It has been hypothesized that use of the noninvasive brain stimulation technique of gamma transcranial alternating current stimulation (tACS) improves mood and cognition among patients with such psychiatric disorders as major depression. A randomized case study on the topic was conducted in a small group of patients, all of whom had been experiencing major depression. Results of the study were published in the Journal of Psychiatric Research.

The investigators sought to provide additional data on the utilization of different periods of stimulation in patients with major depression and the cognitive outcomes associated with gamma tACS in this clinical population. The case study included 5 male patients and

1 female patient, all of whom were right-handed except for 1 of the men. The mean participant age was 35.7 ± 16.5 years (range, 19 to 56 years). All of the patients had been experiencing major depression for several years (mean, 12.2 ± 10.3 years) and had received various inpatient treatments (2.0 ± 1.5).

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All patients were treated with tACS in gamma (40 Hz) frequency. The participants were randomized into 1 of 2 groups, in which they received either two 10-minute stimulations (group 1) or a 20-minute stimulation (group 2) per day over a period of 10 days. All patients were evaluated with the use of objective and subjective rating instruments at 3 time points: at baseline (BL), after 5 days of stimulation (D5), and after the 10th stimulation (D10).

At BL, D5, and D10, the patients were rated using a number of tests, including the Hamilton Depression Rating Scale (HAMD-21) and the Beck Depression Inventory (BDI). The Comfort 3Rating Questionnaire was conducted to evaluate the side effects of the stimulation. Additionally, at BL, a multiple-choice vocabulary intelligence test (MWT-B) was performed.

Overall, 5 patients completed the study, with 1 patient from group 1 cancelling the D10 tests for personal reasons after having received the complete stimulation series.

A comparison of MWT-B scores revealed 37.3 ± 4.2 points in group 1 and 31.0 ± 2.6 in

group 2. HAMD-21 scores decreased during treatment in both of the study arms — that is, by 85% in group 1 and by 62% in group 2. Further, BDI scores decreased in both groups as well — that is, by 78% in group 1 and by 24% in group 2. Findings from the study also demonstrated an improvement in cognitive functions, as evaluated by word fluency and n-back test. 

The study authors reported that limitations include a small sample size and the lack of control group. In addition, there could have been an overlap between medication and stimulation effects, which may have shadowed effects of the gamma tACS treatment.

The investigators concluded that the results of this study show that the use of gamma tACS might help to synchronize disturbed frequency bands in frontal and prefrontal cortex areas of the brain, thus restoring dysbalanced neural connectivity in patients with psychiatric disorders, including major depression. Larger randomized studies on the use of gamma tACS are warranted, utilizing various neurophysiologic evaluations.

Disclosure: One author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Haller N, Senner F, Brunoni AR, Padberg F, Palm U. Gamma transcranial alternating current stimulation improves mood and cognition in patients with major depression. J Psychiatr Res. 2020;130:31-34. doi: 10.1016/j.jpsychires.2020.07.009