Adult brain plasticity - what is revealed is exciting, what is hidden is critical.

Abstract: Summary This paper is a review conducted to provide an overview of accumulated evidence on contemporary rehabilitation methods for stroke survivors Loss of functional movement is a common consequence of stroke for which a wide range of interventions has been developed Traditional therapeutic approaches have shown limited results for motor deficits as well as lack evidence for their effectiveness Stroke rehabilitation is now based on the evidence of neuroplasticity, which is responsible for recovery following stroke The neuroplastic changes in the structure and function of relevant brain areas are induced primarily by specific rehabilitation methods The therapeutic method which induces neuroplastic changes, leads to greater motor and functional recovery than traditional methods Further, the recovery is permanent in nature During the last decade various novel stroke rehabilitative methods for motor recovery have been developed This review focuses on the methods that have evidence of associated cortical level reorganization, namely task-specific training, constraint-induced movement therapy, robotic training, mental imaging, and virtual training All of these methods utilize principles of motor learning The findings from this review demonstrated convincing evidence both at the neural and functional level in response to such therapies The main aim of the review was to determine the evidence for these methods and their application into clinical practice

Abstract: Adult brains undergo large-scale plastic changes after peripheral and central injuries. Although it has been shown that both the cortical and thalamic representations can reorganize, uncertainties exist regarding the extent, nature, and time course of changes at each level. We have determined how cortical representations in the somatosensory area 3b and the ventroposterior (VP) nucleus of thalamus are affected by long standing unilateral dorsal column lesions at cervical levels in macaque monkeys. In monkeys with recovery periods of 22-23 months, the intact face inputs expanded into the deafferented hand region of area 3b after complete or partial lesions of the dorsal columns. The expansion of the face region could extend all the way medially into the leg and foot representations. In the same monkeys, similar expansions of the face representation take place in the VP nucleus of the thalamus, indicating that both these processing levels undergo similar reorganizations. The receptive fields of the expanded representations were similar in somatosensory cortex and thalamus. In two monkeys, we determined the extent of the brain reorganization immediately after dorsal column lesions. In these monkeys, the deafferented regions of area 3b and the VP nucleus became unresponsive to the peripheral touch immediately after the lesion. No reorganization was seen in the cortex or the VP nucleus. A comparison of the extents of deafferentation across the monkeys shows that even if the dorsal column lesion is partial, preserving most of the hand representation, it is sufficient to induce an expansion of the face representation.

Abstract: The primary motor cortex of mammals has an orderly representation of different body parts Within the representation of each body part the organization is more complex, with groups of neurons representing movements of a muscle or a group of muscles In rats, uncertainties continue to exist regarding organization of the primary motor cortex in the whisker and the neck region Using intracortical microstimulation (ICMS) we show that movements evoked in the whisker and the neck region of the rat motor cortex are highly sensitive to the depth of anaesthesia At light anaesthetic depth, whisker movements are readily evoked from a large medial region of the motor cortex Lateral to this is a small region where movements of the neck are evoked However, in animals under deep anaesthesia whisker movements cannot be evoked Instead, neck movements are evoked from this region The neck movement region thus becomes greatly expanded An analysis of the threshold currents required to evoke movements at different anaesthetic depths reveals that the caudal portion of the whisker region has dual representation, of both the whisker and the neck movements The results also underline the importance of carefully controlling the depth of anaesthesia during ICMS experiments

Abstract: Transection of dorsal columns of the spinal cord in adult monkeys results in large-scale expansion of the face inputs into the deafferented hand region in the primary somatosensory cortex (area 3b) and the ventroposterior nucleus of thalamus. Here, we determined whether the upstream cortical areas, secondary somatosensory (S2) and parietal ventral (PV) areas, also undergo reorganization after lesions of the dorsal columns. Areas S2, PV, and 3b were mapped after long-term unilateral lesions of the dorsal columns at cervical levels in adult macaque monkeys. In areas S2 and PV, we found neurons responding to touch on the face in regions in which responses to touch on the hand and other body parts are normally seen. In the reorganized parts of S2 and PV, inputs from the chin as well as other parts of the face were observed, whereas in area 3b only the chin inputs expand into the deafferented regions. The results show that deafferentations lead to a more widespread brain reorganization than previously known. The data also show that reorganization in areas S2 and PV shares a common substrate with area 3b, but there are specific features that emerge in S2 and PV.

Abstract: Long-term injuries to the dorsal columns of the spinal cord at cervical levels result in large-scale somatotopic reorganization of the somatosensory areas of the cortex and the ventroposterior nucleus of the thalamus. As a result of this reorganization, intact inputs from the face expand into the deafferented hand representations. Dorsal column injuries also result in permanent deficits in the use of digits for precision grip and a loss of fractionated movements of the digits. We determined whether the chronic loss of sensory inputs and the behavioral deficits caused by lesions of the dorsal columns in adult macaque monkeys affect organization of the motor cortex. The results show that, in the primary motor cortex, intracortical microstimulation evokes extension–flexion movements of the thumb at significantly fewer sites compared with the normal monkeys. There is a corresponding increase in the adduction–abduction movements. Furthermore, there is a significant increase in the thresholds of the currents required to evoke movements of the digits. Thus, long-term sensory loss in adult monkeys does not change the overall topography of the movement representation in the motor cortex but results in changes in the details of movement representations.

Abstract: Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom-limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.

