Patient-specific, Effective, and Rational Functional Connectivity Targeting for DBS in OCD

Recently, deep brain stimulation (DBS) has emerged as a potentially circuit-specific
treatment for intractable OCD. DBS is programmable, allowing the clinician to "reshape" the
volume of tissue activated within the standard ventral capsule/ventral striatum (VC/VS)
target.

However, VC/VS DBS' efficacy is limited by two major factors: imperfect targeting and a lack
of decision rules for stimulation adjustment. The VC/VS target is not a single identifiable
structure, but encompasses white matter of the internal capsule and gray matter of the
nucleus accumbens (NAc). In current practice for DBS in OCD, all patients are implanted at
standard x,y,z coordinates in the VC/VS region. Due to this inter-subject anatomical
variability, different fiber tracts are stimulated by ostensibly the "same" parameters in
each subject, leading to variable outcomes. This investigation will identify aspects of VC/VS
circuitry that may determine clinical response. The hypothesis is that good clinical outcomes
may correlate to electrical field capture of either striatal gray matter or of white matter
fibers connecting OFC to thalamus.

The current study looks to extend the neuroimaging investigation using anatomic white matter
targeting, functional gray matter targeting and changes in changes in regional glucose
metabolism of Deep Brain Stimulation (DBS) in severe obsessive-compulsive disorder (OCD) with
the long-term aim of identifying biomarkers that could improve outcomes of this expensive and
invasive therapy. Improved imaging would allow surgeons to place the DBS lead closer to the
biological targets, thus improving efficacy of the treatment.

The objectives of this study are threefold:

- Improve the anatomic white matter targeting of the Deep Brain Stimulator (DBS) implant
by tracing and identifying fibers of passage within the Ventral Capsule (VC) white
matter using advance tractography methods in preoperative diffusion MRI data.

- Improve functional gray matter targeting by studying the overlap of the volume of tissue
activated (VTA) with the VC voxels of maximal preoperative connectivity to the
orbitofrontal cortex (OFC)

- Determine the changes in regional glucose metabolism using preoperative and
post-treatment FDG-PET (Positron Emission Tomography) following 3 months of DBS
treatment

Inclusion Criteria:

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

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

3. Age between 21 and 64 years.

4. Able to understand and comply with instructions.

5. Able to give fully informed, written consent.

6. Approved to be implanted with a DBS device for OCD.

Exclusion Criteria:

1. Current or past psychotic disorder.

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

3. A clinical history of bipolar mood disorder; substance-induced mania is not an
exclusion.

4. Any current clinically significant neurological disorder or medical illness affecting
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 other medical risk
factors for surgery.

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

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

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

10. Clinical history of severe personality disorder.

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

12. Diagnosis of body dysmorphic disorder.

13. Evidence of dementia or other significant cognitive impairment on neuropsychological
evaluation

14. Past or present diagnosis of hoarding disorder.