X Marks the Spot: Challenges for Therapeutic Target Engagement in DBS

Brian H. Kopell, MD, and his team of experts from the Icahn School of Medicine at Mount Sinai have become the first in the United States to perform a deep brain stimulation (DBS) implantation procedure as part of the TRANSCEND trial, investigating this technology for treatment-resistant depression. TRANSCEND follows 10+ years of learning and understanding the approach of DBS in the subcolossal singulate region.

One of the most important things when conceptualizing this approach is ensuring target engagement via stimulating in areas that are affecting the brain in a material way.

"You have to think of depression as a circuit pathology in the brain," said Kopell, "that there is some form of dysrhythmia within a predefined circuit inside the brain."

The use of tractography in terms of imaging the brain has enabled the TRANSCEND trial, shared Kopell. A specific tractographic pattern that exists within the subcolossal cingulate is the means in which investigators ensure target engagement.

"We essentially map this specific pattern for each individual patient. We provide a patient-specific 'x-marks-the-spot' of where this target engagement should occur, centers will implant the leads and ensure that at least 1 contact within the array of electrodes is exactly on this target area."

Dr Kopell is a professor of Neurosurgery, Neurology, Psychiatry, and Neuroscience. He serves as director of the Center for Neuromodulation and codirector of The Bonnie and Tom Strauss Center for Movement Disorders at the Mount Sinai Health System. He has pioneered the use of intraoperative imaging during deep brain stimulation.