Data‐driven identification of subtypes of executive function across typical development, attention deficit hyperactivity disorder, and autism spectrum disorders

Background Impairment of executive function (EF), the goal‐directed regulation of thoughts, actions, and emotions, drives negative outcomes and is common across neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). A primary challe...

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Published in:	Journal of child psychology and psychiatry Vol. 61; no. 1; pp. 51 - 61
Main Authors:	Vaidya, Chandan J., You, Xiaozhen, Mostofsky, Stewart, Pereira, Francisco, Berl, Madison M., Kenworthy, Lauren
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01.01.2020
Subjects:	Adolescent Adolescent Development - physiology Attention Deficit Disorder with Hyperactivity - complications Attention Deficit Disorder with Hyperactivity - diagnostic imaging Attention Deficit Disorder with Hyperactivity - physiopathology Attention deficit hyperactivity disorder Autism Autism Spectrum Disorder - complications Autism Spectrum Disorder - diagnostic imaging Autism Spectrum Disorder - physiopathology Autism Spectrum Disorders Child Child & adolescent psychiatry Child Development - physiology Children Classification Clinical decision making Cognitive Dysfunction - classification Cognitive Dysfunction - diagnostic imaging Cognitive Dysfunction - etiology Cognitive Dysfunction - physiopathology Cohort Studies Developmental disabilities Discovery Disorders Emotional regulation Emotional Regulation - classification Emotional Regulation - physiology Emotions Executive function Executive Function - classification Executive Function - physiology Female Flexibility Functional magnetic resonance imaging functional MRI (fMRI) Functional Neuroimaging - standards Humans individual differences Individuality Inhibition, Psychological Machine Learning Magnetic Resonance Imaging Male Medical decision making Medical diagnosis Membership Memory, Short-Term - physiology Neurobiology Neurodevelopmental disorders Parsing Planners Public use Reproducibility Reproducibility of Results Short term memory Strength Subtypes Validity autism spectrum disorders functional MRI (fMRI) machine learning Attention deficit hyperactivity disorder individual differences
ISSN:	0021-9630, 1469-7610, 1469-7610
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Summary:	Background Impairment of executive function (EF), the goal‐directed regulation of thoughts, actions, and emotions, drives negative outcomes and is common across neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). A primary challenge to its amelioration is heterogeneity in symptom expression within and across disorders. Parsing this heterogeneity is necessary to attain diagnostic precision, a goal of the NIMH Research Domain Criteria Initiative. We aimed to identify transdiagnostic subtypes of EF that span the normal to impaired spectrum and establish their predictive and neurobiological validity. Methods Community detection was applied to clinical parent‐report measures in 8–14‐year‐old children with and without ADHD and ASD from two independent cohorts (discovery N = 320; replication N = 692) to identify subgroups with distinct behavioral profiles. Support vector machine (SVM) classification was used to predict subgroup membership of unseen cases. Preliminary neurobiological validation was obtained with existing functional magnetic resonance imaging (fMRI) data on a subsample (N = 84) by testing hypotheses about sensitivity of EF subgroups versus DSM categories. Results We observed three transdiagnostic EF subtypes characterized by behavioral profiles that were defined by relative weakness in: (a) flexibility and emotion regulation; (b) inhibition; and (c) working memory, organization, and planning. The same tripartite structure was also present in the typically developing children. SVM trained on the discovery sample and tested on the replication sample classified subgroup membership with 77.0% accuracy. Split‐half SVM classification on the combined sample (N = 1,012) yielded 88.9% accuracy (this SVM is available for public use). As hypothesized, frontal‐parietal engagement was better distinguished by EF subtype than DSM diagnosis and the subgroup characterized with inflexibility failed to modulate right IPL activation in response to increased executive demands. Conclusions The observed transdiagnostic subtypes refine current diagnostic nosology and augment clinical decision‐making for personalizing treatment of executive dysfunction in children.
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ISSN:	0021-9630 1469-7610 1469-7610
DOI:	10.1111/jcpp.13114