Risk for Adolescent Substance Use Initiation: Associations with Large-Scale Brain Network Recruitment During Emotional Inhibitory Control

As the brain continues to mature during adolescence, heightened impulsivity in emotional situations may increase the likelihood of initiating substance use. Functional magnetic resonance imaging (fMRI) was used to assess large-scale network activation during an emotional inhibitory control task (Go-NoGo). Participants were healthy, substance-naïve adolescents aged 13-14 years (<i>n</i> = 56, 31 females) who were then followed for 3 years with quarterly substance use evaluations. During follow-up, 24 participants initiated substance use, while 32 remained substance-naïve. Network activation strength was extracted for the Negative NoGo > Neutral NoGo contrast in the left and right lateral frontoparietal networks (lL-FPN, rL-FPN) and the dorsal attention network (DAN) for each participant. The impact of network activation strength on substance use initiation was analyzed via survival analysis (Cox regression). Reduced activation strength of the lL-FPN was associated with significantly higher hazard of initiation of substance use (<i>p</i> = 0.008). No significant effects were observed for rL-FPN or DAN. Diminished engagement of the lL-FPN during inhibitory control in negative versus neutral emotional contexts was associated with earlier substance use initiation. This pattern of network activation may represent a neurobiological marker of self-regulation vulnerability, highlighting a potential target for early identification and prevention strategies during adolescence.