Project Summary The objective of the proposed project is to develop a neuroprosthetic therapy that uses targeted, activity-dependent spinal stimulation to improve arm and hand motor recovery after cervical spinal cord injury (SCI). The project seeks to advance clinical practice through the use of brain-computer-interface technology to harness physiological mechanisms of neural plasticity. Motor deficits severely impact the quality of life of people with SCI, yet current treatments produce limited improvements in movement abilities. Recent clinical and experimental evidence suggests that electrical stimulation of the nervous system can be an effective therapy for a variety of neurological disorders. This preclinical project will evaluate a novel application of electrical stimulation for rehabilitation of forelimb motor deficits in a rat model of SCI. The strategy is designed to enhance the function of spared neural pathways by directing Hebbian plasticity through targeted stimulation of volitionally activated neural circuits. Results will lay the foundation for a future clinical trial using spinal stimulation in human subjects with SCI. Preliminary data demonstrate the effectiveness of one-channel, intraspinal stimulation triggered by activity of a forelimb muscle to improve motor performance in rats with chronic SCI. Specific Aim 1 seeks a) to develop a multi-channel intervention to enhance functional recovery and b) to characterize the interplay between stimulation and physical rehabilitation in order to establish principles for combining the therapies. Specific Aim 2 will determine the relative effectiveness of ECoG vs. EMG as a triggering signal for facilitating behavioral recovery. Specific Aim 3 begins an investigation of the mechanisms of action of the intervention to suggest refinements and combinatorial therapies to facilitate further recovery.