BEHAVIORAL BIOLOGY 17, 333-354 (1976), Abstract No. 5288

Recovery from Electroencephalographic Slowing and Reduced Evoked Potentials after Somatosensory Cortical Damage in Cats 1

ROBERT B. GLASSMAN and BARBARA L. MALAMUT

Department of Psychology, Lake Forest College, Lake Forest, Illinois 60045

In order to search for possible evidence of active compensation during recovery from brain damage, EEG and evoked potential recordings were taken from cats prepared with chronically implanted electrodes in sensorimotor cortex, suprasylvian gyms, and other cortical and deep areas, before and after various sensorimotor cortical lesions. The animals were tested concurrently on a battery of neurological tests. As in an earlier study limited to SI alone, lesions of SI or of SII, or larger ablations involving adjacent tissue, were followed by degenerative changes in potentials evoked by forelimb stimulation and then by partial recovery in some cases. Similarly, only degenerative changes were seen in responsiveness to brain stimulation, tested in some animals. Compensatory hyperresponsiveness was not seen. EEG results were consistent with the clinical literature in showing reduction in amplitudes, particularly of fast activity, sometimes accompanied by increased slow activity, greatest near the site of damage. Though SII might be thought of as partly redundant with SI, and therefore important in recovery, SII was not particularly responsive to damage to SI. Additional, suggestive changes following cortical damage were seen in some cases, e.g., 25-40 Hz spindles in orbital cortex, but these need further corroboration. Although more subtle measures might reveal additional positive f'mdings, outside the range of spontenaous variability in the EEG, future investigations should also consider whether EEG slowing plays an active role in recovery or whether it is epiphenomenal.

Although it is not k n o w n to what extent the phenomenon of recovery from brain damage might represent actual reorganization, as opposed to mere remission of temporary dysfunction due to "diaschisis" (yon Monakow, in Pribram, 1969; Luria, 1963), the knowledge that brains change adaptively during growth and learning provides an additional justification for searching for orderly functional rearrangements during recovery. The phenomena of 1Supported by a grant from the State of Illinois Department of Mental Health and Developmental Disabilities. We thank Joan Goodman for her histological work, Nada Trifunovich, Janet Owens, and Harriet Glassman for their help in preparing the figures. 333 Copyright © 1976 by Academic Press, Inc. All rights of reproduction in any form reserved.

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stimulus constancy or pattern recognition (Milner, 1974) and motor equivalence (Milner, 1970, pp. 67, 71) are additional evidence of some special adaptability of the brain. "Motor equivalence" refers to organisms' remarkable ability, often taken for granted, to perform the same action in a variety of ways. Lashley and others have been particularly interested in the rat's ability to negotiate a learned maze after cerebellectomy or after the maze was flooded, in either case requiring a new set of movements to perform the same learned act (Beach et aI., 1960, pp. 155-163, 238-240). But this ability applies more generally to motivated behaviors and raises the possibility that similar reorganization also can take place neurally, apart from obvious motor alterations. Such reorganization might be in the nature of "new strategies"-i.e., it might involve complex cognitive processes-or it might be a more automatic process of readjustment. (See also Eidelberg and Stein, 1974; Stein et al. 1974; Dawson, 1973; Bogen, 1975; Isaacson, 1975; and LeVere, 1975 for other theoretical discussions of recovery.) The experiments reported here were explorations for evidence of reorganization observable in gross evoked potentials or EEG activity. The sensorimotor cortex of the cat is an example of brain tissue known to participate in behavioral functions which partially recover following ablations. Damage to the posterior sigmoid gyms (PSG), containing the SI body representation, (Woolsey, 1958) is followed by deficits in placing and hopping reflexes and in palpating movements of the forelimb, which recover in large measure. Damage to the anterior ectosylvian gyms (AEG), containing SII (Woolsey, 1958; Haight, 1972) together with adjacent orbital, and anterior sylvian tissue, results in lesser postural deficits but also is followed by partly recoverable losses in cutaneous sensory measures (Glassman, 1970, 1972, and in preparation). In an earlier etectrophysiological study, damage to part of the PSG in four cats was followed by a depression in potentials evoked by peripheral somesthetic stimulation, recorded from tissue adjacent to the lesion, and in the responsiveness of this tissue to elicitation of evoked movements by direct electrical stimulation. Both kinds of responsiveness recovered concurrently with behavioral control of movement but no hyperresponsiveness was observed at any points (Glassman, 1971). These findings are most consistent with an "extreme specificity" view of brain function and with an explanation of recovery in terms of diaschisis. Hosko and Helm (1969) did observe enhancement of evoked potentials in thalamic ventral posterolateral nucleus during ischemic cortical depression. Other experimenters have reported evidence of compensation in single unit recordings (Wall and Egger, 1971) or in anatomical findings of sprouting (see articles in Eidelberg and Stein, 1974; Stein et al., 1974). In the present study both gross evoked potential and EEG recordings were taken from tissue adjacent to damaged sensorimotor tissue, and also

