Archival Report
Reduction in Left Frontal Alpha Oscillations by Transcranial Alternating Current Stimulation in Major Depressive Disorder Is Context Dependent in a Randomized Clinical Trial

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Abstract

Background

Left frontal alpha oscillations are associated with decreased approach motivation and have been proposed as a target for noninvasive 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 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. Eighty-four participants were randomized to receive verum or sham IAF-tACS. Electrical brain activity was recorded during rest and while viewing emotionally salient images before and after stimulation to investigate whether the modulation of alpha oscillation by tACS exhibited specificity with regard 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 with 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.

Conclusions

Together, these results support an important role of tACS in reducing left frontal alpha oscillations as a future treatment for MDD.

Section snippets

Methods and Materials

The experiment was approved by the Institutional Review Board at the University of North Carolina at Chapel Hill. Participants recruited from the Raleigh-Durham-Chapel Hill community provided written consent before participation. The experiment was conducted in the Carolina Center for Neurostimulation from September 2018 to August 2019. The experimental design consisted of two groups, those in an MDE and euthymic control participants, in which each participant received either tACS or an active

Electrical Stimulation Modulates Left Frontal Alpha Power in MDD

Participants were successfully blinded to the stimulation (n = 80, 2 participants did not answer, χ21,80 = 0.2631, p = .608). Of the 42 participants who received verum stimulation, 33 believed that they received verum stimulation. However, of the 40 participants who received sham stimulation, 28 believed that they received verum stimulation (2 chose not to answer). Thus, participants, irrespective of stimulation type, were biased toward believing they received verum, and their accuracy was

Discussion

Patients in an MDE were recruited to receive 40 minutes of tACS in the IAF designed to reduce left frontal alpha oscillations. Electrophysiology was recorded before and after stimulation. In agreement with our previous clinical trial that applied 5 consecutive days of tACS in patients with depression (11), we found a selective decrease in left frontal IAF power for verum versus sham stimulation. The effect was driven by an increase in left frontal IAF power for sham stimulation that was negated

Acknowledgments and Disclosures

This study was supported in part by the National Institute of Mental Health of the National Institutes of Health (Grant Nos. R01MH101547 and R01MH111889 [to FF]) and the postdoctoral training program (JR) in reproductive mood disorders (Grant No. T32MH09331502 [to DRR]).

We thank Alana K. Atkins and Trevor McPherson for help with data collection. We also thank Trevor McPherson for assistance with coding the adjusted log-distribution and experimental presentation scripts and Regina Lapate for

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