Functional connectivity of the anterior insula associated with intolerance of uncertainty in youth

Intolerance of uncertainty (IU) is a trait characteristic marked by distress in the face of insufficient information. Elevated IU has been implicated in the development and maintenance of anxiety disorders, particularly during adolescence, which is characterized by dramatic neural maturation and the onset of anxiety disorders. Previous task-based work implicates the bilateral anterior insula in IU. However, the association between anterior insula intrinsic functional connectivity (iFC) and IU has not been examined in adolescents. Fifty-eight healthy youth (mean age = 12.56; 55% boys) completed the Intolerance of Uncertainty Scale for Children (IUSC-12) and a 6-minute resting state fMRI scan. Group-level analyses were conducted using a random-effects, ordinary least-squares model, including IUSC-12 scores (Total, Inhibitory subscale, Prospective subscale), and three nuisance covariates (age, sex, and mean framewise displacement). IUSC-12 Inhibitory subscale scores were predictive of iFC between the left and right anterior insula and right prefrontal regions. IUSC-12 Prospective subscale scores significantly predicted iFC between the anterior insula and the anterior cingulate cortex. IUSC-12 total scores did not predict significant iFC of the bilateral anterior insula. Follow-up analyses, including anxiety (MASC Total Score) in the models, failed to find significant results. This could suggest that the associations found between IUSC-12 scores and anterior insula iFC are not unique to IU and, rather, reflect a broader anxiety-related connectivity pattern. Further studies with larger samples are needed to tease apart unique associations. These findings bear significance in contributing to the literature evaluating the neural correlates of risk factors for anxiety in youth.