effects of thalamic lesions upon cerebellar dyskinesia in the rhesus monkey

Effects of Thalamic Lesions upon Cerebellar Dyskinesia in the Rhesus Monkey'

MALCOLM B. CARPENTER AND GEORGE R. HANNA Department of Anatomy, College of Physicians and Surgeons, Columbia University, New Ymk, New York

Cerebellar dyskinesia provoked by lesions in the deep cerebellar nuclei, or in efferent fiber bundles from these nuclei, appears to represent the physiological expression of the disordered function of intact neural structures deprived of controlling and regulating cerebellar influences. This thesis is supported by the fact that secondary lesions, in neural structures other than those provoking the dyskinesia, can reduce, ameliorate, or abolish the motor disturbances. Structures considered to be particularly involved in the neural mechanism of cerebellar dyskinesia in- clude the thalamus (Cooper and Polouk- hine, '59; Cooper, '60a, '60b; Martin, '60), the agranular frontal cortex (Aring and Fulton, '36; Bucy, ' 59 ) , and the lateral corticospinal tract (Carpenter and Correll, '61). Data concerning the essential role of the thalamus in cerebellar dyskinesia are incomplete, but available anatomical evidence suggests that specific portions of this complex may be involved in the media- tion of this dyskinesia. Anatomical facts supporting this thesis are: (1) the largest and most important system of cerebellar efferent fibers (i.e,, the brachium conjunctivum) decussates in the midbrain and projects largely to the contralateral ventrolateral nucleus of the thalamus (Jansen and Brodal, '54; Carpenter and Stevens, '57; Cohen, Chambers and Sprague, '58) . ( 2 ) the ventrolateral nucleus of the thalamus projects most of its fibers to the agranular frontal cortex (Walker, '38; Mettler. '47), and ( 3 ) although the corticospinal tract originates from widespread regions of the cerebral cortex, few, if any, of its fibers appear to be infrapallial in origin (Mettler, '44; Lassek and Evans, '45).

No pathway originating in the cerebellum is known to project directly to spinal

levels, though some cerebellar efferent fibers (i.e., fastigiobulbar and descending division of the brachium conjunctiwm) pass to regions of the brain stem reticular formation (Thomas, Kaufman, Sprague and Chambers, '56; Carpenter and Nova, '60). While it is possible that these fiber systems might play some role in the neural mechanism of cerebellar dyskinesia, it has been demonstrated that surgical interruption of reticulospinal fiber systems at high cervical levels does not ameliorate or alter cerebellar dyskinesia in the monkey (Carpenter and Correll, '61).

The object of the current study was to determine the physiological effects of localized stereotaxic lesions in the thalamus upon cerebellar dyskinesia in the monkey produced by lesions of the deep cerebellar nuclei.

MATERIAL AND METHODS

A total of 30 rhesus monkeys were used in this study. Attempts were made to destroy and remove significant portions of th,e deep cerebellar nuclei, particularly the dentate nuclei, by aspiration techniques. Following a suboccipital craniotomy, the dura below the transverse sinus was opened to reveal the posterior aspect of the cerebellum. Small areas of cerebellar cortex in paravermal locations were cau- terized and a glass suction tube approximately 1.5 mm in diameter was inserted into the medullary core of the cerebellum. By this approach portions of the deep cerebellar nuclei were destroyed and as- pirated bilaterally. Following this proce-

1 Supported by research grants B-l630(C2) and B-l630(C3) from the National Institute of Neuro- loeical Diseases and Blindness of the National Insti- tutes of Health, Bethesda, Maryland.

2 Po3tdortoral trainee in neuroanatomy supported by grant 2B-5242CCl) from the Institute of Neurological Diseases and Blindness.

127

128 MALCOLM B. CARPENTER AND GEORGE R. HANNA

dure the dura was sutured with 6-0 silk and muscle layers and skin were closed in the usual manner.

Animals developing characteristic cerebellar dyskinesia were observed daily, and examined neurologically at intervals; cinematographic records of dyskinesia were made on at least two separate occasions following provocative surgery. After an interval of at least two weeks attempts were made to produce localized stereotaxic lesions in the lateral nuclear groups of the thalamus contralateral to the most promi- nent cerebellar disturbances. Coordinate systems for thalamic nuclei were deter- mined from formalin fixed heads with brains in situ (Carpenter and Whittier, ’52). Most thalamic lesions were produced electrolytically by a direct current ( 3 to 5 ma at 400 volts) applied for intervals of 15 seconds; multiple electrode placements were made close together in attempts to produce larger lesions. Attempts were made also to produce lesions by injection of solutions of 3% celloidin and E t ~ p a l i n . ~ Following thalamic lesions, physiological observations, neurological examinations and cinematographic records were made for comparative purposes. Animals were permitted to survive for variable periods of time following thalamic lesions; no animal was sacrificed less than two weeks after secondary surgery.

At the termination of the observation period animals were examined, anesthet- ized, and perfused with : (1) 500 ml of normal saline, and (2) 500 ml of 10% neutral formalin. The brain and spinal cord of each animal were removed in toto and further fixed in 10% neutral formalin. After an appropriate interval brains were sectioned in blocks perpendicular to the axis of the brain stem; blocks of spinal cord were cut transversely. Blocks of brain were embedded in paraffin. cut serially at 15 v, and stained according to the Nissl and Weil techniques. Every tenth section was stained with cresyl violet and every ninth section by the Weil method. For each brain, at least one block of the upper pons containing the brachium conjunctivum was stained according to the Marchi method so that fiber degeneration in this struc- ture could be evaluated. One block of cer-

vical spinal cord was stained also by the Marchi method to determine the presence of degeneration, if any, in the corticospinal tract. In a few cases selected sections of the upper pons and spinal cord were stained by the Nauta-Gygax (’54) technique.

OBSERVATIONS

Cerebellar dyskinesa. Attempts to produce bilateral lesions in the deep cerebellar nuclei in 30 monkeys resulted in persistent cerebellar dyskinesia in 23 animals. The cerebellar disturbances exhibited by these animals were essentially the same as those reported previously (Carpenter and Stevens, ’57; Carpenter and Correll, ’61). Dis- turbances consisted of ataxia, ataxic tremor, simple tremor, head tremor, generalized asynergic phenomena, hypokinesia, variable degrees of hypotonus, and sometimes disturbances of equilibrium. Post- operatively these animals assumed a broad- based stance, were reluctant to move about the cage, and progressed in a grossly ataxic fashion. Most of the animals displayed combined simple and ataxic tremor in both upper extremities; initially simple tremor (“tremor at rest”) was particularly promi- nent, but this type of tremor tended to undergo some attenuation within a few weeks (Carpenter and Stevens, ’57). Ataxic tremor, present during voluntary and associated movement, was characterized by large amplitude, irregular frequency and moderate force. As has been mentioned previously (Carpenter and Correll, ’61 ) tremor of both types was evident particularly in the upper extremities, appeared to involve proximal musculature more than distal musculature, and involved alter- nately flexor and extensor muscle groups. Tremor in the lower extremities was noted frequently but was more difficult to observe because of weight bearing and the tendency of animals to assume postures which in- hibited tremor or made its detection difficult. Tremor in the upper extremities was not constantly present, but usually was seen daily. In animals with particularly marked tremor and asynergic disturbances, tremor involving the head and neck was seen also. Asynergic disturbances were

3 Etopalin, a product of Ciba Pharmaceutical Prod- ucts, Inc., is a mixture of 8% ethyl cellulose, 95% ethyl alcohol and 15% Pantopaque.

