorfibers were being stimulated. No other responses were obtained onstimulation, except a slowing of the respiratory rate. A lesion wasplaced at each reading. Nothing was noted during the placing ofthe lesions except some interference with respiration.

Immediately after the operation both lef t extremities were hypotonic.There was a very fine action tremor in the left lower extremity.Later in the same day a periodic myoclonic contraction of theshoulder muscles causing bilateral shrugging of the shoulders wasnoted; also the animal ground his teeth a t intervals. On the firstpostoperative day the animal was more aggressive than before anyof the operations. His left, 'pupil was enlarged and fixed to light andthere was a mild ptosis on the left, both indications of oculomotor in-volvement. He also showed a mild hypotonus of the right lower ex-tremity. The convulsive attacks of shrugging of the shoulders andgrinding of the teeth still appeared at intervals. During these attackshe also threw back his head and closed his eyes. R e occasionallyshowed, after activity, a fine intention tremor of the lef t lowerextremity. On the 6th postoperative day the convulsive attackspersisted and there was increased tone in the left upper extremity.The other signs were the same as on the first postoperative day. Onthe 8th postoperative day he developed a right torticollis. On the13th postoperative day the torticollis and rigidity had disappearedbut the convulsive attacks remained ; a fine intention tremor waspresent in both left extremities. On the 14th postoperative daythe signs were the same except the ptosis of the lef t eyelid had clearedup. The left pupil still remained fixed.

T h i r d o p e ra t io n (11-17-53) a n d p o s t o p er a t i ve t e s t i n g .


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MACAQUE MIDBRAIN AND BASAL GANGLIA 67F o u r t h o p e r at i on (12-4-53) and postopera t ive tes t ing . The opera-

tive procedures were the same as in the previous three operationsexcept that the readings were for the lef t globus pallidus. Duringstimulation at the most anterior lateral reading, respiration slowedand then ceased for a brief period. The respirations were restoredwhen the stimulation was discontinued. On the second postoperativeday the animal showed convulsive attacks of the nature of p e t i t ma1and also generalized clonic spasms of all 4 extremities and the neck.The deep reflexes were increased on the right in the lower extremity.There were no paresis and no Babinski signs. When he walked, heshowed mild incoordination of movement in all members. All ex-tremities were mildly hypotonic except the left upper extremitywhich showed mild rigidity. H e had an action tremor in both upperextremities, was lethargic and exhibited marked loathness to move.On the 11th postoperative day the findings were the same as on thesecond day.Fifth opera t ion (12-17-53) and postopera t ive tes t ing . The opera-tive procedures were the same as in the previous experiments exceptthat the readings were for the right globus pallidus. Other thanirregularities in the respiratory rate no effects of stimulation o rof the placing of the lesions were observed. On the first postoperativeday the animal exhibited a generalized weakness, a left hemiparesisand increased reflexes in both lower extremities but no Babinski sign.He had rigidity in all 4 extremities but it was more marked on theleft side. He retained a fine action tremor in all 4 extremities and hadclonic spasms of all extremities a nd the neck, comparable to thoseseen clinically in Wilsons hepatolenticular degeneration. The loath-ness to move increased after the fifth operation.Micro sco p ic rep mt . The monkey was sacrificed on 12-18-53. Thebrain was prepared by the Marchi technique. The needle tracks forthe lesions involving the globus pallidus go through area 6. On oneside there is some indication of an involvement of the ventromedialportion of the globus pallidus (fig. 3, right) and of its lateral part(not illustrated). The lesion also extends into the optic tract (fig.4, right) and into the area ventral to the globus pallidus SO thatit interrupts the corticopallidohypothalamic fibers. There are alsolesions in the posterior limb of the internal capsule on both sides(fig. 3 ) . From these lesions degenerated fibers can be traced caudal-ward through the brain stem. Internal to the cerebral peduncle nearthe junction of the diencephalon and mesencephalon there is an injuryto the substantia nigra on the right. The red nucleus and the areaventromedial to it are almost completely destroyed bilaterally. Thedestruction on both sides- ut particularly on the right- s il-


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68 JOSHUA H. CAREYl u s t ra t e d i n f ig u re 5. T h e R I a rc h i m a t e r i a l d i d n o t c u t w e l l a t t h es eb ra in l eve l s ; consequen t ly the pho tomicrographs a re no t en t i r e lysat is factory .

M o n k e y No . 3T h e t h i r d a n i m a l w a s a male Rfacaca mu la t t a th a t was be l l ige ren t,ac t ive an d a le r t w i th n o neuro log ica l signs. H e w e i gh e d 3 .5 k g .F i r s t o p e r a t i o n (1-12-54) n n d p o s t o p er a t i ve t e s t i n g . T h i s a n i m a lwas opera ted upon a f te r be ing anes the t i zed and p laced in the s t e reo -tax ic mach ine . The need le was in se r ted in the r igh t r ed nuc leus inaccordance w i th p rev iously de te rmined r ead ings . S t imula t ions werem ade a t 3-6 vol ts . A t al l rea din gs on s t im ulatio n of 4-6 volts , the

