Divergent neural correlates of intolerance of uncertainty subdimensions: Insights from multimodal analyses of reward processing

Neuroimage. 2025 Dec 15:324:121625. doi: 10.1016/j.neuroimage.2025.121625. Epub 2025 Nov 27.

Abstract

Background: Intolerance of uncertainty (IU) is a transdiagnostic factor in mental disorders, affecting emotional, cognitive, and behavioral functioning. While IU influences the processing of uncertain rewards, analyses of its distinct subdimensions and their associations with different reward modalities remain limited.

Methods: Functional and structural magnetic resonance imaging (MRI) scans were acquired from 243 adult participants (m/f: 89/154). During functional MRI, participants completed a monetary reward paradigm involving both positive and negative reward feedback. Associations between brain function and structure and IU subdimensions prospective IU, inhibitory IU and burden due to IU were examined at the whole-brain level and within the bilateral insula and nucleus accumbens (NAcc).

Results: Burden due to IU was positively associated with left-hemispheric brain activity in cortical and subcortical clusters during negative reward feedback (pFWE ≤ .043), as well as with insular activity in both negative and positive reward conditions (pFWE ≤ .029). In contrast, prospective IU was negatively associated with insular activity during negative reward feedback (pFWE = 0.024). Gray matter volume in the NAcc showed divergent associations with the IU subscales: burden due to IU was positively related to NAcc volume (pFWE = 0.011), whereas prospective IU demonstrated a negative association (pFWE = 0.029).

Conclusions: Our analyses provide evidence that IU dimensions are differentially associated with neural reward-related processing and brain structure, reinforcing the importance of conceptualizing IU as a multifaceted construct. The most salient associations were observed for burden due to IU, which reflects affective distress in response to uncertainty, emphasizing the relevance of emotional experience in IU.

Keywords: Insula; Nucleus accumbens; Reward processing; Uncertainty intolerance; fMRI.

MeSH terms

  • Adult
  • Brain Mapping / methods
  • Brain* / diagnostic imaging
  • Brain* / physiology
  • Female
  • Humans
  • Insular Cortex* / diagnostic imaging
  • Insular Cortex* / physiology
  • Magnetic Resonance Imaging / methods
  • Male
  • Nucleus Accumbens* / diagnostic imaging
  • Nucleus Accumbens* / physiology
  • Reward*
  • Uncertainty
  • Young Adult