Project Abstract This project is a pilot clinical trial of a new brain stimulation treatment for obsessive-compulsive disorder. OCD is a mental illness that affects 4-7 million people in the US. Of those, 50-70% still have substantial symptoms after being treated with medication or talk therapy. Recently, clinicians have started trying to treat OCD with deep brain stimulation (DBS). DBS involves surgically placing electrodes into the brain, then sending electrical stimulation currents through those electrodes. Most investigators think that DBS for OCD works by affecting brain circuits called the cortico-striato-thalamo-cortical loops, or CSTC loops. The belief is that OCD is caused by the CSTC loops being too strongly connected, so that signals get "stuck" in them and become the stuck, perseverative, obsessional thinking of OCD. To interrupt these loops, investigators have placed DBS into the ventral capsule/ventral striatum (VC/VS), the "S" of CSTC. VC/VS DBS has helped several patient who had very treatment-resistant OCD. However, about half do not get better. We hypothesize that this is because DBS does not always influence cortico-striatal loops correctly, because it only affects a single area in this multi-area circuit. Our main objective (Aim 1) is to test a stimulator that affects the deep brain and the cortex (brain surface) at once and tries to break the abnormal CSTC synchrony. It drives two brain areas at slightly different frequencies, keeping them "out of sync". Our second objective is to test whether activity in the CSTC loop correlates to the symptoms of OCD. No study has proven that these two are linked in humans, because it is difficult to record from the human brain, especially over long periods of time and from deep brain areas. We will use a novel technology, the Medtronic PC+S "sensing DBS", to record the brain's activity while delivering the stimulation treatment (Aim 2a). As patients' symptoms improve, we expect to see that connectivity and synchrony between the surface and deep brain decreases along the same trajectory. We will also capture recordings during symptom flares and as patients participate in symptom-triggering activities such as exposure therapy sessions. This will help us further determine how well this brain activity correlates to symptoms. Finally, to help capture clearer signals, we will also collect those recordings while patients do a fear task that is linked to OCD severity, using EEG to further understand the cortico-striatal response to DBS (Aim 2b). This study leverages a broad interdisciplinary team of psychiatrists, statisticians, a neurosurgeon, and electrophysiologists, all with experience in OCD and brain stimulation.

Project Narrative This is a small clinical trial of a new brain stimulation intervention for obsessive-compulsive disorder (OCD). We will use implanted electrodes to stimulate two brain areas related to OCD in a way that should specifically de-synchronize them, while also recording the electrical activity of the brain in response to stimulation. If successful, we will have both a new treatment for OCD and will also learn how the brain's electrical activity changes when stimulation is applied, which should help design better treatments for OCD and other psychiatric disorders.