Altered patterns of brain dynamics linked with body mass index in youth with autism.

Children with autism spectrum disorder (ASD) have higher rates of overweight and obesity (OWOB) compared with typically developing (TD) children. Brain functional connectivity differences have been shown in both ASD and OWOB. However, only one study to date has examined ASD and OWOB concurrently, so little is known regarding the neural mechanisms associated with the higher prevalence of OWOB and its behavioral impacts in ASD. We investigated co-activation patterns (CAPs) of brain regions identified by independent component analysis in 129 children and adolescents between 6 and 18 years of age (n = 68 ASD). We examined the interaction between body mass index (BMI) and diagnosis in predicting dynamic brain metrics (dwell time, DT; frequency of occurrence, and transitions between states) as well as dimensional brain-behavior relationships. The relationship between BMI and brain dynamics was moderated by diagnosis (ASD, TD), particularly among the frequency of CAP 4, characterized by co-activation of lateral frontoparietal, temporal, and frontal networks. This pattern was negatively associated with parent-reported inhibition skills. Children with ASD had shorter CAP 1, characterized by co-activation of the subcortical, temporal, sensorimotor, and frontal networks, and CAP 4 DTs compared with TD children. CAP 1 DT was negatively associated with cognitive flexibility, inhibition, social functioning, and BMI. Cognitive flexibility moderated the relationship between BMI and brain dynamics in the visual network. Our findings provide novel evidence of neural mechanisms associated with OWOB in children with ASD. Further, poorer cognitive flexibility may result in increased vulnerability for children with ASD and co-occurring OWOB. LAY SUMMARY: Obesity is a societal epidemic and is common in autism, however, little is known about the neural mechanisms associated with the higher rates of obesity in autism. Here, we find unique patterns of brain dynamics associated with obesity in autism that were not observed in typically developing children. Further, the relationship between body mass index and brain dynamics depended on cognitive flexibility. These findings suggest that individuals with autism may be more vulnerable to the effects of obesity on brain function. Autism Res 2021, 14: 873-886. © 2021 International Society for Autism Research, Wiley Periodicals LLC.