DESCRIPTION (provided by applicant): Stroke is the leading cause of long-term disability in the United States. Frequently, stroke results in significant impairment of arm function which contributes heavily to the resulting disability. This proposed project will examine the neural mechanisms of practice-induced improvements in functional arm movements in individuals with chronic stroke, with the broad, long-term objective of reducing stroke-related disability due to arm impairment through novel rehabilitation interventions. The rationale is that knowing the neural bases of post- stroke arm movements is crucial for the development of targeted intervention strategies for those with significant impairment. This project will directly contribute to the NIH mission of reducing "the burdens of illness and disability." The aims of the project are to 1) identify brain areas involved in movement performance of the stroke-affected arm, 2) identify brain areas involved in practice-induced improvements in arm function, and 3) determine whether practice-induced improvements could be enhanced with targeted brain stimulation applied during practice. To address these aims, functional magnetic resonance imaging (fMRI) will be used to measure brain activation during reaching movements in moderately-impaired stroke patients and transcranial magnetic stimulation (TMS) and TMS-fMRI co-registration techniques will be used to upregulate activity in specific brain areas associated with practice-induced performance improvement during practice. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page

Relevance: The development of interventions to improve motor abilities of the affected arm after stroke is a vital part of alleviating the disability that results from this prevalent condition. In order to develop effective rehabiliation interventions, the mechanisms of motor recovery in people with substantial stroke-induced arm impairment must be understood.