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

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, cognitive flexibility, in children with a range of abilities (N=132; children with autism spectrum disorder [ASD], attention deficit/hyperactivity disorder [ADHD], and typically developing [TD] children) using directed functional connectivity profiles derived from resting-state fMRI data. Brain regions activated in response to a cognitive flexibility task in adults were used to guide region-of-interest (ROI) 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 executive function 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.