CEREBELLAR DYSKINESIA IN THE MONKEY 129

evident particularly during voluntary and associated movement and sometimes displayed considerable forcefulness and amplitude. In the early postoperative period marked dysmetria made it difficult for animals to pick up food and convey it to their mouths. The severity of bilateral cerebeIlar dyskinesia was not always symmetrical, presumably because cerebellar lesions var- ied in size and disposition. Frequently an animal initially showed some reluctance to use the extremity with the most marked disturbances; this made evaluation of the dyskinesia difficult, but in time this reluctance usually disappeared. Prior studies (Carpenter and Stevens, '57) have shown that although these disturbances in the monkey undergo a gradual attenuation, most of the disturbances persist in a clearly recognizable form for at least six months.

Lesions of the deep cerebellar nuclei in these 23 monkeys showed variations in size, extent, and disposition and were not always symmetrical. Large portions of all intracerebellar nuclei were destroyed bilaterally in six animals. In 16 of the animals the lesions destroyed large parts of the dentate and interposed nuclei, without damaging the roof nuclei. However, Nissl stained sections in these animals revealed significant loss of cells in the roof nuclei indicating interruption of fastigial efferent fibers. Lesions confined to the dentate nuclei were found in only one animal. Although maps of the spatial dis- positions of cerebellar lesions at represent- ative levels through the cerebellum were made for each of these animals, the value of such maps appeared questionable since some lesions spared portions of particular nuclei while interrupting emerging efferent fibers at other locations. For this reason i t was felt that the extent of degeneration in the brachium conjunctivum was the most useful index for comparing and eval- uating the extent of intracerebellar destruction. While fibers from the fastigial nuclei were frequently interrupted by these lesions, prior studies (Carpenter, Brittin and Pines, '58; Carpenter, '59) have shown that these fibers do not enter the brachium conjunctivum, but leave the cerebellum via the uncinate fasciculus and juxtaresti- form body. As in other studies (Carpenter and Stevens, '57; Carpenter and Correll,

Cerebellar lesions.

'61), the severity of cerebellar dyskinesia in the monkey resulting from partial destruction of the dentate nucleus could not be distinguished from that associated with virtually complete destruction of the dentate nucleus or surgical section of the brachium con j unctivum.

Secondary thalamic lesions Attempts were made to produce localized

stereotaxic lesions in the lateral nuclear groups of the thalamus in 23 monkeys with established cerebellar dyskinesia. In 19 monkeys attempts were made to produce unilateral thalamic lesions contralateral to the most marked cerebellar disturbances. It was felt that ipsilateral cerebellar dyskinesia might serve as a type of control, in spite of inherent and recognized limitations. One animal in this group died in the immediate postoperative period. In another animal (C-491) with an un- recognized hydrocephalus due to adhesions around the fourth ventricle, no lesion was produced in the thalamus. A large soften- ing in the head of the caudate nucleus in this animal caused no detectable change in cerebellar disturbances. Three animals ((2-517, (2-525 and C-526) in which initial thalamic lesions produced either no modification of cerebellar dyskinesia, or only transient effects, were subjected to addi- tional operations on the same side. An analysis of the physiological effects of unilateral thalamic lesions upon cerebellar dyskinesia was made in 17 monkeys.

Bilateral thalamic lesions were produced serially in 4 monkeys with cerebellar dyskinesia. Because the initial unilateral thalamic lesions appeared to have little or no effect upon cerebellar disturbances in rhesus C-550, second lesions were infficted in the opposite thalamus. In two animals ((2-527 and C-559) initial lesions produced modifications of contralateral cerebellar disturbances, but lesions in the opposite thalamus, produced later, provoked only minimal changes. Asymmetrical bilateral lesions in rhesus C-528 produced only contralateral effects. Because lesions in these animals were associated with only contralateral alterations of cerebellar dyskinesia, they were considered as unilateral lesions for purposes of analysis.

130 MALCOLM B. CARPENTER AND GEORGE R. H A N N A

It was realized at the outset that even with the most precise stereotaxic technique, it probably would not be possible to produce lesions strictly limited to specific anatomical subdivisions of the thalamus. In spite of this obvious limitation, attempts were made to evaluate the physiological effects of thalamic lesions upon cerebellar dyskinesia with respect to groups of thalamic nuclei partially destroyed. The nomenclature and anatomical divisions of the thalamus designated by Olszewski (‘52) were followed throughout this study.

Ventral anterior nucleus of t he thalamus . Thalamic lesions destroying portions of the ventral anterior nucleus were produced in three monkeys. Although these lesions were similar in location, they var- ied in size and configuration. In rhesus C-489 two relatively small lesions in the ventral anterior nucleus began in the dorsal part of the nucleus and extended caudally and ventrally. Two of the four electrode placements produced lesions in the caudate nucleus which encroached upon some of the fibers in the anterior limb of the internal capsule. Four small lesions confined to the ventral anterior nucleus in rhesus C-496 extended caudally and medi- ally to the oral part of the nucleus ventralis lateralis. No capsular fibers were destroyed by these lesions. The lesion produced in rhesus C-527 (left side) appeared to destroy approximately a third of the ventral anterior nucleus in its central part. The ventral border of the lesion involved capsular fibers at the level of the anterior commissure. No degeneration of corticospinal fibers was evident in sections of the cervical spinal cord stained by the Marchi method in any of these animals.

Cerebellar dyskinesia in two of these animals (C-489 and C-496) appeared un- altered by secondary thalamic lesions. Head tremor, simple tremor, ataxic tremor, and all asynergic disturbances remained. For a few days after surgery cerebellar tremor ipsilateral to the thalamic lesions appeared slightly exaggerated but this was transient. In one animal (‘2-527) the thalamic lesion initially reduced both simple and ataxic tremor contralaterally but did not appear to affect dysmetria or the ataxic gait. Tremor during movement occurred only in short bouts particularly

at the beginning and end of voluntary movement. In addition the animal appeared to have more marked disturbances of equilibrium than prior to thalamic surgery. One week after surgery simple and ataxic tremor contralateral to the thalamic lesion became more evident. Three weeks after surgery tremor in the right extremities was consistently seen, though its amplitude was somewhat reduced. The thalamic lesion in this animal had no effect upon the ataxia and only a transient effect upon tremor.

