The prognosis for partial recovery of function after spinal cord injury (SCI) in humans and mammals appears to depend largely on the degree of sparing of ascending and descending axons. In somatosensory cortical area 3b after a partial spinal cord lesion, the expanded representation of spared afferents which emerges is thought to initiate processes critical for guiding of sensory-motor behaviors. However, nearly nothing is known about reactivation of higher-order somatosensory cortical areas after a spinal cord lesion. We propose that over time after a spinal cord lesion in squirrel monkeys, neurons in the deprived representations of higher-order somatosensory areas 1, 2, and secondary (S2) and parietal ventral (PV) somatosensory areas will become responsive to preserved afferents. Also, behavioral training after such injuries is assumed to improve functional recovery and we propose that one mechanism for this recovery is through cortical reactivation. Functional magnetic resonance imaging (fMRI), acute recordings with single microelectrodes or multi-electrode arrays, sensory-motor behavioral measures and anatomical procedures will be used to address the following aims. 1. To characterize topographical re-organization following partial lesion of afferents in the dorsal column (DC) of the spinal cord in multiple higher-order somatosensory areas in squirrel monkeys with fMRI and microelectrode mapping techniques, and to correlate the time course of behavioral recovery with fMRI activation patterns in higher-order somatosensory cortex of monkeys that had intensive training of the impaired hand and monkeys that had no training. 2. To quantitatively study response properties of reactivated neurons using the 100- electrode Utah array in cortical areas 3b and 1 of squirrel monkeys following partial DC section. Results will be compared between monkeys that had intensive behavioral training and others that did not. 3. To determine possible subcortical anatomical substrates for behavioral and functional recoveries by using markers that can reveal sprouted or previously undetected afferent inputs, and by identifying recovery-promoting histological changes. Results of the proposed research will help us to better understand the consequences of injury on the system-wide transmission of sensory information, and perhaps more importantly to define the processes that support recovery. Such information will yield important clues for developing effective post-injury treatments for humans with spinal cord injury.

Public Health Relevance

The loss of sensory information via damage to the afferents in the dorsal column of the spinal cord, with or without more extensive injury, greatly impairs fine motor control in human so that skilled movements of the hand are lost. Studies in monkeys indicate that the preservation of only a few afferents from the hand led to a reactivation of much of the deprived somatosensory cortex, and considerable recovery of hand use. The proposed research will evaluate the hypothesis that the expanded representation of spared afferents provides useful information for the guidance of motor behavior, and post operational training will improve further functional recovery. Positive results will indicate the need for treatments that encourage the regeneration of even a few cut afferents, and promote the effectiveness of those that are preserved.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
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Gnadt, James W
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Vanderbilt University Medical Center
Schools of Arts and Sciences
United States
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