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.

Structural Brain Alterations and Their Association with Cognitive Function and Symptoms in Attention-Deficit/Hyperactivity Disorder Families

“…The insula component captured the alterations shared by ADHD and their siblings, but no component was related to the symptom dimensions. This contrast might suggest different mechanisms were contributing to the complicated ADHD clinical profile, which was also discovered in previous studies (van Ewijk et al, 2014;Wu et al, 2017).…”

“…In addition, there were no components significantly related to any of the cognitive measures. Overall, this approach suggests that brain areas reflecting genetic liability within ADHD may be partly separate from areas modulating symptom severity, as has been suggested previously (van Ewijk et al, 2014;Wu et al, 2017).…”

Structural and functional neuroimaging in attention‐deficit/hyperactivity disorder

“…S1, online supporting information). Additionally, some neuroimaging studies have evidenced an association between these abnormalities and symptoms of inattention or hyperactivity/impulsivity, thus linking the clinical presentation and the neural correlates of ADHD . ADHD has been associated with functional abnormalities in frontal striato‐thalamic and fronto‐parieto‐cerebellar regions, translated into attention and executive function deficits (especially working memory and inhibition) and reflected in structural abnormalities in brain regions hypothesized to underlie these functions .…”

“…Additionally, some neuroimaging studies have evidenced an association between these abnormalities and symptoms of inattention or hyperactivity/impulsivity, thus linking the clinical presentation and the neural correlates of ADHD. 51,52 ADHD has been associated with functional abnormalities in frontal striato-thalamic and fronto-parietocerebellar regions, 30,[32][33][34] translated into attention and executive function deficits (especially working memory and inhibition) and reflected in structural abnormalities in brain regions hypothesized to underlie these functions. 10 For instance, in a multimodal voxel-based morphometry and functional MRI meta-analysis, 8 an overlapping cluster in the right putamen/anterior insula showed both decreased grey matter volume and reduced inhibition-related activation in individuals with ADHD relative to controls, highlighting the idea that abnormal grey matter volume in the basal ganglia is related to abnormal inhibitory function.…”

White matter microstructure in attention-deficit/hyperactivity disorder: a systematic tractography study in 654 individuals

“…Dimensional analyses allow for modeling of the entire ADHD spectrum (Lahey and Willcutt, 2010). Generally, DWI studies that have applied dimensional analyses have been inconsistent in terms of anatomical location, and counterintuitively indicate that, within the patient population, increased symptom severity ratings are associated with higher FA (Francx et al, 2015b;van Ewijk et al, 2014;Wu et al, 2017). Given that the categorical diagnosis of ADHD has generally been associated with reduced FA, a more in-depth study of these effects is warranted.…”