mrumppxholouin. NoL 28. N. 6, pp .573-584 . 1990Punted in Great Britain .
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0028-393290 53W+0 .00 1990 Pergarnon Press P1,
NEOCORTICAL REPRESENTATIONAL DYNAMICS IN ADULT PRIMATES : IMPLICATIONS FOR NEUROPSYCHOLOGY WILLIAM
M.
JENKINS,* MICHAEL
M.
MERZENICH
and
GREGG RECANZONE
Coleman Laboratory . University of California at San Francisco, San Francisco . CA 94143-0526, U .S .A .
Abstract-Some evidence for functional reorganization of cortical somatosensory representations in adult primates is reviewed . These examples include representation remodeling in cortical area 36 following digit amputation, digit fusion, local intracortical microstimulation, restricted cortical lesions, or as a consequence of behaviorally controlled stimulation of restricted hand surfaces . We suggest that the profound changes in the cortical representations that have been observed after these and other manipulations must bear consequences for the specific behaviors that depend on the operation of this neural machinery . Furthermore, this lifelong dynamic cortical capacity for neuronal response adaptation by use almost certainly also underlies the progressive representational remodeling that we have recorded following brain lesions .
INTRODUCTION its inception, neuropsychology has been concerned with describing the neural bases of FROM complex human mental activities and associated behaviors, with one principal source of insight being human subjects with defined brain lesions . Early investigators who used the focal brain lesion-behavioral deficit approach in human (and animal) models recognized that behavioral deficits following brain damage were not stable over time . Thus, for example, LASHLEY [18] concluded that following a brain lesion there " . . . is a reorganization within a dynamic system of which only a part has been destroyed" . Descriptions of progressive changes in measured or observed behavioral capacities that followed restricted lesions in animals recorded in numerous experiments conducted over more than a century of ablationbehavioral research provide strong support for this conclusion . In summarizing a widely held view on the progress of changes following brain lesions in human, LURIA [20] argued that " . . . a pathological focus arising as a result of a wound, or haemorrhage, or of a tumour disturbs the normal working of a given brain area, abolishes the conditions necessary for the normal working of the particular functional system, and thus leads to reorganization of the intact parts of the brain, so that the disturbed function can be performed in new ways" . Again, manifold human observations support the basic contention that a functional reorganization follows brain injury or stroke, and underlies subsequent, progressive behavioral changes and recoveries . Despite this extensive behavioral evidence for functional remodeling of effective neuronal circuits and/or mechanisms following brain injury, the orgins of recovery from brain damage *Author to whom correspondence should be addressed . 573
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have been surprisingly little studied . Indeed, many fundamental questions remain to be answered about the physiological processes operating within the adult brain that account for the adaptive features of cognitive functions and behavior recorded (a) following brain injury or stroke, much less (b) in normal individuals, or (c) as a consequence of neurological illness . There is currently a growing body of neurophysiological literature indicating that rile neocortex of adult mammals has the capacity Jor functional reorganization, as evidenced by changes in the response properties of individual cortical neurons [36] . Such changes occur as a consequence of both peripheral and central pathophysiological disturbances . Recent evidence also reveals that neocortical functional reorganization occurs in the absence of any pathophysiological conditions, and thus indicates that representational dynamics reflect properties of normal, lifelong neocortical processes . This neocortical capacity for representational remodeling has obvious and important implications for understanding the nervous system origins of progresssive functional recovery following brain lesions- as well as implications for understanding the origins of normal behavioral adaptive processes . Our objective in this brief report is to provide an overview of some of the results from our own electrophysiological studies that illustrate the mutability of somatosensory neocortical representations in adults . Given these few selected examples, we shall briefly discuss the implications of this class of experiments for understanding mechanisms underlying the neural origins of adaptive behaviors . The scope of this report precludes a comprehensive review of the considerable literature on recovery of function in animals and humans [3, 6, 7, 9, 12, 21] . SOME EVIDENCE FOR FUNCTIONAL REORGANIZATION Common and variable features of normal cortical somatosensory representation In an extensive series of electrophysiological studies, we have described many of the details and dynamic aspects of somatotopic representations within the functional subdivisions of primate SI [22, 25, 27, 28] . We have previously considered the sources of intraspecies and interspecies cortical map variability in normal adult primates and have addressed many of the methodological details of the conduct of this class of electrophysiological experiments [26, 34] . Because of convenience of study, most experiments have been conducted within the zones of hand representations in St . The results of those studies indicate several common map features . (a) There was a single complete or nearly complete representation of the glabrous hand surface in area 3b . (b) The distal aspects of the digits were usually represented along the functionally defined 3b-3a (cutaneous-deep) border while the more proximal digit skin surfaces were represented in topographic sequence in progressively more caudal portions of area 3b . (c) The radial aspect of the hand (e .g . digit I) was represented in the lateral portion of the hand representation usually adjacent to the representation of the face, while the more ulnar aspects of the hand were represented in topographic order in progressively more medial portions of area 3b . (d) The cortical area devoted to the representation of each distal phalanx was almost always greater than the cortical area of representation of either the middle or proximal phalanx . (e) The internal topographic order was maintained throughout the field, with few receptive fields out of topographic sequence . (f) The dorsal skin surfaces were represented in a number of small . fragmentary, discontinuous patches embedded in a much larger glabrous digital skin representation . (g) There are normally extremely abrupt representation discontinuities between adjacent digit representations . (h) The sizes of receptive fields on a given skin surface
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were, on the average, roughly inversely related to the size of the cortical representational magnification (cortical area of representation/skin surface area) for that skin surface . There were many other significantly variable map features among different monkeys . (a) The overall shapes and sizes of hand surface representations varied substantially . (b) The actual and proportional areas of representations of different skin surfaces and the cortical magnifications of representations of specific skin surfaces commonly varied several-fold in cortical area 3b . (c) The detailed topographic relationships among skin surface representations varied greatly ; skin surfaces that were represented in adjacent locations in some monkeys were represented in locations many hundreds of microns apart in others . (d) The internal orderliness of representations varied significantly . (e) The completeness of representations of the dorsal hand surfaces was different in every studied monkey . (f) The skin surfaces represented along the borders of the hand representation was idiosyncratic . We hypothesized that the differences in the details of cortical map structure are the consequence of individual differences in lifelong use of the hands [25-28] . By that view, the functional map present at any instance in the life of a monkey (or human) is shaped by the summed, stored changes presumably driven by behaviorally significant experience up to that point in life . This conclusion is consistent with the following examples in which we have experimentally altered the patterns of peripheral stimulation (a) by peripheral or central surgical intervention, and (b) behaviorally .
