The central aims of this proposal are to further characterize interhemispheric interactions that emerge in response to lateralized brain injury, and to apply this understanding to the treatment of stroke-induced aphasia and neglect. Aphasia will serve as a model for investigating the right hemisphere's role in left hemisphere function;neglect will be the model for elucidating the left hemisphere's role in right hemisphere function. The first specific aim is to identify anatomical distinctions in the left frontal lobe for different domains of language processing. Transcranial magnetic stimulation (TMS) will be administered to the left inferior frontal gyrus in normal subjects to disrupt performance, revealing dissociations between language domains. The second specific aim is to identify anatomical distinctions in right hemisphere for different aspects of spatial cognition. TMS will be administered to the right frontal and parietal cortex in normal subjects to alter performance, elucidating structure-function relationships underlying attention. The anatomic hypotheses of the study will be tested further in a treatment trial involving chronic stroke patients who have aphasia or neglect. Each group will undergo assessment of their deficit before and after 10 daily sessions of contralesional TMS. This project meets the candidate's immediate goals by developing his proficiency with study design, psychological measures, and TMS, and by furthering his longstanding interest in the behavioral effects of cortical plasticity. It advances his long-term goal of establishing a career as an independent investigator in cognitive neuroscience and neurology in an academic institution. The University of Pennsylvania is a rich environment for pursuing these goals, featuring resources such as the Center for Cognitive Neuroscience (CCN). The candidate will also augment his career development through coursework and methodological training opportunities offered through the university. Finally, the health implications of this work are far-reaching. Aphasia affects more than 20% of patients with ischemic stroke while hemispatial neglect occurs in 25-30% of stroke-affected individuals. TMS-induced feature-specific effects on aphasia and neglect recovery could point the way toward future therapeutic approaches that may be both more efficacious and better targeted than current therapies.
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