Functional Brain Connectivity Predictors of Prospective Substance Use Initiation and Their Environmental Correlates

Background: Early substance use initiation (SUI) places youth at substantially higher risk for later substance use disorders. Furthermore, adolescence is a critical period for the maturation of brain networks, the pace and magnitude of which are susceptible to environmental influences and may shape risk for SUI.

Methods: We examined whether patterns of functional brain connectivity during rest (rsFC), measured longitudinally during pre- and early adolescence, can predict future SUI. Next, in an independent subsample, we tested whether these patterns were associated with earlier environmental exposures, specifically neighborhood pollution and socioeconomic dimensions. We utilized data from the ABCD (Adolescent Brain Cognitive Development) Study. SUI was defined as first-time use of at least 1 full dose of alcohol, nicotine, cannabis, or other drugs. We created a control group (n = 228) of participants without SUI who were matched to the SUI group (n = 233) on age, sex, race/ethnicity, household income, and parental education.

Results: Multivariate analysis showed that whole-brain rsFC from 9-10 to 11-12 years of age (prior to SUI) prospectively differentiated the SUI and control groups. The SUI-related rsFC pattern was also related to aging in both groups, suggesting a pattern of accelerated maturation in the years prior to SUI. This same pattern of rsFC was predicted by higher pollution but not neighborhood disadvantage (adjusted for family socioeconomic factors) in an independent subsample (n = 2854).

Conclusions: Brain functional connectivity patterns in early adolescence that are linked to accelerated maturation can predict SUI in youth and are associated with exposure to pollution.