White Matter Microstructural Alterations in Children with ADHD: Categorical and Dimensional Perspectives

Abstract

Studies of brain alterations in children with attention-deficit/hyperactivity disorder (ADHD) have shown heterogeneous results. The aims of the current study were to investigate white matter microstructure in children using both categorical and dimensional definitions of ADHD and to determine the functional consequences of observed alterations. In a large single-site sample of children (aged 8-15 years) with ADHD (n=83) and healthy controls (n=122), we used tract-based spatial statistics on diffusion tensor imaging data to investigate whole-skeleton differences of fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD), and mode of anisotropy related to ADHD status (categorical) and symptom severity (dimensional). For categorical differences observed, we analyzed their association with cognitive functioning in working memory and inhibition. Compared with healthy controls, children with ADHD showed decreased FA and increased RD in widespread, overlapping brain regions, mainly in corpus callosum (CC) and major tracts in the left hemisphere. Decreased FA was associated with inhibition performance in the participants with ADHD. Using dimensional definitions, greater hyperactivity/impulsivity symptom severity was associated with higher FA also in widespread regions, mainly in CC and major tracts in the right hemisphere. Our study showed white matter alterations to be related to ADHD status and symptom severity in patients. The coexistence of decreased FA and increased RD in the absence of alterations in MD or AD might indicate altered myelination as a pathophysiological factor in ADHD.