Task-Modulated Brain Activity Predicts Antidepressant Responses of Prefrontal Repetitive Transcranial Magnetic Stimulation: A Randomized Sham-Control Study

Abstract

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.

Critical role of rhythms in prefrontal transcranial magnetic stimulation for depression: A randomized sham‐controlled study

“…Although the clinical outcomes from the subdataset of Li et al (2020) did not show a larger antidepressant effect in terms of percentage changes of HDRS for rTMS (30.19%) in comparison to the sham (14.75%) which may be due to the smaller effect size, the full dataset from Li et al (2020) has shown that piTBS and rTMS have a similar antidepressant effect which was significantly larger than sham. This finding was consistent with the results of our previous studies (Li et al, 2021) and similar to Blumberger et al (2018). In spite of the comparable treatment effect based on the two stimulating protocols, the underlying antidepressant physiological function of rTMS and piTBS might be different and might be represented by distinct patterns of changes in brain oscillations.…”

A review of critical brain oscillations in depression and the efficacy of transcranial magnetic stimulation treatment

“…Moreover, one study manipulated the increased frontal ACC theta by asking the participants to perform an rACC-engaging cognitive task between two resting EEG conditions before the rTMS treatment. The results show that the frontal theta activity after the cognitive task at the pre-treatment phase could predict the antidepressant response up to 89% within the area under the curve (AUC) of the receiver operating characteristic (ROC) ( 49 ); however, this index could not predict the antidepressant efficacy by delivering iTBS ( 50 ). Additionally, the lower relative theta power, which indicated the ratio of theta to total power, in frontal regions at the pre-treatment stage was found in responders than in non-responders, which could predict the antidepressant responses ( 39 , 51 ).…”