DYNAMIC ALTERATION OF CORTICAL MAPS ; SOME EXAMPLES Representational remodeling in cortical area 3b following digit amputation One of the most striking examples of neocortical representational dynamics was observed when all sensory inputs from one or two digits were removed [24] . Recall that within the cortical representation of the hand each digit is represented discretely (i .e . receptive fields very rarely extend beyond a single digit) albeit adjacently in topographical sequence . Such a lack of overlap in the representations of adjacent glabrous digits might indicate that the representations of adjacent glabrous digital surfaces are anatomically separated throughout the somatosensory projection system . If not, then such representational discontinuities must be dynamically established and maintained . This study revealed that the representations of adjacent digits and palmar surfaces expanded topographically to occupy most or all of the cortical territories formerly representing the amputated digit (Fig . I ) . As a consequence of these expanded representations, there were several-fold increases in the cortical magnification (cortical area,: skin surface area) of adjacent digits and systematic decreases in the sizes of receptive fields for neurons within these expanded representations . Theses studies also revealed that the discontinuities between the representations of the digits were translocated several hundred microns after amputation, and sharp new discontinuous boundaries formed where normally separated, expanded digital representations approached each other in the reorganized map . This implied that these map discontinuities are normally dynamically maintained . The spatial distributions and time course of changes in receptive field sizes with the expansion of representations of surrounding skin surfaces into the vacated cortical zone has parallels to positive changes in tactile acuity and sensitivity on the stumps of human amputees [14, 15, 35] . Furthermore, there are no apparent perceptual localization errors with stimulation of the skin surrounding an amputation in humans . The combined human and monkey data suggest that the same cortical neurons can signal locations of inputs from
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different skin surfaces at different times . At present refined behavioral measures of tactile acuity and cortical magnification and receptive field data have not been obtained in the same subject . Representational changes following digital fusion
In another series of experiments, we again took advantage of the representational discontinuities between digits . We and others had hypothesized that a limited subset of inputs generating the excitatory receptive fields in somatosensory neocortex are "selected" from a large afferent input repertoire by adaptive, temporal correlation-based processes [8, 24, 25] . Anatomical evidence suggests that somatosensory thalamocortical afferents terminate across much larger reaches of SI than is predicted by the size and location of receptive fields defined for single cortical neurons [10, 33], thus providing the neuroanatomical substrate for a dynamic input selection process . We knew that the temporal patterns of input activity from nearby locations on any single digit are highly correlated . By contrast, inputs from adjacent digits, given their independent ranges of movement and relative mechanical isolation, are relatively temporally independent . We specifically hypothesized that representational discontinuities arise between digits in somatosensory cortical maps because of the higher probability of non-simultaneous afferent input across these boundaries . As a test of this hypothesis, we fused the skin of two adjacent digits in several adult owl monkeys using microsurgical techniques that allowed us to preserve the normal innervation of both digits [ 1, 3] . This surgery created an artificial syndactyly in which the two fused digits are used in normal behaviors as though it was a single digit . After several months of behavioral experience in which the monkeys were observed to use to syndactylized hands normally (e .g . grasping food, climbing, grooming, etc .) a detailed microelectrode map of area 3b was obtained (see Fig . 2) . For comparison purposes, Fig . 2A depicts an area 3b map of digits 3 and 4 and adjacent surfaces of digits 2 and 5 and of the palm (P) in a normal non-syndactylized hand . Shaded patches are areas of dorsal hand representation . Receptive fields at starred sites are drawn on the hand to the right . Note that for adjacent starred recording sites located at the borders of adjacent digital representational zones the individual receptive fields are located entirely on a single digit . The abrupt shifts in the locations of receptive fields from one digit to the next at adjacent cortical locations serve to illustrate the extremely abrupt representation discontinuities commonly observed between adjacent digits in normal monkeys . By contrast . Fig . 2B depicts a cortical map obtained several months after syndactyly surgery . In this map, the discontinuity between the syndactylized digits (digits 3 and 4) was abolished . The diagonally filled region indicates the cortical zone within which all defined receptive fields overlapped both digits 3 and 4 . The open stars are exemplary recording sites at which the receptive fields drawn on the hand to left were defined . In order to control for possible cross-innervation of the two digits post-surgically, or for potential mechanical coupling artifacts that might affect accurate receptive field definition . the fingers were once again separated . Again receptive fields were defined for cortical locations within the region occupied by so-called "double digit receptive fields" . Most defined receptive fields (94%) still had components on both digits . Three such receptive fields are shown on the hand to the right and were obtained from the same three cortical locations indicated by the stars . These experiments have led us to conclude that the abrupt representational discontinuities observed in normal somatosensory cortical maps derive from central neural mechanisms that rely on temporal input-correlation-based rules [I, 3, 24, 27, 28] . These correlation-
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A Normal
B 62 days after digit 3 amputation
Fig . 1 . (A) Representation of the hand surfaces within and adjacent to area 3b in a normal adult owl monkey . Receptive fields located on the face are indicated by F while penetration sites at which neurons were driven by deep but not cutaneous receptor inputs are marked by X . The large numbers 1-5 denote the digits (e .g . 1=thumb ; d, m, p, are distal, middle . and proximal phalanges, respectively) : P 1-4 are the palmar pads at the base of the digits ; Ph is the hypothenar eminence ; Pt is the thenar eminence . Stippled zones indicate dorsal (hairy) skin on the digits . Solid lines outline territories of representation of the digits and palmar pads . Broken lines mark the borders between phalangeal representational zones . (B) Representation of the hand surfaces derived 62 days after amputation of digit 3 in the same adult owl monkey . Note that the former 3b cortical representation of digit 3 is now occupied by expanded representations of adjacent digits 2 and 4 . and of the palmar pads 2 and 3 . based mechanisms must make a fundamental contribution to the expression
of
normal
topographic details in neocortical representations .
Rapid representational changes follow local intracortical microstimularion In two related series of experiments, the input coincidence of activity within neocortex has been manipulated directly . The intracortical microstimulation technique
(ICMS)
has
commonly been used in experiments defining movement representations in motor cortex . It
ICMS can itself alter movement representations in the motor [13 . 29, 30] . Similar experiments [32] have now been conducted within representation of the somatosensory koniocortical field in rats (SM I ) and
has been demonstrated that cortex
of adults
rats
the body surface
adult primates (areas 3b) . In this study, the specific receptive field defined at a stimulation
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ei al .
