Multiscale functional connectivity reveals imbalanced interplay between higher- and lower-order brain networks in ADHD

Attention deficit hyperactivity disorder (ADHD) is characterized by dysconnectivity among large-scale brain functional networks. How these changes manifest across different spatial scales remains unclear. We investigated ADHD-related functional connectivity alterations at global, region-to-region and network scales using resting-state functional MRI data from 454 children and adolescents with ADHD and typically developing controls from three cohorts. At the global level, individuals with ADHD exhibited hypoconnectivity in default-mode network (DMN) hubs and visual areas. Region‑to‑region analysis revealed hypoconnectivity within the DMN, between DMN hubs and visual regions, and between nodes of salience (SAN) and frontoparietal networks and auditory/sensorimotor areas, alongside hyperconnectivity linking DMN with SAN, frontoparietal and auditory regions. At the network level, SAN-auditory/sensorimotor hypoconnectivity persisted whereas DMN alterations were no longer significant. These results were independent of age and sex but influenced by medication status and comorbidity. Collectively, our findings indicate a scale-dependent imbalanced interplay between higher-order cognitive and lower-order sensory networks in ADHD. In this study, the authors investigate functional connectivity alterations across global, region-to-region and network scales in children and adolescents with ADHD. They highlight an imbalance in interaction between higher-order cognitive and lower-order sensory brain networks.