Developmental changes in dopamine-related neurophysiology and associations with adolescent substance use and...

When substance use begins during adolescence, it is associated with a greater long-term vulnerability to substance use disorders. Developmental changes in dopaminergic functioning may be involved in substance use initiation and escalation during adolescence. We thus used estimates of tissue iron as a noninvasive, indirect measure of dopamine-related neurophysiology to examine associations between basal ganglia tissue iron development, substance use, and incentive-boosted cognitive control in a longitudinal neuroimaging study. Adolescent participants (N = 168; 51.8 % female) underwent an fMRI scan up to four times across 6th to 11th grade (age range: 11.9-18.6 years old) resulting in 469 fMRI timepoints. Time-averaged and normalized T2*-weighted indices were extracted from basal ganglia subregions at each timepoint. Participants self-reported their past year substance use at each timepoint and completed an incentivized cognitive control task at the final time point (n = 76). In confirmation of prior studies, we show developmental increases in tissue iron at the group level. Adolescents who reported substance use showed attenuated age-related increases in tissue iron in comparison to non-users. Additionally, larger incentive-related modulation of cognitive control was associated with lower iron accumulation across adolescence, although tissue iron was not significantly associated with incentive-related changes in brain activity. Overall, findings suggest that adolescents with diminished age-related increases in basal ganglia tissue iron may have a greater propensity toward substance use. These same individuals may also require greater incentive-driven motivation to reach the same cognitive control performance as their peers. These findings suggest a potential developmental neurophysiological phenotype underlying different incentive-driven behaviors during adolescence.