The prospects for recovery of walking after human spinal cord injury (SCI) are dismal after a severe injury. The prognosis for recovery is primarily based on detectable voluntary leg function and this directs the rehabilitative strategy for walking after SCI. This approach is based on assumptions from the conventional hierarchal model of the neural control of locomotion in humans that designates the brain as the primary controller and the spinal cord as a conduit for supraspinal signals and reflex pathways. Recent results from our laboratory and others suggest an integrative model of the neural control of locomotion, allocating the spinal cord as an important neural controller of locomotion that integrates sensory and supraspinal signals to generate effective locomotor output. In this proposal we test this model by understanding sensory and supraspinal signal processing by the human spinal cord during the motor tasks of stepping and standing before and after each task specific training. We theorize that the neural circuitry of the human spinal cord is functionally organized to generate a particular efferent pattern when an expected set of kinematic and kinetic patterns are presented. We hypothesize that this neuralcircuitry can adapt to the repetitive presentation of a specific set of kinematic and kinetic patterns to modulate the efferent output in a predictable manner. We further hypothesize that after incomplete SCI both supraspinal and sensory signals can be integrated by the human spinal cord to generate a specific motor output that is related to repetitive stand or step training. We will study individuals following clinically complete SCI to understand the role of the human spinal cord in processing sensory signals. We will study individuals with clinically incomplete SCI to assess the integrative potential of supraspinal and sensory signals to generate functional output after repetitive stand or step training. We will examine the electromyographic activity, kinematics and kinetics of the lower limbs of these SCI subjects during bilateral and unilateral stepping and during functional tasks using body weight support on a treadmill after repetitive step or stand training. These studies will demonstrate aspects of use-dependent plasticity that are being studied in the animal models of this PPG. Identifying the specific sensory cues that facilitate motor output during stepping; and assessing whether repetitive task specific training can induce activity-dependent plasticity of spinal and supraspinal centers to result in functional improvements after spinal cord injury will have significant implications for new rehabilitative strategies for the recovery of walking after neurologic injury. Further, optimizing training strategies for functional recovery will also be extremely important in combination with promising neural regeneration approaches that are continuously emerging.

Project Start
2007-05-01
Project End
2008-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
26
Fiscal Year
2007
Total Cost
$251,024
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Duru, Paul O; Tillakaratne, Niranjala J K; Kim, Jung A et al. (2015) Spinal neuronal activation during locomotor-like activity enabled by epidural stimulation and 5-hydroxytryptamine agonists in spinal rats. J Neurosci Res 93:1229-39
Tillakaratne, Niranjala J K; Duru, Paul; Fujino, Hidemi et al. (2014) Identification of interneurons activated at different inclines during treadmill locomotion in adult rats. J Neurosci Res 92:1714-22
Terson de Paleville, Daniela; McKay, William; Aslan, Sevda et al. (2013) Locomotor step training with body weight support improves respiratory motor function in individuals with chronic spinal cord injury. Respir Physiol Neurobiol 189:491-7
Johnson, Will L; Jindrich, Devin L; Roy, Roland R et al. (2012) Quantitative metrics of spinal cord injury recovery in the rat using motion capture, electromyography and ground reaction force measurement. J Neurosci Methods 206:65-72
Harkema, Susan; Behrman, Andrea; Barbeau, Hugues (2012) Evidence-based therapy for recovery of function after spinal cord injury. Handb Clin Neurol 109:259-74
Johnson, Will L; Jindrich, Devin L; Zhong, Hui et al. (2011) Application of a rat hindlimb model: a prediction of force spaces reachable through stimulation of nerve fascicles. IEEE Trans Biomed Eng 58:3328-38
Roy, Roland R; Zhong, Hui; Monti, Ryan J et al. (2011) Selectively reshaping a muscle phenotype: functional overload of cat plantaris. Muscle Nerve 43:489-99
Ichiyama, Ronaldo M; Broman, Jonas; Roy, Roland R et al. (2011) Locomotor training maintains normal inhibitory influence on both alpha- and gamma-motoneurons after neonatal spinal cord transection. J Neurosci 31:26-33
Joseph, M Selvan; Bilousova, Tina; Zdunowski, Sharon et al. (2011) Transgenic Mice With Enhanced Neuronal Major Histocompatibility Complex Class I Expression Recover Locomotor Function Better After Spinal Cord Injury. J Neurosci 89:365-372
Kim, Jung A; Roy, Roland R; Kim, Soo J et al. (2010) Electromechanical modulation of catabolic and anabolic pathways in chronically inactive, but neurally intact, muscles. Muscle Nerve 42:410-21

Showing the most recent 10 out of 221 publications