le f t a rm f lexed a t the e lbow a nd wrist and showed r ig id i ty fo r t h edura t ion of th e s t imulus . W he n the s t imula t ion ceased the a r mre laxed and a f ine t r emor appeared . No t r e m o r o f th e t r u n k o r lowerex t r emi t i e s was no ted d u r in g the opera t ion . Les ions were p laced a ta l l r ead ings . D ur in g the p roduc t ion o f the l es ions the l e f t a rmex tended w i th the fist c lenched ; a f ine t rem or of the l e f t l eg and themuscles of the belly on th e le f t s ide app eare d . This t rem or pers isted .T h e l e f t a r m r e l a x e d a n d a f i n e t r e m o r a p p e a r e d i n i t a f t e r t h ecoagu la t ion cu r ren t was d i s con t inued . On the second pos toperat iveda y the re was a mi ld h ypo ton ic i ty of the l e f t a rm an d le f t leg. Af ine t r emo r was p r e se n t i n t h e l e f t l e g, b u t n o n e w a s n o t e d i n t h e l e f ta r m . E v e r y o n e o r tw o m i n u t e s th e m o n k ey y a w n ed a n d g r o u n d h i steeth . H e had a t tac ks of myoclonic spasm of the le f t s ide of t heface an d body , beg inn ing w i th the shou lder. Moreover, h i s movemen tsas a whole were more j e rky in charac te r than be fo re opera t ion .On 6 th pos topera t ive d ay th e monkey had become qu i te aggress ive ;the hypo ton ic i ty was g rea t ly r educed . The f ine t r emo r con t inued bu twas l es s th an on the s econd pos topera t ive day . The yaw ning a ndmyoc lon ic movements were g rea t ly aba ted bu t the vo lun ta ry move-ments were s t i l l less smooth and coordinated than preoperat ively .Second o p er a t i o n (1-19-54) a n d p o s t o p er a t i ve t e s t i n g . T h e pro-

cedures were the s ame a5 in the first opera t ion excep t tha t the needlewas in se r ted in th e l e f t r ed nuc leus . No t r e m o r o r changes in respira-t ion were no ted du r in g s t imula t ion . A f te r the le s ions were made ,the an im al showed a genera l ized t r emor an d r ig id i ty o f a l l 4 extremi-t ies ; these s igns d isappe ared in a few hours . O n the f i rs t pos toperat ived a y a mild , in te rmi t t en t ac t ion t r emor was p resen t . O n t h e 1 0 t hp o st o pe ra t iv e d a y t h e a n i m a l h a d a n a c t io n t r e m o r i n all 4 x t remi t i e sb ut the re were no indicat ions of a n increased tonu s of the muscles.O n t h e 1 3 t h p o st o p e ra t iv e d a y t h e m o n k e y a p p e a r e d e n t i r e ly n o r m a lin his behavior , showing no evidences of hypotonic i ty and no act iont r emor .


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MACAQUE MIDBRAIN AND BASAL GANGLIA 69T h i r d o p e r a t i o n (1-25-54) and pos toperat ive te s t ing . The pro-

cedures were the same as in the first operation except tha t the needlewas inserted in the left globus pallidus in accordance with previouslydetermined readings. The monkey succumbed to anesthesia.Microscopic repor t . This material was checked microscopically onlyf o r the location of the lesions. There are degenerated fibers in theansa lenticularis on the right and destructive lesions in both rednuclei.

M o n k e y No. 4This male Macaca mulatta, weighing 5.3 kg, was curious and active

and had a negative neurologieal examination.F i r s t o p e r t i o n (1-23-54) and pos tope ra t i v e t e s t i ng . The animalwas anesthetized and placed in the stereotaxic instrument. The needlewas placed in the right globus pallidus in accordance with previously

determined readings. The stimulation varied from 3-6 volts. Noresponses were obtained from stimulation except at the most caudo-medial point where, a t all depths, there was interference with respira-tion. Lesions were placed at all readings. No immediate effects werenoted except a t the levels where respiratory changes had been notedon stimulation. At such levels respiration ceased and the placing ofthe lesions were discontinuel. On the second postoperative day theanimal was mildly lethargic and apathetic. On the 6th postoperativeday, he had a very fine shivering of both lower extremities which onlyoccurred when the animal was cold. This fine movement did notappear to be a tremor. He was easily caught and much more docilethan preoperatively. He continued to be apathetic. On the 9th post-operative day he demonstrated mild, generalized convulsive movementswhen attempts were made t A catch him.Se c ond ope ra t ion (2-29-54). The animal was anesthetized andplaced in the stereotaxic instrument. A bone flap was turned but theneedle was not inserted in the brain because the readings did notcheck properly. The monkey was allowed to recover from the anes-thesia.T h i r d o p e ra t io n (2-2-54) and pos toperat ive te s t ing . The operativeprocedures were the same as in the first operation except that theneedle was inserted in the le ft globus pallidus. Some difficulty inmaintaining normal respiration was encountered, due, apparently.to the anesthetic rather than the lesions. On the 6th postoperativeday a fine generalized tremor was present in all 4 extremities whichincreased when the monkey was excited. There was some incoordina-tion in movement of the extremities but the tonus was normal. Thistremor appeared to be more in the nature of an emotional response


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70 J O S H U A H. CAREYthan of a typical basal ganglion tremor. On the 14th postoperativeday the neurological signs had not changed.Fourth operat ion (2-16-54) and pos toperat ive te s t ing . The opera-tive procedures were the same as in the first operation except thatthe neddle was inserted in the right red nucleus and the adjacentarea of the tegmentum. With all readings, stimulation increasedthe tremor in the l e f t hand and produced a temporary rigidity ofthe le ft arm. Accompanying these signs was a marked slowing ofthe respiration. Lesions were placed at all readings in the usnalmanner. On the third postoperative day the animal exhibited ahypotonia of the righ t hind leg, a weak grasp of the lef t foot andsome difficulty with the le ft lower extremity in wallring. A generalized,rapid, alternating action tremor was present in all 4 extremities. Onthe 13th postoperative day the monkey had mild incoordination in a llmovements and occasional generalized, mild clonic convulsions duringwhich he shook all over f o r a few seconds but did not fall. The tremorwas greatly reduced and the general muscle tone was normal.F i f la operat ion (3-1-54) and pos topernt ive te s t ing . The operativeprocedures were the same as in the first operation except that theneedle was inserted in the left red nucleus and the adajcent area ofthe tegmentum. At all but the most caudal readings, stimulationproduced an extension of the right arm at the wrist and flexion ofthe righ t fingers. A tremor of the right hand also appeared. Respira-tion was again slowed du ring the stimulation. Lesions were placedat all readings. On the 10th postoperative day the monkey showedmarked loathness to move. He had mild rigidity an d tremor in all4 extremities. This condition was sti ll present on the 25th and 31stpostoperative days. On the 61st postoperative day he exhibited somereduction in tremor but the rigidity was maintained. He was stillloath t o move but, when he could be persuaded t o do so , he showedmarked incoordination.Sixth operat ion (4-30-54) and pos tope ra t i v e t e s t i ng . The pro-