Abstract: After limited sensory deafferentations in adult primates, somatosensory cortical maps reorganize over a distance of 1 to 2 millimeters mediolaterally, that is, in the dimension along which different body parts are represented. This amount of reorganization was considered to be an upper limit imposed by the size of the projection zones of individual thalamocortical axons, which typically also extend a mediolateral distance of 1 to 2 millimeters. However, after extensive long-term deafferentations in adult primates, changes in cortical maps were found to be an order of magnitude greater than those previously described. These results show the need for a reevaluation of both the upper limit of cortical reorganization in adult primates and the mechanisms responsible for it.

Abstract: Two to nine months after the median nerve was transected and ligated in adult owl and squirrel monkeys, the cortical sectors representing it within skin surface representations in Areas 3b and 1 were completely occupied by 'new' and expanded representations of surrounding skin fields. Some occupying representations were 'new' in the sense that (1) there was no evidence that these skin surfaces were represented in this region prior to median nerve transection; and (2) these skin surfaces retained their normal representation elsewhere within these two cortical representations of hand surfaces. Large 'new' representations of the dorsal surfaces of digits 1 and 2 (innervated by the radial nerve) and large 'new' representations of the hypothenar eminence (innervated by the ulnar nerve) were consistently recorded. Some surrounding skin surface representations expanded into the former median nerve zone, so that bordering skin surfaces (the ulnar insular palmar pad, the third digital palmar pad, glabrous ulnar digit 3, radial hand dorsum) were represented over far larger than normal cortical areas. These expanded representations of always-innervated skin sometimes appeared to move in entirety into the former median nerve representational zone (e.g. in the zone of representation of glabrous digit 4) were also consistently recorded. Reorganizational changes following median nerve sections were much more variable in Area 1 than in Area 3b. The topographic order of the reorganized cortical zone was comparable to normal. In at least most cortical sectors, there was a consistent, maintained relationship between receptive field size and magnification, i.e. as representations enlarged, receptive fields were correspondingly reduced in size. These studies indicate that topographic representations of the skin surface in adult monkeys are maintained dynamically. They clearly reveal that this projection system retains a self-organizing capacity in adult monkeys. They suggest that processes perhaps identical to a part of the original developmental organizing processes (by which details of field topographics are established) are operational throughout life in this projection system in primates. Some of the implications of these studies for the neural origins of tactile perception are discussed.

Abstract: In an earlier study (Neuroscience 8, 33-55, 1983), we found that the cortex representing the skin of the median nerve within parietal somatosensory fields 3b and 1 was completely occupied by 'new' inputs from the ulnar and radial nerves, 2-9 months after the median nerve was cut and tied in adult squirrel and owl monkeys. In this report, we describe the results of studies directed toward determining the time course and likely mechanisms underlying this remarkable plasticity. Highly detailed maps of the hand surface representation were derived in monkeys before, immediately after, and at subsequent short and intermediate time stages after median nerve section. In one monkey, maps were derived before nerve section, immediately after nerve section, and 11, 22 and 144 days later. Thus, direct comparisons in cortical map structure could be made over time in this individual monkey. In other experiments, single maps were derived at given post-section intervals. These studies revealed that: (1) large cortical sectors were 'silenced' by median nerve transection. (2) Significant inputs restricted to the dorsum of the radial hand and the dorsum of digits 1, 2 and 3 were immediately 'unmasked' by median nerve transection. (3) These immediately 'unmasked' regions were topographically crude, and represented only fragments of this dorsal skin. They were transformed, over time, into very large, highly topographic and complete representations of dorsal skin surfaces. (4) Representations of bordering glabrous skin surfaces progressively expanded to occupy larger and larger portions of the former median nerve cortical representational zone. (5) These 'expanded' representations of ulnar nerve-innervated skin surfaces sometimes moved, in entirety, into the former median nerve representational zone. (6) Almost all of the former median nerve zone was driven by new inputs in a map derived 22 days after nerve section. At shorter times (3, 6 and 11 days), 'reoccupation' was still incomplete. (7) Very significant changes in map dimensions within and outside of the former median skin cortical field were seen after the 'reoccupation' of the deprived cortex by 'new' inputs was initially completed. (8) Progressive changes were recorded within the original ulnar and radial nerve cortical representational zones, as skin surfaces originally overtly represented wholly within these regions expanded into the former median nerve zone. (9) Throughout the studied period, the cortical representational loci of many skin sites appeared to change continually and often markedly. (10) The locations of map discontinuities also shifted significantly over time. (11) Concomitant with changes in representational magnification over time, inverse changes in receptive field sizes were recorded.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract: Removal of sensory input from a focal region of adult neocortex can lead to a large reorganization of cortical topography within the deprived area during subsequent months. Although this form of functional recovery is now well documented across several sensory systems, the underlying cellular mechanisms remain elusive. Weeks after binocular retinal lesions silence a corresponding portion of striate cortex in the adult cat, this cortex again becomes responsive, this time to retinal loci immediately outside the scotoma. Earlier findings showed a lack of reorganization in the lateral geniculate nucleus and an inadequate spread of geniculocortical afferents to account for the cortical reorganization, suggesting the involvement of intrinsic cortical connections. We investigated the possibility that intracortical axonal sprouting mediates long-term reorganization of cortical functional architecture. The anterograde label biocytin was used to compare the density of lateral projections into reorganized and non-deprived cortex. We report here that structural changes in the form of axonal sprouting of long-range laterally projecting neurons accompany topographic remodelling of the visual cortex.