# Characterization and Modulation of Functional Connectivity and Fear Extinction Abnormalities in Obsessive-Compulsive Disorder

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2024 · $721,862

## Abstract

ABSTRACT
Approximately 60% of patients with obsessive-compulsive disorder (OCD) respond to the psychotherapy of
choice, exposure and response prevention (ERP). Unfortunately, troubling symptoms persist for most patients,
even treatment responders. ERP is believed to depend on safety learning and engagement of related brain
circuitry. OCD patients have repeatedly demonstrated deficits in safety learning and memory processes, but
important gaps exist in this literature. In particular, there are limited data on neural functions related to safety
learning and memory deficits in OCD. This is important as multiple studies have shown that OCD is associated
with dysconnectivity in large-scale networks that are implicated in fear signaling and to safety learning, namely,
the default mode network (DMN) and salience network (SN). Preliminary research by the PI suggests that that
anodal (excitatory) frontopolar (over the anterior medial prefrontal cortex [mPFC]) multifocal transcranial direct
current stimulation (tDCS) reduced resting functional connectivity between these networks and accelerates
safety learning in community volunteers. Preliminary research by the PI also suggests that frontopolar tDCS
accelerates safety learning during a single session of in vivo ERP with patients diagnosed with OCD. The
proposed R01 project would be the first to examine if OCD is associated with deficits in inhibitory safety
learning – fear extinction learning that is acquired after original fear conditioning has been consolidated into
long-term memory – and would be among the first to probe neural functions associated with extinction deficits
in OCD. The proposed R01 project would also replicate and extend the PI’s exciting preliminary findings to test
if frontopolar tDCS can normalize dysconnectivity and functional activity within and between the DMN and SN
and recover safety learning deficits in patients with OCD. Results from this project would pave the way for
additional experimental therapeutics target engagement research; research that examine the effects of
frontopolar tDCS on neural abnormalities and safety learning deficits in other anxious psychopathology (e.g.,
posttraumatic stress disorder) and clinical trials examining the interactive effects of frontopolar tDCS and ERP
on brain dysconnectivity and symptoms of OCD.

## Key facts

- **NIH application ID:** 10944269
- **Project number:** 1R01MH137471-01
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Thomas G Adams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $721,862
- **Award type:** 1
- **Project period:** 2024-08-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10944269

## Citation

> US National Institutes of Health, RePORTER application 10944269, Characterization and Modulation of Functional Connectivity and Fear Extinction Abnormalities in Obsessive-Compulsive Disorder (1R01MH137471-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10944269. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*