cedures were the same as in the previous operations except that theneedle w as inserted in the right nucleus ventralis lateralis of thedorsal thalamus. A t the anterior readings marked tremor appearedin both arms and choreoathetoid movements of both upper extremitiesincreased. I n the posterior readings, stimulations suggested involve-ment of the interna l capsule. Lesions were placed only a t the anter iorreadings. On the 21st postoperative day the animal showed generalincoordination and generalized hypotonicitmy.No tremor was apparentafter the operation of Apri l 30. Blyoclonic convulsions involving allextremities occurred occasionally. On the 24th postoperative day thecondition of the monkey remained unchanged.


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MACAQUE MIDBRAIN AN D BASAL GANGLIA 7 1S e v e n t h o p e r at i on (5-24-54) a n d p o s to p era ti ve t e s t in g . The opera-

tive procedures were the same as in the previous operations exceptthat the needle was inserted in the left nucleus ventralis lateralisof the dorsal thalamus. Stirnulation a t the more anterior readingsgave a fine tremor in the right arm and right leg. Stimulation morecaudalward indicated that the needle was in the internal capsule.Lesions were placed a t the anterior readings. On the 8th postoperativeday the monkey showed less rigidity than before the last operationand had no tremor. He still had occasional myoclonic attacks similart o those seen in patients with Wilsons lenticular degeneration.N icro sco p ic report. On 6-2-54 the monkey was sacrificed andperfased and the brain prepared by the Marchi technique. I n thismonkey lesions are present in the caudate nucleus on each side (fig. 6 ) ,in the globus pallidus bilaterally (fig. 7, on the left) and in bothsubthalamic nuclei (fig. 7 ) . There is degenerat,ion in the pallidohypo-thalamic t rac t and in the snbthalamic fasciculus. There is evidenceof diffuse degeneration in both red nuclei and both rubrospinal tracts.

M o n k e y No . 5This animal was an active, alert female Macaca cynmologus whowas noisy and very quick in her responses. The neurological exami-nation was negative. She weighed 3.7 kg.First opera t ion (2-9-54) a n d p o s to p era t i ve t e s t in g . The animalwas anesthetized and placed in the stereotaxic instrument. Theneedle was inserted in the right red nucleus in accordance with pre-viously determined readings. Stimulation was from 3-6 volts. Noresponses were obtained on stimulation except when the most cando-laterally placed reading was used. Then the respirations ceased butreturned when the stimulation was discontinued. No lesion was placeda t this most caudolateral location ; otherwise lesions were made at allthe points stimulated.Immediately after the operation the right pupil was larger thanthe left. Muscle tone was reduced in the left arm and le ft leg. Onthe second postoperative day the pupils were equal. The monkey hada weak grasp in the left foot, but the hypotonus was less noticeablein both left extremities than a t the first postoperative testing, althoughstill present. Placing movements with the lef t hind foot were inco-ordinated but she moved about t.he cage with no evident difficulty.On the 10th postoperative day, the monkey still had some hypotoniain the left hind leg, but none could be demonstrated in the left fore-limb. On the 14th postoperative day the monkey had the same signsas on the previous examination.


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72 JOSHUA H. CAREYS eco n d o p er a t i o n (2 -25-54) a n d p o s t o p er a t i ve t p s t i n g . T h e pro-

