Repetitive transcranial magnetic stimulation (rTMS) is an alternative treatment for depression, but the neural correlates of the treatment are currently inconclusive, which might be a limit of conventional analytical methods. The present study aimed to investigate the neurophysiological evidence and potential biomarkers for rTMS and intermittent theta burst stimulation (iTBS) treatment. A total of 61 treatment‐resistant depression patients were randomly assigned to receive prolonged iTBS (piTBS; N = 19), 10 Hz rTMS (N = 20), or sham stimulation (N = 22). Each participant went through a treatment phase with resting state electroencephalography (EEG) recordings before and after the treatment phase. The aftereffects of stimulation showed that theta‐alpha amplitude modulation frequency (fam) was associated with piTBS_Responder, which involves repetitive bursts delivered in the theta frequency range, whereas alpha carrier frequency (fc) was related to 10 Hz rTMS, which uses alpha rhythmic stimulation. In addition, theta‐alpha amplitude modulation frequency was positively correlated with piTBS antidepressant efficacy, whereas the alpha frequency was not associated with the 10 Hz rTMS clinical outcome. The present study showed that TMS stimulation effects might be lasting, with changes of brain oscillations associated with the delivered frequency. Additionally, theta‐alpha amplitude modulation frequency may be as a function of the degree of recovery in TRD with piTBS treatment and also a potential EEG‐based predictor of antidepressant efficacy of piTBS in the early treatment stage, that is, first 2 weeks.

Background Prolonged intermittent theta-burst stimulation (piTBS) and repetitive transcranial magnetic stimulation (rTMS) are effective antidepressant interventions for major depressive disorder (MDD). Cognition-modulated frontal theta (frontalθ) activity had been identified to predict the antidepressant response to 10-Hz left prefrontal rTMS. However, whether this marker also predicts that of piTBS needs further investigation. Methods The present double-blind randomized trial recruited 105 patients with MDD who showed no response to at least one adequate antidepressant treatment in the current episode. The recruited patients were randomly assigned to one of three groups: group A received piTBS monotherapy; group B received rTMS monotherapy; and group C received sham stimulation. Before a 2-week acute treatment period, electroencephalopgraphy (EEG) and cognition-modulated frontal theta changes (Δfrontalθ) were measured. Depression scores were evaluated at baseline, 1 week, and 2 weeks after the initiation of treatment. Results The Δfrontalθ at baseline was significantly correlated with depression score changes at week 1 (r = −0.383, p = 0.025) and at week 2 for rTMS group (r = −0.419, p = 0.014), but not for the piTBS and sham groups. The area under the receiver operating characteristic curve for Δfrontalθ was 0.800 for the rTMS group (p = 0.003) and was 0.549 for the piTBS group (p = 0.619). Conclusion The predictive value of higher baseline Δfrontalθ for antidepressant efficacy for rTMS not only replicates previous results but also implies that the antidepressant responses to rTMS could be predicted reliably at baseline and both piTBS and rTMS could be effective through different neurobiological mechanisms.

Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) have been proven effective non-invasive treatments for patients with drug-resistant major depressive disorder (MDD). However, some depressed patients do not respond to these treatments. Therefore, the investigation of reliable and valid brain oscillations as potential indices for facilitating the precision of diagnosis and treatment protocols has become a critical issue. The current review focuses on brain oscillations that, mostly based on EEG power analysis and connectivity, distinguish between MDD and controls, responders and non-responders, and potential depression severity indices, prognostic indicators, and potential biomarkers for rTMS or iTBS treatment. The possible roles of each biomarker and the potential reasons for heterogeneous results are discussed, and the directions of future studies are proposed.

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