Closed-Loop Deep Brain Stimulation for Treatment-Resistant Bipolar Depression

This is a single-center 3-stage feasibility study of personalized closed-loop stimulation for treatment resistant Bipolar Depression. Depending on participant's results at each stage, he/she might not be eligible to proceed to all 3 stages. Stage 1 of the study will involve surgically implanting small, thin electrodes in brain regions that regulate depression in order to identify personalized treatment sites. The researchers will test stimulation in the different brain regions and their effect on bipolar depression symptoms. The electrodes will be surgically removed at the end of Stage 1. Stage 2 will involve a second brain surgery to implant the NeuroPace RNS® System. Researchers will use information from Stage 1 to decide where to implant the electrodes of the RNS System. Over the next \~4-18 months, participants will have regular study visits in the clinic where the researchers will determine a personalized brain activity pattern that correlates with depression symptoms and can be paired with stimulation to improve depression symptoms. Stage 3 will be 36-40 weeks long and will involve turning ON and OFF the intervention to test its effectiveness. Participants will have a variable start time for Stage 3 to facilitate blinding of both patients and clinician raters. This variable time will be randomized from conditions of 0 days, 2 weeks, or 4 weeks (during which time participants will remain on optimized closed-loop stimulation). Each participant will have three 12-week periods: closed-loop stimulation (intervention), open-loop/fixed intermittent stimulation (active control), and sham (passive control), order counterbalanced. At the end of this stage the participant can choose to continue with long-term follow-up or have the RNS System surgically removed.