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Discrimination of passively received kinesthetic stimuli following sensorimotor cortical ablations in cats
Physiology and Behavior, Vol. 7, pp. 239-243. Pergamon Press, 1971. Printed in Great Britain
Discrimination of Passively Received Kinesthetic Stimuli Following Sensorimotor Cortical Ablations in Cats ' R O B E R T B. G L A S S M A N ~
Center for Brain Research, University of Rochester, Rochester, N.Y., U.S.A. (Received 5 F e b r u a r y 1971) GLASSMAN, R.B. Discrimination of passively received kinesthetic stimuli following sensorimotor cortical ablations in cats. PHYSIOL. BEnAV. 7 (2) 239-243, 1971.--Four cats, restrained in a sling and blindfolded, were trained to discriminate between a passive movement of either forelimb in the anterior versus the posterior direction and were then subjected to a series of unilateral ablations of sensorimotor cortical areas. Measurements of discriminative performance taken following each ablation gave evidence of a contralateral deficit in kinesthesis following combined ablation of the posterior sigmoid gyrus and anterior ectosylvian gyrus. Added ablation of the anterior sigmoid gyrus was followed by a more severe deficit in the kinesthetic discriminative performance. Severe postural and motor deficits observed during neurological testing of these four cats and of four additional cats suggested a direct relation between the degree of kinesthetic and motor deficit.
Kinesthesis
Motor
Proprioception
Sensorimotor
Somatosensory
Somesthesis
testing the ability of cats to discriminate passive movements following ablations of the sigmoid gyrus. As in the earlier study [7], the cruciate sulcus was used as a landmark for the ablations. Although a better dividing line between sensory and motor cortex lies posterior to this point (see Discussion below) the entire sigmoid gyrus receives sensory projections. It appeared advisable to remove the entire PSG rather than look for behavioral effects of a smaller lesion. Four animals were studied extensively by recording their behavior in the passive movement discrimination situation following each of a series of unilateral ablations of sensorimotor cortex. Ablation of the PSG alone, carried out first in two of the animals on the basis of the above reasoning was followed by the usual postural deficits but by little reduction in score in the test of passive movement discrimination. Since the test of passive movement discrimination necessarily involved a certain amount of cutaneous stimulation, A E G ablation alone was carried out unilaterally in two animals. This operation led to the expected deficit in orienting to cutaneous stimuli [7] but again little deficit was observed in the kinesthetic discriminative test. Additional combined ablation of both PSG and AEG in all four animals was followed by a small deficit in this test. Since these findings made it clear that the measure of kinesthetic discrimination was less sensitive to these cortical ablations than were the measures of cutaneous discrimination and motor control used previously [7], the ablations were extended in three of these animals to include the anterior
ALTHOUGH it is known that ablations of the sensorimotor cortex [l 5] of the cat lead to degeneration of the corticospinal tract [5] and to deficits in posture and control of movement, for example in the placing and hopping reflexes [2], it is not known whether these behavioral deficits are associated with a loss in proprioception. The presence in sensorimotor cortex of cells activated by joint movement [3, 9, 10] suggests that there should be such a proprioceptive loss. A number of studies, reviewed previously [7], which demonstrated deficits in somatosensory performance following ablation of sensorimotor cortex used behavioral measures requiring performance of a task such as palpation, which involves motor control as well as cutaneous and proprioceptive sensory input. When the experimental task required discrimination of passively received cutaneous stimuli [7], deficits in discriminative performance were observed following ablation of the anterior ectosylvian gyrus (AEG), including the SII area [15], but not following total removal of the cat's posterior sigmoid gyrus (PSG) which contains the SI representation of trunk and limbs. The same PSG-ablated animals did, however, show pronounced contralateral deficits in tests of posture and motor control. Of particular interest following PSG ablation was a disability in the task of using the forelimb to retrieve a piece of meat from a small cup. The deficit in this food-retrieval task was greater when a cat was blindfolded than when vision was allowed, a finding which suggests that this area of the brain may indeed be important in proprioception. In the present study this question was pursued by
1Supported by Grants NBO3606 and 5TINBO5395 to R. W. Doty from the National Institute of Neurological Diseases and Blindness and Postdoctoral Fellowship 5F2MH34024 from the National Institute of Mental Health. zPresent Address: Department of Psychology, Lake Forest College, Lake Forest, Illinois 60045. 239
240
'. i I ASS M A N
sigmoid gyrus (ASG) and finally, in one of these three, to include the caudate nucleus. At the same time, in order to obtain more information about the m o t o r effects of A S G ablation, particularly in the food-retrieval test for comparison with the earlier results on the m o t o r effects of P S G ablation, four additional animals were prepared with A S G ablations.
METHOD
Animals Eight adult female cats were given limited daily access to food until their weight was gradually reduced to 1.4-1.9 kg over a period of several weeks. D u r i n g the deprivation period they were handled frequently and accustomed to taking pieces of beef spleen f r o m a forceps. F o u r of these animals were tested in the kinesthetic discrimination test while the remaining four received only neurological testing, described below. To facilitate b o t h neurological testing and training in the kinesthetic discrimination situation, all animals were habituated to wearing a binocular blindfold (similar to the m o n o c u l a r mask used by Myers [11]).
Surgical Procedure Up to four serial ablations were performed in the same animal, as indicated in Table 1 and illustrated in Fig. I. The m e t h o d of performing unilateral ablations and then using one side of the body as a control for the other insured that the behavioral results could not be due to any general effects of repeated surgery, handling, motivational changes, etc. Aseptic procedures were tollowed. Animals were anesthetized with sodium pentobarbital and were given 1 mg atropine sulfate subcutaneously. A stereotaxic instrument was used to hold the head. Using trephine and rongeurs, a sufficient area of skull was removed to visualize the entire gyrus to be ablated including the surrounding sulci. After opening the dura mater, the gyrus was ablated by aspiration, including those portions which lie in the depths of the sulci, Rather than risk missing part of the limb areas of SI or SI1, ablations of the PSG and A E G were deliberately extended generously in the direction of the coronal gyrus. The space left by the removed tissue was filled with saline soaked G e l f o a m and exposed adjacent areas were covered with Gelfoam before the incision was closed. The incised dura mater was brought
TABLE 1 MEAN NUMBEROF ERRORSIN 30 DAILY TRIALSBEFOREAND AFTER ABLATIONS Cat
IN47
AT4
AT7
IN41
LFL RFL (R > L)/total*
LFL RFL (L > R)/total*
LFL RFL (R > L)/total*
LFL RFL (R > L)/total*
Preop
LPSG
3.3 1.1 0/9
3.6 3.5 2/6
Preop
LPSG
RAEG
3.6 1.2 5/5
2.2 2.1 4/8
1.9 1.7 3/5
Preop
LAEG
LPSG
1.0 1.2 2/3
1.9 2.1 3/6
Preop
L A E G + LPSG
3.2 1.5 1/9
5.0]1 4.7H 5/10
LAEG 2.1 9.2 10/10+*
0.7 4.4 9/9?
