Project Summary/Abstract Long-term walking impairments are common after stroke, reducing community involvement and physical activity and impairing health status and quality of life. Although improving walking is of high importance in this population, the impact of walking rehabilitation after stroke is limited. The ability to improve walking rehabilitation after stroke is hampered by a lack of knowledge about stroke-related changes in the cortical control of walking. In particular, previous work suggests that changes in the ipsilateral contribution of the contralesional (non-lesioned) hemisphere to motor control of the paretic limb and/or altered interhemispheric imbalance may contribute to walking impairment after stroke. However, more information about these phenomena, particularly during dynamic lower limb movement, is necessary to translate these neurophysiological measurements into improvements in stroke rehabilitation. The goal of this proposal is to evaluate the contribution of the contralesional hemisphere and interhemispheric interactions to dynamic, bilateral lower limb movements after stroke and determine if these constructs relate to walking function. We hypothesize that the ipsilateral contribution of the contralesional hemisphere to paretic limb movements will be greater than the ipsilateral contribution of the ipsilesional (lesioned) hemisphere to movements of the non- paretic limb. We also hypothesize that interhemispheric inhibition will be greater in the ipsilesional hemisphere than in the contralesional hemisphere. We expect both constructs to differ between isometric and dynamic tasks and be related to greater walking impairment. To test these hypotheses, we will provide transcranial magnetic stimulation during dynamic, bilateral ankle movement. In Aim 1, we will assess the contribution of each hemisphere to movements of the paretic and non-paretic limb, and in Aim 2, we will assess the degree of interhemispheric inhibition of each hemisphere by the opposite hemisphere. In Aim 3, we will evaluate walking speed and spatiotemporal characteristics and relate these measures to the ipsilateral contribution of the contralesional hemisphere to movement of the paretic limb and interhemispheric inhibition as measured during Aim 1 and 2. The proposed work is significant because it will further our understanding of functional corticomotor excitability after stroke and expand our knowledge about the motor control of dynamic, bilateral lower limb movements, such as walking. Information from these studies can then be used to optimize rehabilitation strategies, specifically informing the use of neuromodulatory adjuvants to walking rehabilitation. Ultimately, these improvements in post-stroke rehabilitation will lead to health improvements and reduced healthcare burden. Findings from these studies will establish my career as an independent investigator and help me achieve my long-term research objective of determining how motor rehabilitation...