Aberrant Time-Varying Cross-Network Interactions in Children With Attention-Deficit/Hyperactivity Disorder and the Relation to Attention Deficits

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is thought to stem from aberrancies in large-scale cognitive control networks. However, the exact nature of aberrant brain circuit dynamics involving these control networks is poorly understood. Using a saliency-based triple-network model of cognitive control, we tested the hypothesis that dynamic cross-network interactions among the salience, central executive, and default mode networks are dysregulated in children with ADHD, and we investigated how these dysregulations contribute to inattention. Methods: Using functional magnetic resonance imaging data from 140 children with ADHD and typically developing children from two cohorts (primary cohort = 80 children, replication cohort = 60 children) in a case-control design, we examined both time-averaged and dynamic time-varying cross-network interactions in each cohort separately. Results: Time-averaged measures of salience network–centered cross-network interactions were significantly lower in children with ADHD compared with typically developing children and were correlated with severity of inattention symptoms. Children with ADHD displayed more variable dynamic cross-network interaction patterns, including less persistent brain states, significantly shorter mean lifetimes of brain states, and intermittently weaker cross-network interactions. Importantly, dynamic time-varying measures of cross-network interactions were more strongly correlated with inattention symptoms than with time-averaged measures of functional connectivity. Crucially, we replicated these findings in the two independent cohorts of children with ADHD and typically developing children. Conclusions: Aberrancies in time-varying engagement of the salience network with the central executive network and default mode network are a robust and clinically relevant neurobiological signature of childhood ADHD symptoms. The triple-network neurocognitive model provides a novel, replicable, and parsimonious dynamical systems neuroscience framework for characterizing childhood ADHD and inattention.