Electrocortical Effects of Sensory Deprivation during Development

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Electrocortical Effects of Sensory Deprivation during Development J. SCHERRER

AND

A. F O U R M E N T

Centre de Recherches Neurophysiologiques, H6pital de la Salpt?trit?re,Paris (France)

The survey of prolonged sensory deprivation has been carried out for many years in animals for the purpose of defining more accurately the anatomical, biochemical and psychological changes caused by a lack of function of an afferent system. The development of the electrophysiological techniques and particularly those applicable to chronic preparations, makes it possible nowadays to define more accurately the modifications of the electrical functioning that are produced by deprivation. We have applied ourselves to tlus problem since 1959. It seems advisable to recall what those surveys which use other techniques than electrophysiology reveal, before going into the data supplied by our studies. Only those researches made on animals will be mentioned in the following resume (for data on man, see Sensory Deprivation, 1961). The results obtained by anatomists often are contradictory. For instance as far back as 1889, Von Gudden did not find any anomaly in rabbits after tarsorraphy, whereas Berger (1 900) maintained that there were gross lesions of the visual cortex in cats and dogs kept in darkness. The more recent views of authors who used conventional histological methods are also in disagreement: Goodman (1932) maintained that the visual tract of dark-reared rabbits was normal, whereas in monkeys kept in red light, Le Gros Clark (1942) observed localized atrophy of the dorsal geniculate nucleus. Irrespective of the conditions of visual deprivation Chow (1955) could not detect damage to that nucleus. Nevertheless the lesions appear to be real at the retinal level. In cats, the lesion consists of a thinning of the internal plexiform layer probably caused by a n atrophy of the Muller fibres (Weiskrantz, 1958), and in chimpanzees, there was a degeneration of the ganglion cells (Riesen, 1960). Electronic microscopy studies of the retina of rabbits kept in the dark revealed reversible modifications of the synaptic vesicles (De Robertis and Franchi, 1956). Cytocheiiiical researches disclosed that light deprivation will give rise to metabolic disturbances at the retina level. A decrease in the enzymatic activities was observed (Schimke, 1959), and also a fall of the pentose-nucleoprotein fraction of the ganglion cells in rabbits (Brattgard, 1952). A smaller concentration of ribonucleic acid in ganglion cells and an increase of the nucleolar volume was found in various understimulated animals by Rasch et al., (1959). Hellstrom and Zetterstrom (1956) showed a reduction of SH groups in light deprivation and correlated this reduction with the References p . 111/112

