In a first-of-its-kind study from researchers at the University of North Carolina (UNC) School of Medicine, a new kind of non-invasive electrical brain stimulation has been trialed in patients with major depression. The results show this new technique to be extraordinarily promising in reducing depressive symptoms, with larger trials set to explore this novel treatment in greater detail.

Brain stimulation is a fascinating area of research, with scientists exploring a variety of different ways to tweak the brain, from firing magnetic pulses to excite certain neural pathways, to utilizing surgically implanted electrodes that zap specific regions of the brain. The UNC research, led by Flavio Frohlich, concentrates on a technique called transcranial alternating current stimulation (tACS).

Unlike deep brain stimulation (DBS), which requires surgical implantation of electrodes, tACS is non-invasive. It also investigates a different kind of treatment paradigm, looking at using mild electric currents to bring the electrical oscillations of different brain regions into sync with each other. In recent years tACS has been experimented with to treat auditory hallucinations in patients with schizophrenia and decrease sensations of chronic lower back pain. TACS has also shown promise in improving memory when delivered to sleeping subjects.

While other forms of brain stimulation are being investigated for depression, this newly published tACS study is the first randomized control trial to examine the efficacy of this technique for major depressive disorder. The study recruited 32 subjects with clinical depression and each subject was blindly separated into one of three groups: a sham placebo group, a control group receiving a 40-Hertz tACS intervention, and a treatment group receiving a 10-Hertz tACS intervention.

The hypothesis being investigated was based on prior observations finding patients with major depressive disorder often exhibit elevated oscillatory activity in the left frontal areas of the brain. This results in a condition called "frontal alpha asymmetry" where electrical activity in the left frontal cortex is markedly out of sync with the same activity in the right frontal cortex. The hope is that by bringing that electrical activity into sync, it would reduce depressive symptoms. This specific alpha oscillation sits between 8 and 12 Hertz, meaning the 40-hertz intervention could function as an effective control helping assess whether any effects are frequency-dependent or just stimulation-dependent.

For five days each subject received 40 minutes of stimulation, with two- and four-week follow up evaluations after the treatment period. The results were undeniably mixed, with no significant difference between all three groups at the four-week follow-up point. Strangely, however, a very significant difference was identified at the earlier two-week follow-up point. A stunning 70 percent of the 10-Hertz group reported at least a 50 percent reduction in their depression symptoms at the two-week mark. This was dramatically higher than both the placebo and the 40-Hertz control at the same point.

Being the first study of its kind it is unclear exactly what can be concluded from these results. The researchers do stress this was a small, exploratory pilot study and at the very least these results demand further investigation in larger sample sizes. Frohlich and the UNC team are already rolling out studies to explore the potential for tACS to treat symptoms of depression.

"It's important to note that this is a first-of-its kind study, when we started this research with computer simulations and preclinical studies, it was unclear if we would see an effect in people days after tACS treatment – let alone if tACS could become a treatment for psychiatric illnesses," says Frohlich. "It was unclear what would happen if we treated people several days in a row or what effect we might see weeks later. So, the fact that we've seen such positive results from this study gives me confidence our approach could help many people with depression."

The new study was published in the journal Translational Psychiatry.