A
2
500 p Fig .? (A)Area3breconstructionoftherepresentationofdigits3and4andportionsofdigits2and5 . Small Ill led squares are electrode penetration sites at which receptive fields were defined . Stars (A-F) are selected sites near digit representation borders . (R) Receptive fields defined for sites A- F are drawn as stippled areas on the hand to the right . Note that for adjacent recording sites on either side of digit borders the receptive fields are exclusively on one or the other digit . site came to be represented at many cortical locations more than 600 fim away from the stimulation site . Such changes in the representational topography progressed throughout the course of stimulation . Again, these studies suggest that the temporal patterns of cortical-cortical!cortical-thalamic interactions play a direct role in the formation of individual receptive fields and cortical map topographies . Hand surface representations are dramatically reoryani :ed following restricted cortical lesions In another class of input-alteration studies, we have changed patterns of cortical-cortical and cortical-thalamic interactions by the creation of small focal area 3b lesions [16] . The
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locations and extents of these cortical lesions were defined in electrophysiological mapping experiments conducted within and across the boundaries of area 3b in adult primates . In initial studies, no attempt was made to provide behavioral therapy for the affected hand, nor were sensory and motor deficits identified using standardized testing protocols . We considered (indeed, are now investigating) the possibility that such post-lesion testing, ;training could alter the form of any consequent map reorgnization, or might significantly alter the functional use of the affected hand . During an initial several-week period after such lesions, monkeys used their affected hands only for crude motor tasks . For example, over this early post-lesion period the hand was used for grasping the cage bars when climbing-but not for manipulating or retrieving food pellets, a behavior that requires more refined motor control of the digits . However, within several weeks after these small area 3b lesions, no great differences in hand use were observed . Several months after induction of these cortical lesions, mapping experiments were again conducted in the region flanking the lesion within area 3b . Substantial reorganization of the hand representation was recorded in all of these adult monkeys . As a consequence of that representational remodeling, neurons over a broad surround region at least several millimeters in extent were driven by newly acquired inputs . and skin surfaces formerir represented in the cortical -one of the lesion came to be represented in entirety in the cortex surrounding the lesion . One result of this functional reorganization was the development of unusual, complicated representational topographies within the surrounding reorganized representation . For example, the location of a restricted area 3b cortical lesion immediately after induction is shown in Fig . 3A . No neural responses were seen at locations within the zone of the lesion (indicated in black). The lesion destroyed the entire area 3b representation of digit 3, pad 2, pad 3 and a portion of digits 2 and 4 . A reconstruction of the area 3b hand representation medial to the cortical lesion obtained 58 days after induction is shown in Fig . 3B . The zone of representation of skin surfaces fomerly located only in the zone of the lesion but now represented in the cortex flanking the lesion is indicated by stippling . Diagonal lines mark the cortical sectors at which cutaneous receptive fields were significantly larger than normal . Note that the small cortical zone representing portions of digit 3 and digit 4 is located medial and dorsal to the digit 5 representation . This form of representational topography has never been observed in normal monkeys . We hypothesize that this dramatic topographic reorganization in the region surrounding an infarct likely constitutes a fundamental basis for recovery from brain injury [16] . Of course, reorganization can occur only when a sector or a cortical area with given qualitative inputs survives the cortical lesion . We also wish to emphasize that other models of recovery from stroke such as processing substitution models may also contribute to the recovery process [e .g . 19, 21] . The unusual representational topographies and large receptive fields observed in our experimental cases might be expected to be reflected by some lasting behavioral deficits, but that tentative conclusion remains unproven . Also, we do not yet know whether rehabilitative strategies that are believed to alter the functional recovery from brain lesions [4] would alter details of representational maps surrounding such lesions, but other experiments in our series (see below) indicate that that is likely . Cortical maps can he representationally distorted by a period the heauh engagement of restricted hand surfaces
of behavioral
training involving
We have also undertaken a series of behavioral experiments that were designed to produce high levels of temporally correlated activity over a restricted skin surface [ 16, 17] . Adult owl
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A
Day 0
B
* Fig . 3 . Representation of the hand in area 3b in adult owl monkey immediately after and 58 days after introduction of a restricted cortical lesion . (A) The hand region defined immediately after the cortical lesion (black) . No neural responses were seen in penetrations within the zone oft his lesion . Cut aneous receptive fields were defined for electrode penetration sites lateral, medial and caudal to the lesion . The lesion destroyed the entirecortical area 3h representation of digit 3, pad 2,pad 3 anda portion of digits 2 and 4 . (R) Representation of the ulnar aspect of the hand in the cortical zone medial to the lesion 58 days after lesion induction . The zone of represention of skin surfaces formerly located in the zone of the lesion but now found in the adjacent cortex is indicated by stippling . Diagonal lines mark a cortical sector in which cutaneous receptive fields were extraordinarily large . Stars are fiducial points corresponding to common vascular landmarks . monkeys were trained using operant conditioning techniques to contact a cutaneous stimulus delivery device in order to obtain food rewards . During each episodic contact, cutaneous stimuli were delivered exclusively to the glabrous skin on the distal phalanx of one or two digits . By such means, each animal experienced several hundred thousand cutaneous stimuli delivered daily to a selected skin surface . Electrophysiological mapping experiments were conducted prior to and immediately after several months of differential stimulation experience . In these experiments, the zones of representation within area 3b of such heavily stimulated skin surfaces enlarged greatly in extent in otherwise normal adult owl monkeys (e .g . compare the representation of distal phalanges 2 and 3 in Fig . 3A to that in Fig . 3B) . In
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C DM I %ulngaa Catd lhagSAoaUn
OM 1 Distal Phalanges After stimulation
E E
J Digits
Fig . 4 . (A) Reconstruction of the hand representation in area 3b prior to differential stimulation . IB) Post-stimulation reconstruction of hand representation after 109 days ofdaily differential stimulation totaling about 1 .5 hr per day . Skin surfaces on the tips of digits 2 and 3 and occasionally the tip of digit 4 were stimulated . (C) Cortical magnification x 103 of the glabrous representation of all five digits is plotted, for normal and post-stimulation distal . middle, and proximal phalanges. Note that the magnification of the representation of each phalangeal surface is relatively constant across the five fingers in both monkeys at these two stages of life except for the striking increase in the magnification of stimulated phalanges . Arrows indicate the locations of skin surfaces differentially stimulated . (D) Cortical magnification (black squares) for distal phalanges obtained after differential stimulation (ordinate is on the left axis) . Mean receptive field size in mm' (open squares) plotted for these same skin surfaces obtained after differential stimulation (ordinate on the right axis) . Note that in this exemplary case these two functions are roughly inversely related . That is, as cortical representations of these struck surfaces expanded, they came to be represented in finer grain .
