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Effects of caudate nuclei or frontal cortex ablations in cats: III. Recovery of limb placing reactions, including observations in hemispherectomized animals
EXPERIMENTAL NEUROLOGY53,289-303
(1976)
Effects of Caudate Nuclei or Frontal Cortex Ablations in Cats: III. Recovery of Limb Placing Reactions, Including Observations in Hemispherectomized Animals’ JAIME
R. VILLABLANCA,
ROBERT J. MARCUS, CHARLEZ AND DAVID L. AVERY
E. OLMSTEAD,
of Psychiatry and Mental RetardationResearch Center, University of California, Los Angeles, California 90024
Department
Received
February
9, 1976
This is a long-term study of the time course of impairments of the limb placing reactions in cats following bilateral removal of the frontal cortical areas (n = 9), bilateral (n = ll), or unilateral (n = lo), ablation of the caudate nuclei or removal of one cerebral hemisphere (n = 5). In addition the effects of n-amphetamine and of removal of the remaining frontal cortex on the placing reactions of the limbs contralateral to the hemispherectomy were assessed. The main results were: (i) a substantial recovery of the contact placing reactions was observed in frontal cats ; the recovery started very late (third or fourth month) and was considered as complete within 6 to 9 months in four cats. (ii) A variable degree of impairment of the contact placing reactions occurred in caudatectomized cats ; both the magnitude of the impairments and the length of the recovery period (up to 4 months) were proportional to the extent of the ablation. (iii) No recovery of the contact placing reactions was observed in limbs contralateral to the hemispherectomy eitEer spontaneously, under the action of n-amphetamine (producing a transient enhancement of proprioceptive components and a pseudocontact placing reaction), or following removal of the remaining frontal cortex. The meaning of the above findings in the context of pertinent literature, the mechanisms of compensation following frontal ablation, and the possible participation of the caudate in the physiological control of the contact placing reactions are discussed.
INTRODUCTION Since Bard’s observations (4, 5) it has been accepted that the tactile component of the limb placing reactions or contact placing reaction in cats is permanently lost following ablation of the frontal cortical areas. In con1 This research was supported by USPHS 04612. 289
co yligat 1976 by AcademicPress Inc. AlPri&tso 9 mpmductionin any ford reserved
Grants MH-07097,
HD-05958,
and HD-
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trast, recent reports indicate that some recovery of the contact placing reaction may occur not only following restricted frontal cortical ablations (1, 11-13) but also following more extensive forebrain lesions (6-8, 17). In the latter situation however, recovery seemsto occur only under special conditions involving an additional cortical ablation, i.e., removal of the remaining frontal lobe in hemispherectomized cats (6, f), or following the use of central nervous system stimulating drugs in hypothalamic (S) or neodecorticate (17) cats. Little is known regarding the effects of caudate lesions on placing reactions. However, the close anatomical and functional relationships of the frontal lobes with the nuclei (2.5, 26) as well as observations in caudate lesion studies (14, 15, 20)) suggest that this structure may play a role in controlling placing reactions. Our preliminary findings (22) further emphasized this possibility and the need for a thorough study. In the present experiments the following aspects of cats limb placing reactions were studied : (a) rate of recovery in chronic cats with frontal ablations ; (b) effects of bilateral or unilateral caudate removal ; (c) effect of ablation of the remaining frontal pole in cats with previous contralateral hemispherectomy ; and (d) effects of D-amphetamine on the contralateral placing reactions in cats with chronic hemispherectomy. METHODS The experiments were performed on 39 adult cats: nine with bilateral removal of frontal cortical areas, 11 with bilateral removal of the caudate, 10 with unilateral removal of the caudate, five with removal of a cerebral hemisphere, and four sham-operated cats, i.e., cats with midline cortical and callosal area lesions. Surgical Procedures. The surgical procedures and postoperative care were previously described (19, 21, 25). In all five hemispherectomized cats the ablation was on the left side ; following an interval of 2 to 6 months the right frontal cortex was ablated in four of them. The extent of the ablation was similar to that previously described (25) for cats with bilateral removal of frontal cortical areas. Testing Procedures. The aspects of the placing reactions studied, with an emphasison the contact components, were as follows: (i) Paw placing upon a surface following contact with an edge of the surface (vision exeluded). For the forepaws, the dorsal, lateral (cubital), and medial (radial) aspects were tested, For the rear paws, only the dorsal surface was systematically tested. (ii) Paw placing upon a surface following chin contact with the surface. (iii) Replacing of a limb following pushing the paw off an edge. (iv) Retrieval of a limb passively abducted. (v) Walking on a narrow plank. (vi) Frontal and lateral hopping of a forelimb accompany-
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ing passive body displacement. (viii) Proprioceptive and visual placing of the paws. A standard protocol for testing the placing reactions was developed based on Bard’s methods (4, 5). The reactions were first screened for normal presence or total absence. If present but abnormal, the contact placing reactions were evaluated either as “slow,” “occasional,” “lifting only,” or “hypermetric” and the magnitude of the stimulation needed was noted (light or coarse contact). In the chin test, the two paws were allowed to move freely and any asymmetries, e.g., one paw leading, were evaluated ; thereafter each paw was independently tested. The “speed,” “latency,” and “accuracy” of retrieval when passively abducting or pushing the legs off an edge were recorded. Plank walking was tested by using a 4 x 75-in. wooden plank. The food-deprived cat was placed on the plank, standing if possible, and walking and turning were induced by presenting food. Speed, steadiness,ability to turn around, frequency of paw’s slipping off of the edges and any right versus left asymmetries were observed. In testing the hopping reactions, the approximate degree of adduction or abduction of the limb needed to elicit a corrective postural movement as well as the separation of the corrective steps following the cat’s lateral or frontal displacements were evaluated. Proprioceptive placing was tested by progressively bending a limb forward over an edge ; the degree of bending in relation to a vertical axis needed for the foot to be placed upon the surface was estimated. Visual placing was tested (5) by carrying the cat obliquely forward and downward toward a broad surface. The two forelegs were first allowed to place to evaluate any asymmetry ; thereafter the test was repeated with one leg restrained. A “test confidence rating” and an overall subjective evaluation of the animal’s performance were the last two items of the protocol. Bilateral frontal cats were tested every 15 to 30 days. Other cats were tested often during the first postoperative month and every 15 to 30 days thereafter. Trials with n-amphetamine were not started earlier than 30 days following surgery in hemispherectomized cats; the test was repeated two to four times for each cat at intervals of more than ‘15 days. The drug was injected in doses of 1 to 10 mg/kg, ip, and testing began about 5 min after the injection and was repeated many tinies thereafter at variable intervals. Several testing sessionswere recorded on 8 and 16 mm film. Histological Procedures. The cats were killed with an overdose of barbiturate. The lesions were evaluated following procedures already described (25). RESULTS Szlrvival. As shown on Table 1, all bilateral frontal cats were kept for more than 4 months with three of them living for more than a year. All
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TABLE Days
for Partial Nine
AL.
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or Total Recovery of Contact Frontal Cats Ranked According
Placing Reactions to Their Survival Days
Cat number 112 122 128 115 129 97 126 113 132
to recovery
Survival
Total
530 488 405 306 181 167 137 126 121
222 199
(CPRs) Perioda of CPRs
Partial
402 284 181 l.i4 134 126 121
FIG.
