Limbic System White Matter in Children and Adolescents with ADHD: A Longitudinal Diffusion MRI Analysis

Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized as a disorder linked to atypical white matter development across large-scale brain networks. However, current research predominantly focuses on cortical networks, leaving the developmental trajectories of many subcortical networks, including the limbic system, largely unexplored. The limbic system is crucial for emotion and cognition, making it a key area of interest in ADHD research. This study employed multi-shell high angular resolution diffusion magnetic resonance imaging to map the development of limbic system white matter in individuals with ADHD (n = 72) and controls (n = 97) across three time points between ages 9 and 14. Diffusion kurtosis imaging and graph theory metrics were used to characterize limbic system white matter, alongside assessments of emotional regulation and ADHD symptom severity. Compared to controls, individuals with ADHD exhibited significantly lower microstructural organization, particularly in kurtosis anisotropy, within the bilateral cingulum bundle from childhood to adolescence. Brain-behavior analyses further revealed that higher ADHD symptom severity was associated with a lower number of limbic system white matter connections, notably decreased routing efficiency and network density. These findings offer novel insights into the role of disrupted limbic system white matter in ADHD pathophysiology, broadening our understanding of the disorder’s neural mechanisms and opening promising avenues for future exploration of subcortical brain networks.