addition, these distorted representations eventually returned to a normal skin surface representation after the behavioral task was halted . The enlargement in representation in an adult behaving monkey occurred only for stimulated skin surfaces, This can be seen in the example shown in Fig . 4C, for example, where the cortical magnification of all digital segments (phalanges) is plotted prior to stimulation (open symbols) and after tactile stimulation (closed symbols) . There was nearly a three-fold increase in the cortical territory representing the principal stimulated phalanx (i .e . digit 2-distal phalanx) . Recall that in both normal and other examples of reorganized neocortical maps, there was a roughly inverse relationship between receptive field size and the area of representation for a
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given skin surface . Such a relationship was also seen in these behavioral experiments . In Fig . 4D the black squares indicate the cortical magnification (scale on the left ordinate) and the open squares indicate the mean receptive field size (scale on the right ordinate) for each of the five distal phalanges . The distal phalanx (digit 2) with the largest cortical magnification (23 .37 x 10') had the smallest mean receptive field size (4 .676 mm') . The distal phalanx (digit 5) with the smallest cortical magnification (7 .06 x l0') had the largest mean receptive field size (9 .852 mm') . Limits of fimetional reorganization It is well recognized that behavioral deficits can be reliably obtained following cortical lesions and that depending on the size and locus of the lesion variable degrees of recovery are obtained . Whatever recovery mechanisms obtain, they must have some limitations or else behavioral deficits following focal brain damage would be more rare than they are . The results from our own experiments suggest that reorganization occurs over a limited distance [24] . For example, in a two-stage post-amputation mapping study the cortical representation of a remaining digit was not significantly different at 8`, as compared with 2 months following amputation . A spatial limit for reorganization is also indicated by the appearance of a persistent, cutaneously nonresponsive zone within the former territories or representation of multiple amputated digits . These studies suggest that for area 3b the reoccupation process rapidly approaches a physical limiting distance of about 700 µm . The areal extents of possible changes would be limited in any given field, we believe, by the extents of the divergences and convergences of inputs projecting to that field . It should be noted that nearly all of the somatosensory experiments described here were conducted in the koniocortical field, area 3b . This field has the most constrained anatomical distribution of the inputs of any somatosensory representation and thus is presumably the least alterable of the eight or so somatosensory cortical representations in anthropoids . Consistent with this conclusion, much greater map changes after peripheral lesions, differential skin use, cortical infarct and far greater cortical map variablity in normal adults, have been recorded in the more divergently/convergently connected cortical areas I or SI I than in cortical area 3b [e .g . 23, 26 . 31] .
CONCLUSIONS Stich profound changes in the cortical area of representation, of receptive fields sizes, or in the details of topographical relationships within neocortical representations almost certainly must bear consequences for the specific behaviors that depend on the operation of this neural machinery . There are innumerable behaviors for which long-term, continual performance gains are recorded with practice [2, 6] . Like cortical representational plasticity in monkeys, this capacity for the acquistion of skill and for improvements in perceptual capacities with practice is lifelong . This lifelong dynamic cortical capacity for neuronal response adaptation by use almost certainly also underlies the progressive representational remodeling that we have recorded following brain lesions . These common adaptive processes are discoverable and delineable, in detail . Given their revelation, behaviorally driven or lesion-induced representational alterations can be directly related to alterations in perceptual and cognitive capacities in normal and brain-damaged subjects . We turn now to those tasks .
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LURIA, A ., NAYDIN . V ., TSVETKOFVA, L . and VINARSKAYA, E . Restoration of higher cortical function following local brain damage . In Handbook of Clinical Neurology, Vol . 3, R . J . VINKEN and G . W . BRUYN (Editors), pp . 368--433,1969 . 20 . LURIA, A . R . The Working Brain : An Introduction to Neuropsychology . Basic Books Inc . . New York, 1973 . 21 . MARSHALL, J . F. Brain function : neural adaptations and recovery from injury . Ann . Rev . Psvchol .35, 377-308, 1984 . 22 . MERZENICH . M . M ., SUR, M ., NELSON, R . J . and KAAS, J . H . Organization of the Si cortex : multiple cutaneous representations in Areas 3b and I of the owl monkey . In Cortical Sensory Organization . Vol . 1 : Multiple Somatic Areas, C . N . WOOLSEY (Editor), pp . 47 .66 . Human Press, Clifton, New Jersey, 1981 . 23 . MERZENICH, M . M ., KAAS, J . H ., WALL, J . T., NELSON, R . J ., SUR, M . and FELLEMAN, D . Topographic reorganization of somatosensory cortical areas 3b and I in adult monkeys following restricted deafferentation . Neuroscience. 8, 33-55, 1983 . 24 . MERZENICH, M . M ., NELSON, R . J . . STRYKER, M . S ., CYNADER, M . S ., SCHOPPMANN, A . and ZOOK, J . M . Somatosensory cortical map changes following digit amputation in adult monkeys . J. comp . Neurol. 224, 591-605,1984 . 25 . MERZENICH, M . M . Sources of intraspecies and interspecies cortical map variability in mammals : conclusions and hypotheses . In Comparative Neurobiology : Modes of Communication in the Nervous System, M . CoHEN and F . STRUMWASSER (Editors), pp . 138-157. John Wiley, New York, 1985 . 26 . MERZENICH, M . M ., NELSON, R . J ., KAAS, J . H ., STRYKER, M . P ., JENKINS, W . M ., ZOOK, J . M ., CYNADER, M . S . and SCHOPPMANN, A . Variability in hand surface representations in areas 3b and I in adult owl and squirrel monkeys . J . comp . Neurol . 258, 281-297, 1987. 27 . MERZENICH . M . M . Dynamic neocortical processes and the origins of higher brain functions . In The Neural and Molecular Bases of Learning, J . P . CHANGEUx and M . KoNisni (Editors), pp . 337 358 . John Wiley, New York, 1987 . 28 . MERZENICH, M . M ., RECANZONE, G ., JENKINS, W . M ., ALLARD, T . T . and NuDD, R . J . Cortical representational plasticity . In Neurobiology ofNeocortex, P . RAKIC and W. SINGER (Editors), pp . 41-67 . John Wiley, New York, 1988 .
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movements .
1
0028-393290 53W+0 .00 1990 Pergarnon Press P1,
NEOCORTICAL REPRESENTATIONAL DYNAMICS IN ADULT PRIMATES : IMPLICATIONS FOR NEUROPSYCHOLOGY WILLIAM
M.
JENKINS,* MICHAEL
M.
MERZENICH
and
GREGG RECANZONE
Coleman Laboratory . University of California at San Francisco, San Francisco . CA 94143-0526, U .S .A .
