Asymmetry of attentive networks contributes to adult Attention-deficit/hyperactivity disorder (ADHD) pathophysiology

Diffusion imaging studies in Attention-deficit/hyperactivity disorder (ADHD) have revealed alterations in anatomical brain connections, such as the fronto-parietal connection known as superior longitudinal fasciculus (SLF). Studies in neurotypical adults have shown that the three SLF branches (SLF I, II, III) support distinct brain functions, such as attention and inhibition; and that their pattern of lateralization is associated with attention performance. However, most studies in ADHD have investigated the SLF as a single bundle and in children; thus, the potential contribution of the lateralization of the SLF branches to adult ADHD pathophysiology remains to be elucidated. We used diffusion-weighted spherical deconvolution tractography to dissect the SLF branches in 60 adults with ADHD (including 26 responders and 34 non-responders to methylphenidate, MPH) and 20 controls. Volume and hindrance modulated orientational anisotropy (HMOA), which respectively reflect white matter macro- and microstructure, were extracted to calculate the corresponding lateralization indices. We tested whether neurotypical controls differed from adults with ADHD, and from treatment response groups in sensitivity analyses; and investigated associations with clinico-neuropsychological profiles. All the three SLF branches were lateralized in adults with ADHD, but not in controls. The lateralization of the SLF I HMOA was associated with performance at the line bisection, not that of the SLF II volume as previously reported in controls. Further, an increased left-lateralization of the SLF I HMOA was associated with higher hyperactivity levels in the ADHD group. Thus, an altered asymmetry of the SLF, perhaps especially of the dorsal branch, may contribute to adult ADHD pathophysiology.