1.4 6.1 10/10~
7 week rest
RPSG
RASG
4.2 1.4 8/9§
10.7 4.9 I0/10~
LASG 2.1 6.7 10/I0++
1.7 6.2 10/10~
9.8 2.8 10/10++
7week rest
9.6 1.5 10/10~
L Caud 1.9 6.9 10/10,+
1.8 9.1 10/10+,
LASG 6.1 10.6 9/9t
1.5 6.8 10/10++
Abbreviations: ASG, anterior sigmoid gyrus; PSG, posterior sigrnoid gyrus; AEG, anterior ectosylvian gyrus; L Caud, left caudate nucleus; LFL, left forelimb; RFL, right forelimb. *The statistic (R > L)/total or (L > R)/total refers to the number of days on which the error score of the affected leg was greater than that of the other leg, over the total number of days on which there were nonequal error scores. All of these scores are based on 10 days of testing except for the preoperative baseline testing of cats AT7 and AT4 (first column), based on 5 days. Days on which both legs had equal error scores are subtracted for purposes of reporting the (R > L)/total or (L > R)/total scores although the error scores for these days are included in the calculation of mean errors. ~-p ~- 0.002, one-tailed binomial test +*p~ 0.001, one-tailed binomial test §p ---~0.02, one-tailed binomial test IIOf fifteen postoperative testing sessions only the scores for the last 10 are included. In the first postoperative testing session 10 days after surgery, this animal responded randomly to stimulation on either forelimb. Within the next four sessions, spread over 9 days, the score on both forelimbs climbed to and remained steady at the same level as the average score for the final 10 sessions, shown in the table.
FIG. 1. Please see overleaf for caption.
(facing page 240)
FIG. 1. Diagram of intended extent of lesions and photographs of terminal condition of the brains of the 4 animals trained in the passive movement discrimination situation is overleaf. The brains of the 4 additional animals tested for motor effects of precruciate damage are shown on this page. Note that in the case of PSG ablation migration of overlying marginal gyrus tissue occurred postoperatively, making the ablation look smaller in the photographs. (The nick in the right ASG of one brain shown on this page, ,,~AT0, occurred during the postmortem manipulations.)
KINESTHESIS AND SENSORIMOTOR CORTEX back over the ablated area but was not sutured. The left caudate nucleus of one cat (AT'/) was approached frontally, and ablated by aspiration, during a separate operation, subsequent to the removals of the sigrnoid and anterior ectosylvian gyri.
Neurological Testing Neurological testing was carried out several times during the first week following each operation and on repeated occasions thereafter. Animals were tested for performance of contact and visual placing, hopping, maintenance of normal limb posture while at rest, and orientation to tactile stimuli [7]. In addition, two of the cats which were trained in the kinesthetic discrimination test were also trained to retrieve a piece of meat from a cylindrical cup with an opening of 4.5 cm dia. both with vision and while blindfolded. All four of the remaining animals were also trained and tested in this food retrieval task.
Apparatus Four animals were habituated to restraint in a sling which was constructed of canvas and suspended from an aluminum frame. During training the animal was held in the sling by means of laces across its back. The sling was set at a height such that the cat's legs hung free. An aluminum panel 10 cm high by 7.5 cm wide was suspended on either side of the cat's head. Learned responses consisted of pressing one or the other panel, by means of a head movement, through a distance of 1 cm, until the panel hit a stop. F o r correct responses, the animal was rewarded with a piece of raw beef spleen presented manually through a hole 2.5 cm dia. drilled near the bottom of the panel.
Learned Discrimination The animals were trained to press one panel when either forelimb was moved passively in the anterior direction and the other panel when the limb was moved in the posterior direction. In order to minimize cutaneous cues a strip of plastic foam was bound firmly around the forelimb just below the wrist. An elastic band, attached to the piece of plastic foam, ran anteriorly and was tied to the aluminum frame while another elastic band connected the strip of plastic foam to a point on the frame posterior to the limb. Stimuli were presented by the experimenter's pulling on either the anterior or posterior elastic band to move the limb through a distance of about 5 cm. The displacement of the limb was maintained until a response occurred. If, as often occurred during early training or postoperatively, the response latency was more than about one second, the limb was oscillated with repeated small movements around the displaced position. After a response occurred the limb was allowed to return to its normal position under the animal. Trials were initiated as soon as the cat was still and had recovered the neutral position of the head. Care was taken that trials were not associated systematically with any preparatory positions of the cat's head. The possibility of encountering a deficit in ability to perform the discriminative response following certain ablations (see below) as well as the impossibility of presenting kinesthetic cues devoid of any cutaneous component are two difficulties which were recognized beforehand. Although pilot experiments were run trying other methods, the present procedure appeared the most practical for testing kinesthetic sensation in cats. It was difficult to train the animals in this situation,
241 taking 18--46 daily sessions of 50 trials each with different individual cats until the performance reached a level of 80 per cent correct responses and remained consistently above this level, with the stimuli applied to the initially trained leg. It took another 6-18 days to train the animals with the stimuli applied to the other forelimb. In addition, since the cats failed to show improvement in scores during the early sessions, a number of techniques were introduced to encourage learning and maintained performance of the appropriate responses. Shocks, applied across two pieces of solder wire wrapped around the hindlimbs, were presented when errors occurred or when responses occurred in the absence of a conditioned stimulus (spontaneous responses). Animals were coached during the earliest stages of training by auditory and tactile cues leading the head to turn to the correct panel as the discriminative stimulus was presented to a limb. This technique was not used during the final, recorded preoperative baseline measurements or during the postoperative period. If 10 consecutive responses occurred toward the same panel the position habit was broken by giving larger pieces of meat for the correct nonpreferred response until two successive correct responses occurred on the nonpreferred panel. Sessions were run 5-7 days a week. After a cat was trained with the stimuli applied to each forelimb, preoperative baseline measurements of performance were taken for at least 5 days. During this preoperative interval and during the postoperative period 60 trials were presented in each daily session, 30 on each forelimb, by running alternate blocks of 10 trials with the stimuli applied first to one forelimb then the other. Trials were run according to a Gellermann sequence. If the preoperative performance was consistently better with the stimuli applied to one of the limbs, the first brain lesion was made contralateral to that limb. White noise (70 db measured by General Radio Co. Sound Level Meter Type 1551-A) was present continuously during training and testing to mask any possible weak auditory cues associated with the presentation of stimuli. Beginning 1-10 days after each operation, depending on the general condition of the animal, the cats were tested for 10 daily sessions except in certain instances, as noted below, when a greater number of postoperative daily sessions was run.
