PROJECT SUMMARY: Difficulty incorporating the weaker arm in everyday activities significantly contributes to impaired function and quality of life after stroke. Most prevalent rehabilitation approaches that focus on improving the unimanual performance of the weaker arm have had limited impact on weaker arm use and integration in the real world. In contrast to the unimanual focus of rehabilitation approaches, most tasks of daily living engage both arms in a highly coordinated and interactive manner. After unilateral stroke, the interactive coordination between the two arms is significantly impaired, even in patients with mild unimanual deficits, and is seldom remediated by unimanual training. Impaired bimanual coordination may greatly limit the integration of the weaker arm in daily activities, most of which are bimanual. Therefore, targeted training of bimanual coordination is necessary to achieve a more complete functional arm recovery. Designing effective training however requires a clear characterization of the fundamental deficits in how stroke survivors coordinate their arms, and how task demands influence that coordination. Further, to move in the direction of more definitive clinical investigations of bimanual training, it is important to identify factors that help explain individual variability in bimanual coordination after stroke. The proposed studies will determine: (a) how motor and perceptual task demands of a bimanual reaching task interact to influence coordination between arms in stroke survivors compared to age- matched controls, (b) the immediate effects of changing perceptual and motor task demands on bimanual coordination in stroke survivors and (c) the behavioral, neuroanatomic and neurophysiologic contributors to individual differences in bimanual coordination after stroke. The approach is strong in that it aims to determine the fundamental nature of bimanual control deficit(s) after stroke and then tests specific strategies to target the underlying deficit(s). Particularly innovative is the manipulation of perceptual task demands in a virtual environment to influence coordination between hands. Also, multimodal investigation to identify the contribution of lesion and neural connectivity to bimanual coordination in stroke survivors is novel. The proposed project is significant because it will provide fundamental understanding of brain-behavior relationship for bimanual coordination after stroke. This will advance the science of rehabilitation with a stronger clinical impact. For instance, identifying which patients have impaired bimanual coordination and who show improvements with perceptual cueing will provide crucial information for testing evidence-based targeted training of bimanual coordination in future studies. The results from this project will set the stage for future investigations aimed at the development of intervention protocols to improve bimanual coordination necessary for more complete functional arm recovery after stroke. Finally, this proposal takes us closer to achievement of the NIH mission to reduce the burden of neurological disorders and enhance the quality of life of people with disabilities.