Functional Connectivity of Frontoparietal and Salience/Ventral Attention Networks Have Independent Associations With Co-occurring Attention-Deficit/Hyperactivity Disorder Symptoms in Children With Autism

Background: Children with autism spectrum disorder (ASD) and co-occurring attention-deficit/hyperactivity disorder (ADHD) symptoms have worse functional outcomes and treatment response than those without ADHD symptoms. There is limited knowledge of the neurobiology of ADHD symptoms in ASD. Here, we test the hypothesis that aberrant functional connectivity of two large-scale executive brain networks implicated in ADHD-the frontoparietal and salience/ventral attention networks-also play a role in ADHD symptoms in ASD.

Methods: We compared resting-state functional connectivity of the two executive brain networks in children with ASD (n = 77) and typically developing control children (n = 82). These two executive brain networks comprise five subnetworks (three frontoparietal, two salience/ventral attention). After identifying aberrant functional connections among subnetworks, we examined dimensional associations with parent-reported ADHD symptoms.

Results: Weaker functional connectivity in ASD was present within and between the frontoparietal and salience/ventral attention subnetworks. Decreased functional connectivity within a single salience/ventral attention subnetwork, as well as between two frontoparietal subnetworks, significantly correlated with ADHD symptoms. Furthermore, follow-up linear regressions demonstrated that the salience/ventral attention and frontoparietal subnetworks explain unique variance in ADHD symptoms. These executive brain network-ADHD symptom relationships remained significant after controlling for ASD symptoms. Finally, specificity was also demonstrated through the use of a control brain network (visual) and a control co-occurring symptom domain (anxiety).

Conclusions: The present findings provide novel evidence that both frontoparietal and salience/ventral attention networks' weaker connectivities are linked to ADHD symptoms in ASD. Moreover, co-occurring ADHD in the context of ASD is a source of meaningful neural heterogeneity in ASD.