Differential effects of individualized vs. fixed-frequency tACS on clinical and EEG outcomes in major depressive...

Major depressive disorder (MDD) is a prevalent affective disorder with limited treatment efficacy. Transcranial alternating current stimulation (tACS) represents a promising non-invasive intervention for MDD; however, optimal stimulation parameters and the neural mechanism underlying tACS require further investigation.

The study used a randomized double-blind controlled design that included 72 outpatients with MDD, who were randomly divided into a low-administration (once daily) fixed (10 Hz) group, a low-administration (once daily) individual alpha frequency (IAF) group, a high-administration (twice daily) fixed (10 Hz) group, and a high-administration (twice daily) IAF group in a 1:1:1:1 randomization. The study period was 4 weeks, with an intervention period (2 weeks) and a follow-up period (2 weeks). During the intervention period, patients were required to complete 20 sessions of tACS and EEG were acquired pre- and post-treatment.

No significant differences were observed between IAF and fixed groups or between high-and low-administration-frequency in clinical efficacy. However, high-administration-frequency and fixed groups showed a favorable trend in symptom improvement. EEG analysis revealed reduced alpha power spectral density (PSD) in the parietal lobe for high-administration-frequency stimulation and enhanced frontal functional connectivity in the two fixed groups.

The results suggested potential symptom improvement of tACS. However, in the absence of a sham control, the findings should be interpreted cautiously and regarded as preliminary evidence. EEG analyses revealed significant modulation of brain oscillatory patterns by tACS. Overall, this study provides the first comparison of antidepressant treatment effects under different stimulation frequencies or protocols and offers insights into the neural mechanisms underlying tACS.