TMS to explore interhemispheric interactions and to treat aphasia and neglect

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The central aim of this proposal is characterize structure-function relationships in the frontal lobes related to semantic, phonologic, and morphologic language processing, and to apply this understanding of domain- specific organization to the treatment of aphasia. The first specific aim is to test the hypothesis that anatomical distinctions exist in the left inferior frontal gyrus for different domains of language processing. Transcranial magnetic stimulation (TMS) will be administered to normal subjects to disrupt subject performance, revealing dissociations between language domains. The second aim is to test the hypothesis that interhemispheric interactions between the left frontal language areas and homologous contralateral regions are domain-specific. TMS in normal subjects will elucidate whether manipulation of the right hemisphere influences morphologic, phonologic, and semantic processing. The anatomic hypotheses of the study will be tested further in aphasic subjects, in whom language domains will be assessed before and after 10 daily sessions of right-sided TMS. We will also use functional magnetic resonance imaging (fMRI) to further test these functional-anatomic hypotheses. This project meets the candidate's immediate goals by developing his proficiency with, study design, psychological measures, TMS, and fMRI, 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 Functional Neuroimaging (CfN) and the Center for Cognitive Neuroscience (CCN). The candidate will also augment his career development through coursework and methodologic training opportunities offered through the university. Finally, the health implications of this work are far- reaching. Aphasia is a common and often devastating consequence of strokes, affecting approximately 1 million patients in the United States and 80,000 new patients in this country annually. TMS-induced feature- specific effects on aphasia recovery could point the way toward future therapeutic approaches, including brain stimulation, that may be both more efficacious than current therapies for aphasia and which focus on patients' specific language deficits.