Ventrolaterul nucleus of the thalamus. Thalamic lesions produced in two monkeys with established cerebellar dyskinesia destroyed portions of the ventrolateral nucleus selectively. MuItiple electrode placements in rhesus C-526 produced a large lesion (maximal dimensions 2.5 X 5 mm) which destroyed the dorsal and lateral part of the ventrolateral nucleus (pars oralis) without apparent encroachment upon the ventral anterior or ventral posterior lateral nucleus. This lesion concomitantly destroyed small portions of the caudate nucleus and corpus callosum dorsally. The relatively small thalamic lesions found in rhesus C-550 (right side) involved the dorsal and caudal part of the ventrolateral nucleus (pars caudalis), and portions of the dorsomedial nucleus. No descending degeneration was seen in Marchi sections of the spinal cord of rhesus C-550. In rhesus C-526 descending degeneration in the spinal cord was present bilaterally in the sulcomarginal area and in the ventral parts of the lateral funiculi. Fiber degeneration in these locations was considered to be a consequence of concomitant damage to vestibular nuclei found in associa- tion with the lesions in the deep cerebellar nuclei. No Marchi degeneration was found in the dorsal half of the lateral funiculus.

The large thalamic lesion in rhesus C-526 produced a marked reduction in contralateral simple and ataxic tremor. Simple tremor, which prior to thalamic surgery had been almost continuously present, practically disappeared. A1 though ataxic tremor was not abolished, it was greatly reduced in amplitude, force and frequency of occurrence. In spite of some residual dysmetria contralateral to the thalamic lesion, the animal preferred to


use this hand for feeding. The mild disturbances of equilibrium, present prior to the thalamic lesion, persisted as did the ataxia. Head tremor was reduced, but not abolished. Comparisons of the cinematographic records before and after the lesion in the thalamus indicated that cerebellar tremors contralateral to the lesion were greatly ameliorated. This reduction in tremor persisted until the animal was sacrificed.

Thalamic lesions produced in rhesus C- 550 appeared to cause a reduction in simple and ataxic tremor contralaterally which lasted about one week. Other cerebellar disturbances showed no attenuation during this period. Tremor during voluntary and associated movement gradually reappeared and 26 days after surgery was un- questionably most severe opposite the thalamic lesion. This thalamic lesion appeared to have no lasting effect upon any of the cerebellar disturbances.

Ventral anterior and ventrolateral nuclei of the thalamus. Secondary thalamic lesions destroyed portions of the ventral anterior and ventrolateral thalamic nuclei in four animals. In rhesus C-497 four small confluent lesions rostrally destroyed a ventrolateral area in the ventral anterior nucleus and the adjacent reticular nucleus of the thalamus. Caudally these lesions en- tered the ventral and oral part of the ventrolateral nucleus; the lesions terminated without involving the ventral posterior lateral nucleus. Destruction appeared maximal in the junctional area between the ventral anterior and the ventrolateral nuclei. The four electrode placements made in rhesus C-507 produced a single large lesion in the dorsolateral part of the ventral anterior nucleus. At this location the lesion meas- ured 3 X 4 mm. Caudally the lesion en- tered the dorsal part of the ventrolateral nucleus, adjacent to the internal capsule. The lesion diminished slightly in size as it passed caudally. The thalamic lesion in rhesus C-508 was similar to that in rhesus C-507 except that it was smaller, more medial and extended further caudally. Examination of Marchi stained sections of the cervical spinal cord revealed no descending degeneration in two animals (C- 497 and C-508). In rhesus C-507 a small number of degenerated fibers were scat-

tered throughout the dorsal half of the lateral funiculus on the right side.

In the fourth animal (C-528, right side) of this group two lesions which began in the caudate nucleus extended caudally to destroy parts of the ventral anterior and ventrolateral nuclei. In the ventrolateral nucleus destruction was largely limited to the pars caudalis. No damage to fibers of the internal capsule was apparent and no descending degeneration could be seen in sections of the spinal cord.

Although these thalamic lesions were not identical in size or location, their physiological effects upon prior cerebellar dyskinesia were similar. In all of these animals a marked reduction of both simple and ataxic tremor contralateral to the thalamic lesion was noted upon recovery from an- esthesia. Tremor at rest appeared to be abolished while tremor occurring during voluntary and associated movement did not entirely disappear. A few tremor cycles sometimes were seen at the beginning and end of voluntary movement, or when the animal was excited. This modification of tremor in three animals persisted without change until the animals were sacrificed 19 days after secondary surgery. No recrudescence of tremor contralateral to the thalamic lesion in rhesus C-528 was seen during an observation period of eight weeks. In this animal another thalamic lesion was produced subsequently on the opposite side (page 133).

Combined types of tremor ipsilateral to the thalamic lesions were unchanged, though initially the tremor seemed to be somewhat exaggerated. Two of the animals developed feeding preferences for the hand ipsilateral to the thalamic lesions, but the other two (C-497 and C-528) consistently preferred the opposite hand for mono- manual feeding. In spite of the significant reduction of tremor by the thalamic lesions, no alteration of ataxia or general awkwardness in the performance of skilled movements was seen on either side. The stance remained broad-based and the gait was insecure and ataxic. In one animal ((2-508) a moderate disturbance of equilibrium was noted along with a tendency to lean to the side opposite the thalamic lesion. This disturbance underwent a gradual attenuation and disappeared after two


weeks. None of these animals appeared to have any paresis or impairment of sensation detectable upon examination.

Ventroluteral and ventral posterior lateral nuclei of the thalamus. Thalamic lesions produced in two monkeys (C-565 and C-594) with established cerebellar dyskinesia destroyed selectively portions of the ventrolateral and ventral posterior lateral nuclei. Four electrode placements made in each of these animals produced identifiable eIectrode tracks in the internal capsule ventral to the caudate nucleus and in the lateral portions of the ventral anterior nucleus. Electrode tracks consisted of small localized areas of dense gliosis seen readily in Nissl stained sections; no lesions were found in this region. Destruc- tion found in the central part of the ventrolateral nucleus (pars oralis) consisted of four individual lesions approximately one millimeter in diameter arranged at the corners of a rhombus with two millimeter sides. This constellation of lesions extended caudally and ventrally into the ventral posterior lateral nucleus (pars oralis) without appreciable reduction in size. Thalamic lesions with this disposition and location were similar in these animals. No part of the internal capsule was destroyed by these lesions. Although no degeneration was evident in sections of the spinal cord stained by the Marchi method, Nauta stained sections revealed modest pretenninal degeneration about cells of the anterior horn in upper cervical segments contralateral to the lesions. This minimal degeneration presumably was produced by electrodes traversing portions of the internal capsule.

