The Principal Investigator of the study was Dr. Edward F. Chang, MD, who is a UCSF Health neurosurgeon, a Professor of Neurosurgery and member of the UCSF Weill Institute for Neurosciences. His research lab focuses on the neuroscience of language and mood. The lead authors were Dr. Vikram R. Rao, MD, PhD, and Dr. Kristin K. Sellers, PhD. Dr. Rao is an Assistant Professor of Neurology at UCSF, a neurologist at UCSF Health and a member of the UCSF Weill Institute for Neurosciences, while Dr. Sellers is a post-doctoral fellow in Dr. Chang's lab.

Electrical stimulation of the brain has been used for a long time for treating patients with Parkinson's disease and epilepsy, but its use in patients with depression have so far produced mixed results. These earlier treatments focused on stimulation of deeper regions of the brain such as the cingulate cortex and basal ganglia, which are known to play a major role in emotional responses. However, little is known about the OFC and its possible role in emotion.

What is the Orbitofrontal Cortex (OFC)?

The OFC is an area of the prefrontal cortex, located in front of the frontal cortex, which is responsible for thought-processing and decision-making functions. The OFC sits just above the orbits or eye sockets, at the very front of the brain and has extensive connections with the deeper parts of the brain such as the limbic system, which is concerned with emotional functions.

In this regard, Chang said: "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."

Study Procedure

The study participants included 25 patients (14 males and 11 females aged 20-60 years) from Dr. Chang's epilepsy clinic, who indicated that they were suffering from moderate to severe depression. These patients were advised to record the changes in their mood patterns on a daily basis using a tablet-based app, while they were admitted in the hospital.

Since, the patients had implanted electrodes in their brain, it was possible for the research team to study the brain wave patterns and electrical activity of the brain and correlate them with the mood-swings experienced by the patients. This allowed the team to explore new areas of the brain that could be subjected to electrical stimulation to alleviate the symptoms of depression.

The research team followed a technique used by neurologists to map specific areas of the brain that would be targeted for surgery. Following this technique, the researchers applied mild electrical currents to disrupt the brain activity in specific areas of the brain that could be associated with emotion and mood. These areas included the limbic system, consisting of the hippocampus, amygdala, and cingulate cortex, as well as the OFC.

While stimulating these areas, the patients were asked how they felt. The graded scale that was used to record the patients' responses included terms like "calm" to "restless" or "hopeful" to hopeless". Based on these responses, the research team was able to transcribe the language using advanced computer software to generate quantitative and meaningful data.

Study Findings

It was observed that there was no improvement in the patients' condition by stimulation of most areas of the brain. However, even when one side of the OFC was stimulated for just 3 minutes, there was a dramatic improvement in the mood of these patients suffering from moderate to severe depression.

The patients were thrilled about the experience and expressed their happiness and satisfaction, which was quite evident from what they said, as well as their body language.

The research team made two other important observations pertaining to stimulation of the lateral OFC:

• Stimulation of the lateral OFC resulted in widespread brain activity patterns that resembled the brain activity observed in the patients when their mood was naturally elevated, during the days prior to undergoing brain stimulation.
• Stimulation of the lateral OFC resulted in improvement of the moods of patients who were suffering from moderate to severe depression. But this had no effect in case of mild depression.

"These two 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," said Rao. "This is in line with previous observations that OFC activity is elevated in patients with severe depression and suggests electrical stimulation may affect the brain in a way that removes an impediment to the positive mood that occurs in people with depression."

Concluding Remarks

In spite of the highly promising results of the study, there is a need to exercise caution as the sample size in the present study was small and so the study should be repeated in a larger sized cohort. This will reveal whether stimulation of the lateral OFC would result in long-term alleviation of symptoms of depression. Moreover, with improvement in the understanding of the functions of the OFC with reference to emotional processes, it may be possible to identify "biomarkers" that could be used for developing novel approaches for the personalized treatment of depression.

"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," said Dr. Heather Dawes, PhD, an academic coordinator at UCSF who helped to oversee the research. "Perhaps by understanding how these emotion circuits go wrong in the first place, we can even one day help the brain 'unlearn' depression."

Funding Source

The research received funding from the Defense Advanced Research Projects Agency (DARPA) under its Systems-Based Neurotechnology for Emerging Therapies (SUBNETS) program, launched in 2014 under the auspices of the White House BRAIN Initiative, USA.

Reference :

1. Brain Stimulation Relieves Depression Symptoms - (https://www.ucsf.edu/news/2018/11/412416/brain-stimulation-relieves-depression-symptoms)

Source: Medindia