Altered white matter microstructure in children with attention-deficit/hyperactivity disorder

Abstract

Objective: Identification of biomarkers is a priority for attention-deficit/hyperactivity disorder (ADHD). Studies have documented macrostructural brain alterations in ADHD, but few have examined white matter microstructure, particularly in preadolescent children. Given dramatic white matter maturation across childhood, microstructural differences seen in adolescents and adults with ADHD may reflect compensatory restructuring, rather than early neurophenotypic markers of the disorder.

Method: Using tract-based spatial statistics, mean fractional anisotropy (FA) maps were created using diffusion tensor imaging. FA, mean diffusivity (MD), and associated axial and radial diffusivities were compared between 16 children with ADHD and 20 healthy children (age 7-9 years).

Results: Youth with ADHD showed decreased FA in frontoparietal, frontolimbic, cerebellar, corona radiata, and temporo-occipital white matter compared with controls. In addition, ADHD was associated with lower MD in the posterior limb of the internal capsule and frontoparietal white matter and greater MD in frontolimbic white matter. Lower axial diffusion and/or higher radial diffusion were differentially observed for youth with ADHD in earlier versus later maturing areas of group FA/MD difference.

Conclusions: This study suggests that, even prior to adolescence, ADHD represents a disorder of altered structural connectivity of the brain, characterized by distributed atypical white matter microstructure. In addition, later maturing frontolimbic pathways were abnormal in children with ADHD, likely due to delayed or decreased myelination, a finding not previously demonstrated in the adolescent or adult stages of the disorder. These results suggest that disruptions in white matter microstructure may play a key role in the early pathophysiology of ADHD.

Figure 1

Regions attention-deficit/hyperactivity disorder (ADHD) youth have significantly lower a.) fractional anisotropy (FA) (shown in red) and b.) mean diffusivity (MD) (shown in blue) compared to healthy controls (cluster volume ≥ 25 μL, voxelwise and clusterwise α < .01; corrected p/voxel = 0.00000369). ACR = anterior corona radiata; CG = cingulum; ICP = inferior cerebellar peduncle; ILF = inferior longitudinal fasciculus; PLIC = posterior limb of the internal capsule; PCR = posterior corona radiata; SCR = superior corona radiata; SLF = superior longitudinal fasciculus; UF = uncinate fasciculus.