Parsing Heterogeneity in Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder with Individual Connectome Mapping

Dina R. Dajani, Catherine A. Burrows, Mary Beth Nebel, Stewart H. Mostofsky, Kathleen M. Gates, Lucina Q. Uddin

    Research output: Contribution to journalArticlepeer-review

    4 Scopus citations

    Abstract

    Traditional diagnostic systems for neurodevelopmental disorders define diagnostic categories that are heterogeneous in behavior and underlying neurobiological alterations. The goal of this study was to parse heterogeneity in a core executive function (EF), cognitive flexibility, in children with a range of abilities (N = 132; children with autism spectrum disorder, attention-deficit/hyperactivity disorder [ADHD], and typically developing children) using directed functional connectivity profiles derived from resting-state functional magnetic resonance imaging data. Brain regions activated in response to a cognitive flexibility task in adults were used to guide region-of-interest selection to estimate individual connectivity profiles in this study. We expected to find subgroups of children who differed in their network connectivity metrics and symptom measures. Unexpectedly, we did not find a stable or valid subgrouping solution, which suggests that categorical models of the neural substrates of cognitive flexibility in children may be invalid. Exploratory analyses revealed dimensional associations between network connectivity metrics and ADHD symptomatology and EF ability across the entire sample. Results shed light on the validity of conceptualizing the neural substrates of cognitive flexibility categorically in children. Ultimately, this work may provide a foundation for the development of a revised nosology focused on neurobiological substrates as an alternative to traditional symptom-based classification systems.

    Original languageEnglish (US)
    Pages (from-to)673-691
    Number of pages19
    JournalBrain connectivity
    Volume9
    Issue number9
    DOIs
    StatePublished - Nov 2019

    Bibliographical note

    Funding Information:
    This work was supported by the National Institute of Health (R01MH107549), the Canadian Institute for Advanced Research, and a University of Miami Gabelli Senior Scholar Award to L.Q.U. K.M.G. is supported by the National Institute of Health (R01EB022904). S.H.M. is supported by Autism Speaks and the National Institute of Health (R01NS048527, R01MH085328, R01MH078160, R01MH106564), the Johns Hopkins University School of Medicine Institute for Clinical and Translational Research, and NIH/NCRR CTSA Program, UL1-RR025005.

    Publisher Copyright:
    © Copyright 2019, Mary Ann Liebert, Inc., publishers 2019.

    Keywords

    • cognitive flexibility
    • executive function
    • functional connectivity
    • nosology

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