Brain Oscillation-synchronized Stimulation of the Frontal Cortex in Major Depressive Disorder

Evidence from rTMS in the motor system suggests that synchronization of the individual TMS pulses with the negative (in a reference-free Laplacian transform) peak of endogenous EEG-derived brain oscillations results in LTP-like increase in cortical excitability, with the negative peak corresponding to a high-excitability state. A previous proof-of-principle study (BOSSFRONT, funded in the "AKF Anreizprogramm") showed that this approach can be used in patients suffering from major depressive disorder. Recent data from our lab in healthy volunteers indicates that the negative peak of frontocentral theta oscillations may play a similar role in frontal networks, and was therefore chosen with a dorsomedial prefrontal stimulation target in this study aiming to demonstrate therapeutic efficacy of a brain-oscillation synchronized stimulation protocol. The study is a single-site randomized standard TMS therapy-controlled double-blind parallel-group design clinical trial comparing theta-synchronized rTMS over left DMPFC with standard iTBS over left DLPFC in 30 patients with MDD. The primary outcome measure of the study is the difference in MADRS change (baseline / end of treatment) between the two treatment arms.