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Background Younger siblings of children with autism spectrum disorder (ASD) are themselves at increased risk for ASD and other developmental concerns. It is unclear if infants who display developmental concerns, but are unaffected by ASD, share similar or dissimilar behavioral and brain phenotypes to infants with ASD. Most individuals with ASD exhibit heterogeneous difficulties with language, and their receptive-expressive language profiles are often atypical. Yet, little is known about the neurobiology that contributes to these language difficulties. Methods In this study, we used behavioral assessments and structural magnetic resonance imaging to investigate early brain structure and associations with later language skills. High-risk infants who were later diagnosed with ASD (n = 86) were compared to high-risk infants who showed signs of early language delay (n = 41), and high- and low-risk infants who did not have ASD or language delay (n= 255, n = 143, respectively). Results Results indicated that diminished language skills were evident at 12-months in infants with ASD and infants with early language delay. At 24-months of age, only the ASD infants displayed atypical receptive-expressive language profiles. Associations between 12-month subcortical volumes and 24-month language skills were moderated by group status, indicating disordinal brain-behavior associations among ASD infants and language delay infants. Conclusions These results suggest that there are different brain mechanisms influencing language development in ASD and language delay infants, and that the two groups likely experience unique sets of genetic and environmental risk factors.

The social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist [11C]raclopride, voxel-wise binding potential (BPND) was compared between groups (controls = 12, ASD = 10) in the striatum. Striatal clusters showing significant between-group BPND differences were used as seeds in whole-brain fMRI general functional connectivity analyses. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system.

We propose that predicting the response to balance perturbations in older fallers, at least that measured using local dynamic stability, likely requires measuring that response directly.

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