# Neurology of Effortful Neutralization of Threat in Obsessive-Compulsive Disorder

> **NIH NIH P20** · LAUREATE INSTITUTE FOR BRAIN RESEARCH · 2024 · $265,715

## Abstract

Obsessive-compulsive disorder (OCD) confers substantial individual and societal burden, and first-line 
treatments are only effective in some of cases. One roadblock to treatment improvement is limited 
understanding of compulsions, OCD’s characteristic behavioral patterns, which maintain distress and 
contribute substantially to functional impairment. Experimental research into the psychological and neural basis 
of compulsions is critically needed to enable the development of more effective treatment approaches. Existing 
research on the neurobiology of OCD has found increased activity and hyperconnectivity in cortico-striatothalamo- 
cortical (CSTC) circuitry, involving the orbitofrontal cortex, cingulate cortex, and striatum, at rest and in 
response to affective and attentional tasks. However, findings have been mixed, perhaps in part due to the 
heterogeneity of tasks that are presumed to mirror OCD-relevant processes. Advances in the understanding of 
the basic neural mechanisms of threat-related behavior offer a promising path forward. Experimental research 
has identified neural circuitry implicated in a wide range of defensive behaviors that protect against threats of 
varying severity, predictability, and imminence. This literature has largely focused on active avoidance, in 
which the individual moves away from the source of perceived threat, and passive avoidance, in which the 
individual withholds an action to avoid encountering a perceived threat. However, compulsions in OCD are 
distinct from active and passive avoidance in that they consist of repetitive, often highly effortful behavior 
aimed at neutralizing a perceived threat, a phenomenon which has received limited attention to date. This is a 
significant omission, given that compulsions contribute substantially to distress and impairment. To address 
this gap, we propose a cross-sectional, task-based neuroimaging approach investigate behavioral and neural 
biomarkers related to effortful neutralization of threat (ENT) in OCD. Individuals with OCD (n=35) and healthy 
comparison individuals with no psychiatric diagnoses (HC; n=35) will complete a novel fMRI paradigm 
developed by the RPL, the Tap-To-Safety (TTS) task, which is the first to directly elicit repetitive, effortful, 
threat-neutralizing behavior. The task will assess ENT in various threat contexts, and will measure neural 
activity associated with stimulus onset and decision-making. We hypothesize that individuals with OCD will 
demonstrate excessive neutralization behavior during the task, as well as heightened activity in and 
connectivity within CTSC circuitry during the task. The RPL is currently conducting a funded pilot study with 
healthy participants to inform task development; the aims of the current proposal therefore focus on identifying 
OCD-specific patterns of behavior and neural activity associated with ENT. The ultimate aim is to establish 
foundational knowledge regarding decision-making in OCD for...

## Key facts

- **NIH application ID:** 11093603
- **Project number:** 5P20GM121312-07
- **Recipient organization:** LAUREATE INSTITUTE FOR BRAIN RESEARCH
- **Principal Investigator:** Hannah E Berg
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $265,715
- **Award type:** 5
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11093603

## Citation

> US National Institutes of Health, RePORTER application 11093603, Neurology of Effortful Neutralization of Threat in Obsessive-Compulsive Disorder (5P20GM121312-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11093603. Licensed CC0.

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