cedures were the same as fo r th e f ir s t opera tion excep t th a t the need lewas p laced in the l e f t red nucleus . On s t imulat ion there was somee levat ion an d r e t r ac t ion o f bo th shou lder s a t a l l r ead ings . S t imu -la t ion a t the more cauda l r ead ings p roduced a t r ans ien t , f ine , con-t r a la te ra l t r em or an d the r ig h t a rm became r ig id . Les ions were madea t a l l read ings. Wh i le these l es ions were be ing p laced a t the morecauda l r ead ings , the r ig id i ty of t h e r i g h t a r m d i s ap p e a r ed . I m m e d i -a te ly pos topera t i r e ly the monkey appeared normal in a l l r e spec t s ,excep t fo r j e rk y movements of the head a nd neck .T h i r d o p e r a t i o n (3 -18-54) a n d p o s t o p er a t i ve t e s t i n g . T he pro-cedures were the s ame a s f o r th e first opera t ion excep t th a t th e need lew a s in s e rt e d i n t h e r i g h t r e d n u c le u s a n d t h e a r e a d o r sa l a n d l a t e r a lto i t. On s t imula t ion some coarse movements of t he r igh t upp er an dlower extremit ies were obta ined , associa ted wi th a ma rked s lowingof respiration. No changes of any s ignif icance resul ted on p lacingthe les ions except temporary s lowing of r esp i r a tion . On the 7 thpos toperat ive day th is monkey showed loathness to move and hypo-ton ic i ty in the l e f t ex t r emi t i e s . She had no t r emor bu t occas iona l lyshowed a myoclonic convulsion. On the 1 4 th pos topera tive d ay th ef ind ings were t he s ame as o n t h e 7 t h d a y .F o u r t h o p e r a t i o n ( 4 - 1 - 5 4 ) a n d p o s t o p er a t i ve t e s t i n g . T h e p r o -c e d u r es w e r e t h e s a m e as f o r t h e first o p e r at i on e x c e p t t h a t t h e n e ed l ew a s i n s e r t e d i n t h e l e f t r e d n u c l e u s a n d the a r e a d o r s a l a n d l a t e r a lto it. St imu la t ion p roduced marked t r emo r of bo th upp er ex t r emi t i es .Whi le the l e s ion was be ing p laced , a the to id movements of t h e r i g h ta r m a n d r i g i d i t y of a l l 4 ex t remi t i e s were app are n t . These s ignsd i s a p p e a r e d w h e n t h e d e s t r u c ti v e c u r r e n t w a s t u r n e d off. A t t h eend o f the opera t ion the monkey was somnolen t and had a p tos i s ofthe r ig h t eye (pa r t i a l ocu lomotor invo lvemen t ) . A l l 4 ex tr emi ti e sexh ib it ed r eg id i t y ; th i s rig id i ty was g rea te r on the r igh t . On thefirst pos topera t ive c lay the an imal was ex t r emely loa th to move ands t i l l somew hat s leepy. Mild r ig id i ty an d a f ine act ion t remor wereevident in a l l 4 extremit ies . She fe l l t o t h e l e f t as she walked aboutthe cage an d her head w as f lexed toward he r l e f t shou lder. She hada the to id movements in bo th upper ex t remi t ie s . On the 7 th postopera -t i v e d a y t h e s i g n s w e r e t h e s a m e .Fifth o p er a t i o n ( 4 -8 -54 ) a n d p o s t op er n ti u e t e s t i n g . The p roceduresw e r e t h e s a m e a s f o r t h e first opera t ion excep t tha t the need le wasin se r ted in the r igh t nuc leus ven t r a l i s la te ra l is . S t im ula t ion ind i -ca ted tha t the in te rna l capsu le was invo lved and no les ions wereplaced.Sixth o p er a t i o n (4 -14-54) and p o s t o p er a t i ve t e s t i n g . The same

p r o c e d u r e u s e d i n t h e 5 t h o p e r a t i o n w a s r e p e a t e d b u t w i t h u n s a t i s -


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M A C A Q U E MIDBRAIN A N D B A S A L G A N G L I A 73factory results on stimulation. No lesions were placed. On the secondpostoperative day examination disclosed the same signs as after the4th operation.

The monkey was sacrificed on 5-21-54, andthe brain was prepared by the Marchi technique. I n the brain ofthis monkey there a re bilateral lesions in the nucleus ventralis la teralis(fig. 8) and the nucleus ventralis anterior (fig. 8) of the dorsalthalamus. One lesion, which is situat,ed too for medially, destroyeda part of the midline nuclear gray of the dorsal thalamus. Both rednuclei show lesions ; the right lesion involves crossing fibers of theoculomotor root (fig. 9, right) . There are also areas of destructionin the deep tegmental gray, lateral and dorsolateral to the red nucleus(fig. 10, right) on either side of the brain. Degenerated rubrospinaland tegmentospinal fascicles can be traced caudalward through thebrain stem (fig. 10).

M o n k e y No . 6This male Macaca cynmologus was an alert animal with a negative

neurological examination. His weight was 3.2 lrg.Firs t o p era t io n (3-11-54) a n d p o s t o p er a t i v e t e s ti n g . This animalwas anesthetized and placed in the stereotaxic machine. The needlewas inserted in the left globns pallidus and in the adjoining leftinternal capsule, in accordance with previously determined readings.For stimulation the current had a voltage of 3-6 volts. On stimu-lation, the more medial regions gave movements consistent with in-ternal capsule involvement. No movements were elicited at the mostrostral and the most caudal readings. At internal capsule levels,through the genu and rostral part of the posterior limb, contralateralface, wrist and hand movements were obtained. Fa rthe r caudally,contralateral upper arm movements succeeded the wrist movements.At other points (presumably outside of the internal capsule) noeffects of the stimulations were noted during the operation. Lesionswere placed in all areas stimulated. On the first postoperative day,the monkey showed a flaccid paresis of the right forelimb with amarked loss of fine movements in the involved hand. There wereincreased deep reflexes in the right upper extremity and the sng-gestion of a Babinski in the right lower extremity but no otherevidences of pyramidal trac t involvement. On the 5th postoperativeday the monkey had weakness and spasticity of all 4 extremities.This condition continued until the 8th day when the monkey died.

i l l ioroscopic report . Postmortem examination demonstrated an ab-scess at the spinomedullary junction. Slides stained f o r acid fastbacteria showed the presence of numerous bacteria of this type.

Microscopic r ep o r t .


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74 JOSHUA H. CAREYP r o b a b l y t h e lesion was a tuberc ulou s abscess. Grossly there is asmal l les ion in t l ie ventromecl ia l t ip of the g lobus pa l l idus wh ichex tends ven t r a l to it. Some f ibers of the a nsa len t icular is a re involved.There a re need le t r acks in the in te rna l capsu le .

