DESCRIPTION (provided by applicant): Stroke is the leading cause of serious, chronic disability in adults worldwide. Over 750,000 new strokes occur in the United States each year accounting for over half of all acute neurological hospital admissions in both civilian and Veterans' hospitals. The most persistent stroke-related motor impairments affect the upper- extremity (UE)14. Among survivors, 73-88% present with sensorimotor impairments affecting upper-extremity function and 55-75% experience difficulty using the arm for activities of daily living activities. To date, upper- extremity rehabilitation fr post-stroke hemiparesis has produced highly variable outcomes revealing minimal genuine change in motor impairment or functional use of the affected arm. Our long-term goal is to restore UE motor function following stroke. The overall objective of this proposal is to improve our understanding of neural mechanisms contributing to inter-limb and inter-hemispheric transfer following non-paretic limb exercise to task failure. We will use transcranial magnetic stimulation to probe acute adaptations in cortical excitability, intracortical and inter-hemispheri circuits that accompany behavioral facilitation of the paretic hand. The work proposed in the current application will enable us to obtain three data elements that are critical to our current working hypothesis. We will: 1) investigate changes in intracortical and interhemispheric inhibition in both hemispheres following non-paretic limb exercise to task failure; 2) test behavioral effects on paretic limb function using a motor task involving manipulation and dexterity; 3) determine the persistence (i.e., time course) of acute neural and behavioral facilitation and its consistency over repeated sessions. Our results will inform regarding the mechanisms of inter-limb and inter-hemispheric transfer post-stroke and contribute development of a clinical intervention to be tested in future studies. The data obtained in this small study wil prevent failure of a larger, clinical investigation by enabling us to develop appropriately focused mechanistic hypotheses, understand the effects elicited and therefore project a sample size to afford appropriate statistical power in our future study. Ultimately, the work conducted in this small project and future studies will advance our knowledge regarding the neurobiology of motor recovery following stroke, providing insight regarding the phenomenon of interlimb transfer and the associated mechanisms of neural plasticity. Keywords: stroke, recovery, neurophysiology, rehabilitation, upper-extremity

PUBLIC HEALTH RELEVANCE: Stroke is the leading cause of chronic disability in the United States. More than 15,000 Veterans are hospitalized for stroke each year. The most persistent stroke-related motor impairments affect the upper-extremity (UE)14. Among survivors, 73-88% present with sensorimotor impairments affecting UE function and 55-75% experience difficulty using the UE for daily living activities. To date, rehabilitation for UE hemiparesis post-stroke has produced highly variable outcomes revealing minimal genuine change in motor impairment or functional use of the affected UE. This lack of therapeutic efficacy results from limited understanding of motor recovery following stroke. The prevalence and persistence of stroke-related motor dysfunction points to an urgent, unmet need to develop therapies that restore UE motor function. The outcomes of the proposed research are therefore central to the VA Health Care Mission.