Neurology of Effortful Neutralization of Threat in Obsessive-Compulsive Disorder

NIH RePORTER · NIH · P20 · $265,715 · view on reporter.nih.gov ↗

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
LAUREATE INSTITUTE FOR BRAIN RESEARCH
Principal Investigator
Hannah E Berg
Activity code
P20
Funding institute
NIH
Fiscal year
2024
Award amount
$265,715
Award type
5
Project period
2024-07-01 → 2028-06-30