ABSTRACT / PROJECT SUMMARY Most stroke survivors present with gait dysfunction resulting in reduced community participation and quality of life. A promising rehabilitation intervention for mitigating post-stroke gait deficits is the combination of fast walking and functional electrical stimulation (FastFES). Dr. Trisha Kesar (primary mentor) is currently leading an NIH funded R01 comparing the long-term effects (18 sessions and up to 12-week follow-up) of FastFES versus conventional Fast on walking function and corticospinal excitability. Despite its promise, FastFES, like virtually all gait interventions, faces the problem of variation in individual response to treatment. Neurophysiological testing takes aim at the root of this problem by exploring the neural mechanisms underlying each individual’s unique response. Because neuromotor circuit plasticity is a core component of treatment response, quantifying this adaptation potentially provides a means for identifying likely responders and non- responders early in the treatment process. A promising tool for non-invasively assessing changes in corticomotor excitability is transcranial magnetic stimulation (TMS). In fact, TMS response has already been correlated with retention of functional improvement in other post-stroke motor interventions. However, whether TMS-derived measures correlate with response to Fast or FastFES training is unknown. Additionally, TMS- induced measures do not differentially account for changes at the spinal reflex circuit or the motoneuron level, which can be evaluated by measuring H-reflexes in response to peripheral nerve stimulation, another non- invasive technique that can probe spinal circuit neuroplasticity. Thus, I propose to gather additional TMS and H-reflex data prior to and following the first training session in Dr. Kesar’s parent R01 study, which will be compared to biomechanical changes during and at 48-hours following (retention) the training, to test the hypothesis that baseline corticomotor and spinal excitability, as well as training-induced acute neurophysiologic responses to Fast and FastFES are associated with locomotor learning of biomechanical improvements. Finally, corticomotor or spinal circuit changes in response to a single intervention do not indicate whether an individual who exhibits a ‘response’ or non-response to the treatment does so due to poor intervention matching or a generalized decrease in neuroplasticity capacity. Thus, I propose a baseline measurement of individual responses to paired associative stimulation (PAS), a non-invasive method to quantify an individual’s capacity for neuroplastic change. We hypothesize that baseline PAS response will be associated with biomechanical and neurophysiological response to the gait treatment. In addition to providing novel insights into neural correlates of acute responses to stroke gait training, this F31 project will provide the PI valuable training in ...