Histology The animals were perfused through the heart with saline followed by formol-saline while deeply anesthetized with sodium pentobarbital. After hardening for two weeks in formalin the brains were photographed and then blocked according to the standard coronal stereotaxic plane. The brains were then embedded in celloidin, and sectioned at 40 ~t. Weil and cresyl violet stained sections were prepared of every 10th section extending posteriorly from the level of the medial geniculate nucleus and anteriorly to the frontal end of the brain. RESULTS
Learned Kinesthetic Discrimination Three of the four cats showed a significant deficit in the discrimination of passive movements of the forelimb contralateral to combined ablation of the PSG and AEG. The fourth animal showed a significant deficit only after the A S G was also removed. In Table 1 is shown the order in which the ablations were carried out in individual cats and the average
242
number of errors made in each daily session of 30 trials on each limb, under the preoperative and each postoperative condition. No clear deficit in discrimination resulted from ablation of only the PSG or only the A E G on one side of the brain. In addition to error scores, Table 1 also indicates the proportion of days, under each condition, when the score for the forelimb contralateral to the effective ablation was poorer than the score for the other forelimb. The calculations of statistical significance are based on this comparison between limbs, rather than on pre- versus postoperative performance of a given limb, in order to preclude the possibility that a difference in score was due to deficient ability to perform the learned responses of turning the head and pressing the panel. Such a deficiency, which would be expected to affect the score on both forelimbs, was in fact observed and probably accounts at least in part for the increase in errors shown by the leg ipsilateral to the brain lesion in several instances (Table 1). In these cases, the animals were slower in turning toward the panel contralateral to the lesion and they appeared to have more difficulty in locating the panel. Although such a bilateral reduction in score makes it difficult to determine, from the score of the first 10 postoperative sessions, whether the ablation of the ASG did cause an increased deficit in cat AT4, subsequent testing of this animal helped to clarify this question. In a number of cases cats were tested for more than one series of I0 daily sessions under a given lesion condition; the average scores for these series are given in Table 1. Cat AT4, by the third series of 10 sessions following ASG ablation (last column on right of Table 1), finally recovered an error score on the right forelimb equal to that shown before this operation while the left forelimb error score was still elevated. This suggests that the ASG ablation did enhance the contralateral kinesthetic deficit in this animal. Similarly, examination of the error scores of cats AT7 and IN41 during the two series of 10 daily sessions following A S G ablation, and following additional damage to the caudate nucleus in one of these animals, suggests that both of these ablations were followed by decrements in the discrimination of passive movement by the contralateral limb.
Neurological Testing The postural and motor deficits which follow extensive ablation of the PSG or of the A E G have been reported previously [7]. Briefly, while A E G ablation is followed by a deficit in responding to cutaneous stimuli, PSG ablation is followed both by severe deficits in placing, hopping and other posturai adjustments similar to those which follow broader sensorimotor cortical ablations [2, 5] and also by a marked deficit in the ability to retrieve a piece of meat from a plastic cylindrical cup of 4.5 cm dia. [7]. Such animals scratch repeatedly on the outside of the cup with gross movements of the forelimb contralateral to the ablation. In contrast, the forelimb opposite intact cortex enters the opening and retrieves the meat reliably with a well-coordinated movement. Ablation of the ASG, added to the earlier ablations of PSG and A E G in three of the present animals (AT4, AT7, IN41) was followed by an increase in the severity of the deficits in posture and motor control contralateral to the lesion. Two of these animals (AT4, AT7), previously trained in t h e food retrieval situation, now missed the cup entirely whether blindfolded or not; typically the forelimb would make a weak movement insufficient to reach the cup and passing under the cup. Although recovery of postural and motor function has been observed during the weeks
(i LASS M A N
following these surgical ablations, these two animals remained severely deficient in performance on this test, making only stereotyped, crude reaching or swiping movements of the affected forelimb during up to 1 month (cat AT7) or 3.5 months (cat AT4) of postoperative testing. To check further on the motor effects of ASG ablation, four additional cats, not trained in the passive movement discrimination situation, were prepared surgically and then tested repeatedly for at least two months. In one of these animals, which had reached an asymptotic level of recovery following the second stage of a bilateral PSG ablation one year earlier, additional unilateral A S G ablation was followed by increased contralateral deficiencies in posture and in the food retrieval test similar to those described above. Of the three remaining animals, two sustained ablation of the ASG on one side and of the PSG on the other while one sustained unilateral ASG ablation alone. In all three cases the ASG ablation alone was followed by contralateral deficits in the food retrieval test and in the postural tests comparable in severity and duration to those described above which had been observed to follow combined ablation in stages of the ASG, PSG and AEG, e.g. during the early postoperative period the affected limb made only weak passes under the cup, failing to contact it.