Abstract-Some evidence for functional reorganization of cortical somatosensory representations in adult primates is reviewed . These examples include representation remodeling in cortical area 36 following digit amputation, digit fusion, local intracortical microstimulation, restricted cortical lesions, or as a consequence of behaviorally controlled stimulation of restricted hand surfaces . We suggest that the profound changes in the cortical representations that have been observed after these and other manipulations must bear consequences for the specific behaviors that depend on the operation of this neural machinery . Furthermore, this lifelong dynamic cortical capacity for neuronal response adaptation by use almost certainly also underlies the progressive representational remodeling that we have recorded following brain lesions .
INTRODUCTION its inception, neuropsychology has been concerned with describing the neural bases of FROM complex human mental activities and associated behaviors, with one principal source of insight being human subjects with defined brain lesions . Early investigators who used the focal brain lesion-behavioral deficit approach in human (and animal) models recognized that behavioral deficits following brain damage were not stable over time . Thus, for example, LASHLEY [18] concluded that following a brain lesion there " . . . is a reorganization within a dynamic system of which only a part has been destroyed" . Descriptions of progressive changes in measured or observed behavioral capacities that followed restricted lesions in animals recorded in numerous experiments conducted over more than a century of ablationbehavioral research provide strong support for this conclusion . In summarizing a widely held view on the progress of changes following brain lesions in human, LURIA [20] argued that " . . . a pathological focus arising as a result of a wound, or haemorrhage, or of a tumour disturbs the normal working of a given brain area, abolishes the conditions necessary for the normal working of the particular functional system, and thus leads to reorganization of the intact parts of the brain, so that the disturbed function can be performed in new ways" . Again, manifold human observations support the basic contention that a functional reorganization follows brain injury or stroke, and underlies subsequent, progressive behavioral changes and recoveries . Despite this extensive behavioral evidence for functional remodeling of effective neuronal circuits and/or mechanisms following brain injury, the orgins of recovery from brain damage *Author to whom correspondence should be addressed . 573
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have been surprisingly little studied . Indeed, many fundamental questions remain to be answered about the physiological processes operating within the adult brain that account for the adaptive features of cognitive functions and behavior recorded (a) following brain injury or stroke, much less (b) in normal individuals, or (c) as a consequence of neurological illness . There is currently a growing body of neurophysiological literature indicating that rile neocortex of adult mammals has the capacity Jor functional reorganization, as evidenced by changes in the response properties of individual cortical neurons [36] . Such changes occur as a consequence of both peripheral and central pathophysiological disturbances . Recent evidence also reveals that neocortical functional reorganization occurs in the absence of any pathophysiological conditions, and thus indicates that representational dynamics reflect properties of normal, lifelong neocortical processes . This neocortical capacity for representational remodeling has obvious and important implications for understanding the nervous system origins of progresssive functional recovery following brain lesions- as well as implications for understanding the origins of normal behavioral adaptive processes . Our objective in this brief report is to provide an overview of some of the results from our own electrophysiological studies that illustrate the mutability of somatosensory neocortical representations in adults . Given these few selected examples, we shall briefly discuss the implications of this class of experiments for understanding mechanisms underlying the neural origins of adaptive behaviors . The scope of this report precludes a comprehensive review of the considerable literature on recovery of function in animals and humans [3, 6, 7, 9, 12, 21] . SOME EVIDENCE FOR FUNCTIONAL REORGANIZATION Common and variable features of normal cortical somatosensory representation In an extensive series of electrophysiological studies, we have described many of the details and dynamic aspects of somatotopic representations within the functional subdivisions of primate SI [22, 25, 27, 28] . We have previously considered the sources of intraspecies and interspecies cortical map variability in normal adult primates and have addressed many of the methodological details of the conduct of this class of electrophysiological experiments [26, 34] . Because of convenience of study, most experiments have been conducted within the zones of hand representations in St . The results of those studies indicate several common map features . (a) There was a single complete or nearly complete representation of the glabrous hand surface in area 3b . (b) The distal aspects of the digits were usually represented along the functionally defined 3b-3a (cutaneous-deep) border while the more proximal digit skin surfaces were represented in topographic sequence in progressively more caudal portions of area 3b . (c) The radial aspect of the hand (e .g . digit I) was represented in the lateral portion of the hand representation usually adjacent to the representation of the face, while the more ulnar aspects of the hand were represented in topographic order in progressively more medial portions of area 3b . (d) The cortical area devoted to the representation of each distal phalanx was almost always greater than the cortical area of representation of either the middle or proximal phalanx . (e) The internal topographic order was maintained throughout the field, with few receptive fields out of topographic sequence . (f) The dorsal skin surfaces were represented in a number of small . fragmentary, discontinuous patches embedded in a much larger glabrous digital skin representation . (g) There are normally extremely abrupt representation discontinuities between adjacent digit representations . (h) The sizes of receptive fields on a given skin surface
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were, on the average, roughly inversely related to the size of the cortical representational magnification (cortical area of representation/skin surface area) for that skin surface . There were many other significantly variable map features among different monkeys . (a) The overall shapes and sizes of hand surface representations varied substantially . (b) The actual and proportional areas of representations of different skin surfaces and the cortical magnifications of representations of specific skin surfaces commonly varied several-fold in cortical area 3b . (c) The detailed topographic relationships among skin surface representations varied greatly ; skin surfaces that were represented in adjacent locations in some monkeys were represented in locations many hundreds of microns apart in others . (d) The internal orderliness of representations varied significantly . (e) The completeness of representations of the dorsal hand surfaces was different in every studied monkey . (f) The skin surfaces represented along the borders of the hand representation was idiosyncratic . We hypothesized that the differences in the details of cortical map structure are the consequence of individual differences in lifelong use of the hands [25-28] . By that view, the functional map present at any instance in the life of a monkey (or human) is shaped by the summed, stored changes presumably driven by behaviorally significant experience up to that point in life . This conclusion is consistent with the following examples in which we have experimentally altered the patterns of peripheral stimulation (a) by peripheral or central surgical intervention, and (b) behaviorally .