N o n l c e y No . 7T h i s a c t iv e , a l e r t m a l e h I ac a ca m u l a t t a h a d a negat ive neurologicale x a m in a ti o n b u t a p p e a r e d u n de r w ei g ht a n d t h in . R e w eig he d 2.3 kg.F i r s t o p e r a t i o n (5-4-54) a n d p o s t o p er a t i ve t e s t i n g . T h e a n i m a lwas anes the t ized an d p laced i n the s t e reo tax ic in s t rume n t . The need lew a s i n s e r t e d i n t h e r i g h t g l o b u s p a l l i d u s a n d t h e u n d e r l y i n g w h i t e

mat te r in accordance w i th p rev ious ly de te rmined r ead ings . Thecur ren t u sed fo r s t imula t ion had a voltage of 3-6 volts. A t the mos tan te romed ia l po in t s , s t imu la t ion gave b i la te ra l shou lder sh rugs . O ther -wise no responses were obta ined . The monkey never complete lyr e co v e re d f r o m t h e o p e ra t io n . H e was du l l , loa th to move a nd g radu-a l ly wen t in to coma. H e succumbed on 5-8-54.Postnaortena report . Exa mina t ion showed tubercu los is of the lungs.The b ra in was no t r emoved .

M o n k e y No. 8This f emale Macaca m ul a t t a was a n aggress ive, be l l ige ren t an dac t ive an imal wh ich had a negat ive neurological examinat ion . Sheweighed 5 .3 lrg.F i r s t o p e r a t i o n (9-28-54) and p o s t o p er a t i ve t e s t i n g . T h e a n i m a lwas anes thet ized and a cran io tomy was per fo rmed to expose the l e f to rb i t a l su r face . The a rea ind ica ted by x on f igure 11 was removedb y s u c ti o n, t h e d u r a c lo se d a n d t h e e x t r a d u r a l ti ss u e s u t u r e d i n l a y e rs .The sk in was closed w i th in te r ru p te d su tu res . On th e fi rs t an d 8 thpos toperat ive days , examinat ion d isc losed no changes in behaviorand no neurological s igns .Second oppra t ion (10-5-54). The p rocedures were the s ame asthose employed in t h e first opera t ion excep t th a t the l e s ion was p lacedi n t h e r i g h t o r b i t a l r e g i o n of the hemisphere . The an im al was es -aniiiied 011 th e second an d 5 th pos topera t ive days and n o changes

v e r e observed.Third optrcrtion (20-16-54) an d p o s t o p er a t i ve t e s t i n g . T h e o p e r a -t ive p rocedures were the same as thme employed for t l ie f i r s t op erat ione x c ep t t h a t t h e t i p of thc r ig ht tem pora l pole w as c.;posecl a n d removedw i t h a s u c k e r. D u r i n g t h e first 24 hours a f t e r opera t ion th i s inonkeywas markedly le thargic . Wlie i i s t imulated she ~ ~ o u l c lpen her eyes


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MACAQUE MIDBRAIN AND BASAL GANGLIA 75an d s i t u p b u t a s soon a s the s t imula t ion ceased she closed he r eyesan d wen t back to s leep .Microscopic r ep o r t . Th e anim al was sacrif iced on 12-19-54 a n dt h e b r a i n w a s p r e p a r e d b y t h e M a r c h i t ec h n iq u e . T h e M a r c h i m a -te r ia l was no t su i t ab le f o r microscop ic s tudy bu t g ros s ly the re wereles ions p resen t on th e r igh t an d l e f t su rfaces of the o rb i t a l gy r i an da t t h e t i p of the r ight temporal pole (see f ig . 11).

M o n k e y No . 9This female Macaca cynmologus was noisy , cur ious and quick torespond. Th e neurological exam inat ion was negat ive . She weighed

2.3 kg.F i r s t o p e r a t i o n (10-23-54) and p o s t o p er a t i ve t e s t i n g . T h e a n i m a lwas anes the t i zed and a c ran i tx tomy was pe r fo rmed to expose thetip of t h e r i g h t te m p o r a l lo be . T h e m e d i a l p a r t of t h e t e m p o r a l p o l ewas r emoved by suc t ion . Exa mina t ion on the first a n d 1 2 t h post-opera t ive days showed n o changes f ro m th e p reopera t ive t e s ts .S e c o n d o p e r a t io n (11-5-54) and pos topera t i ve t es t ing . T h e o p e r a -t ive t echn iques employed were the s ame as in the p rev ious exper i -m e n t s. T h e t i p of t h e l e f t te m p o r a l p o le a n d p a r t of t h e a m y g d a l awere removed by suct ion . The monkey was examined a t in te rva l sf r o m t h e first t o the 34 th postopera t ive days . A t no t ime were anychanges in behav io r o r any neurological s igns demons trable .Ni cr o s co p i c r ep o r t . Th e an im al wa s sacrif iced on 12-19-54 a n dthe b ra in was p repared by the March i t echnique . The Ma rch i ma te r ia lwas unsa t i s f ac to ry . Th is s e r ies was used mere ly to loca te the e x te n tof the co r t i ca l ab la tion .

DISCUSSIONThis paper is an at tempt to study experimentally, by irri-tative and destructive lesions, involuntary movements, rigidity

an d loathness to move. Any of these signs, or all of them,may characterize a patient with a Parkinsonian syndrome.An action tremor was obtained in several monkeys followingstimulation or destruction of the red nucleus and of the regionsadjoining it dorsolaterally. The tremor following the de-struction was of less amplitude than that resulting fromstimulation. It was increased in bilateral as compared withunilateral lesions. It tended t o decrease gradually duringthe postoperative period. Some evidence of tremor persistedfo r months. This tremor could be elicited not only during


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76 JOSHUA H. CAREYmovement but also following activity, although it was notobserved in a completely resting monkey. Therefore it wasnot a true resting tremor.

