Neeraj Jain

Abstract: Somatotopic maps in the cortex and the thalamus of adult monkeys and humans reorganize in response to altered inputs. After loss of the sensory afferents from the forelimb in monkeys because of transection of the dorsal columns of the spinal cord, therapeutic amputation of an arm or transection of the dorsal roots of the peripheral nerves, the deprived portions of the hand and arm representations in primary somatosensory cortex (area 3b), become responsive to inputs from the face and any remaining afferents from the arm. Cortical and subcortical mechanisms that underlie this reorganization are uncertain and appear to be manifold. Here we show that the face afferents from the trigeminal nucleus of the brainstem sprout and grow into the cuneate nucleus in adult monkeys after lesions of the dorsal columns of the spinal cord or therapeutic amputation of an arm. This growth may underlie the large-scale expansion of the face representation into the hand region of somatosensory cortex that follows such deafferentations.

Abstract: Sensory stimuli to the body are conveyed by the spinal cord to the primary somatosensory cortex. It has long been thought that dorsal column afferents of the spinal cord represent the main pathway for these signals, but the physiological and behavioural consequences of cutting the dorsal column have been reported to range from mild and transitory to marked. We have re-examined this issue by sectioning the dorsal columns in the cervical region and recording the responses to hand stimulation in the contralateral primary somatosensory cortex (area 3b). Following a complete section of the dorsal columns, neurons in area 3b become immediately and perhaps permanently unresponsive to hand stimulation. Following a partial section, the remaining dorsal column afferents continue to activate neurons within their normal cortical target territories, but after five or more weeks the area of activation is greatly expanded. After prolonged recovery periods of six months or more, the deprived hand territory becomes responsive to inputs from the face (which are unaffected by spinal cord section). Thus, area 3b of somatosensory cortex is highly dependent on dorsal spinal column inputs, and other spinal pathways do not substitute for the dorsal columns even after injury.

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: We determined the somatotopy of the face and the oral cavity representation in cortical area 3b of New World owl monkeys and squirrel monkeys Area 3b is apparent as a densely myelinated strip in brain sections cut parallel to the surface of flattened cortex A narrow myelin-light septum that we have termed the "hand-face septum" separates the hand representation from the more lateral face and mouth representation The face and oral cavity representation is further divided into a series of myelin-dense ovals We show that three ovals adjacent to the hand representation correspond to the upper face, upper lip, and chin plus lower lip, whereas three or four more rostral ovals successively represent the contralateral teeth, tongue, and the ipsilateral teeth and tongue Strips of cortex lateral and medial to the area 3b ovals, possibly corresponding to area 1 and area 3a, respectively, have similar somatotopic sequences Although previous results suggest the existence of great variability within and across primate species, we conclude that the representations of the face and mouth are highly similar across individuals of the same species, and there are extensive overall similarities across these two species of New World monkeys

