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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS045764-05
Application #
7175296
Study Section
NST-2 Subcommittee (NST)
Program Officer
Sutherland, Margaret L
Project Start
2004-02-01
Project End
2009-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
5
Fiscal Year
2007
Total Cost
$176,094
Indirect Cost
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Meister, Ingo G; Wu, Allan D; Deblieck, Choi et al. (2012) Early semantic and phonological effects on temporal- and muscle-specific motor resonance. Eur J Neurosci 36:2391-9
Lin, Chien-Ho Janice; Fisher, Beth E; Wu, Allan D et al. (2009) Neural correlate of the contextual interference effect in motor learning: a kinematic analysis. J Mot Behav 41:232-42
Wu, Allan D; Fregni, Felipe; Simon, David K et al. (2008) Noninvasive brain stimulation for Parkinson's disease and dystonia. Neurotherapeutics 5:345-61
Fisher, Beth E; Wu, Allan D; Salem, George J et al. (2008) The effect of exercise training in improving motor performance and corticomotor excitability in people with early Parkinson's disease. Arch Phys Med Rehabil 89:1221-9
Deblieck, Choi; Thompson, Benjamin; Iacoboni, Marco et al. (2008) Correlation between motor and phosphene thresholds: a transcranial magnetic stimulation study. Hum Brain Mapp 29:662-70
Molnar-Szakacs, Istvan; Wu, Allan D; Robles, Francisco J et al. (2007) Do you see what I mean? Corticospinal excitability during observation of culture-specific gestures. PLoS One 2:e626
Wu, Allan D; Petzinger, Giselle M; Lin, Chien-Ho J et al. (2007) Asymmetric corticomotor excitability correlations in early Parkinson's disease. Mov Disord 22:1587-93
Meister, Ingo G; Wilson, Stephen M; Deblieck, Choi et al. (2007) The essential role of premotor cortex in speech perception. Curr Biol 17:1692-6
Wu, Allan D (2007) Functional neuroimaging and repetitive transcranial magnetic stimulation in Parkinson's disease. Rev Neurol Dis 4:1-9
Koski, Lisa; Lin, Janice Chien-Ho; Wu, Allan D et al. (2007) Reliability of intracortical and corticomotor excitability estimates obtained from the upper extremities in chronic stroke. Neurosci Res 58:19-31

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