Interleaved TMS-fMRI based dosing for treatment of depression

Transcranial magnetic stimulation (TMS) on a target in the dorsolateral prefrontal cortex (DLPFC) is an FDA approved treatment option for major depression disorder (MDD). While generally highly effective some patients do not respond adequately. Recent studies propose the orbitofrontal cortex (OFC) as alternative stimulation site. Specifically the targets AF8 and F8 are in the focus for further research due to their strong functional connectivity to the subgenual cingulate cortex (sgACC), a region implicated in depression. The neural mechanisms of response to OFC-TMS, however, are not well characterized. Given that the targets in OFC are still very much unexplored, many questiones have to be tackled to perform TMS-fMRI. Starting with the right settings for stimulation in the MRI bore, positionings of coils have to be optimized as well as a close examination of the signal quality in the examined brain regions will be done. Additionally, the huge variability in scalp to cortex distance in the region of the OFC (above the eyes), demands for a detailled investigation of the electric field induced in the brain. This investigation can be done by simulating the electric field using a software tool. In this thesis investigations on the technical feasibility and optimization of interleavedTMS-fMRI (functional magnetic resonance imaging) for assessment and dosing these alternative targets are conducted. The thesis is constructed into two parts: Part I provides a comprehensive physical and technical background on nuclear magnetic resonance (NMR), MRI, TMS, and the principles of their integration. Part II presents experimental data from fMRI acquisitions with TMS stimulation on AF8 and F8, including the development of coil positioning strategies, evaluation of artifact suppression through trigger delay modulation, and electric field simulations using SimNIBS. With the findings of this thesis the use of interleaved TMS-fMRI for targeted stimulation of the OFC is supported and the potential for individualized depression treatment approaches is highlighted. Future studies can be encouraged and the validation of the new targets in the OFC region using a broad group of subjects will be a following step.