Each year more than 200,000 Americans suffer from sensory disorders caused by injuries or lesions of nerves. Clinical management and design of strategies for improving recovery would benefit from a better understanding of the central nervous system (CNS) changes that underlie these disorders. Given this perspective, the long-term objective of the planned research is to understand the central consequences of nerve injury in humans. In working toward this objective, the research will use nonhuman primates to study how injuries of nerves to the hand affect the function and structure of central somatosensory circuits that process touch and related sensory information. The research will also study structural organization in the ascending somatosensory circuits of humans to develop insight into how findings from nonhuman primates extrapolate to humans. The 4 specific aims are to: (1) evaluate how adjacencies of connections at cortical and subcortical levels of the somatosensory neuraxis contribute to reorganization in the area 3b somatosensory cortex after nerve injury in adult monkeys, (2) identify functional and structural changes in the cuneate nucleus that may contribute to cortical reorganization after nerve injury in adult monkeys, (3) assess how nerve repair in neonatal monkeys affects cortical and subcortical organization, and (4) evaluate patterns of structural parcellation in somatosensory neuropil of the human brain. Neurophysiological mapping, transganglionic transport of horseradish peroxidase from peripheral nerves and skin, and cytochrome oxidase histochemistry will be used to evaluate central organization. The results of the research will fill gaps in current understanding of: (a) how pre-injury circuit organization constrains early central reactions to nerve injury, (b) the relative reorganizational capacities of somatosensory connections at cortical and subcortical levels of the neuraxis, (c) age-related differences in central recovery after nerve repair, and (d) potential limitations in the applicability of animal models of injury to the human CNS. The research is directly relevant for understanding neurological changes related to sensory neuropathies, nerve injury, and limb amputation, and for understanding central mechanisms of recovery of tactile and somatic perception following neural regeneration.
Showing the most recent 10 out of 20 publications
