Altered resting functional connectivity patterns associated with problematic substance use and substance use disorders during adolescence

Background: Adolescence is typified by increasing rates of substance use and the development of substance use disorders (SUD). Aberrant connectivity between cortical regions involved in executive control, and subcortical regions has been suggested to be associated with SUD and problematic substance use among adolescents. Few studies, however, have investigated system-level or whole-brain functional connectivity (FC) in order to test this hypothesis. Methods: In a sample of 114 adolescents (mean age = 17.62 years, SD = 1.23, 61F) from the community, the present study used resting-state functional magnetic resonance imaging and independent component analysis to study executive control-subcortical network (ECN-SCN) coupling in adolescent SUD (n=18) and problematic substance use (n=34). In addition, whole-brain FC analyses were also conducted. Results: Problematic substance use, but not SUD, was associated with increased negative ECN-SCN coupling (p = 0.026). The whole-brain FC analysis showed insula-associated hypoconnectivity in the SUD group (p = 0.037), which was negatively correlated with frequency of substance use. Conclusions: Findings implicate different neural circuitry underlying adolescent SUD versus problematic use. Greater negative coupling between the SCN and ECN in adolescents with problematic substance use could underlie risk for future development of SUD or other mental health problems. Although we cannot infer directionality, hypoconnectivity within the insula in adolescents with SUD may indicate addiction-related alterations in interoceptive awareness or impairments in decision-making.