Brain Stimulation Improves Depression Symptoms, Restores Brain Waves in Clinical Study

With a weak alternating electrical current sent through electrodes
attached to the scalp, UNC School of Medicine researchers successfully
targeted a naturally occurring electrical pattern in a specific part of
the brain and markedly improved depression symptoms in about 70 percent
of participants in a clinical study.

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Flavio Frohlich, PhD, associate professor of psychiatry and director of the Carolina Center for Neurostimulation. (Photo: Business Wire)

The research, published
in Translational Psychiatry, lays the groundwork for larger
research studies to use a specific kind of electrical brain stimulation
called transcranial alternating current stimulation (tACS) to treat
people diagnosed with major depression.

“We conducted a small study of 32 people because this sort of approach
had never been done before,” said senior author Flavio Frohlich, PhD,
associate professor of psychiatry and director of the Carolina Center
for Neurostimulation. “Now that we’ve documented how this kind of tACS
can reduce depression symptoms, we can fine tune our approach to help
many people in a relatively inexpensive, noninvasive way.”

Frohlich, who joined the UNC School of Medicine in 2011, is a leading
pioneer in this field who also published the first clinical trials of
tACS in schizophrenia
and chronic
pain.

His tACS approach is unlike the more common brain stimulation technique
called transcranial direct stimulation (tDCS), which sends a steady
stream of weak electricity through electrodes attached to various parts
of the brain. That approach has had mixed results in treating various
conditions, including depression. Frohlich’s tACS paradigm is newer and
has not been investigated as thoroughly as tDCS. Frohlich’s approach
focuses on each individual’s specific alpha oscillations, which appear
as waves between 8 and 12 Hertz on an electroencephalogram (EEG). The
waves in this range rise in predominance when we close our eyes and
daydream, meditate, or conjure ideas – essentially when our brains shut
out sensory stimuli, such as what we see, feel, and hear.

Previous research showed that people with depression featured imbalanced
alpha oscillations; the waves were overactive in the left frontal
cortex. Frohlich thought his team could target these oscillations to
bring them back in synch with the alpha oscillations in the right
frontal cortex. And if Frohlich’s team could achieve that, then maybe
depression symptoms would be decreased.

His lab recruited 32 people diagnosed with depression and surveyed each
participant before the study, according to the Montgomery–Åsberg
Depression Rating Scale (MADRS), a standard measure of depression.

The participants were then separated into three groups. One group
received the sham placebo stimulation – a brief electrical stimulus to
mimic the sensation at the beginning of a tACS session. A control group
received a 40-Hertz tACS intervention, well outside the range that the
researchers thought would affect alpha oscillations. A third group
received the treatment intervention – a 10-Hertz tACS electrical current
that targeted each individual’s naturally occurring alpha waves. Each
person underwent their invention for 40 minutes on five consecutive
days. None of the participants knew which group they were in, and
neither did the researchers, making this a randomized double-blinded
clinical study – the gold standard in biomedical research. Each
participant took the MADRS immediately following the five-day regimen,
at two weeks, and again at four weeks.

Prior to the study, Frohlich set the primary outcome at four weeks,
meaning that the main goal of the study was to assess whether tACS could
bring each individual’s alpha waves back into balance and decrease
symptoms of depression four weeks after the five-day intervention. He
set this primary outcome because scientific literature on the study of
tDCS also used the four-week mark.

Frohlich’s team found that participants in the 10-Hertz tACS group
featured a decrease in alpha oscillations in the left frontal cortex;
they were brought back in synch with the right side of the frontal
cortex. But the researchers did not find a statistically significant
decrease in depression symptoms in the 10-Hertz tACS group, as opposed
to the sham or control groups at four weeks.

But when Frohlich’s team looked at data from two weeks after treatment,
they found that 70 percent of people in the treatment group reported at
least a 50 percent reduction of depression symptoms, according to their
MADRS scores. This response rate was significantly higher than the one
for the two other control groups. A few of the participants had such
dramatic decreases that Frohlich’s team is currently writing
case-studies on them. Participants in the placebo and control groups
experienced no such reduction in symptoms.

“It’s important to note that this is a first-of-its kind study,”
Frohlich said. “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. 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.”

Frohlich’s lab is currently recruiting for two similar follow-up
studies.

Other authors of the Translational Psychiatry paper are co-first
authors Morgan Alexander, study coordinator and graduate student, and
Sankaraleengam Alagapan, PhD, a postdoctoral fellow, both in the
department of psychiatry at UNC-Chapel Hill; David Rubinow, MD, the
Assad Meymandi Distinguished Professor and Chair of Psychiatry at the
UNC School of Medicine; former UNC postdoctoral fellow Caroline
Lustenberger, PhD; and Courtney Lugo and Juliann Mellin, both study
coordinators at the UNC School of Medicine.

This research was funded through grants from the Brain Behavior
Research Foundation, National Institutes of Health, the BRAIN
Initiative, and the Foundation of Hope.

Frohlich holds joint appointments at UNC-Chapel Hill in the
department of cell biology and physiology and the Joint UNC-NC State
Department of Biomedical Engineering. He is also a member of the UNC
Neuroscience Center.

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