This is a resubmission for the competing continuation renewal of our research on the therapeutic utility of repetitive transcranial magnetic stimulation (rTMS) to improve speech in chronic, nonfluent and severe aphasia. Functional MRI studies in these patients have shown """"""""over-activation"""""""" in right (R) perisylvian language homologues; possibly representing a maladaptive plasticity. Our hypothesis is that suppression of this over-activation with IMS may improve speech. Significant improvement in picture naming was observed immediately following rTMS for 10 min. to suppress R pars triangularis (R BA 45), with decreased reaction time (RT). rTMS to 3 other R ROIs produced no improvement. In a later phase, we applied 1-Hz rTMS to R BA 45 for 20 min. daily, 10 days. Significant improvement in picture naming was observed at 2 Mo. post- TMS; and at 8 Mo.post-TMS, despite no individualized speech therapy. Pilot studies with sham rTMS have shown no effect. We propose a blinded, sham-controlled, incomplete crossover design, over a 5-Yr. period (20 mild-moderate nonfluent; 20 severe nonfluent patients) with fMRI to study mechanisms of action of TMS. To insure recruitment of an adequate number of patients, we have added a second site, the Univ. of PA, where half of the patients will be studied. We have developed an overt naming fMRI BOLD paradigm for use with nonfluent patients. Pilot data indicate that pre-rTMS, there is over-activation in R frontal areas (including R inferior frontal gyrus, R BA 45; and motor cortex-mouth), with little activation in temporal lobe and poor naming performance. Post-rTMS where 1-Hz rTMS was applied to R BA 45 for 20 min. daily, 10 days, improved naming was associated with less over-activation in R BA 45 and M1-mouth, with new temporal lobe activation. Overt naming fMRI will be obtained pre-real/sham rTMS, and at 2 Mo. post-real/sham rTMS. Those receiving sham rTMS are then crossed-over to real-rTMS. We hypothesize that patients who receive real rTMS will have significant improvement in picture naming at 2 Mo. post-real rTMS, versus those who receive sham rTMS. Only the real rTMS group will show suppression of R BA 45 on fMRI. Relevance to public health: The U.S. population is increasing in age; thus, an increase in stroke and need for sophisticated treatment. The number of people with aphasia in the U.S. today is estimated to be 1 million; 80,000 new cases each year. This research has direct clinical relevance for aphasia patients. ? ? ?
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