Combined Cortical/Subcortical Recording and Stimulation as a Circuit-Oriented Treatment for Obsessive-Compulsive Disorder

Inclusion Criteria:

1. OCD, diagnosed by Structured Clinical Interview for DSM-5 (SCID-5), judged ofdisabling severity with a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of atleast 28.

2. Persistence of severe symptoms and impairment for five or more years despite: i. atleast three adequate (≥3 months at the maximum tolerated dose) serotonin transporterinhibitor trials (may use any serotonin or serotonin-norepinephrine inhibitors, butmust include a trial of clomipramine) alone or in combination with ii. adequatebehavior therapy (≥20 sessions of expert exposure and response prevention; At least 20 sessions of behavioral therapy must be attempted), and iii. augmentation of oneof the selective SRIs with a neuroleptic or clonazepam.

3. Age between 21 and 65 years.

4. Able to understand and comply with instructions.

5. Able to give fully informed, written consent in the judgment of the site ConsentMonitor.

6. Either drug free or on a stable drug regimen for at least 6 weeks.

7. Good general health.

8. A family member or significant other, in contact with the patient every 1-3 days, isavailable and willing to communicate with the research team if the patient'sclinical status worsens, and if necessary to accompany patients to study visits.

9. The local referring psychiatrist is willing to provide ongoing care during and afterthe trial.

10. Patient is aware of, able to adhere to, and willing to tolerate the frequency ofvisits associated with adjustment of the dual-stimulation configuration and/orcollection of brain recordings. This will usually mean limitation to patients wholive close to the study site.

11. Platelet count greater than 125,000 per cubic millimeter and a PT and PTT withinnormal limits.

Exclusion Criteria:

1. Current or past psychotic disorder.

2. Full-scale IQ below 75 on the Wechsler Abbreviated Scale of Intelligence (WAIS) orcognitive impairment that would affect a participant's ability to give informedconsent or provide interview or self-report data reliably, as determined by theconsent monitor and the site psychiatrist. A questionnaire assessing consentcomprehension will be used with all study subjects, to ensure that they understandthe key procedures of the study, and its risks and benefits. An independent monitorwill administer that questionnaire.

3. A clinical history of bipolar mood disorder. We will not exclude substance-inducedmania or hypomania. In our prior studies, a history of induced hypomanic symptoms did not predictDBS-related hypomania.

4. Any current clinically significant neurological disorder or medical illnessaffecting brain function, other than tic disorders or Tourette syndrome.

5. Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI).

6. Any labeled DBS contraindication and/or inability to undergo presurgical MRI (cardiac pacemaker, pregnancy, metal in body, severe claustrophobia), infection,coagulopathy, inability to undergo an awake operation, significant cardiac or othermedical risk factors for surgery.

7. Current or unstably remitted substance abuse, dependence, or a positive urinetoxicology screen.

8. Pregnancy and women of childbearing age not using effective contraception.

9. Unable to adhere to operational and administrative study requirements (in theinvestigators' judgment).

10. Clinical history of severe personality disorder.

11. Imminent risk of suicide or an inability to control suicide attempts (in theinvestigators' judgment). History of serious suicidal behavior or one or more interrupted suicide attemptswith potential lethality judged to result in serious injury or death.

12. Diagnosis of body dysmorphic or hoarding disorder.

13. Evidence of dementia or other significant cognitive impairment on neuropsychologicalevaluation or through cognitive screening (MOCA).