Investigation of white matter functional networks underlying different behavioral profiles in attention-deficit/hyperactivity disorder.

Background: Cortical functional network alterations have been widely accepted as the neural basis of attention-deficit/hyperactivity disorder (ADHD). Recently, white matter has also been recognized as a novel neuroimaging marker of psychopathology and has been used as a complement to cortical functional networks to investigate brain-behavior relationships. However, disorder-specific features of white matter functional networks (WMFNs) are less well understood than those of gray matter functional networks. In the current study, we constructed WMFNs using a new strategy to characterize behavior-related network features in ADHD. Methods: We recruited 46 drug-naïve boys with ADHD and 46 typically developing (TD) boys, and used clustering analysis on resting-state functional magnetic resonance imaging data to generate WMFNs in each group. Intrinsic activity within each network was extracted, and the associations between network activity and behavior measures were assessed using correlation analysis. Results: Nine WMFNs were identified for both ADHD and TD participants. However, boys with ADHD showed a splitting of the inferior corticospinal-cerebellar network and lacked a cognitive control network. In addition, boys with ADHD showed increased activity in the dorsal attention network and somatomotor network, which correlated positively with attention problems and hyperactivity symptom scores, respectively, while they presented decreased activity in the frontoparietal network and frontostriatal network in association with poorer performance in response inhibition, working memory, and verbal fluency. Conclusions: We discovered a dual pattern of white matter network activity in drug-naïve ADHD boys, with hyperactive symptom-related networks and hypoactive cognitive networks. These findings characterize two distinct types of WMFN in ADHD psychopathology.