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from remote areas. Though damage to PSG had not been followed by local evidence of reorganization, anatomical and physiological evidence suggests that the more diffuse connections of AEG (Hand and Morrison, 1970; Jones and Powell, 1973) might make it a better place to search for such an effect (Glassman 1973a; 1974). Therefore, recordings were taken from the AEG and nearby areas before and after damage to PSG or AEG. Since the association areas of the brain are connected directly or indirectly to many other structures, it is conceivable that they are involved somehow in reorganization processes. Consequently, recordings were taken in all but one case from the suprasylvian gyrus (SSG) and in several cases from the anterior sigmoid gyrus (ASG) or orbital cortex (Korn et al., 1966; Buser and Bignall, 1967). For the 'same reason, in some animals electrodes were aimed for subcortical regions known to be connected directly or indirectly with sensorimotor cortex. The purpose of recording from a variety of areas in these preparations was to scan for possible large positive effects. Concurrent neurological tests were carried out in all cases. The behavioral effects of sensofimotor cortical lesions have been studied extensively in 48 cats (86 cases of lesion), not including those of the present experiment, with results as summarized above. In the present study, the rationale for making unusually small lesions in some cases was to observe their effects locally, within tissue that could be considered part of the same functional area. On the other hand, large lesions were sometimes made in an attempt to elicit clear electrical changes at remote points in the brain.

METHOD General Plan

Arrays of electrodes were implanted into 15 adult cats. Each animal was tested on a battery of neurological tests before each operation and on a regular schedule postoperatively. Electroencephalographic measurements were taken from all animals and evoked potentials were recorded from those animals that had electrodes in somatosensory cortex. Four of the animals were also tested for responsiveness to brain stimulation and four were trained and tested on a behavioral test of food retrieval using either forelimb. Figure 1 presents the information about placements of electrodes and brain lesions. Briefly, 14 of the 15 animals had electrodes implanted in SSG, nine had electrodes in AEG, six had electrodes in PSG and four had electrodes in ASG. Nine animals had electrodes implanted in various deep points. Lesions were made unilaterally in the AEG or PSG either electrolytically or by aspiration, after baseline recordings had been taken. In several cases, tissue surrounding the AEG was included in the ablation and three animals sustained a unilateral "frontal lobotomy." To increase chances of Finding positive effects, second and sometimes third lesions were often made in the same animals, as noted in

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Surgery Electrodes were made of 0.25 or 0.3 mm diam full-hard temper, stainless steel orthodontic wire. They were insulated with Epoxylite varnish and sharpened with a hobbyist's grinding wheel, leaving a conical exposed area at the tip, about 1 mm long. The electrodes were assembled into arrays before implantation. Spacing of electrodes in arrays in PSG or AEG was 2 X 2 mm. Surgery was done using aseptic precautions, while the cats were anesthetized with sodium pentobarbital (36 mg/kg, ip). Cortical arrays were placed by direct visualization, using a modified electrode carrier and deep arrays were placed stereotaxically, Poor success with localization of deep electrodes was

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encountered in this series of preparations, but some general comments will be made below about recordings from deep points. To achieve penetration and minimize permanent dimpling, electrodes were advanced an extra 3 to 4 mm and then withdrawn to the proper position. Cortical electrode tips were left 1-3 mm beneath the surface. After all electrodes were firmly placed and all openings in the skull sealed off with acrylic, the electrodes were wired to a 34 pin connector (Winchester SRE34SJ), prepared with color coded Tefloninsulated wires, tinned at the ends. Before surgery, the top ends of the electrodes had been prepared with beads of solder. Care was taken to use just enough heat to make the connection; brief contact of a fine-tipped soldering iron was sufficient. To reduce the danger of scalp infection, the large acrylic skull cap which sealed off the electrodes and connections was made as smooth as possible. In animals that were later to receive ablations by aspiration, an access route was left by leading the connector wires around the target area and leaving only a thin layer of acrylic over this area. Animals were allowed at least a month to recover from implantation before further operations were carried out. Electrolytic lesions were carried out with the unanesthetized animals, using 3 mA for 2 rain in most cases, against a rectal indifferent. To minimize possible aversive stimulation by the lesion current, onset was turned up gradually, taking about a second to reach the stated intensity. No emotional behavior indicating pain was observed during this procedure. Recordings were taken immediately before and after electrolytic lesions.