Abstract: on the face, much as in the normal cortical representaThe dynamic nature of sensory representations in the tions of the face. The reactivated cortex extended some adult brain gives us the lifelong potential to adapt to 10–14 mm mediolaterally and 9–11 mm rostrocaudally, changes in our environment and to compensate for ina much greater extent than found previously after more jury. Reorganizations in sensory systems typically inlimited nerve damage (Merzenich et al., 1984). Moreover, volve relatively limited shifts in the topography of the similar reactivations undoubtedly took place in higherfunctional representations, and in most reorganizations level somatosensory representations such as the secof the somatosensory cortex only neurons within 1–2 ond somatosensory area, S2, and the parietal ventral mm of the borders of the affected zone in cortex acquire area, PV, since these areas depend on inputs from antenew or altered receptive fields (Merzenich et al., 1984). rior parietal cortex. In fact, for many years, it was assumed that this was The report of extensive reactivation of deprived cortex the maximal distance for plasticity in the adult central in these monkeys was soon followed by a description nervous system. Yet, the adult brain is capable of much of a patient with an arm amputation who felt light touch more extensive changes, involving much larger extents to the face as being both on the face and on the fingers of the nervous system. Large-scale peripheral deafferof the missing arm (Ramachandran et al., 1992). This entations, such as limb amputation or spinal cord damobservation suggested that the brains of such individuage, lead to extensive reactivations of the large regions als reorganize after amputation, as in the monkeys with of somatosensory cortex deprived by the injury. These arm deafferentation, and that touching the face leads unusually large changes in cortical organization are not to activation of both face and reactivated hand zones easily explained by cellular mechanisms involving the of cortex, hence the misplaced and double sensations. potentiation of previously existing connections. HowThis supposition was soon given further credibility when ever, there is now evidence that new connections may it became possible to record from the cortex of three grow into regions deprived of primary afferent inputs as monkeys with long-standing therapeutic amputations of a result of injury. Subcortical sensory representations the hand or forelimb. Recordings from area 3b in these are smaller than their cortical counterparts; therefore, monkeys revealed a reactivation of the deprived hand even limited new growth subcortically can lead to masand forelimb cortex by inputs from the stump of the arm sive cortical reactivations. and the face (Figure 1; see also Florence and Kaas, The first suggestion that the somatosensory system 1995). In addition, there is evidence from noninvasive is capable of extensive reorganization came from a reimaging of evoked activity in the brains of humans with port of a single raccoon that had lost a forearm at some arm amputations that cortex formerly devoted to the unknown time prior to its capture (Rasmusson et al., missing hand comes to be activated when the face is 1985). The large representation of the forepaw in primary stimulated (e.g., Flor et al., 1995). Finally, after deactivasomatosensory cortex of this animal had been comtion of large extents of somatosensory cortex by tranpletely reactivated by an expanded representation of section of the dorsal columns of the spinal cord at a high the stump. However, the finding received little attention, cervical level (Jain et al., 1997), the large unresponsive perhaps because the age of the animal when the injury zones of cortex in areas 3a, 3b, and 1 became responoccurred was not known, so it was not conclusive that sive to inputs from the face and the few dorsal column the extensive change reflected mechanisms of adult afferents from the anterior arm that entered the spinal plasticity. Several years later, a subsequent report of cord above the cut (Figure 1). These related findings demextensive cortical change convinced the research comonstrate beyond any doubt that large extents of somatomunity that the adult brain is capable of enormous sensory cortex, when deprived of normal sources of

Abstract: Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.

Abstract: Background and Purpose—Injury-induced cortical reorganization is a widely recognized phenomenon. In contrast, there is almost no information on treatment-induced plastic changes in the human brain. The aim of the present study was to evaluate reorganization in the motor cortex of stroke patients that was induced with an efficacious rehabilitation treatment. Methods—We used focal transcranial magnetic stimulation to map the cortical motor output area of a hand muscle on both sides in 13 stroke patients in the chronic stage of their illness before and after a 12-day-period of constraint-induced movement therapy. Results—Before treatment, the cortical representation area of the affected hand muscle was significantly smaller than the contralateral side. After treatment, the muscle output area size in the affected hemisphere was significantly enlarged, corresponding to a greatly improved motor performance of the paretic limb. Shifts of the center of the output map in the affected hemisphere suggested the recru...

Abstract: One fundamental function of primary motor cortex (MI) is to control voluntary movements. Recent evidence suggests that this role emerges from distributed networks rather than discrete representations and that in adult mammals these networks are capable of modification. Neuronal recordings and activation patterns revealed with neuroimaging methods have shown considerable plasticity of MI representations and cell properties following pathological or traumatic changes and in relation to everyday experience, including motor-skill learning and cognitive motor actions. The intrinsic horizontal neuronal connections in MI are a strong candidate substrate for map reorganization: They interconnect large regions of MI, they show activity-dependent plasticity, and they modify in association with skill learning. These findings suggest that MI cortex is not simply a static motor control structure. It also contains a dynamic substrate that participates in motor learning and possibly in cognitive events as well.

Abstract: In contrast to peripheral nerves, central axons do not regenerate. Partial injuries to the spinal cord, however, are followed by functional recovery. We investigated the anatomical basis of this recovery and found that after incomplete spinal cord injury in rats, transected hindlimb corticospinal tract (CST) axons sprouted into the cervical gray matter to contact short and long propriospinal neurons (PSNs). Over 12 weeks, contacts with long PSNs that bridged the lesion were maintained, whereas contacts with short PSNs that did not bridge the lesion were lost. In turn, long PSNs arborize on lumbar motor neurons, creating a new intraspinal circuit relaying cortical input to its original spinal targets. We confirmed the functionality of this circuit by electrophysiological and behavioral testing before and after CST re-lesion. Retrograde transynaptic tracing confirmed its integrity, and revealed changes of cortical representation. Hence, after incomplete spinal cord injury, spontaneous extensive remodeling occurs, based on axonal sprout formation and removal. Such remodeling may be crucial for rehabilitation in humans.