# Targeting DBS Therapy to the OCD Network Using fMRI and Intracranial Recordings

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $201,875

## Abstract

PROJECT SUMMARY/ABSTRACT
According to the WHO, OCD is one of the top ten causes of disability among young adults, and one in ten
patients have severe symptoms refractory to cognitive and medical therapies. OCD is thought to be mediated
by a cortico-striato-thalamo-cortical (CSTC) circuit anchored in the anterior cingulate cortex (ACC) and
orbitofrontal cortex (OFC). Deep brain stimulation (DBS) is a targeted circuit-based treatment that has been used
to treat severe, refractory cases of OCD. However, DBS remains limited in its use because: 1) currently only 50-
60% of patients respond to therapy, 2) DBS programming is a complex, trial-and-error process that can take
months to years to optimize, and 3) DBS is associated with adverse effects such as sleep disturbance and mania.
We aim to overcomes these limitations by developing methods to target DBS therapy to the neural circuits
underlying OCD. Developments in DBS technology now allow for MR imaging to be performed while DBS is
On/Off and local field potential recordings can now be acquired from DBS leads, providing a unique opportunity
to determine whether DBS therapy is functionally engaging the intended OCD circuitry. Here, we propose to: 1)
Develop protocols for generating personalized spatial activation maps using stimulation-based fMRI, and 2)
Identify individualized electrophysiological biomarkers of OCD and related psychiatric symptoms responsive to
DBS using intracranial recordings. Together, these imaging and electrophysiological methods can be used to
verify that DBS is engaging the OCD network.
In our pilot studies, we demonstrate the feasibility of generating stimulation maps using fMRI protocols in a single
subject, finding activation in the OFC and ACC distant from the empirically determine therapeutic contacts. We
also describe the identification of a gamma biomarker of depression within the bed nucleus of the stria terminalis
(BNST), serving as a proof-of-concept that it is possible to identify electrophysiological biomarkers of psychiatric
symptoms. We currently have FDA investigational device exemption (IDE) approval to implant DBS leads in the
OFC and ACC in addition to the standard anterior limb of the internal capsule (ALIC) DBS target for OCD. This
proposal seeks to determine whether our initial imaging findings will hold in a larger cohort of subjects and to
determine the feasibility of discovering novel OCD biomarkers by performing intracranial recordings across
critical nodes of the OCD network. These studies provide a path towards personalized, circuit-based precision
medicine to improve DBS for OCD.

## Key facts

- **NIH application ID:** 10671069
- **Project number:** 5R21MH130914-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Andrew Moses Lee
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2022-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10671069

## Citation

> US National Institutes of Health, RePORTER application 10671069, Targeting DBS Therapy to the OCD Network Using fMRI and Intracranial Recordings (5R21MH130914-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10671069. Licensed CC0.

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