Neurological Testing The battery of neurological tests and method of scoring has been described in detail elsewhere (Glassman, 1973b; Glassman et al., 1975). The cats were first habituated to a blindfold, which was used during all tests but visual orientation. The tests were as follows: (1) contact placing, tested on the anterior surface of either forelimb with the other held in retroflexion; (2) lateral hopping, tested with a ruler beside the paw; (3) tactile orientationlocalization toward a piece of meat held in a large forceps; (4)auditory orientation to a tapping stimulus; and (5) visual pursuit of a piece of meat and visual distraction from a frontal fixation stimulus. All these tests were scored, on the basis of specifically defined criteria, on a scale from 0 - n o deficit to 3 - t o t a l loss on the indicated side or in the indicated direction. Results from these tests, and from the food retrieval test for fine control of forelimb movement, carried out with four cats that received electrolytic lesions in PSG, were graphed for each animal. In the food retrieval test, contact of a cup with the whiskers of a blindfolded cat signals the availability of food; the animal is scored for the number of successful reaches into the 3.7 cm diam. opening in 20 successive presentations (Glassman, 1970, 1971). Neurological tests were carried out before the lesion and then on a postoperative schedule, usually 2 days, 4 days, 1 week, 2 weeks, 1 month. The results replicated those reported

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in earlier studies of cortical lesions (Glassman, 1970, 1972, and in preparation), briefly summarized above in the Introduction, and will not be described in detail.

EEG and Evoked Potential Recording Electrical measurements were taken on the same scheduled days as the neurological tests, i.e., several times preoperatively and then postoperatively after 2 days, 4 days, 1 week, 2 weeks, and 1 month. Since general anesthesia was not necessary for electrolytic lesions, additional, earlier postlesion measurements were carried out in these cases. Additional, frequent measurements were taken to track electrical changes when the regularly scheduled tests showed evidence of these. For EEG and evoked potential recording the unanesthetized animal was restrained in a canvas sling with limbs suspended above the surface of the table. Recordings were differentially amplified, monopolar, against a stainless steel screw in the bone above the frontal sinus. The animal was grounded via a stainless steel wire, implanted during surgery between scalp and cranium, surrounding the electrode rig. EEG recordings were carried out using an 8 channel Beckman R411 Dynograph. Each animal's complement of 32 electrodes was divided into four groups of eight and this grouping was maintained for all EEG work on a given animal. Recordings were taken from each of these electrode groups for 12-60 sec in each session, while the animal was calm. If there was any doubt about the reliability of the tracings, additional sessions were carried out on the same day. To facilitate examination of the data from each electrode over sessions, the daily records for each cat were separated by electrode groups and collated. Evoked potentials were recorded on the above schedule, from all animals whose initial recordings showed responsiveness. This included all animals with arrays implanted in AEG or PSG. The method of evoked-potential measurement, described earlier (Glassman, 1971), involved delivery of isolated, constant current stimulation (pulses, 5 mA, 0.1 msec, every 1.5 sec, using Grass equipment) to the contralateral forelimb. The stimulation usually elicited a flexion of about 5 - 1 5 m m and appeared not to be painful. A Tektronix 502A oscilloscope was used. After preparation with electrode paste, one stimulating electrode (32 gauge stranded hookup wire, bared at the end for several millimeters and folded to make better contact) was taped to the paw pad while the other was taped to the shaved lateral surface of the elbow. Stimulating points this far apart were selected to ensure that minor variations in placement would have negligible effect and so that there would be no low impedance shunt across the skin surface. To ensure that the impedance of the stimulating circuit was not so high as to be beyond the capability of the constant current unit, this setting was routinely increased for one or two stimulations, while looking for an increase in the vigor of the elicited limb flexion. Photographs of three consecutive traces were recorded at each point

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with an oscilloscope camera and the developed pictures for each session with each cat were pasted up into maps according to the position of the electrodes. At the conclusion of testing, the animals were deeply anesthetized with an overdose of sodium pentobarbital and perfused through the heart with normal saline followed by 10% formalin. The brains were embedded in celloidin, then sectioned at 50 tam. Every fifth section was stained with cresyl violet. These sections were used to check electrode positions and also, together with photographs of the gross brain specimens, to make up the drawings of ablations, shown in Fig. 1.

