Project summary While available tobacco smoking cessation aids, therapies, and public health efforts have reduced the overall smoking rate, patients with schizophrenia spectrum disorders continue to have high rate of smoking. Recent imaging research has identified key brain circuitries likely contributing to the high rate of smoking in these patients, in an overlapping pathophysiological neural circuitry between schizophrenia and nicotine addiction. Targeted correction of this overlapping circuitry may improve the patients' chances of success in quitting smoking. The proposed study is to use a novel approach to design rTMS treatment that is based on a neural circuitry mechanism on nicotine addiction in schizophrenia. The project will recruit patients with schizophrenia spectrum disorders and randomize patients into active rTMS versus sham rTMS groups followed by fMRI based target engagement outcome assessments. The proposal will use new stimulation site conceptualized to be more closely linked to neural circuitry mechanisms of nicotine addiction in schizophrenia. The proposal will include two phases as two separate projects. The first proposed project is a UG3 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 UH3 project for another three years. The trial will test the proposed mechanism of action at brain circuitry level and determine whether the new stimulation site will indeed significantly engage the proposed circuitry through modulating its functional connectivity in the direction for helping patients to reduce and quit smoking.