Brain Changes Pace Minutes After Therapeutic Stimulation During DBS Surgery For Treatment-Resistant Depression
Deep Brain Stimulation (DBS) has been shown to be an effective treatment for many patients with treatment-resistant depression, but it is not known exactly how it works. Scientists around the world are fighting for objective biomarkers of the effectiveness of DBS treatment so that this experimental approach can be optimized, approved and disseminated to those who need it.
New research published on November 3 in Translational Psychiatry, presents new evidence that brief intraoperative exposure to therapeutic stimulation at the time of implantation surgery induces a rapid and constant change in the electrophysiological state of the brain, indexed by a decrease in beta power measured at the stimulation site . These intraoperative changes in brain state are seen in individual subjects and correlate with a significant and sustained decrease in depressive symptoms outside of the operating room without additional stimulation, establishing a reduction in beta potency as new. biomarker for optimization of DBS treatment.
The data presented is from a collaborative study conducted at Emory University and Icahn School of Medicine at Mount Sinai. Led by Helen S. Mayberg, MD, a Mount Sinai professor of neurotherapy and founding director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai, this research is part of an ongoing grant funded by the National Institutes of Health (NIH) BRAIN Initiative.
Deep Brain Stimulation is approved by the United States Food and Drug Administration to treat essential tremors, Parkinson’s disease, epilepsy, and obsessive-compulsive disorder. This is a neurosurgical procedure involving the placement of a neurostimulator (sometimes called a “brain stimulator”), which sends high-frequency electrical impulses through electrodes implanted deep in the brain to specific areas responsible for symptoms. every trouble. Although still an experimental treatment, DBS of the subcallosal cingulate (SCC, zone 25), an area of ââthe brain that has been implicated as playing a major role in depression, has been shown to many. times as a promising intervention for patients with treatment-resistant depression. .
Acute behavioral changes and a long-term antidepressant response can be reliably elicited with stimulation of this well-defined and surgically targeted depression circuitry, using individualized neuroimaging guidance. Although the clinical efficacy of DBS over six months of treatment has been repeatedly demonstrated, there are differences in time to recovery between different patients. Understanding the mechanisms of these rapid and reproducible initial behavioral effects and their role in predicting the most critical long-term response trajectories will be key to effective treatment and future study design.
âWhat we found was that a few minutes after the stimulation inside the operating room, there was a change in the beta brain rhythm. Patients who had larger changes then felt a greatest relief from their depression within a week of surgery, “Allison C. Waters, Ph.D., assistant professor of psychiatry and neuroscience, told Icahn Mount Sinai and co-lead author of the article. âBeta rhythm is classically associated with the brain’s determination to stop or continue with a course of action, which is why neurologists target beta with DBS to treat movement disorders. clear signal to target with DBS for depression, but now we can speculate on how the beta signal might work in this context: a release of the brake that generates fatigue and sluggishness, or the interruption of a cycle habit of self-centered negative thoughts. “
âWe were able to leverage machine learning and explainable artificial intelligence approaches to explore unknown (hidden) changes in brain state that would explain the obvious behavioral changes previously observed,â said Mohammad Sendi, MSc, Ph.D. candidate in the Department of Biomedical Engineering at Emory University and the Georgia Institute of Technology and co-first author of the article.
Eight patients with treatment-resistant depression underwent electrophysiologic recording in the operating room during their DBS lead implantation surgeries. Using patient-specific tractography models before surgery, the researchers identified the âoptimalâ target within the SCC for lead placement. The stimulation was then delivered to the operating room for an hour while local field potentials (LFPs) – electrical signals between neurons deep in the brain – were recorded simultaneously. A machine learning classification method was then used to discriminate between intracranial LFPs recorded at baseline (naÃ¯ve stimulation) and after the first exposure to stimulation inside the operating room. The spectral inputs (theta, 4-8 Hz; alpha, 9-121 Hz; beta, 13-30 Hz) to the model were then evaluated for their importance to the success of the classifier and tested as predictors of the antidepressant response. A decrease in depression scores of 45.6% was observed after one week and this early antidepressant response correlated with a decrease in the beta potency of SCC LFP, which contributed the most to the success of the classifier.
“We generally believe that treatment for depression takes weeks to months to show stable and significant changes in the main clinical features of the disease,” said Dr. Mayberg. “This study shows reproducible and consistent changes in a brain reading during the first few minutes of optimized stimulation in the operating room in individual patients. This provides a new mechanistic understanding of the ‘depression switch’ that brings a patient out of the dump. ‘a state of sustained mental pain and stillness to relief and the renewed ability to move and engage. “
âThis research offers people who have battled depression a sense of hope through advancements in existing technology,â said John Ngai, Ph.D., director of the NIH BRAIN initiative. “We are making tremendous progress in better understanding debilitating mental and brain health issues with these findings, and we look forward to seeing how deep brain stimulation will continue to improve people’s lives.”
Studies that continue to track these biomarkers of brain condition during ongoing DBS therapy are ongoing at the Nash Family Center for Advanced Therapeutics in Mount Sinai West in New York City. Phase II of this 5-year NIH BRAIN Initiative grant is currently recruiting new subjects.
Researchers boost human mental function with brain stimulation
Intraoperative neural signals predict the rapid antidepressant effects of deep brain stimulation, Translational Psychiatry (2021).
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