RESULTS AND DISCUSSION

Evoked Potentials (EPs) From earlier work (Glassman, 1970, 1972, and in preparation) it is known that (a) complete extirpation of the PSG (body component of SI) is not followed by a cutaneous deficit but is followed by severe deficits in posture and control of movement, (b) extensive lesions of AEG (SII) and adjacent tissue are followed by clear cutaneous deficits and by lesser postural deficits than those which follow ablation of PSG, but (c) small lesions within SII are not followed by any deficits. One possible reason why small brain lesions are sometimes ineffective might be that there is an immediate compensation by adjacent tissue (Geschwind, 1974). If this is true, in the case of damage to a sensory system one might expect to see evidence of such compensation in the evoked potentials (EPs). In the case of SII, such a hypothesis is the more plausible because of the relative diffuseness of anatomical projections, as contrasted with those to SI (Hand and Morrison, 1970; Jones and Powell, 1973). Results obtained in this study do not support this hypothesis, i.e., either no compensation occurs or, if any compensation does occur to sustain cutaneous perception following small electrolytic lesions in SII, such compensation is not reflected in the gross EPs. No evidence was obtained of redistributed EPs in AEG following partial, electrolytic lesions of AEG (four cases) nor was redistribution of EPs seen in AEG following partial (three cases) or complete (four cases) ablation of PSG (SI). As in an earlier study of PSG only (Glassman, 1971), cortical ablation was followed by decreased EPs at the points of lesion and at nearby points. Partial recovery of these EPs was then seen at some points whether the damage was in AEG or when replications of the earlier study were conducted by looking at points near a lesion in PSG, but no points came to show greater responsiveness than before the lesion. Figure 2 shows a case in which slight recovery of EPs was observed following a small electrolytic lesion, which did not cause any deficits in the neurological tests. Eight prelesion mappings are shown in Fig. 2, in addition to the postlesion mappings, to give an idea of the good reliability of

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the technique, but also to show that there is a certain degree of variability of evoked potentials which occurs independently of deliberate manipulations. Figure 3 illustrates the evoked potential results from all eight animals which sustained electrolytic lesions within AEG (first four cases) or PSG (last four cases). For each animal, that line of electrodes was selected which contained the point showing the largest prelesion evoked potential. The evoked potential amplitudes for each point in that line are graphed to show the results of successive measurements before and after lesioning. For cases in which a behavioral deficit was observed, adjacent graphs show the neurological test results from each animal. Considering first the cases of SII lesion shown in Fig. 3, it is seen that the behavioral results are in accord with those past results described above. That is, the three cases of small lesion within SII (cats SU 16, SU 18, SP 8; refer also to Fig. 1), at the focus of maximal potential evoked from the forelimb, were followed by no cutaneous or other deficit on the forelimb or elsewhere, observable with these tests or in general handling. The one case of large electrolytic ablation of SII (SP 13) was followed by a severe deficit in cutaneous orientation-localization and also by deficits in the other neurological measures. There was behavioral recovery in this animal, however no recovery in the evoked potentials was seen at any points in this case. Thus, considering these four cases of lesion together, we may take the partial recovery of EPs sometimes seen as evidence that the tissue in the general region of a lesion does recuperate somewhat from some sort of temporary "shock" (Glassman, 1971, 1974). While we must question whether the partial return o f EPs has direct relevance to the observed behavioral recovery following ablations of AEG, their return suggests a general recuperation of tissue properties, some of which may be causally related to behavioral recovery. Even when the lesion is so large that EPs do not recover, other capacities of adjacent tissue may return. The four cases of electrolytic damage to SI shown in Fig. 3 corroborate those described earlier (Glassman, 1971) in showing concomitant recovery of evoked potentials and measures of motor competence, especially the food retrieval test. Here too, we cannot be sure that the EP recovery per se bears a causal relation to the behavioral recovery. However, in these cases, as in the SII recordings, we may take the EP recovery as evidence that a lesion is followed by a greater immediate physiological effect than is seen in the long term. Neither in cases of SII nor in cases o f SI damage was any evidence of compensatory hyper-responsiveness seen in the evoked potentials at any point within or near the damaged area. Although these data suggest that SI may Fig. 2. Evoked potential maps of SII taken on successive occasions from cat SU16 before and after an electrolytic lesion in SII. Points of lesion indicated by asterisks. See Fig. 1 for location of points. None of the neurological tests showed a behavioral deficit. Calibrations: 25 msec, 1.0 mV.

