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.
Highlights
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are prevalent neurodevelopmental disorders most commonly diagnosed in the United States according to a symptom-based classification system, the Diagnostic and Statistical Manual of Mental Health Disorders 5 (DSM-5, American Psychiatric Association 2013)
Deficits in cognitive flexibility can occur in healthy children and adults without accompanying mental illness, but deficits are more prevalent in almost every psychiatric population, such as autism spectrum disorder, attention-deficit/hyperactivity disorder, conduct disorder, depression, obsessive-compulsive disorder, substance abuse and schizophrenia (Diamond and Lee 2011, McTeague, Goodkind et al 2016)
An alternative nosology based on neurobiologically homogeneous subgroups will aid in the ultimate goal to identify children who stand to benefit from targeted treatments specific to their brain network connectivity alterations (Cuthbert 2014)
Summary
Participants ages 8 to 13 years (N=132, Table 1) included a subset of children used in our previous study investigating heterogeneity in EF ability in TD, ADHD and ASD groups (Dajani, Llabre et al 2016). Subgroup-GIMME results using low motion sample The group-level model included AR effects for all ROIs, one lagged effect from the right pallidum to the right thalamus, and two contemporaneous effects: right pallidum right thalamus and lSPL rSPL (Figure 3) These paths were estimated for all 132 participants. We assumed a categorical structure would best parse heterogeneity in cognitive flexibility in children based on previous studies that identified subgroups present within ASD and ADHD diagnostic categories, which differed in functional connectivity and/or behavioral metrics. This study was one of the first to use functional connectome data estimated at the individual level for a heterogeneous group of children spanning TD, ASD, and ADHD diagnoses to test whether the neural substrates of EF and psychopathology follow a categorical or dimensional pattern. These results may suggest a dimensional model may better describe individual differences in the neural substrates of cognitive flexibility in children
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