Negative Valence in Obsessive-Compulsive Disorder: A Worldwide Mega-Analysis of Task-Based Functional Neuroimaging Data of the ENIGMA-OCD Consortium

Biol Psychiatry. 2025 Aug 1;98(3):219-229. doi: 10.1016/j.biopsych.2024.12.011. Epub 2024 Dec 24.

Abstract

Objective: Obsessive-compulsive disorder (OCD) is associated with altered brain function related to processing of negative emotions. To investigate neural correlates of negative valence in OCD, we pooled functional magnetic resonance imaging data of 633 individuals with OCD and 453 healthy control participants from 16 studies using different negatively valenced tasks across the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium's OCD Working Group.

Methods: Participant data were processed uniformly using HALFpipe, to extract voxelwise participant-level statistical images of one common first-level contrast: negative versus neutral stimuli. In preregistered analyses, parameter estimates were entered into Bayesian multilevel models to examine whole-brain and regional effects of OCD and its clinically relevant features-symptom severity, age of onset, and medication status.

Results: We provided a proof of concept that participant-level data can be combined across several task paradigms and observed one common task activation pattern across individuals with OCD and control participants that encompasses frontolimbic and visual areas implicated in negative valence. Compared with control participants, individuals with OCD showed very strong evidence of weaker activation of the bilateral occipital cortex (P+ < 0.001) and adjacent visual processing regions during negative valence processing that was related to greater OCD severity, late onset of the disorder, and an unmedicated status. Individuals with OCD also showed stronger activation in the orbitofrontal, subgenual anterior cingulate, and ventromedial prefrontal cortex (all P+ < 0.1) that was related to greater OCD severity and late onset.

Conclusions: In the first mega-analysis of this kind, we replicated previous findings of stronger ventral prefrontal activation in OCD during negative valence processing and highlight the lateral occipital cortex as an important region implicated in altered negative valence processing.

Keywords: Clinical features; Disorder effects; Mega-analysis; Negative valence; Obsessive-compulsive disorder; Task-based fMRI.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Brain Mapping
  • Brain* / diagnostic imaging
  • Brain* / physiopathology
  • Emotions* / physiology
  • Female
  • Functional Neuroimaging
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder* / diagnostic imaging
  • Obsessive-Compulsive Disorder* / physiopathology
  • Obsessive-Compulsive Disorder* / psychology
  • Young Adult