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show more EP recovery than SII, considering variations in lesion size, etc., no conclusions can be drawn in this regard. It is usually observed that when damage is done electrolytically, in the unanesthetized animal, allowing recording immediately afterwards, the reduction in EPs is less severe immediately after the lesion than on the following day (Fig. 2). This finding was also present in some of the data, and the figure, of the previous study (Glassman, 1971), but was not commented on then because of the small number of cases and small size of the effect. Van Sommers and Teitelbaum (1974), similarly, have observed that following electrolytic damage to the lateral hypothalamus, deficits in responsiveness to brain stimulation and regulation of food intake developed progressively over several hours. Although it is already known that there are differences in the anatomical, physiological, and behavioral properties of SI and SII, they do share lemniscal connections and are both topographically organized (Woolsey, 1958; Haight, 1972). The smaller SII might therefore plausibly be hypothesized to provide an example of redundancy in the brain, serving to "back up" SI. The question of division and sharing of function of SI and SII will be dealt with in a report describing the effects of ablations on cutaneous discriminative and motor behaviors (in preparation). Here, it is reported that damage to PSG did not lead reliably to an effect on EPs recorded from AEG. In some cases evoked potentials in AEG were depressed. A promising result occurred in two of the seven animals, when there was a transient enhancement of evoked potentials recorded from some AEG points during mappings taken 2 to 3 weeks after PSG ablation; in one of these cats there was a change at one of the points from 0.9 mV before lesion to 1.3 mV after, in the other cat from 1.3 to 1.9 mV. However, when more preoperative and postoperative sessions were run with subsequent animals to check reliability more closely, it was found that these transient changes were within the range of spontaneous variability, sometimes observed during several months of testing EPs in SI or in SII. In 10 of 14 cats, electrodes in the anterior SSG showed evoked potentials smaller, but equal in latency to those recorded from PSG and AEG (0.2 mV, 5 msec). These potentials responded degeneratively to damage nearby-as did EPs in PSG and AEG described above. Although poor localization was obtained with the deep electrodes in this series of cats, in five animals potentials of 0.1-0.4 mV were recorded from points in or near the ventrobasal complex. In two cases, potentials (0.1-0.2 mV) were recorded from the caudate nucleus. As in the sensory cortical areas, only degenerative changes were seen at these points. No other points showed EPs before or after brain damage. In four animals, responsiveness to electrical stimulation (0.1 msec negative pulses at 50/sec) was tested at each point on each test day after

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electrical recording measurements were finished. In agreement with the earlier study (Glassman, 1971) only degenerative changes in elicited movements were observed, which partially recovered with time. This procedure was discontinued with later animals because of the early negative results and to avoid possible cumulative extraneous effects on the EP and EEG measures (Racine, 1975). EEG