Anatomical Results Because serial ablations were performed on individual animals, only the final anatomical condition of the brain is available for histological examination. Review of the photographs of the gross brain specimens (Fig. 1) and examination of the sections verified that each attempt to completely ablate the PSG or A E G was successful. Because the ASG is less accessible and less well demarcated by sulci it cannot be said to have been completely ablated. While the visible surface was removed there was always sparing of the tissue, in the depths of the cruciate sulcus, which lies under the PSG. Additional, variable amounts of damage were sustained by neighboring areas including coronal, suprasylvian, sylvian, and marginal gyri and gyrus proreus. The caudate nucleus of cat AT7 was successfully destroyed except for the ventromedial portion and the tip of the tail. Degeneration in the cerebral peduncle was observed in each brain ipsilateral to each cortical ablation. In all four cases of animals trained in the passive movement test the final combined ablation of the PSG and A E G or of the ASG, PSG and A E G is associated with virtually complete degeneration of the lateral portion of the ipsilateral ventrobasal complex, severe degeneration of the posterior group, and extensive loss of the medial portion of the ventrobasal complex, reflecting the damage to the coronal gyrus which occurred during ablation of the neighboring areas. Combined ablation of the ASG, PSG and A E G is associated in each of three animals with severe degeneration of the ventrolateral nucleus. In cat AT7, in which the left caudate nucleus was ablated in addition to the overlying sensorimotor cortical areas, there is additional nearly complete degeneration of the lateral posterior and central lateral nuclei. Ablation of the ASG alone is associated with degeneration in the ipsilateral ventrolateral nucleus in each case but not as much as in the brains which sustained more extensive cortical ablations. DISCUSSION
The results indicate that the PSG, A E G and ASG all participate in the discrimination of passive movement as
KINESTHESIS AND SENSORIMOTOR CORTEX
243
measured in the present manner. Although ASG ablation alone was not studied in the discrimination situation, the fact that such ablation added to the other ablations caused an increase in the kinesthetic deficit indicates that the ASG did participate in the discriminative performance. While the observed losses in discrimination of passive movements were significant, all animals did maintain fairly high scores with the deficient limb. Though additional ablation of the caudate nucleus in one animal was followed by poorer discriminative performance, some discrimination was still present. It is therefore interesting to note that differences in the scores of the forelimbs, indicating deficient kinesthesis in the limb contralateral to the ablation (Table 1), were usually associated with differences in response latency following application of the discriminative stimulus, i.e. it was necessary to maintain the displacement of the deficient forelimb for a longer time before a response occurred. Though not measured, these latency differences were large enough to be grossly observable, usually about a half-second or less for the good limb versus a few seconds for the deficient limb. Thus, it appears that the discrimination scores alone may be conservative estimates of what proportion of the animal's normal capacity for proprioceptive sensation was lost. The punishment contingency for errors, which had been introduced because of the difficulty in training the animals in this test, put a premium on correct responses; waiting longer to respond may have allowed the animal to make more effective use of its remaining capacity and have allowed it more opportunity to pick up possible cues from the non-deficient side of the body, such as those resulting from slight shifting of the body in the sling as the stimulus was applied. Electrophysiological studies of the cat's sensorimotor cortex have indicated that tissue which is mainly sensory (SI) is divided from that which is primarily motor (MI) by the postcruciate dimple [10, 12] or by a line drawn between the
postcruciate dimple and the cruciate sulcus [4, 16]. Taking together the results from the passive movement test and the neurological tests, it appears that the kinesthetic and motor deficits are directly related, i.e. those lesions which were followed by an increase in the kinesthetic deficit were also associated with more severe motor deficits. While it would be interesting to see if these two functions could be partially dissociated with properly selected cortical ablations it now appears that the present methods are not suited to make such a fine quantitative distinction. On the other hand, it is conceivable that no such topographic dissociation can be demonstrated behaviorally. Indeed, the possibility must be considered that a loss in kinesthesis may to some extent be secondary to the motor deficit; that is, normal proprioceptive discrimination may depend on the integrity of the motor outflow. The change in muscle tone which follows interruption of this outflow might result in a tonic feedback or loss of feedback which disrupts normal proprioception. Studies of efferent modulation of sensory information, demonstrated for cutaneous input (e.g. [8]), suggest another way in which interruption of motor outflow might disrupt sensory discrimination. While motor outflow may be necessary for proprioception, the reverse is not always true, as shown by the work of Taub and Berman [13] who found that fine motor control is possible following deafferentation of limbs in the monkey. It is well known that there is a close interrelationship and overlapping of sensory and motor areas of the brain [1, 12, 14, 15]. Gibson [6] has discussed the close interaction between sensation and motor control as organisms actively obtain information about the environment, e.g. by palpation. The observation that animals of the present experiment would occasionally forcefully resist the application of the passive movement stimulus also suggests that performance of this discrimination may have involved some active skeletal process.
REFERENCES 1. Asanuma, H., S. J. Stoney, Jr. and C. Abzug. Relationship between afferent input and motor outflow in cat motorsensory cortex. J. Neurophysiol. 31: 670-681, 1968. 2. Bard, P. Studies on the cerebral cortex I. Localized control of placing and hopping reactions in the cat and their normal management by small cortical remnants. Archs. Neurol. Psychiat. 30: 40--74, 1933. 3. Brooks, V. B., P. Rudomin and C. L. Slayman. Sensory activation of neurons in the cat's cerebral cortex. J. Neurophyaiol. 24: 286-301, 1961. 4. Brooks, V. B., P. Rudomin and C. L. Slayman. Peripheral receptive fields of neurons in the cat's cerebral cortex. J. NeurophyMol. 24: 302-325, 1961. 5. Chambers, W. W. and C-N. Liu. Cortico-spinal tract of the cat. An attempt to correlate the pattern of degeneration with deficits in reflex activity following neocortical lesions. J. comp. Neurol. 108: 23-55, 1957. 6. Gibson, J. J. The Senses Considered as Perceptual Systems. New York: Houghton Mifflin, 1966. 7. Glassman, R. B. Cutaneous discrimination and motor control following somatosensory cortical ablations. Physiol. Behav. 5: 1009-1019, 1970. 8. Kasprzak, H., M. D. Mann and D. N. Tapper. Pyramidal modulation of responses of spinal neurons to natural stimulation of cutaneous receptors. Brain Res. 24: 121-124, 1970. 9. Levitt, J. and M. Levitt. Sensory hind-limb representation in Sm I cortex of the cat. A unit analysis. Expl Neurol. 22: 259-275, 1968.