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appearance of the electroretinogram in kittens. Quite recently, Liberman (1962) revealed that the choliiiesterase activity of the retina of rats bred in darkness was markedly below normal. The results obtained by psychologists after reduction, either of the absolute intensity or of the pattern of stimulation seem to be rather homogeneous: Hebb’s experiments (1 937) and MacAllister’s (1 955) on rats, Goodman’s (1 932) on rabbits, and particularly those that have been conducted since 1947 by Riesen and his coworkers on cats (Riesen and Aarons, 1959) and on chimpanzees (Riesen et al., 1951) revealed that the age at which the animals were subjected to visual deprivation as well as the duration of the deprivation played a decisive role in determining the learning of visual tests and the behaviour of an animal when placed in its normal environment. The role of stimulation on learning, memory and normal behaviour has recently been discussed (Freedman et al., 1961). The problem of sensory deprivation was taken up again recently from the electrophysiological angle. Some authors, using microelectrodes, have compared in cats, the effects of light-deprivation and of transitory (Arduini, 1961) or permanent (Burke and Hayhow, 1960) visual deafferentation. Several other authors have studied the action of light deprivation on electroretinograin (Zetterstrom, 1956; Baxter and Riesen, 1961) and on the electroencephalogram (Baxter, 1959; Riesen, 1961 ; Randt and Collins, 1960). We ourselves have been studying since 1959 (Fourment and Schemer, 1961, 1962) the influence of visual isolation initiated immediately after birth on the development of spontaneous and evoked electrocortical activities in rabbits. The experimental isolation was continued for 4 to 12 months. Precautions were taken in order to avoid any contamination with light in the dark room in which the animals were reared. Health and feeding conditions were taken into consideration. Each animal reared in darkness was examined unrestrained in the course of 6 to 9 trials in succession with a break of a few days between each. During these trials, the spontaneous electrocortical activity was recorded as were also the cortical responses to visual stimulus (flash), sound (clicks) and somesthetic stimulus (electrical shocks applied to the paw). Recordings were made either in the rearing environment or in an environment at first partly dark and subsequently normally lighted. The results obtained under these various conditions are compared with those of control animals. A few trials were carried out under barbiturate anesthesia. The spontaneous and evoked electrocortical activities are studied at the level of the motor, somesthetic, limbic and visual areas. Two general techniques for recording were used. In one group of animals, removable electrodes are fitted in a trephine hole (Chevreau and Lelord, 1958). In the second group bipolar transcortical electrodes were set permanently (Fig. 3B). Each electrode couple was made of two silver wires 0.3 mm in diameter, glued together and insulated to their tips. The ends of the wires were bared, chlorided and placed 2.5 mm apart. The evoked responses were recorded on a cathode ray oscillograph using the averaging method described by Calvet (1958); the spontaneous cortical activity was traced on an electroencephalograph.

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Thc spontaneous electrocortical activity in dark-reared animals should be considered in two different experimental setups, depending on whether it is recorded under the reaing conditions or in a different environment. When the recording was done under rearing conditions, the record was comparable to that of a control animal, showing the same alternation of wakefulness and drowsiness. If stimulation with a sound, a light or an electric shock to the skin was applied, a particularly long arousal reaction was observed. When the recording of the electrocortical activity of a dark-reared animal was carried out in the dark, but in an environment differing from that in which it was reared, an intense and long lasting arousal reaction was observed (Fig. I). The EEG

\ .._..-.., ~

Fig. 1. Electrocorticogram in a test-rabbit and in a dark-reared rabbit as recorded by electrodes placed on the dura. (f) Control-rabbit: at rest. The first 3 recordings are monopolar ones with a frontal reference. (2) Rabbit bred in darkness, examined outside its breeding environment, in semi-darkness. Arousal reactions usually observed during the first recordings. The first 4 records are monopolar with a frontal reference.

arousal decreased during subsequent recordings and specially after the rabbit had been in normal lighted environment for a week or so. EVOKED ELECTROCORTICAL ACTIVITY I N AN ANIMAL BRED

IN LIGHT DEPRIVATION

The evoked electrocortical responses in rabbits reared in darkness were different from Refrrencrs p . I I I 1112

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the usual responses regardless of the conditions under which the examination was made or the method of recording. In control animals, the response evoked by a sensory stimulation was twofold: The stimulation would bring about at the same time, a conventional evoked potential of

An-

Fig. 2. Averaged visual responses obtained in test-rabbits in various cortical areas. Each record shows the average of 50 elementary responses. Detection through surface monopolar lead ; frontal reference. Contlo-lateral stimulation.