The most consistent finding was a reduction in amplitude, particularly of faster activity, recorded from points at which electrolytic lesions had been produced. This was sometimes accompanied by an increase in the amplitude of slower activity. Points adjacent to the lesion were affected consistently, but to a lesser degree, and recovered more quickly. This effect was observed in all 10 cases (eight animals) of cortical electrolytic lesion in PSG (four cases), AEG (four cases), and SSG (two cases). In these preparations, at least one unlesioned electrode point had deliberately been left within 2 mm of the lesion. The reduction in amplitude and slowing was also observed at the points of lesion in all three cases in which subcortical electrolytic lesions were made. In two animals, recordings were taken from areas surrounding AEG before and after aspiration of this gyms. Reduction in fast activity was seen at these points (coronal, anterior sylvian, and orbital gyri) following the lesion. Admittedly, slight mechanical disturbance during the ablation, of the tissue in which the electrodes were already embedded, could have contributed to the effect in these cases. In this regard, in four animals, some electrodes had shown less fast activity during the days following initial implantation of electrodes than did the stabilized, pre-lesion baseline recordings a month later, but this effect was less pronounced than those shown in Figs. 4-6. Various amounts of recovery in EEG activity, typified by the results shown in Fig. 4, occurred in different cases, reaching an asymptotic level in 1 to 2 months. As discussed above, although lesions as small as that shown in Fig. 4 greatly reduced the potentials evoked by stimulation of the forelimb, in addition to changing the EEG record, no behavioral deficits were observed. (It should be mentioned that the cutaneous orientation-localization test is as sensitive as a test of learned discrimination of passively-received cutaneous stimuli; Glassman et al., 1975, p. 483). One might postulate on the basis of such results that some sort of immediate compensation takes place when only a part of a functional region is destroyed-so that behavioral deficits that would appear with a larger lesion are not seen (Geschwind, 1974). Indeed, while the time course of partial EEG recovery appears comparable to that of EP recovery described above, nearing stability about 1 to 2 months after damage, the fact that slower EEG is seen immediately after damage may have relevance to a possible immediate compensatory process. Of course, there are at least two logical alternatives to compensation as an explanation of no

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Fig. 4. Local reduction in fast activity and partial recovery following an electrolyric lesion in cat SP8. Calibrations: 1 see, 0.1 mV. No behavioral deficits were observed in this case. observed deficit; ( 1 ) t h a t a more sensitive behavioral test might be devised to show a deficit even after very small lesions, and (2) that the remainder o f the system is sufficient to support the particular behavior without an active compensation process (LeVere, 1975). The plausibility of the latter suggestion may be seen more easily if we consider an analogy, e.g., o f a board supported

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at many points by blocks; if only a few supports are removed there is virtually no change in the position of the board nor in a weight that may be on top of it. As an additional analogy, consider that many conceivable measures of vision in humans-e.g., reading speed or comprehension-would certainly not show a deficit of 50% if one eye were closed. Although postlesion EP recordings were sought primarily at loci which had shown some EP activity during baseline measurements, in order to scan for possible suggestive changes, EEG activity was recorded from all points in all animals in each session before and after damage. Reduction in fast activity, sometimes together with increase in slow activity, was observed also at points remote from a lesion, though less consistently than adjacent to a lesion. Altogether this was seen in 14 cases out of a total of 31 cases of lesion. Little overall pattern was seen regarding this effect. For example, of the 14 cats having electrodes in SSG, eight showed this effect at some SSG points after one or more instances of brain damage, usually clearer ipsilateral to the damage. Figure 5a shows the effect of a large lesion of the AEG and adjacent tissue on ipsilateral SSG points various distances from the lesion, and on contralateral SSG points. Some recovery of behavioral function occurred with this large lesion in placing and hopping reflexes (Fig. 5b) and the time course of this recovery was comparable to the time course of recovery from EEG slowing, seen in the figure. Severe, permanent deficits (tested to 4 months) in scored orienting and localization responses to contralateral tactile and auditory stimuli remained with this animal, as those reported elsewhere having comparable ablations (Glassman, 1972, and in preparation). Possible compensatory relations between areas known to share connections are of special interest; however following seven cases of PSG damage sufficient to cause contralateral deficits in placing and hopping reflexes, rated 1 to 3 in different cases, recordings from AEG were clearly affected-degeneratively-in only two cases. Thus, the EEG records gave no more evidence of compensation by SII for damage to SI than did the EP measurements. Other alterations were seen which were not persistent over sessions or large enough to be considered outside the range of normal variation of the EEG. However, some clearer cases are worth mentioning briefly. Both animals having electrodes in orbital gyms showed recurring spindles of 25-40Hz following each ablation, appearing at the first postoperative recording and lasting for up to a week. One of these animals had shown smaller spindles in some sessions before a lesion was made. These findings will be followed up in future experiments. In one of these same animals, each of the two instances of brain damage was followed by increase in the amplitude of 20 Hz activity in SSG, seen up to 3 postoperative days. In two of three cases of AEG aspiration in animals with electrodes implanted in ASG, there appeared in each record sporadic, large, pointed slow waves (1-1.5 Hz) lasting for about a