10. Mountcastle, V. B. Modality and topographic properties of single neurons of cat's somatic sensory cortex. J. Neurophysiol. 20: 408-434, 1957. 11. Myers, R. E. Corpus callosum and visual gnosis. In: Brain Mechanisms and Learning, edited by J. F. Delafresnaye. Oxford: Blackwell, 1961, pp. 481-505. 12. Sakata, H. and J. Miyamoto. Topographic relationship between the receptive fields of neurons in the motor cortex and the movements elicited by focal stimulation in freely moving cats. Jap. J. Physiol. lg: 489-507, 1968. 13. Taub, E. and A. J. Bcrman. Movement and learning in the absence of sensory feedback. In: The Neuropsychoiogy of Spatially Oriented Behavior, edited by S. J. Freedman. Homcwood, Illinois: Dorsey Press, 1968, pp. 173-192. 14. Towe, A. L. Neuronal population behavior in the somatosensory systems. In: The Skin Senses, edited by D. R. Kenshalo. Springfield, Illinois: Thomas, 1968, pp. 552-574. 15. Woolsey, C. N. Organization of somatic sensory and motor areas of the cerebral cortex. In: Biological and Biochemical Bases of Behavior, edited by H. F. Harlow and C. N. Woolsey. Madison: University of Wisconsin Press, 1958, pp. 63-81. 16. Woolsey, C. N. Some observations on brain fissuration in relation to cortical localization of function. In: Structure and Function of the Cerebral Cortex, edited by D. B. Tower and J. P. Sehad~. New York: Elsevier, 1960, pp. 64-68.
Discrimination of Passively Received Kinesthetic Stimuli Following Sensorimotor Cortical Ablations in Cats ' R O B E R T B. G L A S S M A N ~
Center for Brain Research, University of Rochester, Rochester, N.Y., U.S.A. (Received 5 F e b r u a r y 1971) GLASSMAN, R.B. Discrimination of passively received kinesthetic stimuli following sensorimotor cortical ablations in cats. PHYSIOL. BEnAV. 7 (2) 239-243, 1971.--Four cats, restrained in a sling and blindfolded, were trained to discriminate between a passive movement of either forelimb in the anterior versus the posterior direction and were then subjected to a series of unilateral ablations of sensorimotor cortical areas. Measurements of discriminative performance taken following each ablation gave evidence of a contralateral deficit in kinesthesis following combined ablation of the posterior sigmoid gyrus and anterior ectosylvian gyrus. Added ablation of the anterior sigmoid gyrus was followed by a more severe deficit in the kinesthetic discriminative performance. Severe postural and motor deficits observed during neurological testing of these four cats and of four additional cats suggested a direct relation between the degree of kinesthetic and motor deficit.
Kinesthesis
Motor
Proprioception
Sensorimotor
Somatosensory
Somesthesis
testing the ability of cats to discriminate passive movements following ablations of the sigmoid gyrus. As in the earlier study [7], the cruciate sulcus was used as a landmark for the ablations. Although a better dividing line between sensory and motor cortex lies posterior to this point (see Discussion below) the entire sigmoid gyrus receives sensory projections. It appeared advisable to remove the entire PSG rather than look for behavioral effects of a smaller lesion. Four animals were studied extensively by recording their behavior in the passive movement discrimination situation following each of a series of unilateral ablations of sensorimotor cortex. Ablation of the PSG alone, carried out first in two of the animals on the basis of the above reasoning was followed by the usual postural deficits but by little reduction in score in the test of passive movement discrimination. Since the test of passive movement discrimination necessarily involved a certain amount of cutaneous stimulation, A E G ablation alone was carried out unilaterally in two animals. This operation led to the expected deficit in orienting to cutaneous stimuli [7] but again little deficit was observed in the kinesthetic discriminative test. Additional combined ablation of both PSG and AEG in all four animals was followed by a small deficit in this test. Since these findings made it clear that the measure of kinesthetic discrimination was less sensitive to these cortical ablations than were the measures of cutaneous discrimination and motor control used previously [7], the ablations were extended in three of these animals to include the anterior
ALTHOUGH it is known that ablations of the sensorimotor cortex [l 5] of the cat lead to degeneration of the corticospinal tract [5] and to deficits in posture and control of movement, for example in the placing and hopping reflexes [2], it is not known whether these behavioral deficits are associated with a loss in proprioception. The presence in sensorimotor cortex of cells activated by joint movement [3, 9, 10] suggests that there should be such a proprioceptive loss. A number of studies, reviewed previously [7], which demonstrated deficits in somatosensory performance following ablation of sensorimotor cortex used behavioral measures requiring performance of a task such as palpation, which involves motor control as well as cutaneous and proprioceptive sensory input. When the experimental task required discrimination of passively received cutaneous stimuli [7], deficits in discriminative performance were observed following ablation of the anterior ectosylvian gyrus (AEG), including the SII area [15], but not following total removal of the cat's posterior sigmoid gyrus (PSG) which contains the SI representation of trunk and limbs. The same PSG-ablated animals did, however, show pronounced contralateral deficits in tests of posture and motor control. Of particular interest following PSG ablation was a disability in the task of using the forelimb to retrieve a piece of meat from a small cup. The deficit in this food-retrieval task was greater when a cat was blindfolded than when vision was allowed, a finding which suggests that this area of the brain may indeed be important in proprioception. In the present study this question was pursued by
1Supported by Grants NBO3606 and 5TINBO5395 to R. W. Doty from the National Institute of Neurological Diseases and Blindness and Postdoctoral Fellowship 5F2MH34024 from the National Institute of Mental Health. zPresent Address: Department of Psychology, Lake Forest College, Lake Forest, Illinois 60045. 239
240
'. i I ASS M A N
sigmoid gyrus (ASG) and finally, in one of these three, to include the caudate nucleus. At the same time, in order to obtain more information about the m o t o r effects of A S G ablation, particularly in the food-retrieval test for comparison with the earlier results on the m o t o r effects of P S G ablation, four additional animals were prepared with A S G ablations.