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in the
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FIG. 1. Dorsal view of the brain of two cats to show the extent of the frontal ablation. In specimen B the removal was slightly asymmetric.
but one Ibilateral acaudate cat were maintained for more than 4.5 months. Six unilateral cats were kept for more than 6 months and the remaining four for about 3 months. The five hemispherectomized cats were maintained for 60, 84, 99, 184, and 223 days, respectively, and observed for more than 1 month following removal of the contralateral frontal pole. Anatomy. All brains were studied. The frontal ablation .was previously described and schematically illustrated (25). Photographs of two representative brains are shown in Fig. 1. Both anterior and posterior sigmoid gyri were ablated in all brains with variations of only 1 to 2 mm in the posterior extent of the removal from subject to subject or from side to side (Fig. 1B). The locus of the posterior limit of the ablation in relation to the sulcus ansatus varied from brain to brain becauseboth the shape and anterior-posterior placement of the sulcus are variable. The posterior limit of the ablation, however, had a constant stereotaxic position (A22)
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FIG. 2. Frontal section at approximately in hemispherectomized cat. Nissl stain.
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A6.5 (20) to show extent of the removal
and was kept, as much as possible,parallel to a coronal plane. Therefore, the removal did not always encompassthe whole posterior sigmoid gyrus as delimited by Woolsey et al, (28). Small remnants of the most ventral portion of the proreus gyri were found in three brains; they were partially disconnected from the brain by aspiration lesions. The amount of the individual caudate ablations was plotted on Fig. 3 for both bilateral (filled circles) and unilateral acaudate (half-filled circles) cats. The features of a caudate removals were also described previously (25). Clear, although small, capsular damage was found in four unilateral and in three bilateral acaudate cats (circles with horizontal bars in Fig. 3) ; such lesions were usually situated in the most rostroventral aspect of the caudate head where the nucleus becomes narrower and deeply “buried” in white matter. The hemisphere removals (Fig. 2) included the whole neocortex, the caudate-putamen complex, most of the limbic system and the corpus callosum. The only cortical areas consistently left connected to the diencephalon were the piriform cortex, the basal forebrain area, most of the anterior perforated substance and parts of the septum ; remnants of the ventral
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hypocampus were also found in three brains. Except for the dorsolateral aspects of the thalamus, the diencephalon was not directly injured by surgery. However, as expected, profuse (9, 10) cellular thalamic degeneration was found on microscopic examination. Placing Reactions Frontal Cats. All placing reactions were absent following surgery. All static and postural abnormalities, repeatedly reported by other authors accompanied this defect. The visual and proprioceptive (4, 5, 7, 11, 17), components were either absent, or markedly depressed, for 2 to 4 and 4 to 8 weeks, respectively. Recovery of the contact component began to appear very late. The course of recovery was approximately as follows. First to reappear-starting 3 to 4 months postoperative-was placing to coarse contact of the dorsal surface of the paws ; initially it was inaccurate or hypermetric (almost ataxic) , slow and irregular, but later it became brisk and delicate as in intact cats. Recovery of frontal hopping and chin placing followed a roughly parallel time course. Recovery of the lateral and medial surfaces of the paw- started later4 to 5 months postoperative-with the medial surface tending to recovery first. Plank walking, lateral hopping, and retrieval of legs pushed off edges were scored as normal only after substantial recovery of medial and lateral paw surfaces had occurred. In four animals the recovery was considered to be complete (Table 1) ; this occurred only after the fifth month. Two of the partially recovered cats, living for 6 months and more than a year, respectively, exhibited only slight defects. Three animals with partial recovery were not kept beyond 4 to 4.5 months. Among the persisting deficits were: (a) contact placing only to coarse contact of medial and lateral surfaces of the paw ; (b) minor impairments in plank walking (such as difficulties in turning around, feet slipping off an edge, etc.) ; and (c) imperfect lateral hopping (too much separation of the corrective steps, need for increased lateral displacement of the leg to trigger correction). In three cats with slightly asymmetrical dorsal cortical removal (Fig. lB), the side contralateral to the smallest removal tended to recover first. Acaudate Cats. These animals exhibited a variable degree of impairment of the pIacing reactions. Both initial deficits and course of recovery were directly correlated (see below) with the extent of caudate removal. Thus, the contact placing reactions were initially absent in all bilateral (bilaterally) and unilateral acaudate (in the contralateral limbs) cats sustaining an ablation larger than 70%. The visual and proprioceptive components were initially absent or markedly depressed. Lesser impairments were seen in, cats with smaller removals, including coarse or inaccurate placing on touching the paw edges, inaccurate retrieval of paws pushed off edges,
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I, 20
30
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/ 50
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, 70
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DAY5 T O RECOVERY OF CPRs
0 B,ldt,al
, 90
, 100
, 110
, 120
C Umlo’wcl
FIG. 3. Days for recovery of contact placing reactions (CPRs) in cats with bilateral (filled circles) or unilateral (half-filled circles) ablationof the caudatenucleiin relation to the amount of caudateremoval in each case (see Resultsfor correlation
coefficients).The horizontal bars in someof the circles indicate bilateral (a bar in each side) or unilateral (a bar in one side) slight capsular lesion. The f sign under three circles indicatesthat the cats were kilIed at or closeto thosedays.
