Brain Structure and Differential Response to Family-Centered Prevention: Evidence for Anterior Cingulate Cortex Moderation in a Randomized Controlled Trial

Family-centered prevention programs improve youth self-regulation, yet intervention effects are heterogeneous, and the mechanisms underlying differential response remain poorly understood. Identifying neural metrics that shape responsiveness to prevention may advance theory and inform program refinement. This study examined whether baseline brain structure moderated response to a telehealth adaptation of the Strong African American Families program (T-SAAF), a prevention intervention targeting self-regulation among Black preadolescents. Youth ages 11-12 and their caregivers (N = 170 families) were recruited in North Georgia and randomly assigned to T-SAAF or a no-treatment control condition. Allocation was 1:1 in a two-group parallel design evaluated within a superiority framework, and we generated the allocation sequence using statistical software. Because randomization followed the pretest assessment, allocation was concealed from participants and from pretest assessors, and condition was revealed only after pretest data collection was complete. Thereafter, families, facilitators, and posttest assessors could not be masked to condition, as T-SAAF is a group-based family program delivered by facilitators. We conducted no interim analyses and used no stopping guidelines; the trial completed as planned. They were assessed at baseline and approximately nine months later. A neuroimaging subsample completed structural MRI prior to intervention exposure. Analyses focused on whether cortical and subcortical structural metrics moderated changes in parent-reported youth self-control. To account for differential engagement, the intervention main effect was tested in a propensity score-matched sample of youth who received the intervention and comparable controls (n = 130); brain by intervention interactions were tested in the neuroimaging subsample (n = 105). Assignment to T-SAAF was associated with a modest increase in self-control (F[1,124] = 4.28, p = .04). Baseline anterior cingulate cortex (ACC) structure moderated this effect. The clearest and most consistent evidence was for rostral ACC thickness and caudal ACC thickness; caudal ACC volume showed the same pattern with weaker but convergent support. Across these metrics, thinner or smaller ACC at baseline was associated with greater intervention-related gains in self-control, whereas youth with higher ACC structural values showed little differential benefit. No moderation was observed for rostral ACC volume, amygdala volume, or nucleus accumbens volume. Findings provide preliminary evidence that individual differences in neural structure, particularly within the ACC, may shape responsiveness to family-centered preventive intervention during preadolescence. By extending neural prediction approaches from adult treatment to developmental prevention, this study indicates that neurodevelopmental markers can clarify mechanisms of differential response and inform program refinement. Confirmation in adequately powered, preregistered research is needed. ClinicalTrials.gov NCT05253235 ( https://clinicaltrials.gov/study/NCT05253235 ); registered February 22, 2022.