DYNAMIC ALTERATION OF CORTICAL MAPS ; SOME EXAMPLES Representational remodeling in cortical area 3b following digit amputation One of the most striking examples of neocortical representational dynamics was observed when all sensory inputs from one or two digits were removed [24] . Recall that within the cortical representation of the hand each digit is represented discretely (i .e . receptive fields very rarely extend beyond a single digit) albeit adjacently in topographical sequence . Such a lack of overlap in the representations of adjacent glabrous digits might indicate that the representations of adjacent glabrous digital surfaces are anatomically separated throughout the somatosensory projection system . If not, then such representational discontinuities must be dynamically established and maintained . This study revealed that the representations of adjacent digits and palmar surfaces expanded topographically to occupy most or all of the cortical territories formerly representing the amputated digit (Fig . I ) . As a consequence of these expanded representations, there were several-fold increases in the cortical magnification (cortical area,: skin surface area) of adjacent digits and systematic decreases in the sizes of receptive fields for neurons within these expanded representations . Theses studies also revealed that the discontinuities between the representations of the digits were translocated several hundred microns after amputation, and sharp new discontinuous boundaries formed where normally separated, expanded digital representations approached each other in the reorganized map . This implied that these map discontinuities are normally dynamically maintained . The spatial distributions and time course of changes in receptive field sizes with the expansion of representations of surrounding skin surfaces into the vacated cortical zone has parallels to positive changes in tactile acuity and sensitivity on the stumps of human amputees [14, 15, 35] . Furthermore, there are no apparent perceptual localization errors with stimulation of the skin surrounding an amputation in humans . The combined human and monkey data suggest that the same cortical neurons can signal locations of inputs from
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different skin surfaces at different times . At present refined behavioral measures of tactile acuity and cortical magnification and receptive field data have not been obtained in the same subject . Representational changes following digital fusion
In another series of experiments, we again took advantage of the representational discontinuities between digits . We and others had hypothesized that a limited subset of inputs generating the excitatory receptive fields in somatosensory neocortex are "selected" from a large afferent input repertoire by adaptive, temporal correlation-based processes [8, 24, 25] . Anatomical evidence suggests that somatosensory thalamocortical afferents terminate across much larger reaches of SI than is predicted by the size and location of receptive fields defined for single cortical neurons [10, 33], thus providing the neuroanatomical substrate for a dynamic input selection process . We knew that the temporal patterns of input activity from nearby locations on any single digit are highly correlated . By contrast, inputs from adjacent digits, given their independent ranges of movement and relative mechanical isolation, are relatively temporally independent . We specifically hypothesized that representational discontinuities arise between digits in somatosensory cortical maps because of the higher probability of non-simultaneous afferent input across these boundaries . As a test of this hypothesis, we fused the skin of two adjacent digits in several adult owl monkeys using microsurgical techniques that allowed us to preserve the normal innervation of both digits [ 1, 3] . This surgery created an artificial syndactyly in which the two fused digits are used in normal behaviors as though it was a single digit . After several months of behavioral experience in which the monkeys were observed to use to syndactylized hands normally (e .g . grasping food, climbing, grooming, etc .) a detailed microelectrode map of area 3b was obtained (see Fig . 2) . For comparison purposes, Fig . 2A depicts an area 3b map of digits 3 and 4 and adjacent surfaces of digits 2 and 5 and of the palm (P) in a normal non-syndactylized hand . Shaded patches are areas of dorsal hand representation . Receptive fields at starred sites are drawn on the hand to the right . Note that for adjacent starred recording sites located at the borders of adjacent digital representational zones the individual receptive fields are located entirely on a single digit . The abrupt shifts in the locations of receptive fields from one digit to the next at adjacent cortical locations serve to illustrate the extremely abrupt representation discontinuities commonly observed between adjacent digits in normal monkeys . By contrast . Fig . 2B depicts a cortical map obtained several months after syndactyly surgery . In this map, the discontinuity between the syndactylized digits (digits 3 and 4) was abolished . The diagonally filled region indicates the cortical zone within which all defined receptive fields overlapped both digits 3 and 4 . The open stars are exemplary recording sites at which the receptive fields drawn on the hand to left were defined . In order to control for possible cross-innervation of the two digits post-surgically, or for potential mechanical coupling artifacts that might affect accurate receptive field definition . the fingers were once again separated . Again receptive fields were defined for cortical locations within the region occupied by so-called "double digit receptive fields" . Most defined receptive fields (94%) still had components on both digits . Three such receptive fields are shown on the hand to the right and were obtained from the same three cortical locations indicated by the stars . These experiments have led us to conclude that the abrupt representational discontinuities observed in normal somatosensory cortical maps derive from central neural mechanisms that rely on temporal input-correlation-based rules [I, 3, 24, 27, 28] . These correlation-
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A Normal
B 62 days after digit 3 amputation
Fig . 1 . (A) Representation of the hand surfaces within and adjacent to area 3b in a normal adult owl monkey . Receptive fields located on the face are indicated by F while penetration sites at which neurons were driven by deep but not cutaneous receptor inputs are marked by X . The large numbers 1-5 denote the digits (e .g . 1=thumb ; d, m, p, are distal, middle . and proximal phalanges, respectively) : P 1-4 are the palmar pads at the base of the digits ; Ph is the hypothenar eminence ; Pt is the thenar eminence . Stippled zones indicate dorsal (hairy) skin on the digits . Solid lines outline territories of representation of the digits and palmar pads . Broken lines mark the borders between phalangeal representational zones . (B) Representation of the hand surfaces derived 62 days after amputation of digit 3 in the same adult owl monkey . Note that the former 3b cortical representation of digit 3 is now occupied by expanded representations of adjacent digits 2 and 4 . and of the palmar pads 2 and 3 . based mechanisms must make a fundamental contribution to the expression
of
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topographic details in neocortical representations .
