This research career development proposal describes a multidisciplinary mentored program allowing the investigator, Dr. Wu, to develop expertise in quantitative motor behavior research methods and transcranial magnetic stimulation (TMS). Dr. Wu will apply this expertise to further the understanding of mechanisms in normal motor control with the long-term goal being to establish how such mechanisms go awry in disease states such as Parkinson's disease (PD), dystonia and sensorimotor stroke. Dr. Wu is a neurologist with current clinical expertise in movement disorders and neurophysiology, who plans to develop a program exploring the research, neuromodulation and eventual treatment potential of TMS in movement disorders. He will be mentored by Dr. Winstein, who brings a quantitative motor behavior approach, as well as access to the support and resources necessary for development of a TMS-equipped neuro-motor physiology laboratory at USC. Drs. lacoboni and PascuaI-Leone will jointly supervise a customized TMS fellowship. Dr. Wu will perform experiments in a practical TMS setting at UCLA under the mentorship of Dr. lacoboni, and will attend semiannual mini-fellowships at Beth Israel Deaconess Medical Center in Boston with Dr PascuaI-Leone. Studies using TMS as a possible therapy for PD, often by targeting TMS over primary motor cortex (M1), have thus far shown inconsistent results, but may be limited by a relative absence of knowledge about how TMS affects normal motor control. Dr. Wu proposes to systematically investigate the effects of TMS over M1 on uni-manual goal-directed aiming movements, a fundamental unit of motor control. Two hypotheses are investigated: 1) The causal importance of M1 in the preparation of discrete aimed movements; and 2) the causal functional asymmetry of M1 for the execution of continuous aimed movements. Results may extend theories of aiming by placing a specific, functionally important, causal role of M1 for aspects of motor control. These studies will form a basis of the outlined career development plan for Dr. Wu from which extrapolation of findings in normal subjects to those with clinical movement disorders (such as PD) may lead to future rational selection of TMS parameters that can predictably and effectively modulate movement disorders symptoms. ? ?
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