RESUMO
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by lack of attention to social cues in the environment, including speech. Hypersensitivity to sensory stimuli, such as loud noises, is also extremely common in youth with ASD. While a link between sensory hypersensitivity and impaired social functioning has been hypothesized, very little is known about the neural mechanisms whereby exposure to distracting sensory stimuli may interfere with the ability to direct attention to socially-relevant information. Here, we used functional magnetic resonance imaging (fMRI) in youth with and without ASD (N=54, age range 8-18 years) to (1) examine brain responses during presentation of brief social interactions (i.e., two-people conversations) shrouded in ecologically-valid environmental noises, and (2) assess how brain activity during encoding might relate to later accuracy in identifying what was heard. During exposure to conversation-in-noise (vs. conversation or noise alone), both neurotypical youth and youth with ASD showed robust activation of canonical language networks. However, the extent to which youth with ASD activated temporal language regions, including voice-selective cortex (i.e., posterior superior temporal sulcus), predicted later discriminative accuracy in identifying what was heard. Further, relative to neurotypical youth, ASD youth showed significantly greater activity in left-hemisphere speech-processing cortex (i.e., angular gyrus) while listening to conversation-in-noise (vs. conversation or noise alone). Notably, in youth with ASD, increased activity in this region was associated with higher social motivation and better social cognition measures. This heightened activity in voice-selective/speech-processing regions may serve as a compensatory mechanism allowing youth with ASD to hone in on the conversations they heard in the context of non-social distracting stimuli. These findings further suggest that focusing on social and non-social stimuli simultaneously may be more challenging for youth with ASD requiring the recruitment of additional neural resources to encode socially-relevant information.
RESUMO
Autism spectrum disorder (ASD) is more prevalent in males than in females, but the neurobiological mechanisms that give rise to this sex-bias are poorly understood. The female protective hypothesis suggests that the manifestation of ASD in females requires higher cumulative genetic and environmental risk relative to males. Here, we test this hypothesis by assessing the additive impact of several ASD-associated OXTR variants on reward network resting-state functional connectivity in males and females with and without ASD, and explore how genotype, sex, and diagnosis relate to heterogeneity in neuroendophenotypes. Females with ASD who carried a greater number of ASD-associated risk alleles in the OXTR gene showed greater functional connectivity between the nucleus accumbens (NAcc; hub of the reward network) and subcortical brain areas important for motor learning. Relative to males with ASD, females with ASD and higher OXTR risk-allele-dosage showed increased connectivity between the NAcc, subcortical regions, and prefrontal brain areas involved in mentalizing. This increased connectivity between NAcc and prefrontal cortex mirrored the relationship between genetic risk and brain connectivity observed in neurotypical males showing that, under increased OXTR genetic risk load, females with ASD and neurotypical males displayed increased connectivity between reward-related brain regions and prefrontal cortex. These results indicate that females with ASD differentially modulate the effects of increased genetic risk on brain connectivity relative to males with ASD, providing new insights into the neurobiological mechanisms through which the female protective effect may manifest.