The effects of these nearly identical lesions upon cerebellar dyskinesia was similar. Simple and ataxic tremor contralateral to the thalamic lesions was virtually abolished, while ipsilateral tremor persisted without change. Other asynergic disturbances and ataxia were not altered significantly, but slight disturbances of equilibrium, not previously present, were noted for a few days. One animal (C-565) had minimal contralateral paresis lasting for six days that subsided without residual. Although tremor opposite the thalamic lesion was aracticallv abolished. both animals prehrred to -feed with’ the hand

ipsilateral to the secondary lesion. Neuro- logical examination disclosed apparent diminution of reactions to painful stimuli contralateral to thalamic lesions. Impair- ment of sensation contralaterally was considered partially responsible for the reluctance of the animals to use these extremities. No recrudescence of tremor contralateral to the thalamic lesions occurred in either animal during an observation period of over four weeks.

Centromedian, ventral posterior medial and ventral posterior lateral nuclei of the thalamus. Secondary thalamic lesions produced in two monkeys involved nuclei in more caudal portions of the thalamus, although electrodes traversed more rostra1 regions. The lesion in rhesus C-595, produced by four electrode placements, destroyed the lateral parts of the centromedian and the ventral posterior medial nuclei throughout their extent and the medial margin of the adjoining ventral posterior lateral nucleus (pars caudalis). This irregular rhomboid shaped lesion measuring 2 X 3 mm in maximal dimensions terminated caudally medial to the medial geniculate body. A smaller, less extensive lesion in rhesus C-596 destroyed the dorsolateral part of the centromedian nucleus and medial portions of the ventral posterior laterd nucleus (pars oralis and caudalis). This lesion also involved a small part of the ventral posterior medial nucleus. Caudally almost all of the lesion was within the boundaries of the centromedian nucleus. No part of the internal capsule was destroyed by the lesions in either of these animals.

These two animals were observed for nearly five weeks prior to thalamic surgery, during which time no attenuation of tremor or other disturbances was apparent. Both animals consistently displayed tremor both at rest and during movement. The combined simple and ataxic tremor seen bilateral in rhesus C-596 was unquestion- ably the most severe and persistent produced in this laboratory by cerebellar lesions.

The described thalamic lesion in rhesus C-595 abolished contralateral simple tremor and greatly reduced ataxic tremor. The only tremor seen opposite the thalamic lesion consisted of a few intermittent CY-

133 CEREBELLAR DYSXINESIA IN THE MONKEY

cles seen at the beginning or end of a voluntary movement. The animal used the contralateral upper extremity exclu- sively for feeding, which was accomplished in a nearly normal manner. Tremor ipsilateral to the thalamic lesion persisted without significant change for two weeks, but after that interval gradually diminished. Three weeks after surgery almost no tremor was present on either side. The gait continued to be unsteady and awkward. Skilled voluntary movements were slow and somewhat clumsy. No evidence of paresis or sensory impairment could be detected. The animal was sacrificed three weeks after thalamic surgery.

Following the thalarnic lesion on the left side in rhesus C-596, all tremor on the right was abolished. The animal had no detectable paresis and persistently preferred the right hand for feeding. Dys- kinesia present in the left extremities was not affected by the thalamic lesion. The generalized ataxia, hypokinesia and slow- ness of movement appeared unchanged. The definitely salutary effects of the thalamic lesion in this animal persisted for four weeks. After this interval it was noted that occasional short bursts of tremor were seen in the right upper extremity. At six weeks the recrudescence of both simple and ataxic tremor on the right side could be seen easily. Although combined types of tremor reappeared contralateral to the thalamic lesion, the dyskinesia was never as marked as that seen on the left, which persisted without change. No further alteration of the cerebellar dyskinesia was apparent during the next two weeks. After eight weeks of observation the animal was sacrificed.

Nuclei of the lateral thalamic group. Stereotaxic lesions produced in six monkeys with cerebellar dyskinesia involved multiple nuclei of the lateral thalamic group. Electrolytic lesions in four animals IC-515, C-525, (2-528 (left side), and C-6041 began in the ventral anterior nucleus as four small discrete lesions; in the ventrolateral nucleus (pars oralis) the individual lesions formed a single large lesion with somewhat irregular borders. These large lesions produced by multiple electrode placements extended caudally into the ventral posterior lateral and me-

dial nuclei without appreciable reduction in size. Lateral portions of the centromedian nuclei were encroached upon or destroyed concomitantly in three animals (C-515, C-525 and C-528). Thalamic lesions in rhesus C-525 consisted of two separate constellations of lesions produced at different times. In addition to the more dorsal lesion, described above, there was a second more ventral lesion destroying fibers of the thalamic fasciculus and portions of the ventral posterior medial nucleus. The lesion in rhesus C-528 (left side) was the largest lesion in any animal of this group measuring 4 X 5 mm in maximal dimensions in the area of over- lap of the ventrolateral and ventral posterior lateral nuclei. Marchi stained sections of the cervical spinal cord in these animals did not reveal evidence of descending degeneration. However, Nauta-Gygax stained sections of the spinal cord in rhesus C-604 disclosed modest preterminal degeneration in the dorsal half of the lateral funiculus contdateral to the thalamic lesion. Electrode tracks in portions of the internal capsule appeared responsible for this degeneration.

The thalamic lesion in rhesus C-552, produced by injection of 0.2 ml of Etop- alin, resulted in a cylindrically shaped lesion which began in the caudate nucleus and successively destroyed portions of the ventral anterior, ventrolateral (pars oralis), ventral posterior lateral, paracentral and centromedian nuclei. The lesion terminated in the caudal part of the ventral posterior lateral nucleus. No fibers of the internal capsule appeared to be destroyed by the lesion and no Marchi degeneration could be detected either in the medullary pyramids or in the spinal cord.

Bilateral thalamic lesions produced serially in rhesus C-559 were found in nearly symmetrical locations in the ventral anterior, ventrolateral and ventral posterior lateral nuclei. Two relatively large lesions on the right side produced by injection of Etopalin not only destroyed more tissue than the electrolytic lesion on the opposite side, but involved the ventral anterior nucleus to a greater extent. No portions of the internal capsule were damaged on either side.


Following thalamic lesions three of these animals (C-515, C-528 and C-604) appeared to have conspicuous reduction of tremor in the contralateral extremities. Tremor at rest was practically abolished while tremor evident during voluntary or associated movement was still present, though reduced in amplitude, force and frequency of occurrence. The latter type of tremor often was seen only at the beginning and end of a purposeful movement; during some observation periods no tremor of any kind was seen. The amelioration of contralateral tremor persisted without recrudescence in all of these animals. Combined types of tremor ipsilat- era1 to the thalamic lesions were initially unchanged or appeared somewhat exaggerated compared with the previous state. Apparent exaggeration of ipsilateral tremor was transient, usually lasting only a few days.