clumsy plank walking, and the paw ipsilateral to a unilateral removal leading in visual or proprioceptive placing. In bilateral acaudate cats with extensive removals it was difficult to evaluate the time course of recovery because of the continuous paw treading previously described (24). It was clear, however, that all cats exhibited signs of improvement within the first month and that the sequenceof recovery was similar to that seen in bilateral frontal animals. Also, the time course of the recovery was highly correlated with the extent of the ablation. [Spearman rank correlation r, = 0.90 (P < 0.001) for bilateral acaudate cats and r, = 0.70 (P < 0.025) for unilateral acaudate cats.] In cats sustaining ablations smaller than 65% of the nucleus (or nuclei), complete recovery occurred within a range of 10 to 30 days whereas those with ablations over 80% the range for recovery was 38 to 120 days (Fig. 3). Additional damage to the rostra1 areas of the internal capsule (see Anatomy) did not affect the time course of recovery (Fig. 3). Sham-Operated Cats. Only minor defects were seen in the immediate postoperative period ; those completely disappeared within 10 days. Cats with Removal of One Hemisphere and Subsequent Contralateral Frontal Ablation. All placing reactions contralateral to the ablation were lost in these cats. The proprioceptive component exhibited some recovery
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only after 2 months but it was still a coarse reaction requiring a forelimb angle of over 45” (in relation to the vertical) to elicit a slow placing. Visual placing was only crudely recovered after 5 months, such that moving the animal toward an edge, with the paw ipsilateral to the removal being restrained, elicited only an inconsistent, slow, hypermetric placing of the contralateral paw. Consequently, plank walking was totally impaired in these cats; they could, at most, stay immobile on the plank crouching on the nonparetic limbs. The removal of the remaining frontal areas did not produce any immediate change in the status of the lost contact placing reactions. There was a slight progression in recovery of the proprioceptive reactions in the limbs contralateral to the hemispherectomy during the 30 to 40 days following the frontal ablation. However, no recovery of the contact placing reactions of that side was seen. Instead, just prior to killing the cats, the visual and proprioceptive aspects of the reactions were clearly better on the side contralateral to the frontal removal and an inconsistent reaction on coarse contact of the dorsal aspect of the paw of that same side was beginning to appear in two of them. Efects of D-Amphetamine in Hemispherectomized Cats. Doses of 1 to 3 mg/kg induced clear stereotyped behavior without exaggerated autonomic effects ( 16) but had no action whatsoever on contact placing reactions. Therefore, larger doses of 7 to 10 mg/kg were used in most experiments. There was a clear improvement of the proprioceptive component in the paw contralateral to the hemispherectomy since placing could now be obtained with limb displacements of 20” to 30”. If the dorsal surface of the affected paw was rapidly brought toward the testing edge (amounting to an almost “hitting contact”), an inconstant, ample forward movement of the leg occurred. This movement was ataxic and hypermetric, but usually resulted in placing of the limb. However, if the surface was narrow, i.e., 2.5 cm, the hypermetric movement would carry the paw to the other side of the surface without any correction to ultimately place the volar aspect of the paw (in contrast, the contralateral paw would accurately place). With less regularity the same reaction could be obtained from lateral aspects of the paw, i.e., following coarse contact, the paw was literally “thrown” straight forward thus failing to perform the corrective lateral movement needed for placing. A pendular, residual movement usually accompanied the hypermetric forward displacement. The changes just described started about 10 to 15 min after the injection, peaked between 20 and 40 min, and tended to rapidly decline thereafter. Other somatic reflexes (withdrawal, crossed extension, tendon jerk) and locomotion (i.e., circling toward the side of the hemispherectomy), were also extremely enhanced concomitant with the above changes in the placing reactions. The autonomic effects were intense 40 to 60 min after injection (panting,
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tachycardia, mydriasis, hyperthermia of 40 to 42 C, etc.) and thereafter became so alarming that Haloperidol had to be administered (2.5 to 3.5 hr after n-amphetamine injection) to block them. DISCUSSION Frontal Cortical Remoual. These experiments demonstrate that a substantial recovery of the contact placing reactions can occur in cats following removal of the frontal cortices. The first indications of recovery became apparent only 3 to 4 months following surgery, and the process was estimated to be complete (in four of nine cats) only after the fifth postoperative month. Bard (4) and Bard and Brooks (5) reported a permanent absence of such reactions following a similar ablation. However, most of their cats were maintained for a shorter period than the time found necessary for recovery of the contact placing reactions in our experiments. Therefore, this study is considered as an extension of Bard’s observations. Other differences from Bard’s experiments were that in most of their cats the extent of the cortical ablation was apparently larger, i.e., always removing all posterior sigmoid gyrus and often including the anterior end of the marginal gyrus and the rostra1 portion of the suprasylvian gyrus (which were not ablated in our cats). Furthermore, because of the more posterior limit of the ablations the cauclates might have also been damaged [see (23, 25) ; indeed, such damage was reported at least in one of Bard’s bilaterally ablated frontal cats (4) 1. The effects of more restricted frontal lesions on contact placing reactions of cats have been examined more recently. Adkins et al. ( 1) found that ablation of the anterior sigmoid gyrus eliminated the reactions for an unspecified period, whereas the reactions were retained following lesions of the posterior sigmoid gyrus. Glassman (11, 12), on the other hand, found that posterior sigmoid gyrus removal was followed by severe deficits of contact placing and posture. The impairments recovered “after weeks or months” and in some cases there was ultimate recovery of the reaction even to stimulation of the guard hairs ; however, the author felt that the responses did not appear to be as brisk or as reliable as the reactions in intact cats. We tend to share this impression. More recently, Glassman (13) reported a “large amount of recovery” of contact placing and hopping in young cats tested 4 months after discrete lesions of individual frontal cortical gyri. Combinations of the individual lesions, while producing a larger overall deficit, still showed substantial recovery with time. That study (13) supports the present results in that it demonstrates that despite the size of the frontal ablation, considerable, or even complete recovery of the contact placing reactions may occur given adequate postoperative survival.
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In summary, it seems that two crucial variables affect the recovery process : (i) the magnitude of the initial deficit (which appears to be related to the extent of the lesion, and (ii) the survival time. The nature of the process (or processes) involved in the recovery will be discussed after considering the results of our caudate lesion experiments. Caudate N&ei Lesions. Even though many caudate lesion experiments have been performed in cats [see (25) 1, little or no attention has been devoted to effects on the placing reactions ; the present study represents, therefore, the first systematic analysis of such effects. Liddell and Phillips (15) stated only that the “tactile” placing reactions were “deficient” on the side contralateral to an electrolytic lesion of the basal ganglia. Gybels et al. (14) found that the visual placing reaction was absent and that “tactile” placing was preserved, although “individual variations were present,” in cats with bilateral, small electrolytic caudate lesions. Indeed, it would have been interesting to have the “individual variations” reported because the description of the locomotor performance of those cats (14) strongly suggests contact placing reaction difficulties. Thompson reported (20) that his cats with over 50% removal of the caudate exhibited “weak or absent placing reflexes” with the severity and duration of the defects being proportional to the size of the lesion. Unfortunately, Thompson’s lesions were performed through the anterior part of the marginal gyrus suggesting that cortical damage could have contributed to the contact placing reactions deficits. In the present series, there was no dorsal cortical damage and the penetration injury to the midline cortex did not affect the placing reactions. Because the additional damage to capsular fibers in a few caudate-ablated cats did not change the time course of recovery or the amount of impairment (and hence, one can assume that any “diaschisis”-type effect would be even less influential), it seems that the deficits observed were indeed due to caudate removal. The positive correlation between the extent of the caudate ablation and both severity and duration of the deficits further support this conclusion. This finding suggests that the striatum may participate in the physiological mechanisms responsible for the contact placing reactions in cats. Such a role might be even more important in development since our preliminary results in kittens (3) indicated that the impairment of the contact placing reactions, as reflected by the delay in their maturation, was larger in acaudate than in frontal animals. Tentative Explanation of Recovery of Contact Placing Reactions following Frontal Ablations. At least two hypotheses can be invoked to explain the recovery of contact placing reactions in cats with extensive frontal cortical removals : The function is taken over either, (i) by the remaining neocortex or (ii) by the caudate. Support for either possibility is found in the literature quoted above. On the one hand, most data presented or
