Project Summary

Ralph Hoffman, M.D. (Independent Investigator 2003) of Yale University, has found repetitive Transcranial Magnetic Stimulation (rTMS) to be beneficial in the treatment of auditory hallucinations (AHs) of speech ("voices") which occur in 50-70% of patients with schizophrenia and often are resistant to medication therapy. Dr. Hoffman has found that targeting a brain region underlying speech perception is more efficacious than sham stimulation in reducing AHs. Although improvements were often clinically significant, patients experiencing AHs at very high frequencies (greater on average than once every two minutes) did not experience much benefit following rTMS. Using functional magnetic resonance imaging (fMRI), Dr. Hoffman can delineate a network of multiple brain regions that produces these experiences. He will now use fMRI maps to position rTMS at multiple brain sites for a clinical trial of patients with very frequent AHs to determine if targeted rTMS based on fMRI data will produce greater improvements than stimulation delivered to a control area found not to be involved in producing AHs, and if rTMS delivered to multiple brain regions based on the fMRI data produces significantly greater improvements in AHs compared to rTMS delivered to a single "standard" site. In addition, an exploratory analysis will be undertaken to determine if stimulation at particular brain sites determined using fMRI data preferentially improves AHs. All brain regions of interest will be tested and clinical outcomes for patients in the proposed fMRI-guided trial will be compared with patients in the previous "single-site" rTMS trial matched in terms of baseline hallucination frequency. This study will provide critical new insights in the neuroanatomic basis of AHs and may lead to a new non-invasive, non-pharmacological treatment for patients with schizophrenia with especially severe hallucinatory syndromes.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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