METHOD
Animals Eight adult female cats were given limited daily access to food until their weight was gradually reduced to 1.4-1.9 kg over a period of several weeks. D u r i n g the deprivation period they were handled frequently and accustomed to taking pieces of beef spleen f r o m a forceps. F o u r of these animals were tested in the kinesthetic discrimination test while the remaining four received only neurological testing, described below. To facilitate b o t h neurological testing and training in the kinesthetic discrimination situation, all animals were habituated to wearing a binocular blindfold (similar to the m o n o c u l a r mask used by Myers [11]).
Surgical Procedure Up to four serial ablations were performed in the same animal, as indicated in Table 1 and illustrated in Fig. I. The m e t h o d of performing unilateral ablations and then using one side of the body as a control for the other insured that the behavioral results could not be due to any general effects of repeated surgery, handling, motivational changes, etc. Aseptic procedures were tollowed. Animals were anesthetized with sodium pentobarbital and were given 1 mg atropine sulfate subcutaneously. A stereotaxic instrument was used to hold the head. Using trephine and rongeurs, a sufficient area of skull was removed to visualize the entire gyrus to be ablated including the surrounding sulci. After opening the dura mater, the gyrus was ablated by aspiration, including those portions which lie in the depths of the sulci, Rather than risk missing part of the limb areas of SI or SI1, ablations of the PSG and A E G were deliberately extended generously in the direction of the coronal gyrus. The space left by the removed tissue was filled with saline soaked G e l f o a m and exposed adjacent areas were covered with Gelfoam before the incision was closed. The incised dura mater was brought
TABLE 1 MEAN NUMBEROF ERRORSIN 30 DAILY TRIALSBEFOREAND AFTER ABLATIONS Cat
IN47
AT4
AT7
IN41
LFL RFL (R > L)/total*
LFL RFL (L > R)/total*
LFL RFL (R > L)/total*
LFL RFL (R > L)/total*
Preop
LPSG
3.3 1.1 0/9
3.6 3.5 2/6
Preop
LPSG
RAEG
3.6 1.2 5/5
2.2 2.1 4/8
1.9 1.7 3/5
Preop
LAEG
LPSG
1.0 1.2 2/3
1.9 2.1 3/6
Preop
L A E G + LPSG
3.2 1.5 1/9
5.0]1 4.7H 5/10
LAEG 2.1 9.2 10/10+*
0.7 4.4 9/9?
1.4 6.1 10/10~
7 week rest
RPSG
RASG
4.2 1.4 8/9§
10.7 4.9 I0/10~
LASG 2.1 6.7 10/I0++
1.7 6.2 10/10~
9.8 2.8 10/10++
7week rest
9.6 1.5 10/10~
L Caud 1.9 6.9 10/10,+
1.8 9.1 10/10+,
LASG 6.1 10.6 9/9t
1.5 6.8 10/10++
Abbreviations: ASG, anterior sigmoid gyrus; PSG, posterior sigrnoid gyrus; AEG, anterior ectosylvian gyrus; L Caud, left caudate nucleus; LFL, left forelimb; RFL, right forelimb. *The statistic (R > L)/total or (L > R)/total refers to the number of days on which the error score of the affected leg was greater than that of the other leg, over the total number of days on which there were nonequal error scores. All of these scores are based on 10 days of testing except for the preoperative baseline testing of cats AT7 and AT4 (first column), based on 5 days. Days on which both legs had equal error scores are subtracted for purposes of reporting the (R > L)/total or (L > R)/total scores although the error scores for these days are included in the calculation of mean errors. ~-p ~- 0.002, one-tailed binomial test +*p~ 0.001, one-tailed binomial test §p ---~0.02, one-tailed binomial test IIOf fifteen postoperative testing sessions only the scores for the last 10 are included. In the first postoperative testing session 10 days after surgery, this animal responded randomly to stimulation on either forelimb. Within the next four sessions, spread over 9 days, the score on both forelimbs climbed to and remained steady at the same level as the average score for the final 10 sessions, shown in the table.
FIG. 1. Please see overleaf for caption.
(facing page 240)
FIG. 1. Diagram of intended extent of lesions and photographs of terminal condition of the brains of the 4 animals trained in the passive movement discrimination situation is overleaf. The brains of the 4 additional animals tested for motor effects of precruciate damage are shown on this page. Note that in the case of PSG ablation migration of overlying marginal gyrus tissue occurred postoperatively, making the ablation look smaller in the photographs. (The nick in the right ASG of one brain shown on this page, ,,~AT0, occurred during the postmortem manipulations.)
KINESTHESIS AND SENSORIMOTOR CORTEX back over the ablated area but was not sutured. The left caudate nucleus of one cat (AT'/) was approached frontally, and ablated by aspiration, during a separate operation, subsequent to the removals of the sigrnoid and anterior ectosylvian gyri.
Neurological Testing Neurological testing was carried out several times during the first week following each operation and on repeated occasions thereafter. Animals were tested for performance of contact and visual placing, hopping, maintenance of normal limb posture while at rest, and orientation to tactile stimuli [7]. In addition, two of the cats which were trained in the kinesthetic discrimination test were also trained to retrieve a piece of meat from a cylindrical cup with an opening of 4.5 cm dia. both with vision and while blindfolded. All four of the remaining animals were also trained and tested in this food retrieval task.
Apparatus Four animals were habituated to restraint in a sling which was constructed of canvas and suspended from an aluminum frame. During training the animal was held in the sling by means of laces across its back. The sling was set at a height such that the cat's legs hung free. An aluminum panel 10 cm high by 7.5 cm wide was suspended on either side of the cat's head. Learned responses consisted of pressing one or the other panel, by means of a head movement, through a distance of 1 cm, until the panel hit a stop. F o r correct responses, the animal was rewarded with a piece of raw beef spleen presented manually through a hole 2.5 cm dia. drilled near the bottom of the panel.