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quoted in this paper support the view of a functional takeover by the caudate. Indeed, as long as the nuclei are intact, the contact placing reactions appear to recover. On the other hand, removal of the caudates alone produces a severe impairment of the contact placing reactions in adult cats and a delay in the maturation together with long-lasting impairments of the reactions in developing kittens (3). Conversely, there are observations suggesting that the remaining neocortex, particularly the areas surrounding the removal, might be involved in the compensation : (a) in the frontal cats of the present study a slight asymmetry in the posterior extent of the removals resulted in a tendency for faster recovery in the side contralateral to the smaller ablation ; (b) Gl assman (11, 12) demonstrated additive effects on the contact placing reaction deficits of sequential, increasingly larger, frontal removals ; and (c) the larger caudal extension of Bard’s cortical ablations (see above) might partially explain the total failure of recovery in his cats [although results of Adkins et al. (1) would disagree with this viewpoint]. Thus, with facts supporting the two hypotheses (which are not mutually exclusive) the issue is still unresolved. Another clue concerning the role of cortical versus subcortical structures in placing reaction control comes from observations in neodecorticate cats. Bard reported (4, 5) no recovery of the contact placing reactions in neodecorticate cats following long survival periods ; however, the caudates were damaged in some of those animals. Conversely, Meyer et al. (17) reported spontaneous recovery of “at least a weak tactile response” in two neodecorticate cats. These were apparently their cats with the largest frontal cortical remnants [see pictures in (17)] and unfortunately, they made no clear statement regarding the integrity of the caudates. Thus, although additional light on caudate participation on placing reaction control comes from observations on hemispherectomized cats discussed in the next section, it is felt that more work in neodecorticate animals with undisputable integrity of the caudates is needed. Frontal Ablation and D-Amphetamine in Helvtispherecto~rtized Cats. The present as well as several previous studies (4-6, 21) failed to show any significant, spopztaneous recovery of the paw contact placing reactions following unilateral or bilateral hemispheric removal(s) in cats. Some investigators have attempted to demonstrate that the structures necessary for the reactions are present in these preparations, and in neodecorticate cats, but inoperative either (a) becauseof a “tonic inhibition” (6, 7) originating in other cortical areas or (b) due to the absenceof an adequate high state of “central excitation” (17). Bogen and Campbell (6, 7) have tested the first (a) of these hypotheses in hemispherectomized cats with a subsequent contralateral frontal pole removal, i.e., a preparation similar to that used in the present study. They reported a “dramatic” recovery of the contact
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placing reactions in the paw contralateral to the hemispherectomy. Our attempt to replicate this result met with failure ; we can not offer any clear explanation for this discrepancy except for the comments regarding testing methods at the end of this section. Glassman (13) did not observe any changes in the ipsilateral contact placing reactions following a frontal lesion inflicted long after a similar contralateral fronta ablation. In an attempt to verify the second (b) hypothesis, Meyer et al. (17) and Bogen et al. (8) have tested the contact placing reactions of neodecorticate cats and of acutely operated animals with ablation of both cerebral hemispheres and dorsal thalamus (hypothalamic cats) under the action of central nervous system stimulants. Meyer et al. (17) concluded that the neuronal circuitry needed for the contact placing reactions is still present in the brain of neodecorticate cats becausehigh dosesof D-amphetamine (10 mg/kg) induced them in such animals. However, in three of their subjects, frontal cortical areas were spared [see pictures in (17)] which, according to Bard’s results (4, 5)) can sustain contact placing reactions in absenceof the remaining neocortex. Furthermore, in two of the remaining three animals no recovery was seen under amphetamine. Thus, we feel that their conclusion (17) is not quite consistent with the results. Bogen et al. (8) reported transient recovery of paw contact placing in six of 12 cats following caffeine administration. Amphetamine, however, in doses similar to those used in the present experiments, failed to induce the reaction in four other hypothalamic cats. We were unable to elicit true contact placing reactions following D-amphetamine in the limbs contralateral to a hemispheral removal. Furthermore, no contact placing components were manifested in any of the other placing reactions tested. The drug, however, clearly potentiated the proprioceptive reaction and induced a response which was considered as a pseudo-contact placing (coarse, sudden contact, probably with a proprioceptive component, was needed to elicit an inaccurate, random placing) which could have resulted from the combined consequences of an extremely enhanced withdrawal response and the improved proprioceptive reaction. In the present study the use of a battery of tests to evaluate the placing reactions was extremeIy valuable for overall reliability and to screen pseudo-contact placing reactions. The plank walking test, in particular, was a most reliable, single indicator of the reactions’ state while representing, at the same time, a natural, spontaneous display of them. That a similar testing strategy was not used in the above studies, might be a factor contributing to the different results. Particularly, in the report of Bogen et al. (8)) the statement that “even in the best experiments, placing was not completely consistent,” leaves one with the question of whether they elicited true contact placing reactions or the pseudo-reactions described for our D-amphetamine-treated hemispherectomized animals.
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The present results and discussion contribute to the evolving concept that there is a complex interaction between cortical and subcortical mechanisms in the physiological control and postlesion recovery of the placing reactions. As a consequence, a sensory-motor response such as contact placing, which once was thought to be strictly localized and rigid, appears now as less center-dependent and more flexible (7, 13, 27). A further elucidation of the mechanisms involved in the functional compensations seen may help to provide a model (2) for understanding the long-term processes involved in the recovery of other injury-altered, high level, sensory-motor functions. REFERENCES 1. ADKINS, R. J., M. R. CEGNAR, and D. D. RAFUSE. 1971. Differential effects of lesions of the anterior and posterior sigmoid gyri in cats. Brain Res. 30: 411414.
2. AMASSIAN, V. E., H. WEINER, and M. ROSENBLUILI. 1972. Neural systems subserving the tactile placing reactions : A model for the study of higher level control of movement. Brai~z Res. 40: 171-178. 3. AVERY, D. L., J. R. VILLABLANCA, R. J. MARCUS, and CH. E. OLMSTEAD. 1975. Development of limb placing reactions in intact, frontal and caudate lesioned kittens. Fed. Proc. 34 : 445. 4. BARD, P. 1933. Studies on the cerebral cortex. Arclt. Newel. Psychiat. 30(l) : 40-74.
5. BARD, P., and C. M. BROOKS. 1932. Localized cortical control of some postural reactions in the cat and rat together with evidence that small cortical remnants may function normally. Proc. Assoc. Res. Nerv. Molt. Dis. 13: 107-1.56. 6. BOGEN, J. E., and B. CAMPBELL. 1962. Recovery of foreleg placing after ipsilateral frontal lobectomy in the hemicerebrectomized cat. Science 135: 309-310. 7. BOGEN, J. E. 1974. Hemispherectomy and the placing reactions in cats. In “Hemisphere Disconnection and Cerebral Function,” W. L. Smith and M. Kinsbourne [Eds.]. C. C Thomas, Springfield, Illinois. 8. BOGEN, J. E., M. SUZUKI, and B. CAMPBELL. 1975. Paw contact placing in the hypothalamic cat given caffeine. J. Neurobiol. 6: 125-127. 9. CARRERAS,M., A. LECHI, A. ZAMPOLLO, and G. JUVARRA. 1969. Residual neurons of the thalamic ventrobasal nuclei. A histological and electrophysiological study in the cat. ArcJt. Ital. Biol. 107: 570-603. 10. EMMERS, R., R. W. M. CHUN, and G. H. WANG. 1965. Behavior and reflexes of chronic thalamic cats. Arch. Itnl. Biol. 103: 178-193. 11. GLASSMAN, R. B. 1970. Cutaneous discrimination and motor control following somatosensory cortical ablations. Pkysiol. BeJzav. 5 : 1009-1019. 12. GLASSMAN, R. B. 1971. Discrimination of passively received kinesthetic stimuli following sensorimotor cortical ablations in cats. Physiol. Behav. 7: 239-243. 13. GLASSMAN, R. B. 1973. Similar effects of infant and adult sensorimotor cortical lesions on cats’ posture. Brain Res. 63: 103-110. 14. GYBELS, J., M. MEULDERS, M. CALLENS, and J. COLLE. 1967. Disturbances of visuomotor integration in cats with small lesions of the caudate nucleus. Arch. Itit. Physiol. Biochim. 75 : 283-302. 1.5. LIDDELL, E. G. T., and C. G. PHILLIPS. 1940. Experimental lesions in the basal ganglia of the cat. Brain 63: 264-274.
