Disrupted Resting Frontal–Parietal Attention Network Topology Is Associated With a Clinical Measure in Children With Attention-Deficit/Hyperactivity Disorder

Purpose: Although alterations in resting-state functional connectivity between brain regions have been reported in children with attention-deficit/hyperactivity disorder (ADHD), the spatial organization of these changes remains largely unknown. Here, we studied frontal–parietal attention network topology in children with ADHD, and related topology to a clinical measure of disease progression. Methods: Resting-state fMRI scans were obtained from New York University Child Study Center, including 119 children with ADHD (male n = 89; female n = 30) and 69 typically developing controls (male n = 33; female n = 36). We characterized frontal–parietal functional networks using standard graph analysis (clustering coefficient and shortest path length) and the construction of a minimum spanning tree, a novel approach that allows a unique and unbiased characterization of brain networks. Results: Clustering coefficient and path length in the frontal–parietal attention network were similar in children with ADHD and typically developing controls; however, diameter was greater and leaf number, tree hierarchy, and kappa were lower in children with ADHD, and were significantly correlated with ADHD symptom score. There were significant alterations in nodal eccentricity in children with ADHD, involving prefrontal and occipital cortex regions, which are compatible with the results of previous ADHD studies. Conclusions: Our results indicate the tendency to deviate from a more centralized organization (star-like topology) towards a more decentralized organization (line-like topology) in the frontal–parietal attention network of children with ADHD. This represents a more random network that is associated with impaired global efficiency and network decentralization. These changes appear to reflect clinically relevant phenomena and hold promise as markers of disease progression.