Longitudinal development of the anterior insula-nucleus accumbens white matter pathway through adolescence predicts...

Adolescence is characterized by increases in risk-taking behaviors, including substance use, sexual activity, and impulsive decision-making. Neuroimaging research implicates the anterior insula (AIns) and nucleus accumbens (NAcc) in risk evaluation and reward motivation; however, little is known about how the structural pathway connecting these regions develops across adolescence or whether variation in its development predicts later risk-taking. In this study, we examined whether longitudinal changes in white-matter connectivity between the AIns and NAcc during adolescence predict risk-taking in early adulthood. A total of 196 youth (ages 9-20 years) contributed 486 diffusion-weighted imaging scans across four waves spanning six years. We reconstructed the AIns-NAcc tract using probabilistic tractography and extracted fractional anisotropy (FA) along the tract. At a fifth assessment (ages 19-23), 105 participants completed the Adolescent and Young Adult Health Questionnaire; exploratory factor analysis identified a risk-taking factor indexing substance use and sexual risk-taking. We used linear mixed-effects models to characterize developmental trajectories of FA and tested their associations with early adult risk-taking, adjusting for biological sex, early life stress, and behavioral sensitivity to reward and punishment. FA increased linearly across adolescence in both hemispheres (right: β=0.17, p < .001; left: β=0.10, p = .023). Critically, individuals exhibiting shallower increases in FA across adolescence in the right hemisphere reported greater engagement in risk-taking behaviors in early adulthood (ΔR²=4.0%, p = .024). These findings suggest that adolescence represents a sensitive period during which individual differences in maturation of the right AIns-NAcc pathway prospectively shape later risk-taking, highlighting the importance of longitudinally modeling structural connectivity in reward-related circuits.