By stimulation and destruction of nucleus ventralis later-alis of the dorsal thalamus, a similar action tremor wasobtained, which again increased when the lesions were bilat-eral. I t also persisted for some time after destructive lesions,gradually decreasing in intensity as the postoperative periodlengthened. Again, although it could be elicited during activityof the monkey, and following such activity, it could not beobtained in a monkey which had been quiet for a long time.Therefore it also was considered not to be a true restingtremor.

In the monkeys experimented upon, tremor was neverelicited from stimulation of basal ganglia alone. One monkeywhich had had destructive lesions in the midbrain tegmentumat an earlier date showed a slight but persistent tremor fol-lowing a destructive lesion of the globus pallidus. In no casedid the lesions of the basal ganglia involve all of these areasand it is possible that larger lesions of these ganglia (orlesions involving more of the putamen) might have producedbetter evidence of tremor.

As has been emphasized, the tremor obtained in this seriesof experiments has been an action tremor- ssentially acerebellar tremor. It is significant that the stimulative anddestructive lesions, which involved the red nucleus, the teg-mental area dorsal and lateral to it and the nucleus ventralislateralis of the dorsal thalamus, are along the course of thedent orubral, cerebellotegmental, and dentothalamic pathways,respectively.

I t should be mentioned that the characteristic tremor inthe Parkinsonian syndrome is a resting tremor. It is possiblethat the rigidity which characterizes patients with Parkin-sons disease and makes it difficult for them to performvoluntary acts may inhibit the tremor (M7ilson, 29) . Themonkeys in these experiments never exhibited a very markeddegree of rigidity.


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MACAQUE MIDBRAIN AND B A S A L G A N G L I A 77In the midbrain tegmentum of the primate there is a

balancing of the impulses from various areas. The basalganglia discharge to each red nucleus is through the ansalenticularis and the lenticular fasciculus (Woodburne, Crosbyand McCotter, '46) . The additional motor areas project im-pulses to this tegmental region over a great range of cortico-striatotegmental systems (Crosby, '56) and corticotegmentalpaths (Crosby and Henderson, '48 ; Crosby, ' 5 6 ) . The cere-bellum discharges t o and through the same tegmental areasover ascending paths of the brachium conjunctivum (Rand,'54; Carrea and Mettler, '54). The interrelations of thevarious systems produce a balancing of discharges that regu-lates tonus and movements. Lesions in any part of the systemmay produce an imbalance. Additional lesions may shift thebalance in another direction. The hypertonicity that occurredwith lesions in the midbrain at or behind red nuclear levelsapparently was due to the destruction of fibers of the superiorcerebellar peduncle (see also Carrea and Mettler, '54) . Therigidity and increased tonus present in Monkey No. 2 becameevident when the region in front of the red nucleus was alsoinvaded, suggesting that a change in imbalance had occurredwhen the paths from the cerebral hemispheres (both basalganglia and additional motor areas) were also involved.

Finally, lesions in the globus pallidus which extend ventralto it involve pathways from the orbital.and, most particularly,the temporal region (as Laursen, '55, also found) o r involve-ments of the orbital and inferior temporal cortical areasproduced monkeys which showed great loathness to move.They could be photographed with the cage door wide open.They were apathetic and fell asleep easily even with foodin front of them. This type of behavior is seen in some, butnot all, patients with the Parkinsonian syndrome. The resultsreported here and by Laursen ('55) for basal ganglia wouldsuggest that patients showing such loathness to move haveinvolvement of the hypothalamic pathways ventral t o thebasal ganglia as well as lesions in the ganglia.


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78 J O S H U A H. CAREYThese experiments illus trate the f act t ha t i n many involve-

ments of the nervous system the balance between the variousportions is upset. The resulting syndrome then may representover-function of uninjured areas rather than deficits fromregions destroyed. Moreover, signs or symptoms of a givensyndrome may be due to involvement of fibers of passagethrough or adjacent t o the area rather than destruction ofthe recognized site of the lesion.S U M M A R Y

This s tudy was car ried out on Macaca mulatta and Macacacynmologus. The deep lesions were made by use of thestereotaxic apparatus. The cortical lesions were producedby direct ablation of the area s with a sucker following crani-otomies in the desired regions. The animals were testedpreoperatively and postoperatively for involuntary move-ments, hypertonicity, motor involvement and reaction totheir surroundings.After sacrifice, in most cases, the brains were perfused andchecked grossly for evidence of pathological changes. Thebrains in which the timing was suitable were prepa red by theMarchi technique and examined for location and extent ofthe lesions. I n some cases it was possible to follow degeneratedfiber systems.Action tremor of essentially the cerebellar type was ob-tained on stimulation and/or destruction of the red nucleus,the tegmental areas lateral and dorsolateral to it and the

nucleus ventralis la terali s of the dor sal thalamus. Thi stremor was increased in bilateral lesions and decrcascd somc-what as the postoperative period lcngthened. Action tremorof essentially similar type was increased on destruction ofthe glohus pallidus bilaterally in a monkey which had hada previous tenmental lesion.

Mild rigidity was obtained with hilateral glohus palliduslesions in one monkey which already had tegmentnl lesions. Inn o monkey was all the globus pallidus destroyed bilaterally.


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MACAQUE MIDBRAIN AND BASAL GANGLIA 79Loathness to move, apathy and drowsiness characterized

two monkeys in which the bilateral lesions involved thecorticohypothalamic system ventral to the globus pallidusas well as the pallidurn itself. Similar but less marked apathywas obtained with cortical ablations which removed portionsof the temporal and/or the orbital cortex.

