Individual alpha peak predicts clinical response in TMS therapy for depression: An independent replication

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), but clinical response varies significantly among individuals. Consequently, neuroimaging and electrophysiology studies are increasingly focused on identifying biomarkers to predict outcomes. Individual alpha peak frequency (iAF), reflecting the dominant oscillation of alpha-generating neural circuits, has shown promise as a predictive biomarker for 10 Hz rTMS due to its reliability and mechanistic interpretability. While earlier studies assessed clinical outcomes broadly, Siddiqi et al. 2020 highlighted that dysphoric and anxiosomatic symptoms-two robust domains-are linked to distinct imaging clusters and exhibit target-specific responses. In this study, we revisited iAF's utility as a predictive biomarker of rTMS treatment response for these domains. We analyzed 27 MDD patients who underwent 5 weeks of left dorsolateral prefrontal cortex (DLPFC) 10 Hz rTMS with baseline EEG, calculating peak alpha frequency (PAF), its proximity to 10 Hz stimulation (PAF_dist), and domain-specific clinical responses. Our findings revealed that iAF was significantly associated with improvements in the dysphoric domain but not in the anxiosomatic domain. Furthermore, better effects were observed in females, and exploratory analysis with a larger dataset (n=121) confirmed notable sex differences, suggesting iAF's predictive utility is stronger in women. These results indicate that iAF's sensitivity as a predictive biomarker may depend on both clinical symptom domains and sex.