Cross-sectional mega-analysis of resting-state alterations associated with autism and attention-deficit/hyperactivity disorder in children and adolescents

Autism spectrum disorder (autism) and attention-deficit/hyperactivity disorder (ADHD) often co-occur, although it remains unclear whether these conditions share common neurobiological foundations or exhibit distinct alterations in resting-state brain connectivity. Here we conducted a cross-sectional mega-analytic comparison of functional connectivity patterns linked to autism and ADHD traits in children and adolescents (ages 6–19 years; n = 10,168), with follow-up analyses considering autism (n = 764 autistic; n = 893 neurotypical) and ADHD (n = 2,026 ADHD; n = 2,409 neurotypical) diagnoses. In total, 12,732 unique child and adolescent participants were included: 3,528 in both analyses, 6,640 in the trait analysis only, and 2,564 in the diagnostic analysis only. Autism traits and diagnosis were associated with reduced connectivity between the thalamus, putamen, salience/ventral attention and frontoparietal networks, whereas ADHD traits showed the opposite pattern. Hyperconnectivity between the default mode and dorsal attention networks was observed in both autistic and ADHD groups relative to neurotypical individuals and associated with ADHD traits. Despite frequent co-occurrence, autism and ADHD traits exhibit distinct neural signatures, with small effect sizes indicating subtle associations. A comparison of functional connectivity patterns linked to autism and attention-deficit/hyperactivity disorder traits in children and adolescents reveals distinct patterns of brain connectivity despite frequent co-occurrence of these conditions.