# + #

The author wishes to express his indebtedness to Dr. Eliza-beth C . Crosby of the Department of Anatomy, Universityof Michigan, whose generous assistance and encouragementwere invaluable. The author also wishes to thank Rlr. GeorgeSmith for technical assistance in preparing the photographs.

L I T E R A T U R E C I TE DARIENS KAPP ERS,C. U., G . C. HUBERND E. C. CROSBY 1936 T h e c o m p a r a t iv e

ana t om y o f t he ne rvous sy st em of ve r t eb ra t e s , i nc l ud i ng m an . T heMacmi l l an Company, New York . 2 vols.

Rela t ion of t he ce reb rum t o the cerebellum.11. Cerebel l a r t remor in t he m onkey and its absence a f t e r rpm ova l o ft he p r i nc i pa l exc i tab l e a r ea s of c e reb ra l co r t ex ( a r e a s 4 a nd 6a, u p p e rp a r t ) . III. Accentua t ion of cerebel lar t re mo r fol low ing lesions of th ep r e m o t o r a r e a ( a r e a 6a, uppe r pa r t ) . A rch. N eu ro l. an d P sych ia t ., 35:

1950 T r e m o r i n t h erhesus monkey produced by d iencep hal i c l esions and s tud ied b y grap hicmethod. J. Comp. Neur. , 93: 1-12.

T h e ana t om y o f t h e p r i m a t e b rach i u rnconjunct ivum and assoc ia t ed s t ruc tures . J. Comp. Neur. 101 : 565-686.

F unc t i ons o f t h e p r i m a t e con junc t ivum an d r e l a t ed s t ruc t u res .J. Comp. Neur . , 108: 151-322.

CROSBY,E. C. Th e role of th e mid bra in as a pa r t o f t he d i s cha rge pa t h sf rom h i ghe r cen t e r s .

CROSBY,E. C., AND J. W. HENDERSON948 T he m am m al i an m i db ra i n andi s thmus reg ions . 11. Fib er connect ions of th e supe r ior co ll icu lus . B.P a t hw ays conce rned i n au t om a t i c eye m ovem en t s . J. Comp. Neur. ,

CROSBY,. C., AND R. T. WOODBURNE 951 T h e m a m m a l i a n m i d b r a i n a n di s t hm us r egi ons . P a r t 11. The fiber connect ions. C. Th e hyp othalam o-t egm en t a l pa t hw ays . J. Comp. Neur. , 9 4 : 1-32.

T he r ed nuc l eus and ad j acen t c e l lgroups. Arch. Neuro l . and Psychia t . , 84 : 257-266.

ARING,C. D., A N D J. F. FULTON936

439-466.CARPENTER, . B., J. R. WHITTIER AN D F. A . M E T T L E R

CARREA, . M. E., AND F. A. METTLER 19541955

1956

88: 53-92.

D A V E N P O R T ,. A ., AN D S. W. R A N S O N 1930


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80 JOSHUA H. CAREYDE JONQ, R. N. 1950 The Neurologic Examination. Pa ul B. Hoeber, Inc.,

New York.DE NNY-BROWN, Diseases of the basal ganglia and subthalaniic nuclei.

Reprinted f rom Oxford Loose-leaf Medicine. Oxford University Press,New York, 115 pp.FERRARO,., AN D W. E. EARRERA The effects of lesions of the superiorcerebellar peduncle in the Macacus rhesus monkey. Bull. Neur. Inst.,New York, 5: 165-179.

GRINKER, R. R., A N D P. C. BUCY 1949 Neurology. 4th Ed., Charles C Thomas,Springfield, Illinois, 1138 pp.

HOL ME S ,G. 1904 O n certain tremors in organic cerebral lesions. Brain, 3 7 :H U B E R , . C., E. C. CROSBY, . T. WOODBURNE ,. A. GILLILAN, . 0. B R O W N N D

B. TAMTHAI 1943 The niammalian midbrain an d isthmus regions.P a r t I. The nuclear pattern. J. Comp. Neur., 78: 129-504.

INGRAM,. R., S. W. R A N S O N , ND R. W. BARRIS1934 The red nucleus. Itsrelation to postural tonus and rig hti ng reactions. Arch. Neurol. andPsychiat., 31: 768-786.

I NGRAM, W. R., S . W. R A N S O N , . I. HANNE T T , . R. ZEISS A N D H. TERWILLICER1932 Results of stimulation of t he tegmentum with the Horsley-Clarkestereotaxic apparatus. Arch. Neurol. and Psychiat., 28: 513-541.

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K E N N A R D ,M. A. 1944 Experimental analysis of the functions of the ba wlganglia in monkeys and chimpanzees. J. Ncnrophysiol., 7: 127-148.

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1946

1936

327-375.

19531934

1929

1955


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PLATESABBREVIATIONS FO R FIGURES

aqueduct : cerebral aqueductcapsula inter., ant. limb: capsula in-

terna, anterior limbcapsula inter., post. limb: capsula in-

terna, posterior limbchiasma opt.: chiasma opticumcomm. ant. : commissure anteriorcomm. post.: commissure posteriorcorpus call. : corpus callosumdec. brach. conj.: decussation

brachium conjunctivumdeep teg. gray : deep tegmental grayfas. subthal. : fasciculus subthalamusglob. pall. : globus pallidusglob. pall. ventromed. tip: globus

pallidus ventromedial tiplemn. med. : lemniscus medialislent. fas.: lenticular fasciculusmidbr. : midbrainnue. ant. thal.: nucleus anteriornue. caudatus: nucleus caudatus

