This application is for a Mentored Patient-Oriented Research Career Development Award entitled """"""""fMRI and TMS of Motor Recovery after Hemiparetic Stroke"""""""". The long-term objective of this work is to understand the neural mechanisms underlying motor recovery after hemiparetic stroke, so to be able to develop new rational therapies that maximize post-stroke recovery in patients. Toward this objective, the proposed research project will conduct a functional magnetic resonance imaging (fMRI) study and a transcranial magnetic stimulation (TMS) study to evaluate a causal connection between reorganization in sensorimotor cortical areas and post-stroke motor recovery. Stroke patients, with good recovery of hand motor function, and normal subjects will participate in both studies. The fMRI study will evaluate the modulation of activation in contralateral and ipsilateral sensorimotor cortical areas by the dexterity challenge of motor tasks, and by the extent of corticospinal tract damage (estimated using diffusion MRI methods). The TMS study will target fMRI-defined sensorimotor cortical sites, using a frameless stereotactic image guided system, to investigate the functional significance of each of these cortical areas to motor control. Transient functional disruption of a sensorimotor cortical site, induced by repetitive TMS, will be used to evaluate if that cortical area is more critical to controlling motor performance of the stroke-affected hand as compared to control hands. Single-pulse TMS, with recording of motor evoked potentials in a target hand muscle, will be used to determine which sensorimotor cortical sites show increased corticospinal excitability related to the stroke-affected hand. The combined use of fMRI and TMS is expected to provide insights into a causal link between reorganization in sensorimotor cortical areas and motor recovery after stroke that could not be gained by using each technology in isolation. The candidate proposes to receive training in three areas necessary to become an independent clinical research scientist in the field of stroke recovery: 1) Theory and practice of advanced human brain mapping technologies, including fMRI, diffusion-weighted MRI, and TMS, 2) basic science and clinical aspects of stroke and stroke recovery, especially with regard to motor control, and 3) clinical research design, statistics and ethics. This training will be achieved through executing the proposed research study, didactic coursework, mentored learning, and seminars.
