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The purpose of this study is to identify abnormal brain signals associated with Obsessive Compulsive Disorder (OCD) and psychiatric symptoms and to investigate novel therapeutic stimulation sites. While treating OCD with standard deep brain stimulation (DBS) therapy, the investigators will also monitor the activity of the anterior cingulate and prefrontal cortex, a region known be involved with OCD, decision making, and emotion regulation, and the investigators will identify abnormal activity corresponding to the severity of a patient's OCD. The investigators will also investigate whether it is possible for stimulation delivered to these parts of the brain can improve OCD symptoms. These investigations have the potential to aid in the development of improved forms of DBS that can better target abnormal OCD brain signatures in the future.
The investigators will implant a cortical electrode in addition to the ALIC DBS electrode and connect these to an implantable pulse generator that care store field potential data (Medtronic Percept). The decision whether the lead is placed in the prefrontal or cingulate cortex bilaterally will be based upon considerations of the surgical risks for a particular patient based upon their anatomy and the required surgical approach.
At multiple time points post-implantation up to 2 years, in our clinic or patient's homes, cortical and subcortical signals will be recorded. Data will be collected while patient are resting or engaged in symptom provocation tasks, emotional/cognitive tasks while cortical stimulation is on and off. In addition to brain signal recordings, symptoms will be assessed using validated questionnaires and tasks to allow identification of neurophysiological correlates of OCD symptoms.
The investigators propose to perform electrophysiological investigations into the corticostriatal circuits mediating severe, refractory obsessive compulsive disorder (OCD) through chronic intracranial recordings and stimulation. This new study will utilize the Medtronic Percept, which is currently is approved for treating OCD under the Humanitarian Device Exemption (HDE).
In addition to their standard therapeutic DBS electrode(s) in the standard subcortical targets (anterior limb of the internal capsule- ALIC), patients enrolled in this study will have a second pair of leads placed in either the prefrontal cortex (PFC) or anterior cingulate cortex (ACC) bilaterally as well the surrounding white matter tracts for a total of 4 DBS leads.
After electrode implantations, patient will undergo 2 phases:
In phase 1 (day 1 - 12 months), the aim will be to identify a biomarker of OCD-related symptoms. Patient will undergo long-term monitoring of their OCD and related psychiatric symptoms along with recordings of cortical and subcortical local field potentials (LFPs). This phase will be conducted in both the outpatient office setting and patient's home environment.
In phase 2 (13 months - 2 years), the investigators will introduce cortical stimulation at either the PFC or ACC/cingulum in addition to stimulation at the ALIC. The investigators will continue to obtain brain recordings and ratings during this period of time to identify the impact of cortical stimulation on these signals.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prefrontal Cortex (PFC) | Experimental | The Prefrontal Cortex (PFC) treatment group will be have an implant bilaterally at the HDE-approved ALIC site and the PFC. |
|
| Anterior Cingulate Cortex (ACC) | Experimental | The Anterior Cingulate Cortex (ACC) treatment group will be have an implant bilaterally at the HDE-approved ALIC site and the ACC. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard Therapeutic Deep Brain Stimulation | Device | DBS to the standard subcortical targets (anterior limb of the internal capsule- ALIC) will be used to treat OCD |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from 12 months to 24 months | The Y-BOCS is an OCD symptom scale used for identifying current OCD symptom severity. The score ranges from 0-40, with higher scores indicating more severe OCD symptoms. The change in Y-BOCS score from 12 months to 24 months will be reported. | 12-24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Montgomery Asberg Depression Rating Scale (MADRS) score from 12 months to 24 months | Effect size of cortical stim + ALIC DBS compared to ALIC DBS (mean difference in Montgomery Asberg Depression Rating Scale (MADRS) score at 12 months and 24 months. Higher MADRS score indicates more severe depression; the overall score ranges from 0 to 60. | 12-24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarker identification in Stage 1 | The number of patients in whom we can identify a neural biomarker that accounts for a significant amount of variance in OCD symptom severity | 1-12 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Andrew M Lee, MD, PhD | Contact | 415-502-5472 | ocdresearch@ucsf.edu | |
| Tenzin Norbu, BS | Contact | 415-514-6489 | ocdresearch@ucsf.edu |
| Name | Affiliation | Role |
|---|---|---|
| Andrew M Lee, MD, PhD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Nancy Friend Pritzker Psychiatry Building | Recruiting | San Francisco | California | 94107 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16650723 | Background | Denys D. Pharmacotherapy of obsessive-compulsive disorder and obsessive-compulsive spectrum disorders. Psychiatr Clin North Am. 2006 Jun;29(2):553-84, xi. doi: 10.1016/j.psc.2006.02.013. | |
| 31906709 | Background | Denys D, Graat I, Mocking R, de Koning P, Vulink N, Figee M, Ooms P, Mantione M, van den Munckhof P, Schuurman R. Efficacy of Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Refractory Obsessive-Compulsive Disorder: A Clinical Cohort of 70 Patients. Am J Psychiatry. 2020 Mar 1;177(3):265-271. doi: 10.1176/appi.ajp.2019.19060656. Epub 2020 Jan 7. |
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| ID | Term |
|---|---|
| D009771 | Obsessive-Compulsive Disorder |
| D003192 | Compulsive Behavior |
| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| D001523 | Mental Disorders |
| D007175 | Impulsive Behavior |
| D001519 | Behavior |
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| Cortical Stimulation for PFC | Device | Patients enrolled in this study will have a second pair of leads placed in the prefrontal cortex (PFC) bilaterally as well the surrounding white matter tracts and stimulation will be delivered through these leads to improve OCD symptoms |
|
|
| Cortical Stimulation for ACC | Device | Patients enrolled in this study will have a second pair of leads placed in the anterior cingulate cortex (ACC) bilaterally as well the surrounding white matter tracts and stimulation will be delivered through these leads to improve OCD symptoms |
|
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