Rapid representational changes follow local intracortical microstimularion In two related series of experiments, the input coincidence of activity within neocortex has been manipulated directly . The intracortical microstimulation technique
(ICMS)
has
commonly been used in experiments defining movement representations in motor cortex . It
ICMS can itself alter movement representations in the motor [13 . 29, 30] . Similar experiments [32] have now been conducted within representation of the somatosensory koniocortical field in rats (SM I ) and
has been demonstrated that cortex
of adults
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adult primates (areas 3b) . In this study, the specific receptive field defined at a stimulation
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500 p Fig .? (A)Area3breconstructionoftherepresentationofdigits3and4andportionsofdigits2and5 . Small Ill led squares are electrode penetration sites at which receptive fields were defined . Stars (A-F) are selected sites near digit representation borders . (R) Receptive fields defined for sites A- F are drawn as stippled areas on the hand to the right . Note that for adjacent recording sites on either side of digit borders the receptive fields are exclusively on one or the other digit . site came to be represented at many cortical locations more than 600 fim away from the stimulation site . Such changes in the representational topography progressed throughout the course of stimulation . Again, these studies suggest that the temporal patterns of cortical-cortical!cortical-thalamic interactions play a direct role in the formation of individual receptive fields and cortical map topographies . Hand surface representations are dramatically reoryani :ed following restricted cortical lesions In another class of input-alteration studies, we have changed patterns of cortical-cortical and cortical-thalamic interactions by the creation of small focal area 3b lesions [16] . The
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locations and extents of these cortical lesions were defined in electrophysiological mapping experiments conducted within and across the boundaries of area 3b in adult primates . In initial studies, no attempt was made to provide behavioral therapy for the affected hand, nor were sensory and motor deficits identified using standardized testing protocols . We considered (indeed, are now investigating) the possibility that such post-lesion testing, ;training could alter the form of any consequent map reorgnization, or might significantly alter the functional use of the affected hand . During an initial several-week period after such lesions, monkeys used their affected hands only for crude motor tasks . For example, over this early post-lesion period the hand was used for grasping the cage bars when climbing-but not for manipulating or retrieving food pellets, a behavior that requires more refined motor control of the digits . However, within several weeks after these small area 3b lesions, no great differences in hand use were observed . Several months after induction of these cortical lesions, mapping experiments were again conducted in the region flanking the lesion within area 3b . Substantial reorganization of the hand representation was recorded in all of these adult monkeys . As a consequence of that representational remodeling, neurons over a broad surround region at least several millimeters in extent were driven by newly acquired inputs . and skin surfaces formerir represented in the cortical -one of the lesion came to be represented in entirety in the cortex surrounding the lesion . One result of this functional reorganization was the development of unusual, complicated representational topographies within the surrounding reorganized representation . For example, the location of a restricted area 3b cortical lesion immediately after induction is shown in Fig . 3A . No neural responses were seen at locations within the zone of the lesion (indicated in black). The lesion destroyed the entire area 3b representation of digit 3, pad 2, pad 3 and a portion of digits 2 and 4 . A reconstruction of the area 3b hand representation medial to the cortical lesion obtained 58 days after induction is shown in Fig . 3B . The zone of representation of skin surfaces fomerly located only in the zone of the lesion but now represented in the cortex flanking the lesion is indicated by stippling . Diagonal lines mark the cortical sectors at which cutaneous receptive fields were significantly larger than normal . Note that the small cortical zone representing portions of digit 3 and digit 4 is located medial and dorsal to the digit 5 representation . This form of representational topography has never been observed in normal monkeys . We hypothesize that this dramatic topographic reorganization in the region surrounding an infarct likely constitutes a fundamental basis for recovery from brain injury [16] . Of course, reorganization can occur only when a sector or a cortical area with given qualitative inputs survives the cortical lesion . We also wish to emphasize that other models of recovery from stroke such as processing substitution models may also contribute to the recovery process [e .g . 19, 21] . The unusual representational topographies and large receptive fields observed in our experimental cases might be expected to be reflected by some lasting behavioral deficits, but that tentative conclusion remains unproven . Also, we do not yet know whether rehabilitative strategies that are believed to alter the functional recovery from brain lesions [4] would alter details of representational maps surrounding such lesions, but other experiments in our series (see below) indicate that that is likely . Cortical maps can he representationally distorted by a period the heauh engagement of restricted hand surfaces
of behavioral
training involving
We have also undertaken a series of behavioral experiments that were designed to produce high levels of temporally correlated activity over a restricted skin surface [ 16, 17] . Adult owl
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B
* Fig . 3 . Representation of the hand in area 3b in adult owl monkey immediately after and 58 days after introduction of a restricted cortical lesion . (A) The hand region defined immediately after the cortical lesion (black) . No neural responses were seen in penetrations within the zone oft his lesion . Cut aneous receptive fields were defined for electrode penetration sites lateral, medial and caudal to the lesion . The lesion destroyed the entirecortical area 3h representation of digit 3, pad 2,pad 3 anda portion of digits 2 and 4 . (R) Representation of the ulnar aspect of the hand in the cortical zone medial to the lesion 58 days after lesion induction . The zone of represention of skin surfaces formerly located in the zone of the lesion but now found in the adjacent cortex is indicated by stippling . Diagonal lines mark a cortical sector in which cutaneous receptive fields were extraordinarily large . Stars are fiducial points corresponding to common vascular landmarks . monkeys were trained using operant conditioning techniques to contact a cutaneous stimulus delivery device in order to obtain food rewards . During each episodic contact, cutaneous stimuli were delivered exclusively to the glabrous skin on the distal phalanx of one or two digits . By such means, each animal experienced several hundred thousand cutaneous stimuli delivered daily to a selected skin surface . Electrophysiological mapping experiments were conducted prior to and immediately after several months of differential stimulation experience . In these experiments, the zones of representation within area 3b of such heavily stimulated skin surfaces enlarged greatly in extent in otherwise normal adult owl monkeys (e .g . compare the representation of distal phalanges 2 and 3 in Fig . 3A to that in Fig . 3B) . In
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C DM I %ulngaa Catd lhagSAoaUn
OM 1 Distal Phalanges After stimulation
E E
J Digits
Fig . 4 . (A) Reconstruction of the hand representation in area 3b prior to differential stimulation . IB) Post-stimulation reconstruction of hand representation after 109 days ofdaily differential stimulation totaling about 1 .5 hr per day . Skin surfaces on the tips of digits 2 and 3 and occasionally the tip of digit 4 were stimulated . (C) Cortical magnification x 103 of the glabrous representation of all five digits is plotted, for normal and post-stimulation distal . middle, and proximal phalanges. Note that the magnification of the representation of each phalangeal surface is relatively constant across the five fingers in both monkeys at these two stages of life except for the striking increase in the magnification of stimulated phalanges . Arrows indicate the locations of skin surfaces differentially stimulated . (D) Cortical magnification (black squares) for distal phalanges obtained after differential stimulation (ordinate is on the left axis) . Mean receptive field size in mm' (open squares) plotted for these same skin surfaces obtained after differential stimulation (ordinate on the right axis) . Note that in this exemplary case these two functions are roughly inversely related . That is, as cortical representations of these struck surfaces expanded, they came to be represented in finer grain .
