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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS067017-03
Application #
8260123
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Gnadt, James W
Project Start
2010-06-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
3
Fiscal Year
2012
Total Cost
$334,358
Indirect Cost
$119,983
Name
Vanderbilt University Medical Center
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Qi, Hui-Xin; Reed, Jamie L; Franca, Joao G et al. (2016) Chronic recordings reveal tactile stimuli can suppress spontaneous activity of neurons in somatosensory cortex of awake and anesthetized primates. J Neurophysiol 115:2105-23
Liao, Chia-Chi; Reed, Jamie L; Qi, Hui-Xin (2016) Anatomical changes in the somatosensory system after large sensory loss predict strategies to promote functional recovery after spinal cord injury. Neural Regen Res 11:575-7
Qi, Hui-Xin; Wang, Feng; Liao, Chia-Chi et al. (2016) Spatiotemporal trajectories of reactivation of somatosensory cortex by direct and secondary pathways after dorsal column lesions in squirrel monkeys. Neuroimage 142:431-453
Liao, Chia-Chi; Qi, Hui-Xin; Reed, Jamie L et al. (2016) Congenital foot deformation alters the topographic organization in the primate somatosensory system. Brain Struct Funct 221:383-406
Liao, Chia-Chi; Reed, Jamie L; Kaas, Jon H et al. (2016) Intracortical connections are altered after long-standing deprivation of dorsal column inputs in the hand region of area 3b in squirrel monkeys. J Comp Neurol 524:1494-526
Liao, Chia-Chi; DiCarlo, Gabriella E; Gharbawie, Omar A et al. (2015) Spinal cord neuron inputs to the cuneate nucleus that partially survive dorsal column lesions: A pathway that could contribute to recovery after spinal cord injury. J Comp Neurol 523:2138-60
Yang, Pai-Feng; Qi, Hui-Xin; Kaas, Jon H et al. (2014) Parallel functional reorganizations of somatosensory areas 3b and 1, and S2 following spinal cord injury in squirrel monkeys. J Neurosci 34:9351-63
Qi, Hui-Xin; Reed, Jamie L; Gharbawie, Omar A et al. (2014) Cortical neuron response properties are related to lesion extent and behavioral recovery after sensory loss from spinal cord injury in monkeys. J Neurosci 34:4345-63
Qi, Hui-Xin; Gharbawie, Omar A; Wynne, Katherine W et al. (2013) Impairment and recovery of hand use after unilateral section of the dorsal columns of the spinal cord in squirrel monkeys. Behav Brain Res 252:363-76
Wang, Zheng; Qi, Hui-Xin; Kaas, Jon H et al. (2013) Functional signature of recovering cortex: dissociation of local field potentials and spiking activity in somatosensory cortices of spinal cord injured monkeys. Exp Neurol 249:132-43

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