Large-Scale Reorganization in the Somatosensory Cortex and Thalamus after Sensory Loss in Macaque Monkeys

Trigeminal sensory system.

Abstract: This chapter addresses the unique anatomy of the pathway for facial sensations, involving the trigeminal ganglion and its associated nuclei within the brainstem. The innervation of specialized cranial structures such as the teeth, tongue, oral and nasal mucosa, cornea, meninges, and conjunctiva are considered. This chapter will also address trigeminal mechanisms in clinically relevant conditions such as toothache, headache and trigeminal neuralgia including using advances in imaging techniques and resolution. Thus it is now possible to obtain functional MR images (fMRI) of the trigeminal pathway from ganglion to cortex. Magnetoencephalography (MEG) and fMRI techniques have provided more details on cortical organization in facial regions of both S1 and S2, while diffusion tensor imaging has been useful for visualizing trigeminothalamic pathways. Plasticity of the system after injury, its association with pain conditions, and the opportunities that this offers for training and rehabilitation, are further areas of current research that are discussed.

From maps to form to space: touch and the body schema.

Abstract: Evidence from patients has shown that primary somatosensory representations are plastic, dynamically changing in response to central or peripheral alterations, as well as experience. Furthermore, recent research has also demonstrated that altering body posture results in changes in the perceived sensation and localization of tactile stimuli. Using evidence from behavioral studies with brain-damaged and healthy subjects, as well as functional imaging, we propose that the traditional concept of the body schema should be divided into three components. First are primary somatosensory representations, which are representations of the skin surface that are typically somatotopically organized, and have been shown to change dynamically due to peripheral (usage, amputation, deafferentation) or central (lesion) modifications. Second, we argue for a mapping from a primary somatosensory representation to a secondary representation of body size and shape (body form representation). Finally, we review evidence for a third set of representations that encodes limb position and is used to represent the location of tactile stimuli relative to the subject using external, non-somatotopic reference frames (postural representations).

Reassessing cortical reorganization in the primary sensorimotor cortex following arm amputation

Abstract: The role of cortical activity in generating and abolishing chronic pain is increasingly emphasized in the clinical community. Perhaps the most striking example of this is the maladaptive plasticity theory, according to which phantom pain arises from remapping of cortically neighbouring representations (lower face) into the territory of the missing hand following amputation. This theory has been extended to a wide range of chronic pain conditions, such as complex regional pain syndrome. Yet, despite its growing popularity, the evidence to support the maladaptive plasticity theory is largely based on correlations between pain ratings and oftentimes crude measurements of cortical reorganization, with little consideration of potential contributions of other clinical factors, such as adaptive behaviour, in driving the identified brain plasticity. Here, we used a physiologically meaningful measurement of cortical reorganization to reassess its relationship to phantom pain in upper limb amputees. We identified small yet consistent shifts in lip representation contralateral to the missing hand towards, but not invading, the hand area. However, we were unable to identify any statistical relationship between cortical reorganization and phantom sensations or pain either with this measurement or with the traditional Euclidian distance measurement. Instead, we demonstrate that other factors may contribute to the observed remapping. Further research that reassesses more broadly the relationship between cortical reorganization and chronic pain is warranted.

Targeted mini-strokes produce changes in interhemispheric sensory signal processing that are indicative of disinhibition within minutes

Abstract: Most processing of sensation involves the cortical hemisphere opposite (contralateral) to the stimulated limb. Stroke patients can exhibit changes in the interhemispheric balance of sensory signal processing. It is unclear whether these changes are the result of poststroke rewiring and experience, or whether they could result from the immediate effect of circuit loss. We evaluated the effect of mini-strokes over short timescales (<2 h) where cortical rewiring is unlikely by monitoring sensory-evoked activity throughout much of both cortical hemispheres using voltage-sensitive dye imaging. Blockade of a single pial arteriole within the C57BL6J mouse forelimb somatosensory cortex reduced the response evoked by stimulation of the limb contralateral to the stroke. However, after stroke, the ipsilateral (uncrossed) forelimb response within the unaffected hemisphere was spared and became independent of the contralateral forelimb cortex. Within the unaffected hemisphere, mini-strokes in the opposite hemisphere significantly enhanced sensory responses produced by stimulation of either contralateral or ipsilateral pathways within 30-50 min of stroke onset. Stroke-induced enhancement of responses within the spared hemisphere was not reproduced by inhibition of either cortex or thalamus using pharmacological agents in nonischemic animals. I/LnJ acallosal mice showed similar rapid interhemispheric redistribution of sensory processing after stroke, suggesting that subcortical connections and not transcallosal projections were mediating the novel activation patterns. Thalamic inactivation before stroke prevented the bilateral rearrangement of sensory responses. These findings suggest that acute stroke, and not merely loss of activity, activates unique pathways that can rapidly redistribute function within the spared cortical hemisphere.