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16. MARCUS, R. J., and J. VILLABLANCA. 1974. Is the striatum needed for amphetamine-induced stereotyped behavior ? PYOC. West Pharmocol Sot. 17: 219-222. 17. MEYER, P. M., J. A. HOREL, and D. R. MEYER. 1963. Effects of d-amphetamine upon placing responses in neodecorticate cats. J. Camp. Physiol. Psychol. 56: 402-404. 18. SNIDER, R. S., and W. T. NIEMER. 1961. “A stereotaxic Atlas of the Cat Brain.” The University of Chicago Press, Chicago. 19. TEASDALL, R. D., J. VILLABLANCA, and J. MAGLADERY. 1965. Reflex responses to muscle stretch in cats with chronic suprasegmental lesions. Bull. I. Hopkim Hosp. 116 : 229-242. 20. THOMPSON, R. L. 1959. Effects of lesions in the caudate nuclei and dorsofrontal cortex on conditioned avoidance behavior in cats. J. Camp. Physiol. Psychol. 52: 650-659. 21. VILLABLANCA, J. R., and R. J. MARCUS. 1972. Sleep-wakefulness, EEG and behavioral studies of chronic cats without neocortex and striatum: The “diencephalic” cat Arch. Ital. Biol. 110: 348-382. 22. VILLABLANCA, J. R., and R. J. MARCUS. 1973. Effects of bilateral, simultaneous ablation of the caudate nuclei in cats. Fed. Proc. 23: 399. 23. VILLABLANCA, J. R., and R. J. MARCUS. 1975. Effects of caudate nuclei removal in cats. Comparison with effects of frontal cortex ablation, pp. 273-311. Zti “Brain Mechanisms in Mental Retardation.” N. A. Buchwald and M. A. B. Brazier [Eds.]. Academic Press, New York. 24. VILLABLANCA, J. R., and R. J. MARCUS. 1975. Recovery of limb placing reactions in cats with frontal or caudate nuclei ablations. Neurosci. A bstr. 1: 506. 25. VILLABLANCA, J. R., R. J. MARCUS, and CH. E. OLIGTEAD. 1976. Effects of caudate nuclei or frontal cortex ablations in cats. Neurology and gross behavior. Exp. Neurol. 52 : 389-419. 26. WEBSTER, K. E. 1965. The cortico-striatal projections in the cat. J. Amt. 99: 329-337. 27. WERTENBAKER, C., R. Ross, and V. E. AMASSIAN. 1973. Modification of contact placing by aversive conditioning. Brain Behav. Evol. 8: 304-320. 28. WOOLSEY, C. N. 1958. Organization of somatic sensory and motor areas of the cerebral cortex, pp. 63-82. In “Biological and Biochemical Basis of Behavior.” H. R. Harlow and C. N. Woolsey [Eds.]. University of Wisconsin Press, Madison.
(1976)
Effects of Caudate Nuclei or Frontal Cortex Ablations in Cats: III. Recovery of Limb Placing Reactions, Including Observations in Hemispherectomized Animals’ JAIME
R. VILLABLANCA,
ROBERT J. MARCUS, CHARLEZ AND DAVID L. AVERY
E. OLMSTEAD,
of Psychiatry and Mental RetardationResearch Center, University of California, Los Angeles, California 90024
Department
Received
February
9, 1976
This is a long-term study of the time course of impairments of the limb placing reactions in cats following bilateral removal of the frontal cortical areas (n = 9), bilateral (n = ll), or unilateral (n = lo), ablation of the caudate nuclei or removal of one cerebral hemisphere (n = 5). In addition the effects of n-amphetamine and of removal of the remaining frontal cortex on the placing reactions of the limbs contralateral to the hemispherectomy were assessed. The main results were: (i) a substantial recovery of the contact placing reactions was observed in frontal cats ; the recovery started very late (third or fourth month) and was considered as complete within 6 to 9 months in four cats. (ii) A variable degree of impairment of the contact placing reactions occurred in caudatectomized cats ; both the magnitude of the impairments and the length of the recovery period (up to 4 months) were proportional to the extent of the ablation. (iii) No recovery of the contact placing reactions was observed in limbs contralateral to the hemispherectomy eitEer spontaneously, under the action of n-amphetamine (producing a transient enhancement of proprioceptive components and a pseudocontact placing reaction), or following removal of the remaining frontal cortex. The meaning of the above findings in the context of pertinent literature, the mechanisms of compensation following frontal ablation, and the possible participation of the caudate in the physiological control of the contact placing reactions are discussed.
INTRODUCTION Since Bard’s observations (4, 5) it has been accepted that the tactile component of the limb placing reactions or contact placing reaction in cats is permanently lost following ablation of the frontal cortical areas. In con1 This research was supported by USPHS 04612. 289
co yligat 1976 by AcademicPress Inc. AlPri&tso 9 mpmductionin any ford reserved
Grants MH-07097,
HD-05958,
and HD-
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trast, recent reports indicate that some recovery of the contact placing reaction may occur not only following restricted frontal cortical ablations (1, 11-13) but also following more extensive forebrain lesions (6-8, 17). In the latter situation however, recovery seemsto occur only under special conditions involving an additional cortical ablation, i.e., removal of the remaining frontal lobe in hemispherectomized cats (6, f), or following the use of central nervous system stimulating drugs in hypothalamic (S) or neodecorticate (17) cats. Little is known regarding the effects of caudate lesions on placing reactions. However, the close anatomical and functional relationships of the frontal lobes with the nuclei (2.5, 26) as well as observations in caudate lesion studies (14, 15, 20)) suggest that this structure may play a role in controlling placing reactions. Our preliminary findings (22) further emphasized this possibility and the need for a thorough study. In the present experiments the following aspects of cats limb placing reactions were studied : (a) rate of recovery in chronic cats with frontal ablations ; (b) effects of bilateral or unilateral caudate removal ; (c) effect of ablation of the remaining frontal pole in cats with previous contralateral hemispherectomy ; and (d) effects of D-amphetamine on the contralateral placing reactions in cats with chronic hemispherectomy. METHODS The experiments were performed on 39 adult cats: nine with bilateral removal of frontal cortical areas, 11 with bilateral removal of the caudate, 10 with unilateral removal of the caudate, five with removal of a cerebral hemisphere, and four sham-operated cats, i.e., cats with midline cortical and callosal area lesions. Surgical Procedures. The surgical procedures and postoperative care were previously described (19, 21, 25). In all five hemispherectomized cats the ablation was on the left side ; following an interval of 2 to 6 months the right frontal cortex was ablated in four of them. The extent of the ablation was similar to that previously described (25) for cats with bilateral removal of frontal cortical areas. Testing Procedures. The aspects of the placing reactions studied, with an emphasison the contact components, were as follows: (i) Paw placing upon a surface following contact with an edge of the surface (vision exeluded). For the forepaws, the dorsal, lateral (cubital), and medial (radial) aspects were tested, For the rear paws, only the dorsal surface was systematically tested. (ii) Paw placing upon a surface following chin contact with the surface. (iii) Replacing of a limb following pushing the paw off an edge. (iv) Retrieval of a limb passively abducted. (v) Walking on a narrow plank. (vi) Frontal and lateral hopping of a forelimb accompany-
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ing passive body displacement. (viii) Proprioceptive and visual placing of the paws. A standard protocol for testing the placing reactions was developed based on Bard’s methods (4, 5). The reactions were first screened for normal presence or total absence. If present but abnormal, the contact placing reactions were evaluated either as “slow,” “occasional,” “lifting only,” or “hypermetric” and the magnitude of the stimulation needed was noted (light or coarse contact). In the chin test, the two paws were allowed to move freely and any asymmetries, e.g., one paw leading, were evaluated ; thereafter each paw was independently tested. The “speed,” “latency,” and “accuracy” of retrieval when passively abducting or pushing the legs off an edge were recorded. Plank walking was tested by using a 4 x 75-in. wooden plank. The food-deprived cat was placed on the plank, standing if possible, and walking and turning were induced by presenting food. Speed, steadiness,ability to turn around, frequency of paw’s slipping off of the edges and any right versus left asymmetries were observed. In testing the hopping reactions, the approximate degree of adduction or abduction of the limb needed to elicit a corrective postural movement as well as the separation of the corrective steps following the cat’s lateral or frontal displacements were evaluated. Proprioceptive placing was tested by progressively bending a limb forward over an edge ; the degree of bending in relation to a vertical axis needed for the foot to be placed upon the surface was estimated. Visual placing was tested (5) by carrying the cat obliquely forward and downward toward a broad surface. The two forelegs were first allowed to place to evaluate any asymmetry ; thereafter the test was repeated with one leg restrained. A “test confidence rating” and an overall subjective evaluation of the animal’s performance were the last two items of the protocol. Bilateral frontal cats were tested every 15 to 30 days. Other cats were tested often during the first postoperative month and every 15 to 30 days thereafter. Trials with n-amphetamine were not started earlier than 30 days following surgery in hemispherectomized cats; the test was repeated two to four times for each cat at intervals of more than ‘15 days. The drug was injected in doses of 1 to 10 mg/kg, ip, and testing began about 5 min after the injection and was repeated many tinies thereafter at variable intervals. Several testing sessionswere recorded on 8 and 16 mm film. Histological Procedures. The cats were killed with an overdose of barbiturate. The lesions were evaluated following procedures already described (25). RESULTS Szlrvival. As shown on Table 1, all bilateral frontal cats were kept for more than 4 months with three of them living for more than a year. All
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AL.