The broad-based stance and ataxic gait characterizing this type of cerebellar dyskinesia was not significantly altered by the thalamic lesions. Skilled movements were not performed with the speed and dexterity of the normal animal and dysmetria was evident upon reaching for food. Although none of these animals appeared to have any paresis, a feeding preference for the hand ipsilateral to the thalamic lesion was persistently seen in two animals (C-528 and (2-604). Since it was not possible to detect impairment of cutaneous or proprioceptive sensibility in these animals, the nature of this deficit could not be defined.

Rhesus C-515 displayed impressive improvement in coordinated motor function contralateral to the thalamic lesion, in addition to reduction in the severity of tremor. Prior to thalamic surgery this animal fed directly from the floor of the cage because the severe ataxic tremor and asynergic disturbances impaired normal feeding patterns. Following the thalamic lesion this animal was able to grasp food in a normal fashion, break it into small pieces and convey it to the mouth in se- quences of smooth and orderly movements. This improvement contralateral to the thalamic lesion persisted.

As reported above two separate thalamic lesions were produced at different times

on the right side in rhesus C-525. The initial lesion destroying portions of all thalamic nuclei in the lateral group and a small part of the centromedian nucleus, abolished contralateral simple tremor and greatly reduced ataxic tremor, but did not modify the generalized ataxia. Both ataxic and simple tremor gradually reappeared opposite this thalamic lesion and four weeks after surgery tremor was essentially the same as prior to the thalamic lesion. Because of this failure to modify any part of the cerebellar dyskinesia, a second thalamic lesion was attempted ventral to the fmt one; this lesion destroyed fibers in the thalamic fasciculus and parts of the ventral posterior medial nucleus. Follow- ing this procedure contralateral tremor was abolished, but skilled movements still were performed in an awkward fashion. Tremor in the ipsilateral extremities also appeared somewhat reduced after the second thalamic lesion, suggesting a possible bilateral effect.

A large unilateral thalamic lesion in rhesus C-552, likewise, seemed to have a bilateral effect upon the cerebellar dyskinesia. Initially the large thalamic lesion, produced by injection of Etopalin, appeared to have no effect upon the cerebellar disturbances, but within six days the tremor and most of the asynergic disturbances disappeared bilaterally. The animal was able to stand, walk, climb and feed without difficulty. There was no evidence of paresis. Although the animal remained moderately hypokinetic, coordinated motor function seemed nearly normal.

In spite of the fact that fairly sym- metric a1 bil ater a1 th a1 amic lesions were produced in rhesus C-559, significant and enduring reduction of tremor was seen only on the left side, contralateral to the largest lesion. Simple tremor was abolished on the left and ataxic tremor was eliminated except for a few tremor cycles appearing at the beginning and end of voluntary movement. No detectable modification of other cerebellar disturbances was seen in this animal.

None of the animals of this group appeared to have disturbances of equilibrium or posture that could be attributed to the secondary thalamic lesions. Even though thalamic lesions destroyed significant por-


tions of sensory relay nuclei, it was not possible to detect impairment of sensory perception.

Thalamic fasciculus. Relatively small stereotaxic lesions in three monkeys with cerebellar dyskinesia interrupted fibers of the thalamic fasciculus dorsal to the zona incerta. Two electrode placements in rhesus C449 produced a single obliquely oriented lesion in the thalamic fasciculus extending dorsally into the ventral posterior medial nucleus. Profuse Marchi degeneration from the lesion projected over a wide area in the ventral part of the lateral nuclear group of the thalamus. A similarly located lesion in rhesus C-450 appeared to interrupt most of the fibers of the thalamic fasciculus, some of the fibers of the lenticular fasciculus and destroyed portions of both the zona incerta and subthalamic nucleus. Destruction in the corpus Luysii was limited to a small dorsolateral region. These lesions did not appear to interrupt fibers in the internal capsule. An attempted right thalamic lesion in rhesus C-527 involved some fibers of the internal capsule, parts of the reticular nucleus of the thalamus rostrally and destroyed a large number of fibers of the thalamic fasciculus. Marchi degeneration also was present in the lenticular fasciculus.

Although secondary stereotaxic lesions in these animals were similar, their physiological effects were not identical. In rhesus C-449 and C-527 modest diminution of both simple and ataxic tremor was seen contralaterally. while the reduction in the severity of the tremor was not as great as that seen in other animals with lesions in the thalamic nuclei, the modification was definite. This reduction in the severity of contralateral cerebellar tremor persisted until the animals were sacrificed four and five weeks, respectively, after surgery. Other features of the cerebellar syndrome were not detectably modified by lesions involving this fiber bundle.

The similarly located lesion in rhesus C-450 did not alter tremor, ataxia, or asynergic disturbances, even though some diminution in the animal's response to painful stimuli seemed to be present contralateral to the lesion.

Other thalamic nuclei. Due to error or misjudgment lesions in three monkeys involved nuclei in portions of the thalamus some distance from the intended locations. The anterior nucleus of the thalamus was destroyed partially on the left side in rhesus C-526. Following this lesion no change in the cerebellar dyskinesia was seen. Af- ter a period of two weeks a second lesion was inflicted; the findings associated with the second lesion, located in the ventrolateral nucleus of the thalamus, have been reported (page 130).

In another animal (C-550) two lesions in the caudal part of the dorsomedial nucleus on the left produced no detectable alteration of cerebellar disturbances. Sub- sequently a second thalamic lesion was made on the right side (page 130).

In rhesus C-517 three separate attempts were made to produce stereotaxic lesions in the right thalamus. These lesions destroyed: ( 1 ) portions of area X (Olszew- ski, '52), the paracentral nucleus, and parts of the lateral central nucleus, (2) parts of the ventrolateral nucleus (pars caudalis), and ( 3 ) parts of the lateral central and posterior lateral nuclei. None of these lesions singly or collectively produced detectable modifications of cerebellar dyskinesia in this animal.

DISCUSSION

Considerable clinical evidence supports the thesis that localized lesions involving the globus pallidus, the pallidofugal fiber systems or the ventrolateral regions of the thalamus can reduce and ameliorate tremor and rigidity associated with paralysis agitans (Wycis and Spiegel, '52; Spiegel and Wycis, '54, '58; Cooper, '56, '60c; Cooper and Bravo, '58a, '58b; Narabayashi, Okuma and Shikiba, '56; Housepian and Pool, '58; Bertrand, Mar- tinez, Poirier and Gauthier, '58; Alajouan- ine, Houdart, Remond, and Morin, '58; Lin and Cooper, '60; van Manen, '60). Similar evidence indicates that lesions in these locations can alleviate the symptoms of dystonia rnusculorum deformans (Cooper, '57, '59; Cooper, Poloukhine and Hoen, '56; Cooper and Bravo, '58b) and reduce or abolish choreoid (Spiegel and Wycis, '50) and ballistic activity (Talair- ach, Pallas and David, '50; Roeder and


Orthner, '56; Cooper, '57; Martin and McCaul, '59; Andy and Brown, '60). Al- though some anatomical confirmation of the location of these lesions is available (Spiegel and Wycis, '58; Bertrand, Marti- nez, Poirier and Gauthier, '58; Smith, '60) more extensive study is needed of surgi- cally produced lesions in patients with dyskinesia. The only available experimental evidence concerns the effects of pallidal and thalamic lesions upon subthalamic hyperkinesia in the rhesus monkey (Carpenter, Whittier and Mettler, '50; Carpenter, '61). These data indicate that lesions destroying significant portions of the globus pallidus or lateral nuclear groups of the thalamus can abolish contralateral subthalamic hyperkinesia without producing paresis.

