N100 as a response prediction biomarker for accelerated 1 Hz right DLPFC-rTMS in major depression
Jack Sheen, Frank Mazza, Davide Momi, Jean‐Philippe Miron, Farrokh Mansouri, Thomas Russell, Ryan Zhou, Molly Hyde, Linsay Fox, Helena Voetterl, Elie Bou Assi, Zafiris J. Daskalakis, Daniel M. Blumberger, John D. Griffiths, Jonathan Downar
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depressive disorder (MDD); however, this treatment currently lacks reliable biomarkers of treatment response. TMS-evoked potentials (TEPs), measured using TMS-electroencephalography (TMS-EEG), have been suggested as potential biomarker candidates, with the N100 peak being one of the most promising. This study investigated the association between baseline N100 amplitude and 1 Hz right dorsolateral prefrontal cortex (R-DLPFC) accelerated rTMS (arTMS) treatment in MDD. Baseline TMS-EEG sessions were performed for 23 MDD patients. All patients then underwent 40 sessions of 1 Hz R-DLPFC (F4) arTMS over 5 days and a follow-up TMS-EEG session one week after the end of theses arTMS sessions. Baseline N100 amplitude at F4 showed a strong positive association ( p < .001) with treatment outcome. The association between the change in N100 amplitude (baseline to follow-up) and treatment outcome did not remain significant after Bonferroni correction ( p = .06, corrected; p = .03, uncorrected). Furthermore, treatment responders had a significantly larger mean baseline F4 TEP amplitude during the N100 time frame compared to non-responders ( p < .001). Topographically, after Bonferroni correction, F4 is the only electrode at which its baseline N100 amplitude showed a significant positive association (p < .001) with treatment outcome. Lack of control group and auditory masking. Baseline N100 amplitude showed a strong association with treatment outcome and thus demonstrated great potential to be utilized as a cost-effective and widely adoptable biomarker of rTMS treatment in MDD. • Baseline F4 N100 amplitude showed a strong association (p<.001) with 1Hz R-DLPFC rTMS treatment outcome. • Treatment responders had a larger mean F4 TEP amplitude during the N100 time frame compared to non-responders (p <.001). • N100 amplitude at F3 and F4 had the strongest association with outcome (F3: p = 0.015, uncorr.; F4 p < .001, corrected). • Our results suggest that N100 amplitude has great potential to be a cost-effective and widely-adoptable biomarker.