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or Total Recovery of Contact Frontal Cats Ranked According
Placing Reactions to Their Survival Days
Cat number 112 122 128 115 129 97 126 113 132
to recovery
Survival
Total
530 488 405 306 181 167 137 126 121
222 199
(CPRs) Perioda of CPRs
Partial
402 284 181 l.i4 134 126 121
FIG.
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in the
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FIG. 1. Dorsal view of the brain of two cats to show the extent of the frontal ablation. In specimen B the removal was slightly asymmetric.
but one Ibilateral acaudate cat were maintained for more than 4.5 months. Six unilateral cats were kept for more than 6 months and the remaining four for about 3 months. The five hemispherectomized cats were maintained for 60, 84, 99, 184, and 223 days, respectively, and observed for more than 1 month following removal of the contralateral frontal pole. Anatomy. All brains were studied. The frontal ablation .was previously described and schematically illustrated (25). Photographs of two representative brains are shown in Fig. 1. Both anterior and posterior sigmoid gyri were ablated in all brains with variations of only 1 to 2 mm in the posterior extent of the removal from subject to subject or from side to side (Fig. 1B). The locus of the posterior limit of the ablation in relation to the sulcus ansatus varied from brain to brain becauseboth the shape and anterior-posterior placement of the sulcus are variable. The posterior limit of the ablation, however, had a constant stereotaxic position (A22)
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FIG. 2. Frontal section at approximately in hemispherectomized cat. Nissl stain.
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A6.5 (20) to show extent of the removal
and was kept, as much as possible,parallel to a coronal plane. Therefore, the removal did not always encompassthe whole posterior sigmoid gyrus as delimited by Woolsey et al, (28). Small remnants of the most ventral portion of the proreus gyri were found in three brains; they were partially disconnected from the brain by aspiration lesions. The amount of the individual caudate ablations was plotted on Fig. 3 for both bilateral (filled circles) and unilateral acaudate (half-filled circles) cats. The features of a caudate removals were also described previously (25). Clear, although small, capsular damage was found in four unilateral and in three bilateral acaudate cats (circles with horizontal bars in Fig. 3) ; such lesions were usually situated in the most rostroventral aspect of the caudate head where the nucleus becomes narrower and deeply “buried” in white matter. The hemisphere removals (Fig. 2) included the whole neocortex, the caudate-putamen complex, most of the limbic system and the corpus callosum. The only cortical areas consistently left connected to the diencephalon were the piriform cortex, the basal forebrain area, most of the anterior perforated substance and parts of the septum ; remnants of the ventral
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hypocampus were also found in three brains. Except for the dorsolateral aspects of the thalamus, the diencephalon was not directly injured by surgery. However, as expected, profuse (9, 10) cellular thalamic degeneration was found on microscopic examination. Placing Reactions Frontal Cats. All placing reactions were absent following surgery. All static and postural abnormalities, repeatedly reported by other authors accompanied this defect. The visual and proprioceptive (4, 5, 7, 11, 17), components were either absent, or markedly depressed, for 2 to 4 and 4 to 8 weeks, respectively. Recovery of the contact component began to appear very late. The course of recovery was approximately as follows. First to reappear-starting 3 to 4 months postoperative-was placing to coarse contact of the dorsal surface of the paws ; initially it was inaccurate or hypermetric (almost ataxic) , slow and irregular, but later it became brisk and delicate as in intact cats. Recovery of frontal hopping and chin placing followed a roughly parallel time course. Recovery of the lateral and medial surfaces of the paw- started later4 to 5 months postoperative-with the medial surface tending to recovery first. Plank walking, lateral hopping, and retrieval of legs pushed off edges were scored as normal only after substantial recovery of medial and lateral paw surfaces had occurred. In four animals the recovery was considered to be complete (Table 1) ; this occurred only after the fifth month. Two of the partially recovered cats, living for 6 months and more than a year, respectively, exhibited only slight defects. Three animals with partial recovery were not kept beyond 4 to 4.5 months. Among the persisting deficits were: (a) contact placing only to coarse contact of medial and lateral surfaces of the paw ; (b) minor impairments in plank walking (such as difficulties in turning around, feet slipping off an edge, etc.) ; and (c) imperfect lateral hopping (too much separation of the corrective steps, need for increased lateral displacement of the leg to trigger correction). In three cats with slightly asymmetrical dorsal cortical removal (Fig. lB), the side contralateral to the smallest removal tended to recover first. Acaudate Cats. These animals exhibited a variable degree of impairment of the pIacing reactions. Both initial deficits and course of recovery were directly correlated (see below) with the extent of caudate removal. Thus, the contact placing reactions were initially absent in all bilateral (bilaterally) and unilateral acaudate (in the contralateral limbs) cats sustaining an ablation larger than 70%. The visual and proprioceptive components were initially absent or markedly depressed. Lesser impairments were seen in, cats with smaller removals, including coarse or inaccurate placing on touching the paw edges, inaccurate retrieval of paws pushed off edges,
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DAY5 T O RECOVERY OF CPRs
0 B,ldt,al
, 90
, 100
, 110
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C Umlo’wcl
FIG. 3. Days for recovery of contact placing reactions (CPRs) in cats with bilateral (filled circles) or unilateral (half-filled circles) ablationof the caudatenucleiin relation to the amount of caudateremoval in each case (see Resultsfor correlation
coefficients).The horizontal bars in someof the circles indicate bilateral (a bar in each side) or unilateral (a bar in one side) slight capsular lesion. The f sign under three circles indicatesthat the cats were kilIed at or closeto thosedays.