Several reports have appeared recently indicating that thalamic lesions may be effective in ameliorating intention tremor associated with cerebellar disease and multiple sclerosis (Cooper and Poloukhine, '59; Cooper, '60a, '60b; Martin, '60; Maz- ars, Droguet and Pansini, '60; Bonduelle, '60; Wertheimer, Bourret and Lapraz, '60). Most of these lesions have been described as destroying portions of the ventrolateral nucleus of the thalamus, though the location of these lesions has not been con- firmed anatomically. Other authors (Guiot, Brion, Fardeau, BettaYeb and Molina, '60; Thurel, Nehlil and OKeefe, '60) have reported significant reduction of intention tremor by stereotaxic lesions said to be located in the posterior limb of the internal capsule. These lesions were considered to encroach upon portions of the thalamus and to interrupt a sufficient number of capsular fibers to suppress intention tremor, but were not so large as to produce clinically detectable motor defi- cits. It is of interest that Guiot (see discussion, Wertheimer, Bourret and Lapraz, '60) has stated, "Cette definition anat- omique de la lesion efficace pour les tremblements parkinsoniens nous parait Btre la mBme pour les dyskinesies volitionnelles d'attitude." This comment suggests that, at least, some of the neural pathways mediating distinctive forms of dyskinesia may be the same, an hypothesis supported by experimental studies (Carpenter, '61). Sir Gordon Holmes' ('22) statement con-

cerning the relationship of "static" tremor to cerebellar lesions appears pertinent in this context. He commented: "Its resem- blance to the tremor of paralysis agitans is unmistakable; it is apparently similar to that which Fenier and Turner (1894) observed after section of the superior peduncles and which is frequently associated with midbrain lesions that involve these peduncles."

Prior experimental studies (Carpenter, Correll and Hinman, '60; Carpenter and Correll, '61) in the monkey indicate that impulses indirectly responsible for both subthalamic hyperkinesia ( a choreoid activity) and cerebellar dyskinesia are transmitted to segmental levels by the same tract, the lateral corticospinal tract. In these forms of experimental dyskinesia interruption of other descending pathways at high spinal levels has no appreciable physiological effect upon the dyskinesia. If fibers of the corticospinal tract consti- tute the primary descending fiber system transmitting impulses concerned with these dyskinesias to segmental levels, the cerebral cortex must play an essential role in these disturbances. Anatomical evidence suggests that impulses concerned with dyskinetic phenomena probably reach the cerebral cortex through the me- diation of thalamic nuclei. Because cerebellar dyskinesia represents one form of motor disturbance that can be produced consistently in the monkey by lesions destroying portions of the deep cerebellar nuclei (Carrea and Mettler, '47, '55; Car- penter and Stevens, '57), it appeared possible to study the physiological effects of secondary thalamic lesions upon dyskinesia. Since the production of thalamic lesions confined to particular anatomical subdivisions of the thalamus is difficult, the analysis of the physiological effects of thalamic lesions on this basis was not always possible.

Evidence from this study indicates that thalamic lesions discretely involving portions of the anterior nuclei (anterior ventral and anterior medial), the dorsomedial nucleus, and the ventral anterior nucleus have no appreciable effect upon any of the motor disturbances in the monkey provoked by large lesions of the deep cerebellar nuclei. From an anatomical basis it


would seem unlikely that lesions involving the anterior nuclear group of the thalamus should have any effect upon cerebellar dyskinesia, since this nuclear group receives most of its afferent fibers from the mammillary body and its cortical projection is primarily to the region of the cingu- late gyrus (Peele, '61). Likewise the cortical projection of the dorsomedial nucleus upon the granular frontal cortex (Mettler, '47) makes it seem unlikely that this nucleus would play an essential role in the neural mechanism of cerebellar dyskinesia. Since fibers projecting to the ventral anterior nucleus of the thalamus are derived in part from the globus pallidus (Ranson and Ranson, '42; Papez, '42; Johnson and Clemente, '59), lesions in this nucleus might conceivably alter some features of the cerebellar syndrome. While i t is possible that more extensive lesions in the ventral anterior nucleus of the thalamus might have produced a different re- sult, it is notable that in one animal with a large lesion in this nucleus only a modest reduction in contralateral tremor was seen. On the basis of volumes of tissue destroyed, lesions in the ventral anterior nucleus of the thalamus appear to have a relatively minor effect upon cerebeuar dyskinesia compared with lesions in other portions of the thalamus.

Secondary stereotaxic lesions involving the caudate nucIeus and the anterior limb of the internal capsule appear to have no appreciable effect upon cerebellar dyskinesia. Findings regarding the caudate nucleus confirm previous observations (Car- penter, Glinsmann and Fabrega, '58) that secondary striatal lesions do not influence cerebellar dyskinesia in the monkey.

Relatively small lesions interrupting fibers of the thalamic fasciculus dorsal to the zona incerta appear to produce only a very modest reduction of cerebellar tremor. Findings in three animals seem significant because they indicate that interruption of fibers of the brachium conjunctivum at diencephalic levels neither exaggerates nor abolishes existing cerebellar disturbances. However, data in one animal (C-525) suggest that interruption of fibers of the thalamic fasciculus may po- tentiate the ameliorative effects of lesions

in the lateral nuclear groups of the thalamus.

Thalamic lesions producing significant alteration of cerebellar dyskinesia appear to involve either the ventrolateral (pars oralis) or the centromedian nuclei. Sec- ondary lesions destroying portions of the ventrolateral (pars oralis) nucleus alone, or in combination with portions of the ventral anterior and/or ventral posterior lat,eral nuclei, appear to reduce contralat- era1 tremor. Tremor at rest (simple tremor) frequently is abolished contralaterally, while intention tremor (ataxic tremor) is greatly reduced opposite the lesion, but usually not eliminated entirely. Residual ataxic tremor contralateral to these thalamic lesions consists of a few tremor cycles at the beginning and end of voluntary movement. Excitement, fear, and antici- pation of feeding frequently tend to bring out tremor which under other circum- stances may not be noticeable. These thalamic lesions appear to have little, if any, effect upon other cerebellar disturbances. The broad-based stance, ataxic gait and asynergic phenomena seen during voluntary and associated movement persist without appreciable change.