short latency in the corresponding projection area and a long latency response over the whole cortex (Hirsch et al., 1961). The visual response derived in the occipital area showed a distinct appearance in all control animals (Fig. 2 and Fig. 3). After a 20.5 3 msec latency, there was a short positive deflection (10 mscc) of approximately 150 ,uV, corresponding to the conventional evoked potential. In the late phenomenon it was possible to distinguish 2 phases; the 1st phase was formed by a positive wave that was comparatively short (15 to 20 msec) of approximately 100 pV and the 2nd phase was comprised of two slow deflections (negative then positive) of a large amplitude (300 ,uV or so). The total duration of the response was 365 f 41 msec. The amplitude of the late phenomena and more specially that of the slow deflections showed substantial variations. It was maximal during rest, decreasing during an arousal reaction or during a period of sleep. The visual stimulation gave rise to a delayed response with a latency of 40 to 50 msec in the somesthetic and in the motor areas. Thus extra-primary response was composed of 2 deflections having an uneven duration and amplitude; the 1st one, which was positive, was short, approximately 50 p V , the 2nd one, negative, longer, and about 100 pV. The whole duration of the response was 150 msec. These extra-primary responses were changeable; they increased markedly when the animal was in a resting condition. Like the flashes, the somesthetic and auditory stimulations evoked 2 types of responses: ( I ) the conventional evoked potential of short latency (10 to 15 msec), in the corresponding specific projection area; (2) long latency responses recorded out-

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Fig. 3. Responses ( C )in a test-rabbit obtained by transcortical electrodes (B), after an electrical shock applied to the skin of the fore-paw and a flash on the side opposite (A) to the recording. Time scale 50 msec. Calibration: 50 yV.

Fig. 4. Responses obtained in a dark-reared rabbit by transcortical electrodes. From left to right: responses to a light stimulus (column 1 and 2), somesthetic (column 3) and sound (column 4). Recordings in the rearing environment (A) after a I5 days exposure to light (B) and in a test-animal (C). Time scale 50 msec; calibration: 50 p V . Refivrnces p. 111/112

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side that cortical area. The latency of responses was comparatively high (30 to 40 msec) and their pattern was similar to that of the extra-primary visual responses. Like the latter, they underwent a large amplitude variation depending on the vigilance level. Those responses to visual, somesthetic, and sound stimulation which were recorded at a distance from the specific projection area were compared. They did not seem to present a preferential topography. They were labile and decreased during the blocking reactions and during sleep. Stimulations given at a fast rate caused them to disappear; barbiturates even in small doses, eliminated them. In dark-reared rabbits, great changes of the electrocortical responses to the various types of stimulation were observed. The changes were to be found in an animal examined in its rearing environment as well as in a different environment. Visual responses of a quite peculiar pattern were recorded from the specific projection area as well as in the somesthetic and motor cortices during the first trial (Fig. 4A). The flash response in the occipital area was different from the usual one. Its latency, of 25 to 30 msec, was intermediate between that of the primary evoked potential and the extra-primary response. The amplitude of the 1st deflection, of a positive polarity was approximately 50 pV. The whole duration of the response was short (1 80 msec) ; its amplitude did not exceed 150 pV. On the other hand, in the somesthetic and motor areas, larger responses were recorded after each light-stimulation. They appeared to have a hgher amplitude (100 to 250 p V ) and a lower latency (30 msec) than that of test animals. They hardly changed with the vigilance level, but seemed to be very sensitive to the rate of stimulation: flashes repeated a t interval shorter than 2 sec entailed a substantial decrease in the response amplitude. In the case of light-stimulation of low intensity by a flash, the responses appeared to be of the same type in all areas: the latency of these responses was 50 to 60 msec. The electrical stimulation applied to the skin and sound stimulation gave rise, in the rabbits reared in darkness, to responses of a great amplitude all over the cortex and notably, in the occipital area. These responses did not vary directly with the vigilance level. In successive trials, the responses to the various stimulus types gradually changed. A transformation of the visual response took place in the occipital area: a positive wave of short latency and of low amplitude appeared. The size of this early and short positive wave grew gradually. It shifted to the positive wave already mentioned. At the same time, the responses registered away from the specific projection area increased in latency and decreased in amplitude. They became unsteady or varied. Similar modifications took place for the long latency responses obtained by somesthetic and auditory stimulation. These modifications take place slowly when the animal was recorded in its usual environment and received only a restricted number of light-stimulations. When the animal was examined in darkness, but outside its habitual environment and underwent multiple light stimulations (500 to 800 in each trial), the changes appeared at the end of the first trial and they progressed rapidly (Fig. 5). However, whatever the recording conditions might be, the responses to the various methods of stimulation of rabbits

