Neurophysiological effects of repetitive transcranial magnetic stimulation (rTMS) in treatment resistant depression

Objective: Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment resistant depression (TRD), but little is known about rTMS' effects on neurophysiological markers. We previously identified neurophysiological markers in depression (N45 and N100) of GABA receptor mediated inhibition. Here, we indexed TMS-electroencephalographic (TMS-EEG) effects of rTMS. Methods: TMS-EEG data was analyzed from a double blind 2:1 randomized active (10 Hz left/bilateral): sham rTMS TRD trial. Participants underwent TMS-EEG over left dorsolateral prefrontal cortex (DLPFC) before and after 6 weeks of rTMS. 30 had useable datasets. TMS-evoked potentials (TEP) and components (N45, N100, P60) were examined with global mean field analysis (GMFA) and locally in DLPFC regions of interest. Results: The N45 amplitude differed between active and sham groups over time, N100 amplitude did not. N45 (t = 2.975, p = 0.007) and N100 amplitudes (t = 2.177, p = 0.042) decreased after active rTMS, demonstrating alterations in cortical inhibition. TEP amplitudes decreased after active rTMS in left (t = 4.887, p < 0.001) and right DLPFC (t = 4.403, p < 0.001) not sham rTMS, demonstrating alterations in cortical excitability. Conclusions: Our results provide important new knowledge regarding rTMS effects on TMS-EEG measures in TRD, suggesting rTMS reduces neurophysiological markers of inhibition and excitability. Significance: These findings uncover potentially important neurophysiological mechanisms of rTMS action. (C) 2021 Published by Elsevier B.V. on behalf of International Federation of Clinical Neurophysiology.