Thalamic lesions destroying portions of the ventrolateral nucleus alone or in combination with parts of the ventral anterior and/or ventral posterior lateral nuclei appear to have no physiological effect upon ipsilateral cerebellar disturbances, including tremor. Some animals with lesions in these thalamic nuclei exhibit disturbances of equilibrium which are transient. In spite of the fact that some lesions destroyed significant parts of the ventral posterior lateral nucleus, sensory loss or impairment usually could not be detected on examination, a finding similar to that sometimes reported in man (Cooper, '60a, 60b; Mark, Ervin and Hackett, '60). It is possible that impairment of certain sensibilities could have accounted for the reluctance of some animals to use the upper extremity contralateral to the thalamic lesions for mono- manual feeding. Unfortunately no thalamic lesions in this series of animals selectively destroyed the ventral posterior lateral nucleus of the thalamus.

Thalamic lesions destroying portions of the centromedian nucleus and parts of the

138 MALCOLM B. CARPENTER AND GEORGE R. H A N N A

ventral posterior lateral and medial nuclei appear effective in reducing contralateral cerebellar tremor, but produce no modification of other cerebellar disturbances. Reduction in contralateral tremor was seen in five monkeys with lesions involving the centromedian nucleus, but recrudescence of tremor occurred in one of these animals after four weeks. In three of these animals (C-525, C-552 and C-595) significant reduction in tremor ipsilateral to the thalamic lesion was observed. These data suggest that thalamic lesions destroying portions of the centromedian nucleus may ameliorate cerebellar tremor bilaterally, to some extent. Theoretically two separate lesions destroying portions of the ventrolateral and centromedian nuclei might be most effective in abolishing cerebellar tremor. The spatial disposition of these nuclei is such that a single stereotaxic lesion destroying them would have to be large and would concomitantly involve a large number of other thalamic nuclei.

In the literature only one report (Ward, McCulloch and Magoun, '48) could be found in which attempts were made to determine the physiological effects of thalamic lesions upon tremor in the monkey. Tremor in this animal (BR 12) was produced by bilateral lesions in the mesen- cephalic and pontine tegmentum involving multiple structures, including the reticular formation, red nuclei, brachia conjunc- tivia and parts of the medial lemnisci. In this animal tremor, probably provoked by destruction of the brachium conjunctivum, was not permanently abolished by lesions in cortical areas 4 and 6, or by a large thalamic lesion subsequently produced in the lateral nuclear group of the thalamus. While this report is open to certain objections, it is difficult to under- stand why the very large thalamic lesion did not reduce or abolish contralateral tremor.

At least one aspect of cerebellar dyskinesia, namely tremor, can be significantly modified by secondary thalamic lesions involving either the ventrolateral (pars oralis) or centromedian nucleus. Modifi- cation of cerebellar tremor by these lesions does not depend upon interruption of corticospinal pathways. The explanation as to

why thalamic lesions in these locations reduce cerebellar tremor cannot be answered definitely. Cerebellar dyskinesia resulting from lesions in the deep cerebellar nuclei would appear to represent the physiological expression of the disordered function of intact neural structures deprived of the controlling and regulating influences of the cerebellum. Because the principal cerebellar efferent fiber system, the brachium conjunctivum, is entirely crossed and projects primarily upon the contralateral ventrolateral nucleus of the thalamus, it might be postulated that this particular thalamic nucleus is "released" from the regulating influences of the cerebellum as a consequence of cerebellar lesions. The unregu- lated discharge of the ventrolateral nucleus upon the cerebral cortex may be responsible for the observed cerebellar disturbances. Prior studies (Carpenter and Correll, '61) have demonstrated that impulses concerned with cerebellar dyskinesia are transmitted to segmental levels via the lateral corticospinal tract. Be- cause the latter system is predominantly crossed, physiological disturbances appear ipsilateral to the cerebellar lesion. The current study suggests that modification of cerebellar tremor in the monkey produced by lesions involving the ventrolateral nucleus of the thalamus may depend primarily upon effective interruption of thalamo-cortical fiber projections from this nucleus. However, previous experiments (Carpenter, Glinsmann and Fabrega, '58) have shown that lesions in the globus pallidus and lenticular fasciculus also ameliorate cerebellar tremor in the monkey, a finding that indicates that pallido- thalamic pathways may also be involved. In any case thalamic lesions would appear to be more effective in modifying cerebellar tremor since lesions involving the ventrolateral nucleus would interrupt thalamo-cortical pathways, as well as pallido-thalamic fiber projections.

Study of the efferent fiber projections of the intracerebellar nuclei in the cat (Cohen, Chambers and Sprague, '58) based upon silver staining techniques indicates that fibers from the dentate and interposed nuclei have more extensive fields of terminal projection within the thalamus than is commonly acknowl-

CEREBELLAR DYSKINESIA I N THE MONKEY 139

edged. These authors reported that a relatively large number of cerebellar afferent fibers project to the midline, intralaminar and reticular nuclei of the thalamus. These anatomical data suggest that these nuclei may be concerned with the medi- ation of cerebellar regulatory influences. While physiological studies (Dempsey and Morison, '42; Jasper, '49) have demonstrated that the intralaminar nuclei, and the centromedian nucleus in particular, participate directly in recruiting responses obtained from widespread areas of the cerebral cortex, anatomical studies (Nauta and Whitlock, '54) have failed to show any direct fiber projections from the centromedian nucleus to the cerebral cortex. Lesions in the centromedian nucleus stained by the Nauta technique have demonstrated abundant fiber projections from this nucleus passing into the lateral nuclear complex which appear to terminate mainly in the ventrolateral nucleus, and to a lesser extent in the ventral anterior, ventral posterior medial and ventral posterior lateral nuclei. Repetitive stimula- tions of the centromedian nucleus in the cat (Purpura and Cohen, '62) have been reported to induce long latency, prolonged (40-80 msec) repolarization and hyper- polarization of neurons in the rostra1 and ventrolateral thalamus, as well as short latency depolarization (10-30 msec). These findings indicate that the centromedian nucleus may provide a strong intrathalamic regulating influence upon the ventrolateral nuclear complex of the thalamus. These anatomical and physiological data suggest that lesions in the centromedian nucleus may modify cerebellar tremor as a consequence of removal of potent intrathalamic influences acting upon the ventrolateral nucleus of the thalamus.

Although cerebellar disturbances usually appear as a constellation of closely related disturbances, the results of the current investigation imply that distinctive neural mechanisms may be involved. The finding that ataxia and asynergic disturbances, other than tremor, are not significantly modified by thalamic lesions in a variety of locations suggests that the neural pathways effecting these phenomena may not involve thalamic nuclei. This hypothesis in some respects resembles that

advanced by Carrea and Mettler ('55) who suggested that ataxia in the monkey could be correlated with degeneration in the descending division OP the brachium conjunctivum. Further study (Mettler, Orioli, Grundfest and Liss, '54) of this question subsequently demonstrated that isolated unilateral destruction of the descending division of the brachium conjunctivum did not produce detectable alteration of motor function.