clumsy plank walking, and the paw ipsilateral to a unilateral removal leading in visual or proprioceptive placing. In bilateral acaudate cats with extensive removals it was difficult to evaluate the time course of recovery because of the continuous paw treading previously described (24). It was clear, however, that all cats exhibited signs of improvement within the first month and that the sequenceof recovery was similar to that seen in bilateral frontal animals. Also, the time course of the recovery was highly correlated with the extent of the ablation. [Spearman rank correlation r, = 0.90 (P < 0.001) for bilateral acaudate cats and r, = 0.70 (P < 0.025) for unilateral acaudate cats.] In cats sustaining ablations smaller than 65% of the nucleus (or nuclei), complete recovery occurred within a range of 10 to 30 days whereas those with ablations over 80% the range for recovery was 38 to 120 days (Fig. 3). Additional damage to the rostra1 areas of the internal capsule (see Anatomy) did not affect the time course of recovery (Fig. 3). Sham-Operated Cats. Only minor defects were seen in the immediate postoperative period ; those completely disappeared within 10 days. Cats with Removal of One Hemisphere and Subsequent Contralateral Frontal Ablation. All placing reactions contralateral to the ablation were lost in these cats. The proprioceptive component exhibited some recovery
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only after 2 months but it was still a coarse reaction requiring a forelimb angle of over 45” (in relation to the vertical) to elicit a slow placing. Visual placing was only crudely recovered after 5 months, such that moving the animal toward an edge, with the paw ipsilateral to the removal being restrained, elicited only an inconsistent, slow, hypermetric placing of the contralateral paw. Consequently, plank walking was totally impaired in these cats; they could, at most, stay immobile on the plank crouching on the nonparetic limbs. The removal of the remaining frontal areas did not produce any immediate change in the status of the lost contact placing reactions. There was a slight progression in recovery of the proprioceptive reactions in the limbs contralateral to the hemispherectomy during the 30 to 40 days following the frontal ablation. However, no recovery of the contact placing reactions of that side was seen. Instead, just prior to killing the cats, the visual and proprioceptive aspects of the reactions were clearly better on the side contralateral to the frontal removal and an inconsistent reaction on coarse contact of the dorsal aspect of the paw of that same side was beginning to appear in two of them. Efects of D-Amphetamine in Hemispherectomized Cats. Doses of 1 to 3 mg/kg induced clear stereotyped behavior without exaggerated autonomic effects ( 16) but had no action whatsoever on contact placing reactions. Therefore, larger doses of 7 to 10 mg/kg were used in most experiments. There was a clear improvement of the proprioceptive component in the paw contralateral to the hemispherectomy since placing could now be obtained with limb displacements of 20” to 30”. If the dorsal surface of the affected paw was rapidly brought toward the testing edge (amounting to an almost “hitting contact”), an inconstant, ample forward movement of the leg occurred. This movement was ataxic and hypermetric, but usually resulted in placing of the limb. However, if the surface was narrow, i.e., 2.5 cm, the hypermetric movement would carry the paw to the other side of the surface without any correction to ultimately place the volar aspect of the paw (in contrast, the contralateral paw would accurately place). With less regularity the same reaction could be obtained from lateral aspects of the paw, i.e., following coarse contact, the paw was literally “thrown” straight forward thus failing to perform the corrective lateral movement needed for placing. A pendular, residual movement usually accompanied the hypermetric forward displacement. The changes just described started about 10 to 15 min after the injection, peaked between 20 and 40 min, and tended to rapidly decline thereafter. Other somatic reflexes (withdrawal, crossed extension, tendon jerk) and locomotion (i.e., circling toward the side of the hemispherectomy), were also extremely enhanced concomitant with the above changes in the placing reactions. The autonomic effects were intense 40 to 60 min after injection (panting,
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tachycardia, mydriasis, hyperthermia of 40 to 42 C, etc.) and thereafter became so alarming that Haloperidol had to be administered (2.5 to 3.5 hr after n-amphetamine injection) to block them. DISCUSSION Frontal Cortical Remoual. These experiments demonstrate that a substantial recovery of the contact placing reactions can occur in cats following removal of the frontal cortices. The first indications of recovery became apparent only 3 to 4 months following surgery, and the process was estimated to be complete (in four of nine cats) only after the fifth postoperative month. Bard (4) and Bard and Brooks (5) reported a permanent absence of such reactions following a similar ablation. However, most of their cats were maintained for a shorter period than the time found necessary for recovery of the contact placing reactions in our experiments. Therefore, this study is considered as an extension of Bard’s observations. Other differences from Bard’s experiments were that in most of their cats the extent of the cortical ablation was apparently larger, i.e., always removing all posterior sigmoid gyrus and often including the anterior end of the marginal gyrus and the rostra1 portion of the suprasylvian gyrus (which were not ablated in our cats). Furthermore, because of the more posterior limit of the ablations the cauclates might have also been damaged [see (23, 25) ; indeed, such damage was reported at least in one of Bard’s bilaterally ablated frontal cats (4) 1. The effects of more restricted frontal lesions on contact placing reactions of cats have been examined more recently. Adkins et al. ( 1) found that ablation of the anterior sigmoid gyrus eliminated the reactions for an unspecified period, whereas the reactions were retained following lesions of the posterior sigmoid gyrus. Glassman (11, 12), on the other hand, found that posterior sigmoid gyrus removal was followed by severe deficits of contact placing and posture. The impairments recovered “after weeks or months” and in some cases there was ultimate recovery of the reaction even to stimulation of the guard hairs ; however, the author felt that the responses did not appear to be as brisk or as reliable as the reactions in intact cats. We tend to share this impression. More recently, Glassman (13) reported a “large amount of recovery” of contact placing and hopping in young cats tested 4 months after discrete lesions of individual frontal cortical gyri. Combinations of the individual lesions, while producing a larger overall deficit, still showed substantial recovery with time. That study (13) supports the present results in that it demonstrates that despite the size of the frontal ablation, considerable, or even complete recovery of the contact placing reactions may occur given adequate postoperative survival.