Spinal Cord Injury Immediately Changes the State of the Brain

Abstract: Spinal cord injury can produce extensive long-term reorganization of the cerebral cortex. Little is known, however, about the sequence of cortical events starting immediately after the lesion. Here we show that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats. Besides the obvious loss of cortical responses to hindpaw stimuli (below the level of the lesion), cortical responses evoked by forepaw stimuli (above the level of the lesion) markedly increase. Importantly, these increased responses correlate with a slower and overall more silent cortical spontaneous activity, representing a switch to a network state of slow-wave activity similar to that observed during slow-wave sleep. The same immediate cortical changes are observed after reversible pharmacological block of spinal cord conduction, but not after sham. We conclude that the deafferentation due to spinal cord injury can immediately (within minutes) change the state of large cortical networks, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury.

Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry

Abstract: Endogenous cytochrome oxidase activity within the mitochondria of neurons and neuropil was demonstrated histochemically under normal and experimental conditions. Since enzymatic changes were noted with chronic neuronal inactivity in the auditory system (Wong-Riley et al), the present study sought to examine functionally induced enzymatic changes in the visual system of kittens. Eight kittens were used experimentally: 5 had monocular lid suture for varying periods of time; one had binocular lid suture followed by monocular suture followed by binocular opening; two had monocular enucleation. All initial procedures were performed before eye opening. Materials from other normal kittens and cats were also used as controls. At the end of the experiments, the animals were perfused with aldehyde solutions and frozen sections of the brains were incubated for cytochrome oxidase activity (a detailed protocol was outlined). The results indicated that the deprivation caused by monocular suture produced a decrease in the cytochrome oxidase staining of the binocular segment of the deprived geniculate laminae. Enucleation yielded a greater decrease in the cytochrome oxidase activity in the affected geniculate laminae. However, the staining in the 'normal' lamina extended across the interlaminar border to include a row of surviving large cells in the 'denervated' lamina. The staining of the monocular segment appeared not to be affected by lid suture, but was decreased by enucleation. At the cortical level, lamina IV in area 17 of normal cats was stained darkly as a continuous band. Following lid suture, this pattern was replaced in part by alternating columns of light and dark staining, suggestive of ocular dominance columns. Thus, a decrease in neuronal activity due to reduced visual stimulation or destruction of the primary afferent nerves led to a significant decrease in the level of oxidative enzyme activity one to several synapses away.

Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation

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.

Somatosensory cortical map changes following digit amputation in adult monkeys

Abstract: The cortical representations ofthe hand in area 3b in adult owl monkeys were defined with use of microelectrode mapping techniques 2-8 months after surgical amputation of digit 3, or of both digits 2 and 3. Digital nerves were tied to prevent their regeneration within the amputation stump. Suc­ cessive maps were derived in several monkeys to determine the nature of changes in map organization in the same individuals over time. In all monkeys studied, the representations of adjacent digits and pal­ mar surfaces expanded topographically to occupy most or all of the cortical territories formerly representing the amputated digit(s). With the expansion of the representations of these surrounding skin surfaces (1) there were severalfold increases in their magnification and (2) roughly corresponding decreases in receptive field areas. Thus, with increases in magnification, surrounding skin surfaces were represented in correspondingly finer grain, implying that the rule relating receptive field overlap to separation in distance across the cortex (see Sur et aI., '80) was dynamically maintained as receptive fields progressively decreased in size. These studies also revealed that: (1) the discontinuities between the representations of the digits underwent significant translocations (usually by hundreds of microns) after amputation, and sharp new discontinuous boundaries formed where usually separated, expanded digital representa­ tions (e.g., of digits 1 and 4) approached each other in the reorganizing map, implying that these map discontinuities are normally dynamically main­ tained. (2) Changes in receptive field sizes with expansion of representations of surrounding skin surfaces into the deprived cortical zone had a spatial distribution and time course similar to changes in sensory acuity on the stumps of human amputees. This suggests that experience-dependent map changes result in changes in sensory capabilities. (3) The major topographic changes were limited to a cortical zone 500-700 JIm on either side of the initial boundaries of the representation of the amputated digits. More dis­ tant regions did not appear to reorganize (i.e., were not occupied by inputs from surrounding skin surfaces) even many months after amputation. (4) The representations of some skin surfaces moved in entirety to locations within the former territories of representation of amputated digits in every

Massive cortical reorganization after sensory deafferentation in adult macaques

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.

Topographic reorganization of somatosensory cortical areas 3b and 1 in adult monkeys following restricted deafferentation

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.