The prognosis for partial recovery of function after spinal cord injury in humans and other mammals appears to depend largely on the degree of sparing of ascending and descending axons, but the reasons why these preserved axons are important are not clear. Previous studies in monkeys have indicated that a few spared afferents from the hand in the dorsal columns (DC) of the spinal cord greatly expand their territory of activation in somatosensory cortex over the first post-lesion month, and that reactivation of the cortex is paralleled by improved use of the hand. The proposed research will evaluate the hypothesis that the expanded representation of spared afferents provides useful information for the guidance of motor behavior. More specifically, we will evaluate the hypothesis that reactivated cortical neurons will gradually recover normal response properties. Sensorimotor functional recoveries, functional magnetic resonance imaging (fMRI), acute recordings with microelectrode arrays, and anatomical procedures will be used to address the following aims: 1. We will use a Cyberkinetics 100-electrode array to study the possibility of the short term changes in response properties of deprived cortical neurons. For each animal, short-term changes in single neuron response properties will be evaluated from recordings before and after partial section of dorsal column afferents during 20 30 hour recording session. 2. We will investigate the long-term time course of recovery in following studies. 2a: Sensorimotor behavior before and over a series of times after DC lesions will be evaluated in two tests of hand use. 2b: Responsiveness to tactile stimulation by using fMRI to evaluate the sizes of the hand and the digit representations in somatosensory areas 3b, 1, and S2 before and over the course of recovery after partial DC lesions. 2c: After fMRI data are collected, each monkey in this group will be undergone a terminal electrophysiological recording session with a 100-electrode arrays at 1, 2, 4 or 6 weeks, or up to 6 months after DC lesions to characterize neuron response properties in reactivated regions of 3b. The results are expected to further understandings of why a few preserved inputs can be functionally so important, and why procedures that permit the growth of even a few afferents past a spinal lesion may disproportionably promote the return of function. Results may lead to more effective post-injury treatments for humans with spinal cord injury. ? ? 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. 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
Small Research Grants (R03)
Project #
1R03NS057399-01A1
Application #
7385276
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Kleitman, Naomi
Project Start
2007-09-30
Project End
2009-07-31
Budget Start
2007-09-30
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$73,540
Indirect Cost
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