thalami

nue. gen. lat.: nucleus geniculatusnuc. gen. med. : nucleus geniculatusN. 111: third nerve rootsnuc. dorsomcd. thal. : nucleus dorso-nuc. lat. thal.: nucleus latera lisnuc. rub.: nucleus rubernuc. subthal. : nucleus subthalamusnuc. vent. ant. : nucleus ventralisnuc. vent. post.: nucleus ventralisstria medull. : str ia medullaris thalamiped. cerebri : pedunculus cerebrisub. nigra: substantia nigrathal. dors. : thalamus dorsalistr. teg-sp. : tractus tegmentospinalistr . rubrospinalis: tractus

lateralismedialis

medialis thalamithalami

lateralisposterior

rubrospinalis

PLATE 1EXPLANATION O F FIQURES

1 and 2 Photomicrographs of selected sections through the rostra1 pa rt of thebasal ganglia of Monkey No. 1. Small lesions are shown in the caudate nucleus,the posterior limb of the inte rna l capsule and th e globus pallidus. Macacuscynmologus. Marchi preparations. X 2.5.

3 A photomicrograph of a section through the foreb rain of Macaca mulatta(Monkey No. 2 ) at the level of the anterior nuclei and the anterior end of theventral nuclear group of the dorsal thalamus. The anterior pa rt of the posteriorlimb of the internal capsule and the ventromedial tip of the globus pallidus areevident in the figure. There is a lesion in the tip of the globus pallidus. Marchipreparations. X 2.

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P L A T E 1


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PLATE 2EXPLANATION O F FIGURES

4 Pliotoiiiicrograph of n section of the sam e brain shown in figure 3 but takensomewhat f artlier candalward. Thc beetion is through the nucleus ventralis latcr :~lis:ind the begiriiiiiig of t l ie nucleus ventrnlis posterior of the dorsa l tlialarnus. Thelorntioti of a lesion involving t h r ventr oniedial part of globus pallidus, the regioiiirrimeclintelg v c n t r t i l t o I t ant1 tlie optic tract is ~ h o m no n the right. M:irc*liiprepmatioils. X 2 .

5 Iliotomici ograph through tlic midb i :iin t cg inrn turn . The scctiori is obliqnc~lgr u t so that the dorsal part of tlic field ~ R S S P S hrough t h e dorsal thalamus nntltlic ventral par t through th r trans ition from midbr:iin t o pons. The lesion involviiigthe red nuclcus, bilateially, are very clear. Mxrclii prepar ations . x 2 .

6 Ihotoi~iirrogrn~~lif a srctioii through th c rostra1 part of the forebrain ofAlonkey No. 4 (hlaeaca iiiitlatta) . The tlegrnrr:ctions in tlic cnutlntc iiuclei :ireevideiit. Marc*liiprrpnratiniih. x 2 . 5 .

84


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hI . \ CAQUE M I D R R A I N A N D UAS;hL G A N G L I AJ O S H U A H. C A R E Y

IL.ATE 3

8 5


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PLATE 3EXPLATTATION OF' FIGURES

7 Pliotoiriicrograph of a section from the samc hr:iiii s l i o n n i!i Gguw 6 )Jutlocated t hrough diei1eeph:rlic lcvcls. The figure shows th e lesioii in t h c glo1) i i rp:dlidus on the left and in both subtli alamic nuclei. Nar cli i prep:ir:rtioiis. x 2.5 .

8 Photomicrograph t h r o u g h the dieiicephalori of Moiikr? SO. 5 ( ~ h ~ : i c i r ~ ~cgnniologus) at a plaiic: cutting th e n u c l e u s vciitr:ilis anterior dors;illy mid tlicxoptic tracts just beyond t,he opt.ic cliiaxma ventrally. Lcsioiis :ire shorsn il l thenucleus ventralis anterior and the nucleus ventr:ilis lntcrnlis of both aidcs. R1;rrcIiipreparations. X 2.6.

9 Photomicrograph of a section ft.o!ii the s:inie brain a s that sliowii ii i f i g u w 8b u t takcn at the most rostr:il midbrain lrvcls. Thtl s e d o i i passes through t l i cposterior eommissure dorsally and the cniergiiig oculomotor roots ventrally. Alesioii is present in the red nucleus on the right which a l so iiirolvcs t h e riglitoculoiiiotor root. Marchi preparations. X 2.5.

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PLATE 3

87


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E X P L A N A T I O N OF FIGURES

10 Pliotoiiiic,rograph of :Isectioii through the brain of hio i ikry X ( I . 5 (RT;icn(*uscyiirnologiis) which J X I S S ~ S hrough tlie superior colliculi slors:iIIy :iii(1 tlic h s e o ftlie po i i s v(wtra1lg. Thi s sre tion was re re rscd so that t h e lesio~is n the right sitl(.o f tlie brain are o n tlic l e f t in the figure. It s h o w h f n r ch i grniirilru in the w g i o i iof the region of the ruhrospiual t ra c t aiitl a tegiiiwtoqJiiia1 systcmii o i l t l ic I i S f ta i d n lesion in th e deep tcgriic~~it:tlr a y o n the riglit,. Riarclii 1iwp:ir:itioiis. x 18.

This figure i u a photomicrograph of n section t h r o u g h tlie roz;tr:il (w11oft h e eere1)r:il Iieniisplierex of M o n k e y No. 8. Th e iiiaterial dil l not rcqioiiil s n t i s -factoriallp t o the Rlnrchi technique l iu t tlie s i t e of tlic lesion is iiillic.:itcll iii tl lcillustrntioii. 3l:icacas cpniiiologus. Marchi prep:tr:itioiis. X 2.5.

11

8 8


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MAC!AQLIE M 1 L ) H R A I N AND B A S A L G A N G L IAJ O S H U A H . C A R E Y

PLATE 4

certain anatomical

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