Functional and Anatomical Substrates of Cognitive Abilities in Autism Spectrum Disorder

Neuroimaging research on Autism Spectrum Disorder (ASD) includes predominantly individuals with higher cognitive abilities (HCA), despite high prevalence of Lower Cognitive Abilities (LCA) in ASD, diminishing ecological validity of prior research. We aimed to increase understanding of brain-behavior relationships associated with cognitive abilities (CA) and earlier developmental abilities preceding CA, in children and adolescents with ASD. Study 1 contrasted resting-state functional connectivity (FC) in children with and without ASD (6-15 years) in LCA and HCA subsamples. Participants with ASD+LCA showed decreased FC between pericalcarine visual cortex (VC) and posterior superior temporal sulcus (pSTS), bilaterally, compared to ASD+HCA peers. Study 2 investigated relationships between cognitive developmental abilities and FC of VC in toddlers and preschoolers (18-55 months) with and without ASD, searching for earlier signs of atypical brain-behavior relationships involving VC in ASD. Independent component analysis of resting-state fMRI scans (collected during natural sleep) was used to generate bias-free VC seeds for FC analyses. A strong positive relationship between VC FC (with pSTS) and cognitive developmental abilities observed in typically developing (TD) children was absent in the ASD group, and VC FC was inversely related to ASD symptom severity. Study 3 tested for atypical relationships between VC neuroanatomy and CA in ASD. Using anatomical MRI scans from ASD and TD children (7-18 years), we derived surface area, cortical thickness, and local gyrification index in four occipital VC regions. An atypical relationship between CA and left lingual gyrus cortical thickness was observed in the ASD group. There were no significant ASD-TD group differences in VC anatomical measures after multiple-comparison correction, however, group-difference effect-sizes were markedly larger in LCA subsamples when participants were stratified by IQ. Overall, findings provide evidence that VC anatomy and VC FC (with regions involved in multisensory integration) are atypically related to CA in children and adolescents with ASD. Moreover, atypical relationships between VC FC and cognitive developmental abilities in autism can be detected as early as the first years of life. Including participants with LCA in neuroimaging research, despite difficulties collecting MRI data in this population, is critical to improving insight into brain structure and functioning in ASD