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

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
JournalNeuroImage: Clinical
DOIs
StateAccepted/In press - Jan 1 2018

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Attention Deficit Disorder with Hyperactivity
Brain
Executive Function
Checklist

Keywords

  • Attention-deficit/hyperactivity disorder
  • Functional connectivity
  • Heterogeneity
  • Modularity

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Large-scale brain functional network topology disruptions underlie symptom heterogeneity in children with attention-deficit/hyperactivity disorder. / Qian, Xing; Castellanos, Francisco Xavier; Uddin, Lucina Q; Loo, Beatrice Rui Yi; Liu, Siwei; Koh, Hui Li; Poh, Xue Wei Wendy; Fung, Daniel; Guan, Cuntai; Lee, Tih Shih; Lim, Choon Guan; Zhou, Juan.

In: NeuroImage: Clinical, 01.01.2018.

Research output: Contribution to journalArticle

Qian, Xing ; Castellanos, Francisco Xavier ; Uddin, Lucina Q ; Loo, Beatrice Rui Yi ; Liu, Siwei ; Koh, Hui Li ; Poh, Xue Wei Wendy ; Fung, Daniel ; Guan, Cuntai ; Lee, Tih Shih ; Lim, Choon Guan ; Zhou, Juan. / Large-scale brain functional network topology disruptions underlie symptom heterogeneity in children with attention-deficit/hyperactivity disorder. In: NeuroImage: Clinical. 2018.
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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.",
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