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In summary, it seems that two crucial variables affect the recovery process : (i) the magnitude of the initial deficit (which appears to be related to the extent of the lesion, and (ii) the survival time. The nature of the process (or processes) involved in the recovery will be discussed after considering the results of our caudate lesion experiments. Caudate N&ei Lesions. Even though many caudate lesion experiments have been performed in cats [see (25) 1, little or no attention has been devoted to effects on the placing reactions ; the present study represents, therefore, the first systematic analysis of such effects. Liddell and Phillips (15) stated only that the “tactile” placing reactions were “deficient” on the side contralateral to an electrolytic lesion of the basal ganglia. Gybels et al. (14) found that the visual placing reaction was absent and that “tactile” placing was preserved, although “individual variations were present,” in cats with bilateral, small electrolytic caudate lesions. Indeed, it would have been interesting to have the “individual variations” reported because the description of the locomotor performance of those cats (14) strongly suggests contact placing reaction difficulties. Thompson reported (20) that his cats with over 50% removal of the caudate exhibited “weak or absent placing reflexes” with the severity and duration of the defects being proportional to the size of the lesion. Unfortunately, Thompson’s lesions were performed through the anterior part of the marginal gyrus suggesting that cortical damage could have contributed to the contact placing reactions deficits. In the present series, there was no dorsal cortical damage and the penetration injury to the midline cortex did not affect the placing reactions. Because the additional damage to capsular fibers in a few caudate-ablated cats did not change the time course of recovery or the amount of impairment (and hence, one can assume that any “diaschisis”-type effect would be even less influential), it seems that the deficits observed were indeed due to caudate removal. The positive correlation between the extent of the caudate ablation and both severity and duration of the deficits further support this conclusion. This finding suggests that the striatum may participate in the physiological mechanisms responsible for the contact placing reactions in cats. Such a role might be even more important in development since our preliminary results in kittens (3) indicated that the impairment of the contact placing reactions, as reflected by the delay in their maturation, was larger in acaudate than in frontal animals. Tentative Explanation of Recovery of Contact Placing Reactions following Frontal Ablations. At least two hypotheses can be invoked to explain the recovery of contact placing reactions in cats with extensive frontal cortical removals : The function is taken over either, (i) by the remaining neocortex or (ii) by the caudate. Support for either possibility is found in the literature quoted above. On the one hand, most data presented or
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quoted in this paper support the view of a functional takeover by the caudate. Indeed, as long as the nuclei are intact, the contact placing reactions appear to recover. On the other hand, removal of the caudates alone produces a severe impairment of the contact placing reactions in adult cats and a delay in the maturation together with long-lasting impairments of the reactions in developing kittens (3). Conversely, there are observations suggesting that the remaining neocortex, particularly the areas surrounding the removal, might be involved in the compensation : (a) in the frontal cats of the present study a slight asymmetry in the posterior extent of the removals resulted in a tendency for faster recovery in the side contralateral to the smaller ablation ; (b) Gl assman (11, 12) demonstrated additive effects on the contact placing reaction deficits of sequential, increasingly larger, frontal removals ; and (c) the larger caudal extension of Bard’s cortical ablations (see above) might partially explain the total failure of recovery in his cats [although results of Adkins et al. (1) would disagree with this viewpoint]. Thus, with facts supporting the two hypotheses (which are not mutually exclusive) the issue is still unresolved. Another clue concerning the role of cortical versus subcortical structures in placing reaction control comes from observations in neodecorticate cats. Bard reported (4, 5) no recovery of the contact placing reactions in neodecorticate cats following long survival periods ; however, the caudates were damaged in some of those animals. Conversely, Meyer et al. (17) reported spontaneous recovery of “at least a weak tactile response” in two neodecorticate cats. These were apparently their cats with the largest frontal cortical remnants [see pictures in (17)] and unfortunately, they made no clear statement regarding the integrity of the caudates. Thus, although additional light on caudate participation on placing reaction control comes from observations on hemispherectomized cats discussed in the next section, it is felt that more work in neodecorticate animals with undisputable integrity of the caudates is needed. Frontal Ablation and D-Amphetamine in Helvtispherecto~rtized Cats. The present as well as several previous studies (4-6, 21) failed to show any significant, spopztaneous recovery of the paw contact placing reactions following unilateral or bilateral hemispheric removal(s) in cats. Some investigators have attempted to demonstrate that the structures necessary for the reactions are present in these preparations, and in neodecorticate cats, but inoperative either (a) becauseof a “tonic inhibition” (6, 7) originating in other cortical areas or (b) due to the absenceof an adequate high state of “central excitation” (17). Bogen and Campbell (6, 7) have tested the first (a) of these hypotheses in hemispherectomized cats with a subsequent contralateral frontal pole removal, i.e., a preparation similar to that used in the present study. They reported a “dramatic” recovery of the contact
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placing reactions in the paw contralateral to the hemispherectomy. Our attempt to replicate this result met with failure ; we can not offer any clear explanation for this discrepancy except for the comments regarding testing methods at the end of this section. Glassman (13) did not observe any changes in the ipsilateral contact placing reactions following a frontal lesion inflicted long after a similar contralateral fronta ablation. In an attempt to verify the second (b) hypothesis, Meyer et al. (17) and Bogen et al. (8) have tested the contact placing reactions of neodecorticate cats and of acutely operated animals with ablation of both cerebral hemispheres and dorsal thalamus (hypothalamic cats) under the action of central nervous system stimulants. Meyer et al. (17) concluded that the neuronal circuitry needed for the contact placing reactions is still present in the brain of neodecorticate cats becausehigh dosesof D-amphetamine (10 mg/kg) induced them in such animals. However, in three of their subjects, frontal cortical areas were spared [see pictures in (17)] which, according to Bard’s results (4, 5)) can sustain contact placing reactions in absenceof the remaining neocortex. Furthermore, in two of the remaining three animals no recovery was seen under amphetamine. Thus, we feel that their conclusion (17) is not quite consistent with the results. Bogen et al. (8) reported transient recovery of paw contact placing in six of 12 cats following caffeine administration. Amphetamine, however, in doses similar to those used in the present experiments, failed to induce the reaction in four other hypothalamic cats. We were unable to elicit true contact placing reactions following D-amphetamine in the limbs contralateral to a hemispheral removal. Furthermore, no contact placing components were manifested in any of the other placing reactions tested. The drug, however, clearly potentiated the proprioceptive reaction and induced a response which was considered as a pseudo-contact placing (coarse, sudden contact, probably with a proprioceptive component, was needed to elicit an inaccurate, random placing) which could have resulted from the combined consequences of an extremely enhanced withdrawal response and the improved proprioceptive reaction. In the present study the use of a battery of tests to evaluate the placing reactions was extremeIy valuable for overall reliability and to screen pseudo-contact placing reactions. The plank walking test, in particular, was a most reliable, single indicator of the reactions’ state while representing, at the same time, a natural, spontaneous display of them. That a similar testing strategy was not used in the above studies, might be a factor contributing to the different results. Particularly, in the report of Bogen et al. (8)) the statement that “even in the best experiments, placing was not completely consistent,” leaves one with the question of whether they elicited true contact placing reactions or the pseudo-reactions described for our D-amphetamine-treated hemispherectomized animals.
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The present results and discussion contribute to the evolving concept that there is a complex interaction between cortical and subcortical mechanisms in the physiological control and postlesion recovery of the placing reactions. As a consequence, a sensory-motor response such as contact placing, which once was thought to be strictly localized and rigid, appears now as less center-dependent and more flexible (7, 13, 27). A further elucidation of the mechanisms involved in the functional compensations seen may help to provide a model (2) for understanding the long-term processes involved in the recovery of other injury-altered, high level, sensory-motor functions. REFERENCES 1. ADKINS, R. J., M. R. CEGNAR, and D. D. RAFUSE. 1971. Differential effects of lesions of the anterior and posterior sigmoid gyri in cats. Brain Res. 30: 411414.
2. AMASSIAN, V. E., H. WEINER, and M. ROSENBLUILI. 1972. Neural systems subserving the tactile placing reactions : A model for the study of higher level control of movement. Brai~z Res. 40: 171-178. 3. AVERY, D. L., J. R. VILLABLANCA, R. J. MARCUS, and CH. E. OLMSTEAD. 1975. Development of limb placing reactions in intact, frontal and caudate lesioned kittens. Fed. Proc. 34 : 445. 4. BARD, P. 1933. Studies on the cerebral cortex. Arclt. Newel. Psychiat. 30(l) : 40-74.
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