Default mode hypoconnectivity underlies a sex-related autism spectrum.

Abstract

Background Females and males differ significantly in the prevalence and presentation of autism spectrum conditions. One theory of this effect postulates that autistic traits lie on a sex-related continuum in the general population, and autism represents the extreme male end of this spectrum. This theory predicts that any feature of autism in males should 1) be present in autistic females, 2) differentiate between the sexes in the typical population and 3) correlate with autistic traits. Here we tested these three predictions for default mode network (DMN) hypoconnectivity during resting state, one of the most robustly found neurobiological differences in autism. Methods We analyzed a primary dataset of adolescents (n=121, 12-18 years) containing a relatively large number of females, and a replication multisite dataset including children, adolescents and adults (n=980, 6-58 years). We quantified the average connectivity between DMN regions, and tested for group differences and correlation with behavioral performance using robust regression. Results We found significant differences in DMN intra-connectivity 1) between female controls and females with autism (p = .001, primary dataset; p = .009, replication dataset), and 2) between female controls and male controls (p = .036, primary dataset; p = .002, replication dataset). We additionally found 3) a significant correlation between DMN intra-connectivity and performance on a mentalizing task (p = .001) in the primary dataset. Conclusions Collectively, these findings provide the first evidence for DMN hypoconnectivity as a behaviorally relevant, neuroimaging phenotype of the sex-related spectrum of autistic traits, of which autism represents the extreme case.