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Fig. 5(b). Neurological test results obtained concurrently with the EEG results shown in 5(a). The deficits occurring on the right at 2 weeks are due to the second lesion. month in ASG. For the time being, these changes are considered merely suggestive. All electrolytic lesions of eight or more points and all aspiration lesions (Fig. 1) were followed by mild to severe deficits (1-3 ratings) in one or more neurological tests, consistent with previous findings. In this context, the EEG changes sometimes seemed surprisingly small. In five o f 15 cases of damage by aspiration, no clear EEG effects were seen, though four of these five cases were followed by neurological deficits. All five of these cases consisted of aspirations o f single gyri (PSG, AEG, or anterior marginal gyrus). Larger ablations were more reliably followed by changes in the EEG recordings. Similar variations in EEG response to brain damage are characteristic of clinical observations. F o r example, in their concluding chapter, Kiloh, McComas, and Osselton (1972, p. 222) state: The electrical potentials recorded in the form of an EEG are an expression of as yet ill-understood dynamic cerebral processes, some physiological and others pathological. Although clearly these discharges are dependent upon neural activity, they do not necessarily indicate the integrity or otherwise of

Fig. 5(a). Slowing at points in ipsilateral suprasylvian gyms and partial recovery, following aspiration of anterior ectosylvian, anterior sylvian, orbital and coronal gyri in cat SP4. In this figure, records from points 23, 24, 25, and 26 are simultaneous with each other but not with points 27, 28, 29, and 30. The second lesion (indicated in Fig. 1, but not in this figure) was made in this animal only 11 days after the first, accounting for the slowing seen in the bottom four traces of the last two records. Calibrations: 1 sec, 0.1 mV.

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the cerebral structure. This is well exemplified by those frequent cases with indisputable clinical evidence of cerebral destruction-and yet the EEG findings are within normal limits. In the case of head injuries, Williams' paradox-that a normal EEG indicates a poor prognosis-stresses the fact that total loss of neurones may have little or no effect upon the EEG patterns as recorded by our present techniques. Also reminiscent of the clinical literature (Gibbs and Gibbs, 1964; Kiloh et al., 1972) is the fact that the largest changes accompanied conditions defined as "illness," which were apparently due to infection, swelling, or other secondary effects. In seven out of 18 cases o f damage by aspiration or l o b o t o m y , occurrence of large, slow waves was seen beginning about 1 week after surgery. Sometimes this occurred first in points close to the lesion, then spread elsewhere. Figure 6 presents a typical case. As illustrated, these illnesses were also accompanied by onset o f behavioral deficits more severe than those which immediately followed the ablation surgery and which reversed the course o f recovery. Typically, an animal was hyperactive, pacing in circles and stepping in the water dish, or else catatonic, facing a comer o f the cage. When the animals refused to eat or drink they were tube-fed 1-3 times daily, a mixture o f Purina Cat Chow and water, prepared with a Waring Blender. These animals showed total losses (3 rating) on all neurological tests on at least one side of the body. The cases just described were judged due to illness on the basis of the unusual, delayed onset of symptoms, which has not been seen during considerable past experience with similar lesions. For example, in the case shown in Fig. 6, the immediate deficit in placing and hopping, but not in orientation-localization is in accord with past results of PSG ablations

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Fig. 6(b). Neurological test results obtained concurrently with the EEG results shown in 6(a). Fig. 6(a). Delayed slowing and then recovery in cat SP8, attributed to illness, following the additional ablation of posterior sigmoid gyrus. Some spiking is also seen. Same points as in Fig. 3. Calibrations: 1 see, 0.1 mV.

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(see above); "illness" was accompanied by onset of severe deficits in all behavioral measures (Fig. 6b). Though the electrode rigs were scrubbed for half an hour in most cases before breaking through to perform the ablation, this apparently was not always adequate. However, one animal's illness may have been due to an abscess, discovered on its hindquarter. Some cases appeared to respond to antibiotic injections (erythromycin ethyl succinate, 50 rag/day, im), although postoperative prophylactic doses did not always prevent the illness. Interestingly, during such a case of illness in one animal it was observed that stimulation of the forelimb (10/sec pulses, similar to those used in EP testing) caused desynchronization of a hypersynchronous record at a point in ASG (Fig. 7). As noted above, dramatic EEG slowing is also observed clinically under conditions of illness not related to direct brain insult, also under various drug conditions or following routine examination of the effects of hyperventilation. Conversely, EEG activity may recover while a clinical deficit persists (Kiloh et al., 1972, p. 134). This raises the possibility that even when slowing is seen immediately following a localized lesion, the cause may be indirect, via some metabolic alteration, and not relevant to any neural recovery process specifically concerned with the function of the damaged area. Therefore, while only very unusual conditions justify implantation of deep electrodes in human clinical patients, future animal experimental work should continue to explore for specific, localized patterns of EEG slowing following brain damage. For example, it might be expected that the nonspecific thalamic nuclei would be involved in augmenting slow activity following brain damage, as they appear to regulate it under other circumstances (Jasper, 1960). The degree of EEG recovery from all of the changes described above in the animals of the present experiment was variable across animals and across