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3

Fig. 5. Averaged visual response in a dark-reared rabbit (averaging of 50 elementary responses). Responses obtained during the first four trials (1-4). Stimulation effected in an animal raised in darkness. Responses of the visual area on the left, of the somesthetic area on the right. From top to bottom, response at the beginning, in the middle and a t the end of the trial which comprises 120 flash-stimulations. Detection by surface monopola, leads. Contro-lateral stimulation.

living in darkness became comparable to those of control animals only after they have been for 2 weeks in an environment similar to that of the control animals. INTERPRETATION OF THE ELECTROCORTICAL ACTIVITY CHANGES

The nature and the type of induced electrocortical modifications in animals raised in sensory deprivation have been described. After they were revealed by a monopolar technique, they were confirmcd by transcortical records on chronic animals. This sort of recording makes it possible to localize with accuracy, the generator of specific electrical activity in the cerebral cortex (Calvet, 1962). The use of animals carrying implanted electrodes confirmed the phenomena obtained a t the start in non-implanted animals. As a matter of fact, the permanent electrodes were well tolerated and made it possible for the recording to be traced in the animal's usual environment. The electrophysiological modifications brought about through a prolonged light deprivation were not linked with a better adaptation to darkness, at least in the sense in which the word adaptation is generally used. Control animals recorded for a 24 h period; that is, in the exact rearing environment, did not show any changes comparable with those observed in animals kept in it ever since they were born. On the other hand, after dark-reared animal following several weeks in the usual well lighted environment, had recovered normal electrocortical responses, a return to a dark environment for several hours did not bring back the responses which were shown Rrfrrrnces p . l l l j l I 2

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during the sensory deprivation period. It seems, therefore, that the transformation of responses was connected with the long stay of the animal in darkness, and not with a process of adaptation to darkness such as would make the visual system more sensitive to light. This fact being established, the physiological meaning of the modification in the responses to the various stimulation types still remains difficult to explain for 2 reasons: (1) because we do not know what the various phases of the response in the visual projection area are supposed to represent; and (2) because we still know very little about the exact meaning of long latency responses which are induced by the various methods of stimulation. Moreover, it would be essential to know the changes in the evoked responses of an understimulated animal, not only at the cortical level, but also at the other levels of the visual, somesthetic and auditory tracts. Nevertheless, it appears possible now to stress a particular aspect of the observations made in animals living in darkness and to put forward a theory in this respect. This theory refers to the increase in the responses to visual, and auditory as well as somesthetic stimulations recorded from other than specific projection areas. We have several reasons to surmise that the long latency responses (Hirsch et al., 1961) result from the use of non-specific systems, at the cortical level as well as at the subcortical one, particularly at the brain stem level. It can be suggested, therefore, that these understimulated animals have a hypersensitivity in these systems. Such an assumption could be supported by the observations made on the long lasting arousal reaction achieved through sensory stimulation in an animal kept in its usual dark environment. The arousal reaction persists for hours after the animal has been taken out of the dark. The increased reactivity of the EEG was observed also by Randt and Collins (1960) and by Riesen (1961). The different electrophysiological observations fit with the latter’s psychological researches; for example, those animals who underwent a visual deprivation of intensity or pattern, show themselves fearful and aggressive when they are placed in a light or patterned environment. The gradual diminution of the long latency responses, the decrease of arousal reactions found in understimulated animals placed in a normal environment should be likened, from the same point of view, to the reversibility of anomalies in the behaviour of those animals which underwent visual deprivation. It should be noted that the duration of time in the light required to achieve normal performances increased with the phylogenetic level. This time was short in rats (Walk et al., 1957), a few days, in rabbits (Goodman, 1932); the adjustment was made slowly in cats and the period required for adjustment may last for more than 6 months in chimpanzees (Riesen, 1961). It would be desirable to have the pertinent electrophysiological researches carried out. It seems most likely, that it is not only a dark environment that will give rise to such an apparent hypersensitivity of the non-specific systems; no doubt, the isolation involved by rearing in darkness plays a role also, perhaps an essential one. It is interesting to liken the assumptions which one is lead to put forward, to those which were recently presented by Lindsley (1961). In animals living in darkness, the changes of the electrical response in the visual

