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Altered Periodic Dynamics in the Default Mode Network in Autism and Attention-Deficit/Hyperactivity Disorder

  • Author Footnotes
    1 PC and JN contributed equally to this work as joint first authors.
    Paul Curtin
    Correspondence
    Address correspondence to Paul Curtin, Ph.D.
    Footnotes
    1 PC and JN contributed equally to this work as joint first authors.
    Affiliations
    Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Author Footnotes
    1 PC and JN contributed equally to this work as joint first authors.
    Janina Neufeld
    Footnotes
    1 PC and JN contributed equally to this work as joint first authors.
    Affiliations
    Center of Neurodevelopmental Disorders at Karolinska Institutet, Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska Institutet and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
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  • Austen Curtin
    Affiliations
    Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Manish Arora
    Affiliations
    Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Sven Bölte
    Affiliations
    Center of Neurodevelopmental Disorders at Karolinska Institutet, Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska Institutet and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden

    Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden

    Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Perth, Western Australia, Australia
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  • Author Footnotes
    1 PC and JN contributed equally to this work as joint first authors.

      Abstract

      Background

      Altered resting-state functional connectivity in the default mode network (DMN) is characteristic of both autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Standard analytical pipelines for resting-state functional connectivity focus on linear correlations in activation time courses between neural networks or regions of interest. These features may be insensitive to temporally lagged or nonlinear relationships.

      Methods

      In a twin cohort study comprising 292 children, including 52 with a diagnosis of ASD and 70 with a diagnosis of ADHD, we applied nonlinear analytical methods to characterize periodic dynamics in the DMN. Using recurrence quantification analysis and related methods, we measured the prevalence, duration, and complexity of periodic processes within and between DMN regions of interest. We constructed generalized estimating equations to compare these features between neurotypical children and children with ASD and/or ADHD while controlling for familial relationships, and we leveraged machine learning algorithms to construct models predictive of ASD or ADHD diagnosis.

      Results

      In within-pair analyses of twins with discordant ASD diagnoses, we found that DMN signal dynamics were significantly different in dizygotic twins but not in monozygotic twins. Considering our full sample, we found that these patterns allowed a robust predictive classification of both ASD (81.0% accuracy; area under the curve = 0.85) and ADHD (82% accuracy; area under the curve = 0.87) cases.

      Conclusions

      These findings indicate that synchronized periodicity among regions comprising the DMN relates both to neurotypical function and to ASD and/or ADHD, and they suggest generally that a dynamical analysis of network interconnectivity may be a useful methodology for future neuroimaging studies.

      Keywords

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      Linked Article

      • Can Chaos Bring Order to the Study of Functional Connectivity in Neurodevelopmental Disorders?
        Biological PsychiatryVol. 91Issue 11
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          The default mode network (DMN) is a system of brain regions that are mostly active at rest, consistently deactivated during attention-driven tasks, yet theorized to support many facets of socially relevant introspection (1). The ability to 1) contextualize one’s own memories by date and location (episodic memory), 2) plan and predict possible futures (prospection), and 3) differentiate one’s own mental states from those of others (theory of mind) are just three types of introspection that are key to successful socialization and supported by the DMN.
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