I II

Fig. 7. Desynchronization, by 10/sec pulse stimulation to the left forelimb, of slow waves due to illness (eat SP8). The top two traces (A) show simultaneous records of points in left anterior sigmoid gyrus (upper) and right anterior sigmoid gyrus (lower) before onset of illness; the bottom two traces (B) show simultaneous records of the same points during the illness. Time marker, 1 sec; calibration, 0.2 mV.

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recording points within an animal, ranging from no recovery to apparently complete recovery. Usually, by the end of 1 to 2 months no more changes were seen. In general, there was a direct relation among size of lesion [comparison among cases of (1) ablations of PSG or AEG alone; (2) ablations of AEG and adjacent gyri; and (3) l o b o t o m y ] , severity of neurological deficit, amount of change and recovery time of the EEG records. As with the evoked potentials, there was a degree of apparently spontaneous variability pre- and postoperatively in the day to day records within an animal, particularly noticeable at points having distinctive features, such as amygdala area spindles. Variability within and across patients is also observed clinically. Therefore, special care was taken to avoid observational errors of the "false positive" type. All changes described were outside the range of this variability and were deafly related to the incidence of injury. REFERENCES Beach, F. A., Hebb, D. O., Morgan, C. T., and Nissen, H. W. (Eds.) (1960). "The Neuropsychology of Lashley." New York: McGraw-Hill. Bogen, J. E. (1975). Hughlings Jackson's heterogram. BIS Reports, in press. Buser, P., and Bignall, K. E. (1967). Nonprimary sensory projections on the cat neocortex. Int. Rev. Neurobiol. 10, 111-165. Dawson, R. G. (1973). Recovery of function: implications for theories of brain function. Behav. Biol. 8, 439-460. Eidelberg, E., and Stein, D. G. (1974). Functional recovery after lesions of the nervous system. Neurosei. Res. Prog. Bull. 12, 191-303. Geschwind, N. (1974). Late changes in the nervous system: an overview. In D. G. Stein, J. J. Rosen, and N. Butters (Eds.), "Plasticity and Recovery of Function in the Central Nervous System," pp. 467-504. New York: Academic Press. Gibbs, F. A., and Gibbs, E. (1964). "Atlas of Electroencephalography. Vol. 3: Neurological and Psychiatric Disorders." Reading, Massachusetts: Addison Wesley. Glassman, R. B. (1970). Cutaneous discrimination and motor control following somatosensory cortical ablations. Physiol. Behav. 5, 1009-1019. Glassman, R. B. (1971). Recovery following sensorimotor cortical damage: evoked potentials, brain stimulation and motor control. Exp. Neurol. 33, 16-29. Glassman, R. B. (1972). Somatosensory and auditory behavioral function of cats' orbital, anterior sylvian and anterior ectosylvian cortex. Abstr. Soc. for Neurosci. Meeting, No. 50.8. Glassman, R. B. (1973a). Persistence and loose coupling in living systems. Behav. Sci. 18, 83-98. Glassman, R. B. (1973b). Similar effects of infant and adult sensorimotor cortical lesions on cats' posture. Brain. Res. 63, 103-110. Glassman, R. B. (1974). Equipotentiality and sensorimotor function in cats. Neurosci. Res. Prog. Bull. 12, 246-249. Glassman, R. B., Forgus, M. W., Goodman, J. E., and Glassman, H. N. (1975). Somesthetic effects of damage to cats' ventrobasal complex, medial lemniscus or posterior group. Exp. Neurol. 48, 460-492. Haight, J. R. (1972). The general organization of somatotopic projections to SII cerebral neocortex in the cat. flrain Res. 44, 483-502.

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