Learned Discrimination The animals were trained to press one panel when either forelimb was moved passively in the anterior direction and the other panel when the limb was moved in the posterior direction. In order to minimize cutaneous cues a strip of plastic foam was bound firmly around the forelimb just below the wrist. An elastic band, attached to the piece of plastic foam, ran anteriorly and was tied to the aluminum frame while another elastic band connected the strip of plastic foam to a point on the frame posterior to the limb. Stimuli were presented by the experimenter's pulling on either the anterior or posterior elastic band to move the limb through a distance of about 5 cm. The displacement of the limb was maintained until a response occurred. If, as often occurred during early training or postoperatively, the response latency was more than about one second, the limb was oscillated with repeated small movements around the displaced position. After a response occurred the limb was allowed to return to its normal position under the animal. Trials were initiated as soon as the cat was still and had recovered the neutral position of the head. Care was taken that trials were not associated systematically with any preparatory positions of the cat's head. The possibility of encountering a deficit in ability to perform the discriminative response following certain ablations (see below) as well as the impossibility of presenting kinesthetic cues devoid of any cutaneous component are two difficulties which were recognized beforehand. Although pilot experiments were run trying other methods, the present procedure appeared the most practical for testing kinesthetic sensation in cats. It was difficult to train the animals in this situation,
241 taking 18--46 daily sessions of 50 trials each with different individual cats until the performance reached a level of 80 per cent correct responses and remained consistently above this level, with the stimuli applied to the initially trained leg. It took another 6-18 days to train the animals with the stimuli applied to the other forelimb. In addition, since the cats failed to show improvement in scores during the early sessions, a number of techniques were introduced to encourage learning and maintained performance of the appropriate responses. Shocks, applied across two pieces of solder wire wrapped around the hindlimbs, were presented when errors occurred or when responses occurred in the absence of a conditioned stimulus (spontaneous responses). Animals were coached during the earliest stages of training by auditory and tactile cues leading the head to turn to the correct panel as the discriminative stimulus was presented to a limb. This technique was not used during the final, recorded preoperative baseline measurements or during the postoperative period. If 10 consecutive responses occurred toward the same panel the position habit was broken by giving larger pieces of meat for the correct nonpreferred response until two successive correct responses occurred on the nonpreferred panel. Sessions were run 5-7 days a week. After a cat was trained with the stimuli applied to each forelimb, preoperative baseline measurements of performance were taken for at least 5 days. During this preoperative interval and during the postoperative period 60 trials were presented in each daily session, 30 on each forelimb, by running alternate blocks of 10 trials with the stimuli applied first to one forelimb then the other. Trials were run according to a Gellermann sequence. If the preoperative performance was consistently better with the stimuli applied to one of the limbs, the first brain lesion was made contralateral to that limb. White noise (70 db measured by General Radio Co. Sound Level Meter Type 1551-A) was present continuously during training and testing to mask any possible weak auditory cues associated with the presentation of stimuli. Beginning 1-10 days after each operation, depending on the general condition of the animal, the cats were tested for 10 daily sessions except in certain instances, as noted below, when a greater number of postoperative daily sessions was run.
Histology The animals were perfused through the heart with saline followed by formol-saline while deeply anesthetized with sodium pentobarbital. After hardening for two weeks in formalin the brains were photographed and then blocked according to the standard coronal stereotaxic plane. The brains were then embedded in celloidin, and sectioned at 40 ~t. Weil and cresyl violet stained sections were prepared of every 10th section extending posteriorly from the level of the medial geniculate nucleus and anteriorly to the frontal end of the brain. RESULTS
Learned Kinesthetic Discrimination Three of the four cats showed a significant deficit in the discrimination of passive movements of the forelimb contralateral to combined ablation of the PSG and AEG. The fourth animal showed a significant deficit only after the A S G was also removed. In Table 1 is shown the order in which the ablations were carried out in individual cats and the average
242
number of errors made in each daily session of 30 trials on each limb, under the preoperative and each postoperative condition. No clear deficit in discrimination resulted from ablation of only the PSG or only the A E G on one side of the brain. In addition to error scores, Table 1 also indicates the proportion of days, under each condition, when the score for the forelimb contralateral to the effective ablation was poorer than the score for the other forelimb. The calculations of statistical significance are based on this comparison between limbs, rather than on pre- versus postoperative performance of a given limb, in order to preclude the possibility that a difference in score was due to deficient ability to perform the learned responses of turning the head and pressing the panel. Such a deficiency, which would be expected to affect the score on both forelimbs, was in fact observed and probably accounts at least in part for the increase in errors shown by the leg ipsilateral to the brain lesion in several instances (Table 1). In these cases, the animals were slower in turning toward the panel contralateral to the lesion and they appeared to have more difficulty in locating the panel. Although such a bilateral reduction in score makes it difficult to determine, from the score of the first 10 postoperative sessions, whether the ablation of the ASG did cause an increased deficit in cat AT4, subsequent testing of this animal helped to clarify this question. In a number of cases cats were tested for more than one series of I0 daily sessions under a given lesion condition; the average scores for these series are given in Table 1. Cat AT4, by the third series of 10 sessions following ASG ablation (last column on right of Table 1), finally recovered an error score on the right forelimb equal to that shown before this operation while the left forelimb error score was still elevated. This suggests that the ASG ablation did enhance the contralateral kinesthetic deficit in this animal. Similarly, examination of the error scores of cats AT7 and IN41 during the two series of 10 daily sessions following A S G ablation, and following additional damage to the caudate nucleus in one of these animals, suggests that both of these ablations were followed by decrements in the discrimination of passive movement by the contralateral limb.
