Intolerance of uncertainty and functional connectivity of the anterior insula during anticipation of unpredictable reward

Individuals with high intolerance of uncertainty (IU) tend to display maladaptive cognitive, behavioral, physi-ological, and/or neural responses during anticipation of uncertain or ambiguous outcomes, both positive and negative in valence. Importantly, high IU has been proposed as a key transdiagnostic phenotypic risk factor for the onset and maintenance of several psychiatric disorders. Within the context of reward processing, high IU has been related to dysfunctional reward anticipation, which may be mediated by hyperactive anterior insula (AIC) response to uncertainty. The present study further investigated the relationship between the AIC and IU by examining the association between individual differences in IU and task-based functional connectivity of the right AIC using functional magnetic resonance imaging (fMRI). Participants (N = 171) completed a self-report measure of IU and a reward anticipation task during fMRI. Generalized psychophysiological interaction (gPPI) analyses were performed with a seed in the right AIC. In the U-threat model, we found that greater self-reported levels of IU were correlated with increased functional connectivity between the right AIC and the dorsal anterior cingulate cortex (dACC) and the right dorsolateral prefrontal cortex (dlPFC). In the P-threat model, we did not find these associations, perhaps indicating that they may be more robust during uncertainty. These preliminary findings suggest that parts of salience and central executive control networks may be impacted by and underlie the expression of IU. Future studies should examine the generalizability of these findings to clinical populations and investigate how disruption of these functional networks may contribute to psychopathology.