A new study from the University of California, San Francisco has found that electrically stimulating an area of the brain called the orbitofrontal cortex (OFC) results in significant mood improvements for patients suffering from moderate to severe depression.

Deep brain stimulation (DBS) involves the surgical implantation of what is commonly referred to as a "brain pacemaker." This device is designed to electrically stimulate specific regions of the brain and is most prominently used as a treatment to reduce tremors associated with Parkinson's disease.

DBS has also been investigated as a way to mange severe cases of treatment-resistant depression, however, a large volume of research has so far delivered reasonably inconclusive results. Several studies into using DBS to treat depression have found only a mild difference between active and placebo subjects, and some researchers suspect prior work has failed due to targeting the wrong regions of the brain.

The new UCSF study set out to home in on the most effective region of the brain for DBS to target for depression by recruiting 25 patients with epilepsy. These patients were in line for surgery which would temporarily implant electrodes in the their brains to help surgeons accurately identify the specific brain tissue responsible for their seizures.

While these electrodes were temporarily present the researchers used the opportunity to identify correlations between mood and brain stimulation in different regions. A variety of brain regions were systemically delivered a mild electrical current while patients were simultaneously asked to report the effect on their mood.

Interestingly, in most cases the brain stimulation had virtually no effect on the subjects' mood. Stimulation of the amygdala, cingulate cortex, insula, and hippocampus generally produced no notable mood improvements, however, the researchers did reveal impressive mood-lifting results when the lateral region of the orbitofrontal cortex (OFC) was stimulated.

This specific brain region is a relatively new target in depression research. A study from earlier this year revealed the OFC to play a key role in the relationship between sleep disruption and depression. Prior research also found that stronger activity in this region of the brain could lead to low-self-esteem.

"The OFC has been called one of the least understood regions in the brain, 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," says Eddie Chang, senior author on the new study.

The researchers say that that just minutes of mild stimulation to the lateral OFC resulted in virtually immediate improvements to the mood of patients suffering from moderate to severe depression.

"Patients said things like 'Wow, I feel better,' 'I feel less anxious,' 'I feel calm, cool and collected,'" says Kristin Sellers, another researcher working on the project. "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."

Of course, it's early days for the research with a great deal of work needing to be done to verify these results. It's unclear how long-lasting the mood improvements post-stimulation actually are, and it's also unclear whether less invasive methods, such as transcranial magnetic stimulation, would be just as effective. After all, surgically implanting electrodes into a person's brain is not the most ideal way to treat depression, but at the very least this study delivers strong evidence adding to the hypothesis that depression and mood can be effectively modulated by directly influencing brain circuits.

The new study was published in the journal Current Biology.