Reduction in left frontal alpha oscillations by transcranial alternating current stimulation in major depressive disorder is context-dependent in a randomized-clinical trial

Background Left frontal alpha oscillations are associated with decreased approach motivation and have been proposed as a target for non-invasive brain stimulation for the treatment of depression and anhedonia. Indeed, transcranial alternating current stimulation (tACS) at the alpha frequency reduced left frontal alpha power and was associated with a higher response rate than placebo stimulation in patients with major depressive disorder (MDD) in a recent double-blind placebo controlled clinical trial. Methods In this current study, we aimed to replicate such successful target engagement by delineating the effects of a single session of bifrontal tACS at the individualized alpha frequency (IAF-tACS) on alpha oscillations in patients with MDD. Electrical brain activity was recorded during rest and while viewing emotionally-salient images before and after stimulation to investigate if the modulation of alpha oscillation by tACS exhibited specificity with regards to valence. Results In agreement with the previous study of tACS in MDD, we found that a single session of bifrontal IAF-tACS reduced left frontal alpha power during the resting state when compared to placebo. Furthermore, the reduction of left frontal alpha oscillation by tACS was specific for stimuli with positive valence. In contrast, these effects on left frontal alpha power were not found in healthy control participants. Conclusion Together these results support an important role of tACS in reducing left frontal alpha oscillations as a future treatment for MDD. National Clinical Trial NCT03449979, “Single Session of tACS in a Depressive Episode (SSDE)” https://www.clinicaltrials.gov/ct2/show/NCT03449979