Connectivity-Based Brain Network Supports Restricted and Repetitive Behaviors in Autism Spectrum Disorder Across Development.

ABSTRACT

Introduction: Autism spectrum disorder (ASD) is a lifelong condition. Autistic symptoms can persist into adulthood. Studies have reported that autistic symptoms generally improved in adulthood, especially restricted and repetitive behaviors and interests (RRBIs). We explored brain networks that are related to differences in RRBIs in individuals with ASDs among different ages. Methods: We enrolled 147 ASD patients from the Autism Brain Imaging Data Exchange II (ABIDEII) database. The participants were divided into four age groups children (6-9 years old), younger adolescents (10-14 years old), older adolescents (15-19 years old), and adults (≥20 years old). RRBIs were evaluated using the Repetitive Behaviors Scale-Revised 6. We first explored differences in RRBIs between age groups using the Kruskal-Wallis test. Associations between improvements in RRBIs and age were analyzed using a general linear model. We then analyzed RRBIs associated functional connectivity (FC) links using the network-based statistic method by adjusting covariates. The association of the identified FC with age group, and mediation function of the FC on the association of age-group and RRBI were further analyzed. Results: Most subtypes of RRBIs improved with age, especially stereotyped behaviors, ritualistic behaviors, and restricted behaviors (p = 0.012, 0.014, and 0.012, respectively). Results showed that 12 FC links were closely related to overall RRBIs, 17 FC links were related to stereotyped behaviors. Among the identified 29 FC links, 15 were negatively related to age-groups. The mostly reported core brain regions included superior occipital gyrus, insula, rolandic operculum, angular, caudate, and cingulum. The decrease in FC between the left superior occipital lobe and right angular (effect = -0.125 and -0.693, respectively) and between the left insula and left caudate (effect = -0.116 and -0.664, respectively) might contribute to improvements in multiple RRBIs with age. Conclusion: We identified improvements in RRBIs with age in ASD patients, especially stereotyped behaviors, ritualistic behaviors, and restricted behaviors. The decrease in FC between left superior occipital lobe and right angular and between left insula and left caudate might contribute to these improvements. Our findings improve our understanding of the pathogenesis of RRBIs and suggest potential intervention targets to improve prognosis in adulthood.