Deep stimulation improves cognitive control by augmenting brain rhythms


In a new study
that could improve the therapeutic efficacy of deep-brain stimulation
(DBS) for psychiatric disorders such as depression, a team of scientists
shows that when DBS is applied to a specific brain region, it improves
patients’ cognitive control over their behavior by increasing the power
of a specific low-frequency brain rhythm in their prefrontal cortex.

The findings, published in Nature Communications,
suggest that the increase in “theta” rhythms, readily detectable in EEG
recordings, could provide neurosurgeons and psychiatrists with the
reliable, objective and rapid feedback they’ve needed to properly
fine-tune the placement and “dosage” of DBS electrical stimulation. In
Parkinson’s disease, where DBS has been most successful, that kind of
feedback is available through a reduction in a patient’s tremors. But
for depression or obsessive-compulsive disorder, symptoms can be more
subtle, subjective and slowly emergent.

“This is a major step forward for psychiatric brain
stimulation,” said Alik Widge, the lead and corresponding author on the
paper. Widge began the work while a Picower Clinical Fellow at the
Picower Institute for Learning and Memory at MIT and a research fellow
at Massachusetts General Hospital (MGH). He is now an assistant
professor of psychiatry at the University of Minnesota Medical School.
“This study shows us a specific mechanism of how DBS improves patients’
brain function, which should let us better identify who can benefit and
how to optimize their individual treatment.”

DBS increases control

Heading into the research, the team, also led by Earl Miller,
Picower Professor of Neuroscience at MIT and Darin Dougherty, Associate
Professor of Psychiatry at Harvard Medical School and Director of the
Division of Neurotherapeutics at MGH, knew that DBS applied to the
brain’s ventral internal capsule and ventral striatum (VCVS) has shown
mixed results in treating OCD and depression. A common feature of both
conditions is a deficit of cognitive control, the function of
controlling automatic or habitual behaviors through conscious will (for
instance, overcoming recurring negative emotions that are a hallmark of
depression). Cognitive control is performed in part by the prefrontal
cortex, which is involved in circuits passing through the VCVS region.
Moreover, theta rhythms are believed to be a means by which neurons in
the prefrontal cortex could synchronize and drive the activity of
neurons in other regions.

The team’s working hypothesis, therefore, was that
DBS might help patients by increasing theta rhythms in these crucial
cognitive control circuits linking prefrontal cortex to VCVS, thereby
allowing the cortex to be more effective in controlling atypical
emotions. If they could read out a patient’s theta rhythms and optimally
amplify those with DBS, they reasoned, maybe they’d see an increase in
cognitive control.

To find out, they worked with 14 volunteers at MGH,
12 of whom had previously received DBS treatment for depression and the
other two for OCD. The researchers gave each participant a “conflict”
task in which they had to identify the numeral in a sequence of three
numbers that was different (like the “2” in “332”) despite the vivid and
intentional background distraction of an emotionally evocative image
(like adorable puppies or a vicious shark). An increase in cognitive
control would mean a quicker reaction time in being able to identify the
correct unique digit.

The researchers recorded brain waves of the
subjects while they performed the task, once with DBS switched on and
once with it off. What they found was that with DBS on, people indeed
made their selection faster (overcoming the “interference,” or conflict
of the emotional picture). There was no difference in accuracy, meaning
that subjects were not sacrificing accuracy to gain more speed.
Meanwhile theta rhythms in the cortex increased markedly in association
with both the stimulation in VCVS and the behavioral improvement of the
faster reaction time.

“This study demonstrates the value of closed-loop
stimulation,” Miller said. “We read the brain’s natural rhythms and then
enhanced them by stimulation.  We augmented the rhythms that were
already there.  It suggests that brain rhythms play a role in cognition
and that we can treat cognitive deficits by manipulating those rhythms.”

The authors acknowledged that the study was
relatively small, and because all of the participants were receiving DBS
as a treatment, the exact stimulation settings were different between
individual participants. Widge cautioned that a more standardized study
would be important to verify the results. However, the authors said that
with further research, theta rhythms could provide a biomarker to
calibrate DBS treatments for psychiatric disorders where cognitive
control is crucial. Moreover, individual tuning of theta rhythms via DBS
of the VCVS could lead to new treatments for psychiatric disorders
where cognitive control – and the flexibility of behavior that comes
from exerting conscious intent over recurring emotions or compulsions –
is crucial.

“The current study demonstrates that DBS at an FDA
approved target for psychiatric illness is shown to affect a specific
symptom underlying multiple psychiatric illnesses, namely cognitive
flexibility,” Dougherty said. “These findings suggest that looking at
effects of DBS ‘underneath’ a diagnosis, at the symptom level, may lead
to utility for other psychiatric illnesses in the short term and perhaps
to more personalized medicine approaches to DBS in the longer term.”

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