addition, these distorted representations eventually returned to a normal skin surface representation after the behavioral task was halted . The enlargement in representation in an adult behaving monkey occurred only for stimulated skin surfaces, This can be seen in the example shown in Fig . 4C, for example, where the cortical magnification of all digital segments (phalanges) is plotted prior to stimulation (open symbols) and after tactile stimulation (closed symbols) . There was nearly a three-fold increase in the cortical territory representing the principal stimulated phalanx (i .e . digit 2-distal phalanx) . Recall that in both normal and other examples of reorganized neocortical maps, there was a roughly inverse relationship between receptive field size and the area of representation for a
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given skin surface . Such a relationship was also seen in these behavioral experiments . In Fig . 4D the black squares indicate the cortical magnification (scale on the left ordinate) and the open squares indicate the mean receptive field size (scale on the right ordinate) for each of the five distal phalanges . The distal phalanx (digit 2) with the largest cortical magnification (23 .37 x 10') had the smallest mean receptive field size (4 .676 mm') . The distal phalanx (digit 5) with the smallest cortical magnification (7 .06 x l0') had the largest mean receptive field size (9 .852 mm') . Limits of fimetional reorganization It is well recognized that behavioral deficits can be reliably obtained following cortical lesions and that depending on the size and locus of the lesion variable degrees of recovery are obtained . Whatever recovery mechanisms obtain, they must have some limitations or else behavioral deficits following focal brain damage would be more rare than they are . The results from our own experiments suggest that reorganization occurs over a limited distance [24] . For example, in a two-stage post-amputation mapping study the cortical representation of a remaining digit was not significantly different at 8`, as compared with 2 months following amputation . A spatial limit for reorganization is also indicated by the appearance of a persistent, cutaneously nonresponsive zone within the former territories or representation of multiple amputated digits . These studies suggest that for area 3b the reoccupation process rapidly approaches a physical limiting distance of about 700 µm . The areal extents of possible changes would be limited in any given field, we believe, by the extents of the divergences and convergences of inputs projecting to that field . It should be noted that nearly all of the somatosensory experiments described here were conducted in the koniocortical field, area 3b . This field has the most constrained anatomical distribution of the inputs of any somatosensory representation and thus is presumably the least alterable of the eight or so somatosensory cortical representations in anthropoids . Consistent with this conclusion, much greater map changes after peripheral lesions, differential skin use, cortical infarct and far greater cortical map variablity in normal adults, have been recorded in the more divergently/convergently connected cortical areas I or SI I than in cortical area 3b [e .g . 23, 26 . 31] .
CONCLUSIONS Stich profound changes in the cortical area of representation, of receptive fields sizes, or in the details of topographical relationships within neocortical representations almost certainly must bear consequences for the specific behaviors that depend on the operation of this neural machinery . There are innumerable behaviors for which long-term, continual performance gains are recorded with practice [2, 6] . Like cortical representational plasticity in monkeys, this capacity for the acquistion of skill and for improvements in perceptual capacities with practice is lifelong . This lifelong dynamic cortical capacity for neuronal response adaptation by use almost certainly also underlies the progressive representational remodeling that we have recorded following brain lesions . These common adaptive processes are discoverable and delineable, in detail . Given their revelation, behaviorally driven or lesion-induced representational alterations can be directly related to alterations in perceptual and cognitive capacities in normal and brain-damaged subjects . We turn now to those tasks .
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S . On the instability of a cortical point Proc . R . Soc . 85, 250-277 . 1912 . 14 . HABER, W. B . Effects of loss of limb on sensory functions . J . Psychol 40, 115-123, 1955 . 15 . HABER, W. B . Reactions to loss of limb : physiological and psychological aspects . Ann . N .1' . Acad. Sci . 74,14-24, 1958 . 16 . JENKINS, W. M . and MERZENICH, M . M . Reorganization of neocortical representations after brain injury : a neurophysiological model of the bases of recovery from stroke . In Progress in Brain Research, F . J . Sea, E . HERBERT and B. M . CARLSON (Editors), pp . 249-266 . Elsevier, Amsterdam, 1987 . 17 . JENKINS, W . M ., MERZENICH, M . M ., OcHS, M . T ., ALLARD, T . ano Guic, E . Functional reorganization of somatosensory representations within area 3b of adult owl monkey after behviorally controlled tactile stimulation . J. Neurophysiol ., 63, 1990 (in press) . 18 . LASHLEY, K . S . Integrative functions of the cerebral cortex. Physiol . Rev . 13, 1-42, 1933 . 19 . LURIA, A ., NAYDIN . V ., TSVETKOFVA, L . and VINARSKAYA, E . Restoration of higher cortical function following local brain damage . In Handbook of Clinical Neurology, Vol . 3, R . J . VINKEN and G . W . BRUYN (Editors), pp . 368--433,1969 . 20 . LURIA, A . R . The Working Brain : An Introduction to Neuropsychology . Basic Books Inc . . New York, 1973 . 21 . MARSHALL, J . F. Brain function : neural adaptations and recovery from injury . Ann . Rev . Psvchol .35, 377-308, 1984 . 22 . MERZENICH . M . M ., SUR, M ., NELSON, R . J . and KAAS, J . H . Organization of the Si cortex : multiple cutaneous representations in Areas 3b and I of the owl monkey . In Cortical Sensory Organization . Vol . 1 : Multiple Somatic Areas, C . N . WOOLSEY (Editor), pp . 47 .66 . Human Press, Clifton, New Jersey, 1981 . 23 . MERZENICH, M . M ., KAAS, J . H ., WALL, J . T., NELSON, R . J ., SUR, M . and FELLEMAN, D . Topographic reorganization of somatosensory cortical areas 3b and I in adult monkeys following restricted deafferentation . Neuroscience. 8, 33-55, 1983 . 24 . MERZENICH, M . M ., NELSON, R . J . . STRYKER, M . S ., CYNADER, M . S ., SCHOPPMANN, A . and ZOOK, J . M . Somatosensory cortical map changes following digit amputation in adult monkeys . J. comp . Neurol. 224, 591-605,1984 . 25 . MERZENICH, M . M . Sources of intraspecies and interspecies cortical map variability in mammals : conclusions and hypotheses . In Comparative Neurobiology : Modes of Communication in the Nervous System, M . CoHEN and F . STRUMWASSER (Editors), pp . 138-157. John Wiley, New York, 1985 . 26 . MERZENICH, M . M ., NELSON, R . J ., KAAS, J . H ., STRYKER, M . P ., JENKINS, W . M ., ZOOK, J . M ., CYNADER, M . S . and SCHOPPMANN, A . Variability in hand surface representations in areas 3b and I in adult owl and squirrel monkeys . J . comp . Neurol . 258, 281-297, 1987. 27 . MERZENICH . M . M . Dynamic neocortical processes and the origins of higher brain functions . In The Neural and Molecular Bases of Learning, J . P . CHANGEUx and M . KoNisni (Editors), pp . 337 358 . John Wiley, New York, 1987 . 28 . MERZENICH, M . M ., RECANZONE, G ., JENKINS, W . M ., ALLARD, T . T . and NuDD, R . J . Cortical representational plasticity . In Neurobiology ofNeocortex, P . RAKIC and W. SINGER (Editors), pp . 41-67 . John Wiley, New York, 1988 .
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movements .
