Change in striatal functional connectivity networks across 2 years due to stimulant exposure in childhood ADHD: results from the ABCD sample

Widely prescribed for Attention-Deficit/Hyperactivity Disorder (ADHD), stimulants (e.g., methylphenidate) have been studied for their chronic effects on the brain in prospective designs controlling dosage and adherence. While controlled approaches are essential, they do not approximate real-world stimulant exposure contexts where medication interruptions, dosage non-compliance, and polypharmacy are common. Brain changes in real-world conditions are largely unexplored. To fill this gap, we capitalized on the observational design of the Adolescent Brain Cognitive Development (ABCD) study to examine effects of stimulants on large-scale bilateral cortical networks’ resting-state functional connectivity (rs-FC) with 6 striatal regions (left and right caudate, putamen, and nucleus accumbens) across two years in children with ADHD. Bayesian hierarchical regressions revealed associations between stimulant exposure and change in rs-FC of multiple striatal-cortical networks, affiliated with executive and motor control, which were not driven by general psychotropic medication. Of these connections, one was selective to stimulant exposure, showing increased rs-FC between right nucleus accumbens and somatomotor network in children with ADHD who were exposed to stimulants relative to those who were not. This pattern of rs-FC change was similar to that in typically developing children suggesting a potential normalizing effect of stimulants. However, rs-FC change over time was not associated with reliable reduction in ADHD symptoms. Thus, stimulant exposure for a two-year period under real-world conditions modulated ventral striatal-cortical functional connectivity, but the link to potential therapeutic effects.