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projection area, cannot be directly linked with a hypersensitivity of non-specific structures. It would, therefore, be the functioning of the primary visual tract which is changed. The decrease in the initial part of the response that is the positive surface wave, which virtually disappears in the case of the very first stimulations, seems to represent the principal modification. As this positive surface probably reflects faithfully the progress of conduction through the primary visual tract its decrease might correspond to some functional deficiency in that tract. In other words, as the tract was hardly used, it did not acquire its final properties and might transmit the afferent messages imperfectly. If we admit such an interpretation, we could liken the responses obtained in an animal reared in sensory deprivation to those of the newborn. We know, in fact, that in cats the early part of the visual response appears in the focal area only after the last part of the response has bzen established (Marty, 1962). REFERENCES ARDUINI, A., (1961); Influence of visual deafferentation and continuous retinal illumination on the excitability of geniculate neurons. The Visual System: Neurophysiology and Psychophysics. I. B. Germany, L. Jung and Kornhuba, Editors. Symposium Freiburg. Berlin. Springer (p. 117-124). B. L., (1959); An Electrophysiological Study of the Effects of Sensory Deprivation. Ph. D. BAXTER, Dissertation. University of Chicago (Ill.). BAXTER, B. L., AND RIESEN,A. H., (1961); Electroretinogram of the visually deprived cat. Science, 131, 1626-1627. BERGER, H., (1900); Experimentell-anatomische Studien uber die durch den Mangel optischer Reize veranlassten Entwicklungshemmungen im Occipitallappen des Hundes und der Katze. Arch. Psychiat., 33, 521-567. S. O., (1952); The importance of adequate stimulation for the chemical composition of BRATTGARD, retinal ganglion cells during early postnatal development. Acta Radiol. Suppl. (Stockh.), 96, 1-80. BURKE, w., AND HAYHOW,w. R., (1960); Disuse of a central synapse and spontaneous activity in the optic nerve. Nature, 188, 668-669. J., (1958); Methodes d'intkgration. Application a I'etude des potentiels evoques chez l'homme. CALVET, Me'moire pour le Certificat d'e'tudes sp.4ciales d'Electvoradiologie. Paris. J., (1962); Comparaison de I'activite electroencephalographique derivee par electrodes de CALVET, surface et par electrodes transcorticales. J . Physiol. (Paris), 54, 308-309. CHEVREAU, R., AND LELORD, G., (1958); Technique particulitre de pose d'klectrodes pour electroendphalographie de routine au laboratoire de physiologie. J. Physiol. (Paris), 50, 1007-1010. CHOW,K. L., (1955); Failure to demonstrate changes in the visual system of monkeys kept in darkness or in colored lights. J. comp. Neurol., 102, 597-606. DEROBERTIS, E., AND FRANCHI, C. M., (1956); Electron microscope observations on synaptic vesicles in synapses of the retinal rods and cones. J . biophys. biochem. Cytol., 2, 307-318. J., (1961); Reponses electrocorticales du lapin eleve dans I'obscurite. FOURMENT, A., AND SCHERRER, J . Physiol. (Paris), 53, 340-341. FOURMENT, A., AND SCHERRER, J., (1962); Deprivation sensorielle temporaire et potentiels Bvoquks corticaux chez le lapin. C . R . Acad. Sci. (Paris), 255, 179-181. FREEDMAN, S. J., RIESEN,A. H., HELD,R., TEUBER, H. L., AND HEBB,D. O., (1961); Sensory deprivation: Facts in search of a theory. Symposium of the American Psychological Association, Cincinnati, Ohio. J. nerv. ment. Dis., 132, 1744. GOODMAN, L., (1932); Effect of total absence of function on the optic system of rabbits. Amer. J . Physiol., 100, 46-63. HEBB, D. O . , (1937); The innate organisation of visual activity. 1. Perception of figures by rats reared in total darkness. J. genet. Psychol., 51, 101-126. B., (1956); The effect of light on the manifestation of the electroHELLSTROM, B., AND ZETTERSTROM, retinogram and on histochemically demonstrable SH groups in the retina. Exp. Cell Res., 10, 248-25 1. HIRSCH, J. F., ANDERSON, R. E., CALVET, J., AND SCHERRER, J., (1961); Short and long latency cortical responses to somesthetic stimulation in the cat. Exp. Neurol., 4, 562-583,

