Researchers Bring Precision Medicine to Hard-to-Treat Psychiatric Conditions
Author: | April 4, 2019
MINNEAPOLIS, MN- April 4, 2019 – A new study, published in Nature Communications, could improve the therapeutic efficacy of deep-brain stimulation (DBS) for psychiatric disorders such as depression and obsessive compulsive disorder.
Lead and corresponding author, Alik Widge, Assistant Professor of Psychiatry at the University of Minnesota Medical School, and team found that when DBS, is applied to a specific brain region, it improves patients’ control over their behavior. It happens by increasing the power of a specific low-frequency brain rhythm in their prefrontal cortex.
According to the National Institute of Mental Health, an estimated 17 million adults in the United States have experienced at least one major depressive episode, and 50 percent to 66 percent of patients with depression do not recover fully on an antidepressant medication.
“This is a major step forward for psychiatric brain stimulation,” said Widge, who began the work while a clinical fellow at the Picower Institute for Learning and Memory at MIT and a research fellow at Massachusetts General Hospital, and finished the study 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 is a technique in which an electrode implanted deep in the brain stimulates cells. DBS has helped patients with Parkinson’s disease and similar disorders, but until now has not worked as well for severe illnesses like major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). DBS electrodes must be custom programmed for individual patients. Because depression and obsessive thoughts don’t suddenly disappear when the electrode is adjusted, programming involves some guesswork. 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 Massachusetts General Hospital, discovered that for OCD and MDD patients, finding the optimal stimulation “dose” could be guided by a patient’s performance on difficult mental tasks and a boost in low-frequency “theta” waves in the prefrontal cortex of the brain.
“Even when the stimulator is in the right place in the brain, we need to fine-tune it to change the targeted brain circuit in just the right way,” said Widge. “These increases in theta activity and in mental performance can signal us when we’ve got it right. We could measure them in the operating room or in a doctor’s office.”
The study involved 14 volunteers, 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 different numeral in a sequence of three numbers (like the “2” in “332”) despite the vivid and intentional distraction of an emotionally evocative image (like adorable puppies or a vicious shark) in the background. 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 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 the internal capsule and the behavioral improvement of the faster reaction time.
There is still more work to be done. “A more standardized study is still needed to verify the results,” said Widge. “However, with further research, this could lead to new treatments for patients.”
“Both depression and OCD can take a person away from their family, their job, and their ability to participate in everyday life,” said Dougherty. “We’ve been able to give some patients that life back with DBS, but we need to find ways to make it work for everyone.”
In addition to Widge, Miller and Dougherty, the paper’s other authors are Samuel Zorowitz, Ishita Basu, Angelique C. Paulk, Sydney Cash, Emad Eskandar, and Thilo Deckersbach.
Several of the authors have applied for patents on technologies related to DBS and modulation of oscillations.
The study was funded by The Brain & Behavior Research Foundation, the Picower Family Foundation, the MIT Picower Institute Innovation Fund, The National Institutes of Health, and the Defense Advanced Research Projects Agency.
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