Chronic Exposure to Stimulants in Youth Moderates Resting-State and ADHD Severity Over Two Years

Psychostimulants are the most common medication for Attention-Deficit/Hyperactivity Disorder (ADHD) and acute administration attenuates symptoms via upregulation of striatal dopamine activity. Less is known about the effects of long-term psychostimulant exposure, in particular how resting-state functional connectivity (rs-FC) and resting-state networks may change due to long-term psychostimulant exposure compared to psychostimulant-naïve ADHD. We explored exposure-dependent changes in striatal and cortical rs-FC and their relation to symptom outcome across two years in the Adolescent Brain Cognitive Development (ABCD) dataset. We found that L nucleus accumbens-sensorimotor and dorsal-ventral attention rs-FC became stronger during the 2-year period in stimulant-exposed children with ADHD who had more improvement in symptoms. Stronger rs-FC between L nucleus accumbens, a reward region, and primary sensory and motor cortices over 2 years predicted symptom improvement in ADHD children treated with psychostimulants, as did stronger rs-FC between attention networks. Future work should continue to investigate the role of rs-FC networks and long-term psychostimulant use in ADHD.