Structural and Functional Correlates of Clinical Response to rTMS Treatment in Schizophrenia Patients With Resistant Auditory Hallucinations

The potential of non-invasive Transcranial Magnetic Stimulation (TMS) as a therapeutic tool for improving schizophrenic symptoms, in particular resistant hallucinations, has been increasingly studied over the past decades. Several studies have demonstrated that low-frequency patterns of repetitive TMS (rTMS) on the left temporoparietal junction (TPJ), which are known to decrease local activity, significantly reduce auditory verbal hallucinations in schizophrenic patients. In spite of highly promising results, a high level of inter-individual variability in the response to non-invasive brain stimulation treatments, and the fact that rTMS may prove ineffective in some patients, keep spurring controversy on the efficacy of these approaches as currently performed, and on how to increase its efficacy and consistency. To date, few studies have aimed to explain this variability when, in fact, a better understanding of this common phenomena in the neurostimulation domain would clearly increase the effectiveness of this treatment, and lead to individualized therapeutic approaches specifically tailored to the conditions of each patient. Moreover, many questions stand, particularly regarding the influence of rTMS treatment on the anatomical and functional connectivity in schizophrenic patients. Accordingly, the objectives of this project are to better understand the impact of rTMS on the brains of patients with resistant auditory hallucinations, and to use this information not only to better understand this condition but to develop more efficient and consistent therapies. The investigators hypothesize that there is a baseline difference in anatomical and/or functional connectivity between responder and non-responder patients who are treated with rTMS. Therefore, this project aims to determine some anatomical and functional connectivity markers of response to rTMS treatment in patients with schizophrenia. For this, the investigators compare the patterns of diffusion tensor imaging (DTI) white matter tractography and resting-state functional magnetic resonance imaging (fMRI) data between responder and non-responder patients to rTMS treatment. Moreover, the investigators believe that rTMS can increase the functional connectivity between frontal and temporo-parietal cortices in schizophrenic patients associated with improvements in auditory hallucinations. Therefore, the second objectives of this work are to evaluate the impact of rTMS in functional connectivity in patients with schizophrenia by comparing the DTI and resting-state fMRI data before and after rTMS treatment in both responder and non-responder patients.