A New Platform Based on Individualized Intracranial Recording and Stimulation
The success of deep brain stimulation (DBS) for movement disorders has encouraged many groups around the world to apply the DBS platform to treat severe and refractory psychiatric disorders. We are running an NIH BRAIN Initiative funded (UH3 NS103549) trial of DBS for treatment-resistant depression (TRD). This trial focuses on depression patients who have tried and failed conventional treatments, including anti-depressant medications, behavioral therapy, and electroconvulsive therapy. Sameer Sheth is the contact principle investigator and co-primary investigators are Wayne Goodman, M.D., professor and chair of psychiatry at Baylor College of Medicine, and Nader Pouratian, M.D., Ph.D., professor and chair of neurological surgery at UT Southwestern Medical Center
Early open-label trials of DBS for TRD demonstrated promising results, but two large industry-sponsored pivotal trials were halted at interim analyses and were not able to substantiate efficacy. With this history as context, we planned our current trial with a different approach in mind. Patients with the same diagnosis of TRD may yet have very different constellations of symptoms, different “phenotypes.” We reason that these different phenotypes are manifestations of different brain network activity patterns across individuals. Thus, to optimize delivery of DBS therapy to a particular individual, we have to derive a detailed understand of his/her depression-relevant brain networks, such as those regulating mood, affect, anxiety, attention, cognition, etc. The better we understand these pathological networks within the individual, the better we will be able to engage them and restore balanced, healthy function.
To this end, we borrow an approach common to epilepsy surgery, but not previously applied to most other neurological or psychiatric conditions. We employ semi-chronically implanted stereo-EEG (sEEG) electrodes to perform intracranial recordings and stimulation to understand network activity at the individual patient level. TRD patients in this trial are implanted with DBS electrodes targeting two previously studied targets, the ventral capsule/ventral striatum (VCVS) and subgenual cingulate (SGC). We also temporarily implant sEEG electrodes in depression-relevant regions (prefrontal, mesial temporal, etc.) and keep the patient in the epilepsy monitoring unit (EMU) for 1.5 weeks. During this time, we perform a number of recording and stimulation studies to understand the patient’s network activity and how it responds to stimulation. Patients then transition to the outpatient phase, during which we use the EMU-derived information to optimize programming of the DBS system. We expect that this trial will provide an unparalleled understanding of symptomatic networks in TRD and how they can be engaged and manipulated back to a healthy state with individualized DBS. More broadly, we hope that this approach of using the intracranial EEG platform can be applied to many other neurological and psychiatric disorders whose circuit-level dysfunction remains incompletely understood.
For more information: View the clinical trials listing.