Neurological Testing The postural and motor deficits which follow extensive ablation of the PSG or of the A E G have been reported previously [7]. Briefly, while A E G ablation is followed by a deficit in responding to cutaneous stimuli, PSG ablation is followed both by severe deficits in placing, hopping and other posturai adjustments similar to those which follow broader sensorimotor cortical ablations [2, 5] and also by a marked deficit in the ability to retrieve a piece of meat from a plastic cylindrical cup of 4.5 cm dia. [7]. Such animals scratch repeatedly on the outside of the cup with gross movements of the forelimb contralateral to the ablation. In contrast, the forelimb opposite intact cortex enters the opening and retrieves the meat reliably with a well-coordinated movement. Ablation of the ASG, added to the earlier ablations of PSG and A E G in three of the present animals (AT4, AT7, IN41) was followed by an increase in the severity of the deficits in posture and motor control contralateral to the lesion. Two of these animals (AT4, AT7), previously trained in t h e food retrieval situation, now missed the cup entirely whether blindfolded or not; typically the forelimb would make a weak movement insufficient to reach the cup and passing under the cup. Although recovery of postural and motor function has been observed during the weeks
(i LASS M A N
following these surgical ablations, these two animals remained severely deficient in performance on this test, making only stereotyped, crude reaching or swiping movements of the affected forelimb during up to 1 month (cat AT7) or 3.5 months (cat AT4) of postoperative testing. To check further on the motor effects of ASG ablation, four additional cats, not trained in the passive movement discrimination situation, were prepared surgically and then tested repeatedly for at least two months. In one of these animals, which had reached an asymptotic level of recovery following the second stage of a bilateral PSG ablation one year earlier, additional unilateral A S G ablation was followed by increased contralateral deficiencies in posture and in the food retrieval test similar to those described above. Of the three remaining animals, two sustained ablation of the ASG on one side and of the PSG on the other while one sustained unilateral ASG ablation alone. In all three cases the ASG ablation alone was followed by contralateral deficits in the food retrieval test and in the postural tests comparable in severity and duration to those described above which had been observed to follow combined ablation in stages of the ASG, PSG and AEG, e.g. during the early postoperative period the affected limb made only weak passes under the cup, failing to contact it.
Anatomical Results Because serial ablations were performed on individual animals, only the final anatomical condition of the brain is available for histological examination. Review of the photographs of the gross brain specimens (Fig. 1) and examination of the sections verified that each attempt to completely ablate the PSG or A E G was successful. Because the ASG is less accessible and less well demarcated by sulci it cannot be said to have been completely ablated. While the visible surface was removed there was always sparing of the tissue, in the depths of the cruciate sulcus, which lies under the PSG. Additional, variable amounts of damage were sustained by neighboring areas including coronal, suprasylvian, sylvian, and marginal gyri and gyrus proreus. The caudate nucleus of cat AT7 was successfully destroyed except for the ventromedial portion and the tip of the tail. Degeneration in the cerebral peduncle was observed in each brain ipsilateral to each cortical ablation. In all four cases of animals trained in the passive movement test the final combined ablation of the PSG and A E G or of the ASG, PSG and A E G is associated with virtually complete degeneration of the lateral portion of the ipsilateral ventrobasal complex, severe degeneration of the posterior group, and extensive loss of the medial portion of the ventrobasal complex, reflecting the damage to the coronal gyrus which occurred during ablation of the neighboring areas. Combined ablation of the ASG, PSG and A E G is associated in each of three animals with severe degeneration of the ventrolateral nucleus. In cat AT7, in which the left caudate nucleus was ablated in addition to the overlying sensorimotor cortical areas, there is additional nearly complete degeneration of the lateral posterior and central lateral nuclei. Ablation of the ASG alone is associated with degeneration in the ipsilateral ventrolateral nucleus in each case but not as much as in the brains which sustained more extensive cortical ablations. DISCUSSION
The results indicate that the PSG, A E G and ASG all participate in the discrimination of passive movement as
KINESTHESIS AND SENSORIMOTOR CORTEX
243
measured in the present manner. Although ASG ablation alone was not studied in the discrimination situation, the fact that such ablation added to the other ablations caused an increase in the kinesthetic deficit indicates that the ASG did participate in the discriminative performance. While the observed losses in discrimination of passive movements were significant, all animals did maintain fairly high scores with the deficient limb. Though additional ablation of the caudate nucleus in one animal was followed by poorer discriminative performance, some discrimination was still present. It is therefore interesting to note that differences in the scores of the forelimbs, indicating deficient kinesthesis in the limb contralateral to the ablation (Table 1), were usually associated with differences in response latency following application of the discriminative stimulus, i.e. it was necessary to maintain the displacement of the deficient forelimb for a longer time before a response occurred. Though not measured, these latency differences were large enough to be grossly observable, usually about a half-second or less for the good limb versus a few seconds for the deficient limb. Thus, it appears that the discrimination scores alone may be conservative estimates of what proportion of the animal's normal capacity for proprioceptive sensation was lost. The punishment contingency for errors, which had been introduced because of the difficulty in training the animals in this test, put a premium on correct responses; waiting longer to respond may have allowed the animal to make more effective use of its remaining capacity and have allowed it more opportunity to pick up possible cues from the non-deficient side of the body, such as those resulting from slight shifting of the body in the sling as the stimulus was applied. Electrophysiological studies of the cat's sensorimotor cortex have indicated that tissue which is mainly sensory (SI) is divided from that which is primarily motor (MI) by the postcruciate dimple [10, 12] or by a line drawn between the
postcruciate dimple and the cruciate sulcus [4, 16]. Taking together the results from the passive movement test and the neurological tests, it appears that the kinesthetic and motor deficits are directly related, i.e. those lesions which were followed by an increase in the kinesthetic deficit were also associated with more severe motor deficits. While it would be interesting to see if these two functions could be partially dissociated with properly selected cortical ablations it now appears that the present methods are not suited to make such a fine quantitative distinction. On the other hand, it is conceivable that no such topographic dissociation can be demonstrated behaviorally. Indeed, the possibility must be considered that a loss in kinesthesis may to some extent be secondary to the motor deficit; that is, normal proprioceptive discrimination may depend on the integrity of the motor outflow. The change in muscle tone which follows interruption of this outflow might result in a tonic feedback or loss of feedback which disrupts normal proprioception. Studies of efferent modulation of sensory information, demonstrated for cutaneous input (e.g. [8]), suggest another way in which interruption of motor outflow might disrupt sensory discrimination. While motor outflow may be necessary for proprioception, the reverse is not always true, as shown by the work of Taub and Berman [13] who found that fine motor control is possible following deafferentation of limbs in the monkey. It is well known that there is a close interrelationship and overlapping of sensory and motor areas of the brain [1, 12, 14, 15]. Gibson [6] has discussed the close interaction between sensation and motor control as organisms actively obtain information about the environment, e.g. by palpation. The observation that animals of the present experiment would occasionally forcefully resist the application of the passive movement stimulus also suggests that performance of this discrimination may have involved some active skeletal process.
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