Effect of Repetitive Transcranial Magnetic Stimulation on Resting State Brain Activity in Schizophrenia

Background. The sub-Investigator Dr. Mennemeier has been using repetitive transcranial magnetic stimulation (rTMS) to treat phantom sound perception in subjects with tinnitus. The Principal Investigator (PI), Dr. Messias, now aims to team up with Drs. Mennemeier and James, to learn how rTMS influences phantom sound perception in schizophrenia. rTMS has already been shown to be an effective treatment for both tinnitus and schizophrenia. rTMS is a non-invasive method of regional brain stimulation that can significantly reduce phantom sound perception temporarily in 50% of subjects with tinnitus and schizophrenia. This study will go further than previous investigations by analyzing how different frequencies of rTMS influence not only auditory hallucinations (AH) in schizophrenia but also brain connectivity in schizophrenia. The investigators want to learn if rTMS decreases AH by normalizing brain connectivity. Whereas this study focuses on schizophrenic subjects with AH, the design is very similar to ongoing work on tinnitus so the findings will be comparable. Tinnitus and AH in schizophrenia are prevalent and disabling disorders of sound perception. The investigators understanding of the precise mechanisms of these disorders is lacking. Interestingly, the symptoms of both disorders respond positively to rTMS of the temporal cortex in ways that defy contemporary understanding of the nature of these symptoms and of how rTMS should work to improve them. For example, phantom sound perception in both tinnitus and schizophrenia are linked to maladaptive, hyperactivity of auditory processing regions of temporal cortex; however, it is increasingly clear that these pathological changes alone are insufficient to explain the pronounced intrusiveness and negative emotional valance of symptoms in each disorder. Therefore, a barrier to understanding these disorders lies in understanding how changes in auditory cortex are synchronized with changes in other cortical regions that regulate perception and emotion. Additionally, at present, the decision of which rTMS frequency to apply as a treatment for phantom sound perception has no firm theoretical or empirical basis. Whereas, low frequency rTMS has traditionally been used, based upon contemporary models, to "inhibit" hyperactivity in auditory cortex; high frequency rTMS, which should induce an opposite effect on neuronal processing, not only works to improve symptoms but may be more effective for some subjects than low frequency rTMS. Therefore, contemporary models designed to explain how the frequency of rTMS influences neuronal activity immediate following stimulation are insufficient to explain how low and high frequencies of rTMS can mitigate phantom sound perception for days, weeks and months following a single course of treatment. Hypothesis. The investigators propose that phantom sound perception in schizophrenia result from an imbalance of excitatory and inhibitory neural process in auditory networks and from synchronized, maladaptive changes in linked brain regions that regulate perception and emotion. Treating auditory cortex with repetitive, external magnetic stimulation can decrease phantom sound perception and distress by reversing the maladaptive brain reorganization that is set in motion by these underlying neural imbalances.