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Large-scale brain functional network topology disruptions underlie symptom heterogeneity in children with attention-deficit/hyperactivity disorder.
Neuroimage Clin. 2019; 21:101600.NC

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.

Authors+Show Affiliations

Center for Cognitive Neuroscience, Neuroscience & Behavioral Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore.NYU Child Study Center, NYU Langone Medical Center, New York, NY, United States.Department of Psychology, University of Miami, Coral Gables, FL, United States.Center for Cognitive Neuroscience, Neuroscience & Behavioral Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore.Center for Cognitive Neuroscience, Neuroscience & Behavioral Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore.Center for Cognitive Neuroscience, Neuroscience & Behavioral Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore.Department of Child and Adolescent Psychiatry, Institute of Mental Health, Singapore, Singapore.Department of Child and Adolescent Psychiatry, Institute of Mental Health, Singapore, Singapore.School of Computer Science and Engineering, Nanyang Technological University, Singapore, Singapore.Center for Cognitive Neuroscience, Neuroscience & Behavioral Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore.Department of Child and Adolescent Psychiatry, Institute of Mental Health, Singapore, Singapore.Center for Cognitive Neuroscience, Neuroscience & Behavioral Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore; Clinical Imaging Research Centre, The Agency for Science, Technology and Research-National University of Singapore, Singapore, Singapore. Electronic address: helen.zhou@duke-nus.edu.sg.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30472167

Citation

Qian, Xing, et al. "Large-scale Brain Functional Network Topology Disruptions Underlie Symptom Heterogeneity in Children With Attention-deficit/hyperactivity Disorder." NeuroImage. Clinical, vol. 21, 2019, p. 101600.
Qian X, Castellanos FX, Uddin LQ, et al. Large-scale brain functional network topology disruptions underlie symptom heterogeneity in children with attention-deficit/hyperactivity disorder. Neuroimage Clin. 2019;21:101600.
Qian, X., Castellanos, F. X., Uddin, L. Q., Loo, B. R. Y., Liu, S., Koh, H. L., Poh, X. W. W., Fung, D., Guan, C., Lee, T. S., Lim, C. G., & Zhou, J. (2019). Large-scale brain functional network topology disruptions underlie symptom heterogeneity in children with attention-deficit/hyperactivity disorder. NeuroImage. Clinical, 21, 101600. https://doi.org/10.1016/j.nicl.2018.11.010
Qian X, et al. Large-scale Brain Functional Network Topology Disruptions Underlie Symptom Heterogeneity in Children With Attention-deficit/hyperactivity Disorder. Neuroimage Clin. 2019;21:101600. PubMed PMID: 30472167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Large-scale brain functional network topology disruptions underlie symptom heterogeneity in children with attention-deficit/hyperactivity disorder. AU - Qian,Xing, AU - Castellanos,Francisco Xavier, AU - Uddin,Lucina Q, AU - Loo,Beatrice Rui Yi, AU - Liu,Siwei, AU - Koh,Hui Li, AU - Poh,Xue Wei Wendy, AU - Fung,Daniel, AU - Guan,Cuntai, AU - Lee,Tih-Shih, AU - Lim,Choon Guan, AU - Zhou,Juan, Y1 - 2018/11/19/ PY - 2018/05/16/received PY - 2018/11/13/revised PY - 2018/11/16/accepted PY - 2018/11/26/pubmed PY - 2019/12/27/medline PY - 2018/11/26/entrez KW - Attention-deficit/hyperactivity disorder KW - Functional connectivity KW - Heterogeneity KW - Modularity SP - 101600 EP - 101600 JF - NeuroImage. Clinical JO - Neuroimage Clin VL - 21 N2 - 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. SN - 2213-1582 UR - https://www.unboundmedicine.com/medline/citation/30472167/Large_scale_brain_functional_network_topology_disruptions_underlie_symptom_heterogeneity_in_children_with_attention_deficit/hyperactivity_disorder_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-1582(18)30348-6 DB - PRIME DP - Unbound Medicine ER -