Exploring Characteristic Alteration of the White Matter Functional Networks at Rest in Children with Attention-Deficit/Hyperactivity Disorder

Abstract

Background: Previous studies mapping intrinsic brain connectivity have facilitated the neuropathological model of attention-deficit/hyperactivity disorder (ADHD) which encompasses a number of different large-scale networks. However, these studies have traditionally focused on the functional connectivity within grey matter regions, ignoring the critical role played by white matter in supporting brain functions. This study aimed to investigate the characteristic alterations of activity and connectivity within white matter functional networks in children with ADHD. Methods: K-means clustering was performed on the white matter resting-state fMRI data to identify white matter functional networks for a total of ninety-nine drug-naive children with ADHD and typically developing controls. Intrinsic activity in each network and functional connectivity between each network were assessed as well as the associations between network activity and ADHD clinical symptoms. Outcomes: Eight distinct white matter functional networks were identified. DMN, SMN, DAN and VAN showed lower spontaneous neural activity in children with ADHD. In particular, the DMN and SMN mainly showed increased connectivity with other networks while the DAN and VAN had more decreased connectivity. Interpretation: This study for the first time uncovered the feature of intrinsic functional organization of white matter networks in children with ADHD. Our findings demonstrated that the abnormal white matter network activity and connectivity in DMN, SMN, DAN and VAN share similar characteristic changes with those of grey matter, which suggests abnormal white matter network interactions that encode neural activity may underlie ADHD neuropathology. Funding Statement: This study was supported by the National Natural Science Foundation (Grant No. 81671669) and Science and Technology Project of Sichuan Province (Grant No. 2017JQ0001). Declaration of Interests: The authors stated: None declared. Ethics Approval Statement: The Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University approved the study. All participants and their parents were fully informed about the purpose and procedures of this study, and written informed consent was obtained from the parents.