SUMMARY AND CONCLUSIONS

A study was made to determine the physiological effects of localized lesions in the thalamus upon cerebellar dyskinesia in the monkey produced bilaterally by large lesions destroying portions of the intracerebellar nuclei. In animals developing appropriate and persistent cerebellar dyskinesia attempts were made to destroy various anatomical subdivisions of the thalamus. Thalamic lesions were inflicted contralateral to the most severe cerebellar disturbances two to six weeks after cerebellar surgery. Physiological observations, neurological examinations, and cinematographic records were made after cerebellar surgery and following place- ment of thalamic lesions. Serial sections of the brains were stained according to the Nissl, Weil and Marchi techniques. Sections of the cervical spinal cord were stained by the Marchi and /or Nauta- Gygax methods.

The following conclusions were drawn from observations made on 21 monkeys with established cerebellar dyskinesia in which thalamic lesions were produced :

1. Thalamic lesions destroying portions of the ventrolateral (pars oralis) or centromedian nuclei can effectively diminish contralateral tremor in monkeys with cerebellar dyskinesia, but such lesions do not modify other cerebellar disturbances.

2. Stereotaxic lesions in the ventrolateral nucleus (pars oralis) of the thalamus alone, or concomitantly destroying portions of the ventral anterior, and/or the ventral posterior lateral (and medial) nuclei, only diminish contralateral tremor in the monkey.

3. Localized lesions involving portions of the centromedian nucleus and adjacent anatomical subdivisions of the thalamus


may produce bilateral reductions in the severity, amplitude and force of cerebellar tremor, but do not alter other features of cerebellar dyskinesia in the monkey.

4. Thalamic lesions localized to portions of the ventral anterior nucleus, the dorsomedian nucleus, or the anterior nuclear group (anterior ventral and anterior medial nuclei) of the thalamus have little, if any, effect upon cerebellar dyskinesia in the monkey.

5. Discrete unilateral lesions in the thalamic fasciculus dorsal to the zona incerta produce only minimal or questionable reductions in contralateral cerebellar tremor and have no effect upon other cerebellar disturbances.

6. Unilateral stereotaxic lesions destroying portions of the caudate nucleus and/or the anterior limb of the internal capsule have no appreciable effect upon cerebellar dyskinesia in the monkey.

7. Reduction and amelioration of cerebellar tremor in the monkey by lesions in specific nuclear groups of the thalamus can be effected without injury to fibers of the corticospinal tract.

Two hypotheses are presented : 1. Although cerebellar disturbances pro-

duced by lesions in the deep cerebellar nuclei appear as a constellation of closely related and interdependent disturbances, the neural mechanism responsible for cerebellar tremor seems distinct and different from that und,erlying ataxia and other asynergic disturbances.

2. The modification of cerebellar tremor in the monkey by localized thalamic lesions would seem to depend upon: (1 ) effective interruption of thalamo-cortical fiber projections from the ventrolateral nucleus (pars oralis), or (2) removal of potent intrathalamic influences which the centromedian nucleus may exert upon the activity of the ventrolateral nucleus.

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141 CEREBELLAR DYSgINESIA IN THE MONKEY

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PLATE 1

EXPLANATION OF FIGURES

1 Rhesus C-527. Photomicrograph of intercerebellar lesions destroying significant portions of the dentate and interposed nuclei bilaterally. Weil. x 5.

2 Rhesus C-550. Photomicrograph of cerebellar lesions destroying parts of all intracerebellar nuclei. Weil. x 5.

Rhesus C-527 and C-550. Photomicrographs demonstrating fiber degeneration in brachium conjunctivum resulting from cerebellar lesions shown in figures 1 and 2. Marchi. x 14, x 13.

5-6 Rhesus C-450 and C-449. Secondary stereotaxic lesions destroying fibers of the thalamic fasciculus in the region of the zona inccrta. Weil. x 7.5. Marchi. X 7.5.

3 4

CEREBELLAR DYSKINESIA IN THE MONKEY Malcolm B. Carpenter and George R. Hanna

PLATE 1

143

PLATE 2

EXPLANATION OF FIGURES

7 Rhesus C-489. Photomicrograph of a relatively small stereotaxic le-

8 Rhesus C-527. Photomicrograph of large irregular electrolytic lesion in the ventral anterior nucleus of the thalamus involving parts of the reticular nucleus and fibers in the internal capsule. This lesion transiently reduced contralateral cerebellar tremor. Marchi. x 8.

9 Rhesus C-526. Photomicrograph demonstrating two separate thalamic lesions: ( 1 ) a small lesion destroying part of the anterior medial nucleus, and (2) a large lesion destroying part of the ventrolateral nucleus (pars oralis). The lesion in the ventrolateral nucleus appeared limited to this nucleus and produced a marked reduction of contralateral cerebellar tremor. Weil. x 7 .

Rhesus C-507. Photomicrograph of a lesion in the ventrolateral nucleus (pars oralis) of the thalamus. Rostrally this lesion destroyed parts of the ventral anterior nucleus. Weil. X 6.

11 Rhesus C-508. Photomicrograph of lesion in ventrolateral nucleus (pars oralis) somewhat more medial than that seen in rhesus C-507. Weil. x 7 .

12 Rhesus C-595. Photomicrograph of a stereotaxic lesion which dc- stroyed parts of the centromedian, ventral posterior lateral and ventral posterior medial nuclei of the thalamus. This thalamic lesion

sion in the ventral anterior nucleus of the thalamus. Weil. X 6.5.

10

appeared to reduce cerebellar tremor bilaterally (see page 132). Weil. x 8.

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PLATE 2

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PLATE 3

EXPLANATION O F FIGURES

13-14 Rhebus C-528. Two photomicrographs of a thalamic lesion which involved all nuclei of the lateral group. Weil. X 5, X 8.

15 Rhesus C-525. The dorsal lesion destroyed parts of all thalamic nuclei in the lateral group, while the ventral lesion interrupted fibers of the thalamic fasciculus. Weil. x 6.

16 Rhesus C-552. This large thalamic lesion destroyed parts of all nuclei in the lateral group plus portions of the paracentral and centromedian nuclei. This lesion, produced by injection of Eto- palin, appeared to abolish cerebellar tremor bilaterally. Weil. x 6.

17-18 Rhesus C-559. Photomicrographs of thalamic lesions inflicted serially on the left and right sides. The left sided lesion was produced electrolytically, while the other lesion was produced by injection of Etopalin. Appreciable reduction of cerebellar tremor occurred contralateral to the lesion on the right side. Weil. x 6.

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PLATE 3

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effects of thalamic lesions upon cerebellar dyskinesia in the rhesus monkey

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