caused a significant improvement in the mood of patients with
moderate to severe
. This is an important step forward as
it will help develop new therapies for depression patients who don't respond to
medications, which accounts for nearly 30 percent of patients with depression.
The study has been
published in Current Biology
Elsevier and Cell Press publication.
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.
of the brain has been used for a long time for treating
patients with Parkinson's
, 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
. 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."
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.
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.
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
"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,"
- 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.
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."
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
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
- Brain Stimulation Relieves Depression Symptoms - (https://www.ucsf.edu/news/2018/11/412416/brain-stimulation-relieves-depression-symptoms)