New research shows that deep brain stimulation can tackle treatment-resistant depression. Stimulating a brain area called the orbitofrontal cortex led to "significant" improvements in mood for people with moderate to severe depression.

Major depressive disorder affects over 16 million adults per year in the US and is the "leading cause of disability worldwide."

A significant proportion of people who are living with major depression do not get any relief from existing treatments.

In fact, up to 30% of those affected by depression have an intractable form of the condition.

Recently, deep brain stimulation (DBS) has emerged as a potential therapy that may succeed where other treatments have failed.

In DBS, specialists surgically implant stimulating electrodes in the brain to send electrical currents to targeted areas.

In the new study, Dr. Eddie Chang and his colleagues used DBS in 25 people who had symptoms of depression. They report their findings in the journal Current Biology.

Dr. Chang is also a professor of neurosurgery at the University of California San Francisco (UCSF).

Studying depression and key brain areas

Dr. Chang explains what made the researchers focus on the orbitofrontal cortex in this study. The area "has been called one of the least understood regions in the brain," he reports, "but it is richly connected to various brain structures linked to mood, depression, and decision-making, making it very well positioned to coordinate activity between emotion and cognition."

The team had access to a clinic that specializes in epilepsy. People with epilepsy have electrodes surgically implanted in their brains as part of routine preparation for surgery.

For this study, Dr. Chang and team recruited 25 participants with epilepsy who also had mild to severe depression.

With the electrodes already in place, the participants reported how they were feeling a few times per day using an app. This enabled the researchers to link changes in brain activity with different moods, focusing on the brain area that was most involved in depression and also accessible with DBS.

The scientists also used mild electrical stimulation on different brain regions and asked participants to say how it affected their mood using specific keywords.

Afterward, they—with the help of a specific piece of software—quantified and analyzed the words that the volunteers had used.

DBS led to a 'naturally positive mood'

The study revealed that, while stimulating most brain areas had no effect on the participants' mood, 3 minutes of stimulating the lateral orbitofrontal cortex led to significant improvements.

The successful results were only seen among those with moderate to severe depression; there was no effect in people with mild depression symptoms.

Study co-author Kristin Sellers, PhD—who is a postdoctoral researcher in Dr. Chang's laboratory—reports on the results. "Patients said things like 'Wow, I feel better,' 'I feel less anxious,' 'I feel calm, cool, and collected.'"

"And just anecdotally, you could see the improvements in patients' body language. They smiled, they sat up straighter, they started to speak more quickly and naturally."

The patterns of brain activity also supported these noticeable improvements in mood. The authors note that the participants' brain activity after the stimulation resembled the brain activity that occurred when the volunteers reported feeling naturally good.

Dr. Vikram Rao, Ph.D.—an assistant professor of neurology at UCSF and the study's first author—explains what these findings mean.

"These [...] observations suggest that stimulation was helping patients with serious depression experience something like a naturally positive mood state, rather than artificially boosting mood in everyone."

—Dr. Vikram Rao

"This is in line with previous observations," he adds, "that [orbitofrontal cortex] activity is elevated in patients with severe depression and suggests electrical stimulation may affect the brain in a way that removes an impediment to positive mood that occurs in people with depression."

The researchers note, however, that more studies will be needed before they can conclude that stimulating the orbitofrontal cortex improves mood in the long-term.

"The more we understand about depression at this level of brain circuitry, the more options we may have for offering patients effective treatments with a low risk of side effects," says study co-author Heather Dawes, PhD.

"Perhaps by understanding how these emotion circuits go wrong in the first place, we can even one day help the brain 'unlearn' depression."