Personalized connectivity- and electric field-guided transcranial modulation of the subgenual anterior cingulate cortex in major depression

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The aim of the project is the further development and personalized optimization of repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) for the treatment of major depression. To this end, we have firstly developed a new optimization method for the positioning/orientation of the TMS coil based on individual mapping of the connectivity between the DLPFC and the subgenual anterior cingulate cortex (sgACC) as well as individual modelling of the TMS-induced electric field in the DLPFC, and secondly, established and optimized an innovative method for individualization of the stimulation intensity which compares the TMS-induced electric fields in motor cortex and DLPFC with reference to the individual motor threshold. A pilot randomized clinical trial in patients with major depression will investigate the feasibility, tolerability and efficacy of our individualized connectivity- and electric field-guided rTMS of the left DLPFC and compare it with state-of-the-art rTMS treatments for major depression. In addition, using simultaneous TMS-fMRI measurements we will also investigate the role of activation and modulation of the sgACC as a mechanism of action of rTMS therapy. In further experiments in healthy volunteers, we will systematically investigate TMS-induced neuronal activation and modulation of the sgACC as a function of DLPFC-sgACC connectivity and stimulation intensity using connectivity- and electric field-guided (r)TMS and simultaneous TMS-fMRI measurements to determine optimal stimulation parameters for the most effective activation and modulation of the sgACC.