Characterizing intrinsic functional connectivity in relation to impaired self-regulation in intellectually able male youth with autism spectrum disorder

Abstract

While a considerable number of youth with autism spectrum disorder exhibit impaired self-regulation (dysregulation), little is known about the neural correlates of dysregulation in autism spectrum disorder. In a sample of intellectually able boys with autism spectrum disorder (further categorized as those with and without dysregulation) and typically developing boys (aged 7–17 years), we conducted a multivariate connectome-wide association study to examine the intrinsic functional connectivity with resting-state functional magnetic resonance imaging. Dysregulation was defined by the sum of Attention, Aggression, and Anxiety/Depression subscales on the Child Behavior Checklist. We identified that both categorical and dimensional neural correlates of dysregulation in youth with autism spectrum disorder involved atypical connectivity among the components of multiple brain networks, especially between those subserving sensorimotor processing and salience encoding, beyond higher-level cognitive control circuitries. Interaction within the attention network might serve as autism spectrum disorder–specific neural correlates underpinning dysregulation. Our results highlight that the inter-individual variability in dysregulation might contribute to the inconsistency in the neuroimaging literature of autism spectrum disorder. Collectively, the present findings provide evidence to suggest that dysregulation might be considered as both categorical and dimensional moderators to parse heterogeneity of autism spectrum disorder.

Lay Abstract

Impaired self-regulation (i.e., dysregulation in affective, behavioral, and cognitive control), is commonly present in young people with autism spectrum disorder (ASD). However, little is known about what is happening in people’s brains when self-regulation is impaired in young people with ASD. We used a technique called functional MRI (which measures brain activity by detecting changes associated with blood flow) at a resting state (when participants are not asked to do anything) to research this in intellectually able young people with ASD. We found that brains with more connections, especially between regions involved in sensorimotor processing and regions involved in the processes that enable peoples to focus their attention on the most pertinent features from the sensory environment (salience processing), were related to more impaired self-regulation in young people with and without ASD. We also found that impaired self-regulation was related to increased communication within the brain system involved in voluntary orienting attention to a sensory cue (the dorsal attention network) in young people with ASD. These results highlight how different people have different degrees of dysregulation, which has been largely overlooked in the earlier brain imaging reports on ASD. This might contribute to understanding some of the inconsistencies in the existing published literature on this topic.