Brain network localization of gray matter alterations and executive dysfunction in pediatric ADHD

Abstract

Background Attention‐deficit/hyperactivity disorder (ADHD) is characterized by gray matter alterations and executive dysfunction. Whether the spatially distributed regional abnormalities reported in previous meta‐analyses converge within large‐scale networks of the developing brain remains unclear. Using coordinate‐informed functional connectivity network mapping (FCNM), we mapped the network architecture of meta‐analytic gray matter volume (GMV) and executive dysfunction coordinates in pediatric ADHD and evaluated its reproducibility and cross‐disorder specificity. Methods We extracted neuroimaging coordinates from published meta‐analyses reporting GMV alterations and task‐based executive dysfunction in pediatric ADHD ( n cases = 5,015, n controls = 5,915). To map these disparate regional coordinates onto common functional circuits, we applied FCNM utilizing a large‐scale, high‐quality pediatric normative connectome from the Chinese Child Brain Development (CCBD) project ( n = 2,120). The spatial overlap between the derived abnormality networks and canonical brain networks was quantified using Dice coefficients. Furthermore, network robustness was validated using independent pediatric clinical cohorts (from the ADHD‐200 dataset and CCBD), and disease specificity was assessed via cross‐disorder connectomic comparison with autism spectrum disorder (ASD). Results Despite the spatial dispersion of the input coordinates, the FCNM‐derived connectivity maps showed differential overlap with large‐scale brain networks. Specifically, the network associated with gray matter alterations localized predominantly to the default mode network (DMN) (Dice = 0.457; P NCT = 0.001) and the ventral attention network (VAN) (Dice = 0.237; P NCT = 0.03), while the network underlying executive dysfunction localized primarily to the VAN (Dice = 0.319; P NCT = 0.001). Importantly, this dual‐network architecture demonstrated robust reproducibility across independent clinical validation cohorts and exhibited clear topological specificity when compared to ASD‐related networks. Conclusions Using a large pediatric normative connectome, coordinate‐informed FCNM mapped ADHD‐related abnormalities onto partially overlapping DMN and VAN architectures, providing a reproducible framework for understanding distributed abnormalities in ADHD and identifying biologically defined targets for neuromodulation and early intervention.