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LEGROSCLARK, W. B., (1942); The anatomy of cortical vision. Trans. OphthalSoc. U.K.,62,229-245. LIBERMAN, R., (1962); Retinal cholinesterase and glycosis in rats reared in darkness. Science, 135, 372-313. LINDSLEY, D. B., (1961); Common factors sensory deprivation, sensory distortion and sensory overload. Sensory Deprivation. P. Solomon and A.P. Coll, Editors. Cambridge (Mass.), Harvard University Press (p. 174-1941, MACALLISTER, W. R., (1 955); Visual deprivation and learning of a brightness discrimination problem. Amer. Psychologist, 10, 406407. MARTY,R., (1962); Developpement post-natal des reponses sensorielles du cortex ckrtbral chez le chat et le lapin. Arch. Anat. micr. Morph. exp., 51, 129-264. RANDT,C. T., A N D COLLINS, W. F., (1960); Sensory deprivation in the cat. Arch. Neurol., 2,565-572. RASCH,E., RIESEN,A. H., A N D CHOW,K . L., (1959); Altered structure and comrosition of retinal cells in dark-reared cats. J. H/stochem. Cytochem., 7 , 321-322. RIESEN,A. H., (1960); Brain and behaviour: Session I Symposium 1959. 1V. Effects of stimulus deprivation on the development and atrophy of the visual sensory system. Amer. J . Orfhopsychiat., 30, 23-36. RIESEN,A. H., (1961); Excessive arousal effects of stimulation after early sensory deprivation. Sensory Deprivation. P. Solomon and A.P. Coll, Editors, Cambridge (Mass.), Harvard University Press (P. 34). RIESEN,A. H., A N D AARONS,L., (1959); Visual movement and intensity discrimination in cats after early deprivation of pattern vision. J. Comp. Physiol. Psychol., 52, 142-149. RIESEN,A. H., CHOW,K. L., SEMMERS, J., AND NISSEN,H. W., (1951); Chimpanzee vision after four conditions of light deprivation. Amer. Psychologist, 6, 282. SCHIMKE, R. T., (1959); Effects of prolonged light deprivation on the development of retinal enzymes in the rabbit. J . biol. Chenz., 234, 700-703. SOLOMON, P., AND COLL,A.P., (1961); Sensory Deprivation: A symposium at Harvard Medical School. Cambridge (Mass.). Harvard University press. VON GUDDEN,B., (1889); Gesammelte und hinterlassene Abhandlungen Wiesbaden. Quoted by Goodman. WALK,R. D., GIBSON, E. J., AND TIGHE,R. J., (1957); Behaviour of light and dark raised rats on a visual cliff. Science, 126, 80-81. WEISKRANTZ,L., (1958); Sensory deprivation and the cat’s optic nervous system. Nature. 182, 1047-1050. ZETTERSTROM, B., (1956); The effect of light on the appearance and development of the electroretinogram in newborn kittens. Acta physiol. scand., 35,272-279.