DESCRIPTION (provided by applicant): Stroke is the leading cause of serious, chronic disability in adults worldwide. Over 750,000 cases of first- ever stroke occur in the United States each year accounting for over half of all acute neurological hospital admissions. While two-thirds of persons who suffer a stroke regain the ability to walk, the resulting gait pattern is slow, asymmetrical and metabolically inefficient Walking dysfunction represents one of the greatest physical limitations post-stroke and improved walking is among the most frequently articulated goals of neurorehabilitation. To date, rehabilitation for walking dysfunction post-stroke has produced highly variable outcomes revealing minimal genuine change in walking function including walking speed or pattern. Our long-term goal is to improve walking post-stroke. The objective of this proposal is to investigate the neurophysiological mechanisms that underlie the capacity for locomotor recovery post-stroke. Specifically, our aim is to identify neurophysiologic measures differentiating stroke survivors who do or do not to a therapeutic intervention. We postulate that the efficacy of descending motor tracts to the distal leg muscles (plantar and dorsiflexors) is greatly reduced in low functioning stroke survivors, while this efficacy is at least partially preserved in higher functioning individuals. The first aim of this project seeks to differentiate high and low functioning stroke survivors based upon the proportion of distinguishable motor evoked potentials (MEPs) observed in the distal leg muscles during walking. We anticipate lower functioning individuals will have a smaller percentage of distinguishable MEPs compared to higher functioning individuals. In the second aim of this project we will evaluate the relationship between corticomotor function in the distal leg and biomechanical function during walking. Our preliminary data suggest a link between the corticospinal function and force production during walking. Specifically, we expect MEP modulation across the gait cycle correlates with ankle plantarflexor power generation during walking. In the third aim of the proposal we will evaluate whether corticospinal efficacy can predict post-intervention improvements in walking function. Using an efficacious intervention developed in our previous work, we will conduct a study of power training to pilot comparisons of pre-intervention measures of corticospinal efficacy with post-intervention gains in walking function. We anticipate that individuals with higher corticospinal efficacy will show the largest improvements in gait speed and locomotor function post-intervention. The results of this study will fill a gap in current knowledge by providing a prognostic indicator of an individual's capacity to recover walking function post-stroke. Furthermore, insights gained from this study can be used to develop targeted rehabilitation strategies to maximize neurorehabilitation.

PUBLIC HEALTH RELEVANCE: Stroke is the leading cause of serious, chronic disability in adults worldwide affecting more than 15,000 Veterans each year. While approximately two-thirds of these individuals regain the ability to walk, their gait is slow, asymmetrical, and metabolically inefficient. Functional impairments vary markedly among individuals post-stroke affecting the capacity for recovery and making it difficult to predict response to intervention. This knowledge gap significantly limits the efficacyof rehabilitation interventions, and likely explains why only 50% of individuals with stroke-related walking dysfunction respond to therapeutic intervention. The purpose of the proposed project is to develop a prognostic indicator of an individual's capacity for walking recovery. Insights gained from this work will contribute to the development of targeted intervention strategies, thereby improving the efficacy and efficiency of neurorehabilitation. These strategies can be implemented in the VA Health Care System, to further improve the quality of life for Veterans who have had a stroke.