Related Experiment Video
Updated: Jun 1, 2026
Robotically Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Treatment-Resistant Depression
Published on: April 10, 2026
Suppression of endogenous alpha power predicts clinical response to 10 Hz tACS in major depressive disorder: A
Tobias Schwippel1, Francesca Pupillo2, Hadden LaGarde2
1Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; Carolina Center for Neurostimulation, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; Present Address: Department of Psychiatry, Psychotherapy and Psychosomatics, Goethe University Frankfurt, Frankfurt, 60528, Germany.
Background:
Transcranial alternating current stimulation (tACS) is a promising non-pharmacological intervention for major depressive disorder (MDD), but its effects on endogenous alpha oscillatory dynamics and their relationship to clinical improvement remain unclear.
Methods:
In this double-blind, sham-controlled randomized clinical trial, 20 adults with MDD received five consecutive days of prefrontal 10 Hz tACS or sham. Resting 128-channel EEG was acquired before stimulation on Day 1 (D1), Day 5 (D5), and two-week follow-up. Changes in alpha power spectral density were quantified at the stimulation frequency (10 Hz) and at each participant's individual alpha frequency (IAF), using prefrontal regions of interest and whole-head topographical analyses. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS-17).
Results:
Between-group comparisons revealed no significant differences in prefrontal alpha power changes at either 10 Hz or IAF during the intervention week or at follow-up, although right prefrontal 10 Hz power showed a trend-level reduction with tACS. In contrast, within the tACS group, greater reductions in prefrontal IAF power were associated with greater HDRS-17 improvement from D1 to follow-up, and early IAF power suppression during the intervention week predicted later symptom improvement. ANCOVA analyses confirmed this condition-dependent association, with lower IAF power relating to lower follow-up HDRS-17 scores in tACS relative to sham. Whole-head analyses identified a posterior cluster of reduced 10 Hz power at follow-up in the tACS group relative to sham, whereas clinically relevant correlations were specific to IAF power and distributed across frontal-central and parietal electrodes. Depression scores improved over time in both groups, with numerically greater reductions in HDRS-17 scores observed in the tACS group.
Conclusions:
Findings suggest that five days of 10 Hz tACS engages depression-relevant alpha mechanisms, with symptom improvement linked to modulation of alpha power at IAF. These results support future trials testing personalized tACS approaches.
