Neural Signatures of Cognitive Control Predict Future Adolescent Substance Use Onset and Frequency.

Background: Adolescent substance use is a significant predictor of future addiction and related disorders. Understanding neural mechanisms underlying substance use initiation and frequency during adolescence is critical for early prevention and intervention.

Methods: The current longitudinal study followed 91 substance-naïve adolescents annually for seven years from ages 14 to 21 to identify potential neural precursors that predict substance use initiation and frequency. Cognitive control processes were examined using the Multi-Source Interference Task to assess functional neural connectivity. A questionnaire assessed substance use frequency.

Results: Stronger connectivity between the dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (dlPFC) at Time 1 predicted a delayed onset of substance use, indicative of a protective effect. A notable decline in this dACC-dlPFC connectivity was observed one year prior to substance use initiation. Conversely, lower connectivity of the dACC with the supplementary motor area and heightened connectivity of the aINS with the dorsal medial prefrontal cortex and Angular gyrus were predictive of greater frequency of future substance use. These findings remained after controlling for demographic and socioeconomic covariates.

Conclusions: This study highlights the critical role of cognitive control-related neural connectivity in forecasting substance use initiation and frequency during adolescence. The results imply that efforts to strengthen and monitor the development of the top-down cognitive control system in the brain from early adolescence can be protective and deter progression into problematic substance use. Furthermore, for adolescents with heightened frequency of substance use, interventions may prove more effective by targeting interoceptive processes in cognitive control training.