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

Abstract

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.

Cognitive and behavioural flexibility: neural mechanisms and clinical considerations

“…Data-driven techniques are now being used to identify key dimensions of functioning that overlap across diagnostic categories and also present heterogeneously within diagnostic categories 81 . For example, transdiagnostic executive function subtypes have been identified with use of community detection algorithms, and children within the subtype characterized by inflexibility showed a failure to modulate parietal lobe activation in response to increasing executive task demands 82 . Other work examining ASD, ADHD and co-morbid ASD and ADHD using latent profile analysis also provides evidence for transdiagnostic executive function classes 65 .…”

Executive Functions in Neurodevelopmental Disorders: Comorbidity Overlaps Between Attention Deficit and Hyperactivity Disorder and Specific Learning Disorders

“…Although the neuropsychological profile of ADHD is heterogeneous, numerous studies indicate that it involves impairments in various executive function (EF) domains (Barkley et al, 1992 ; Pennington and Ozonoff, 1996 ; Sergeant et al, 2002 ). Reported findings are hardly conclusive, however, since the mean effect sizes range from small to moderate for EF measures, and not all children with ADHD show EF deficits (Willcutt et al, 2005 ), which can also be seen in typically-developing (TD) children (Vaidya et al, 2020 ), suggesting that none of these EF deficits is a necessary or sufficient explanation for the ADHD profile (Willcutt et al, 2003 ).…”

The Effect of Comorbid with Attention-Deficit/Hyperactivity Disorder Symptoms on Face Encoding and Retrieving in Children with Autism Spectrum Disorder

“…For example, the experience of short-term VSWM in ASD showed that the reducing efficiency of process was associated with the deficit of planning [30]. Importantly, ASD and ADHD may have overlap but distinct characteristics in the domain of EF [31,32]. Moreover, varying subtypes of EF could contribute to distinguish and better understand the cognitive characteristics [12,33].…”