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Large-scale brain functional network topology disruptions underlie symptom heterogeneity in children with attention-deficit/hyperactivity disorder

By Xing Qian, Francisco Xavier Castellanos, Lucina Q. Uddin, Beatrice Rui Yi Loo, Siwei Liu, Hui Li Koh, Daniel Fung, Cuntai Guan, Tih-Shih Lee, Choon Guan Lim, Juan Zhou and Wendy Xue Wei Poh

Abstract

Accumulating evidence suggests brain network dysfunction in attention-deficit/hyperactivity disorder (ADHD). Whether large-scale brain network connectivity patterns reflect clinical heterogeneity in ADHD remains to be fully understood. This study aimed to characterize the differential within- and between-network functional connectivity (FC) changes in children with ADHD combined (ADHD-C) or inattentive (ADHD-I) subtypes and their associations with ADHD symptoms. We studied the task-free functional magnetic resonance imaging (fMRI) data of 58 boys with ADHD and 28 demographically matched healthy controls. We measured within- and between-network connectivity of both low-level (sensorimotor) and high-level (cognitive) large-scale intrinsic connectivity networks and network modularity. We found that children with ADHD-C but not those with ADHD-I exhibited hyper-connectivity within the anterior default mode network (DMN) compared with controls. Additionally, children with ADHD-C had higher inter-network FC between the left executive control (ECN) and the salience (SN) networks, between subcortical and visual networks, and between the DMN and left auditory networks than controls, while children with ADHD-I did not show differences compared with controls. Similarly, children with ADHD-C but not ADHD-I showed lower network modularity compared with controls. Importantly, these observed abnormal inter-network connectivity and network modularity metrics were associated with Child Behavioral Checklist (CBCL) attention-deficit/hyperactivity problems and internalizing problems in children with ADHD. This study revealed relatively greater loss of brain functional network segregation in childhood ADHD combined subtype compared to the inattentive subtype, suggesting differential large-scale functional brain network topology phenotype underlying childhood ADHD heterogeneity.NMRC (Natl Medical Research Council, S’pore)MOH (Min. of Health, S’pore)Published versio

Topics: Functional Connectivity, Engineering::Computer science and engineering, Attention-deficit/Hyperactivity Disorder
Year: 2018
DOI identifier: 10.1016/j.nicl.2018.11.010
OAI identifier: oai:dr.ntu.edu.sg:10356/83148
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