Alternative Stimulation Mode and Location for Auditory Hallucination Neuromodulation Treatment

Project summary: Current efforts to use rTMS to treat auditory hallucinations refractory to available antipsychotic medications show promising efficacy but replicability of the effect in well-controlled clinical trials remain unsatisfactory. The proposed study is to use a novel approach to design rTMS treatment for auditory hallucination that is based on a strong neural circuitry mechanism on auditory hallucination formation. The project will recruit patients with schizophrenia spectrum disorders and randomize patients into active rTMS versus sham rTMS groups followed by four fMRI based target engagement outcome assessments at baseline and after 10, and 20 visits of daily rTMS plus a 2 week maintenance phase. The proposal will use new stimulation site and stimulation mode combinations that are different from previous rTMS trials on auditory hallucination, but are conceptualized to be more closely linked to neural circuitry mechanisms of auditory halluciantion formation. The proposal will include two phases as two separate projects. The first proposed project is a R61 for two years. If the Go/Nogo milestones are not met, the study will end. If all Go/Nogo milestones are met, it will proceed to a R33 project for three more years. The trial will test the proposed mechanism of action at brain circuitry level and determine whether the new stimulation site and mode strategy will indeed significantly engage the proposed circuitry of action through modulating its functional connectivity in the direction for improving auditory hallucination.