Direct electrical stimulation of the lateral orbitofrontal cortex (OFC) acutely improves mood in patients with depressive symptoms, new research shows.

OFC stimulation “broadly modulates mood-related circuitry, revealing a new brain stimulation target with strong therapeutic potential,” the investigators, led by Edward F. Chang, MD, professor of neurosurgery, University of California San Francisco, write.

The OFC, a small region on the lower surface of the brain just above the eyes, is “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,” Chang said in news release.

The study was published online November 29 in Current Biology.

Shedding New Light

The investigators studied 25 patients with epilepsy who were implanted with intracranial electrodes for seizure localization. Baseline depression traits ranged from mild to severe based on the Beck Depression Inventory.

Unilateral stimulation of the lateral OFC “consistently produced acute, dose-dependent mood-state improvement across subjects with baseline depression traits.”

This “stimulation induced neural features associated with positive mood states,” the researchers report. Sham stimulation of the OFC produced no discernible change in mood.

“Our findings shed light on how brain activity relates to mood symptoms and how symptom-relieving stimulation effects that activity,” co-study leader Kristin Sellers, PhD, postdoctoral researcher in Chang’s lab, told Medscape Medical News.

“These observations advance our understanding of the brain networks that underlie mood disorders and suggest ways in which we might use that understanding to develop therapies that are better-informed and more effective,” said Sellers.

Questions Remain

Heather Dawes, PhD, co-director of the Defense Advanced Research Projects Agency (DARPA) Systems-Based Neurotechnology for Emerging Therapies (SUBNETS) program at UCSF, cautioned that there is still “much work to be done to see whether this stimulation approach can help patients with depression actually recover from their illness; so far, we’ve only been able to look at short-term effects.”

“Some of this continuing work will be conducted in the context of clinical trials, using implanted recording and stimulation devices to enable longer tracking of potential therapeutic effects. In addition, we are working to optimize the effect, and to make sure that stimulation of this part of the brain is safe and effective as a possible longer-term treatment,” Dawes, who worked on the study, told Medscape Medical News.

Helen Mayberg, MD, behavioral neurologist and founding director of the Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai in New York City, agrees that more study is needed and urged caution in interpreting the study data.

“There are a lot of areas in the brain that you can stimulate and get an acute effect, so this is another interesting piece of the puzzle,” but it’s unclear if the effect is long-lasting, she told Medscape Medical News.

The OFC, said Mayberg, is “an area of the brain that connects to areas that we already do stimulate, so the results are certainly not contradictory, but it’s also not a paradigm shift.”

Mayberg said it’s also important to note that depression was not the primary diagnosis in these patients. “These were epilepsy patients and some of them had high Beck Depression Inventory scores, which basically is a trait depression rating. It’s not a diagnosis of depression. This needs to be replicated in patients with major depression.”