A prospective evaluation of infant cerebellar-cerebral functional connectivity in relation to behavioral development in autism

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TitleA prospective evaluation of infant cerebellar-cerebral functional connectivity in relation to behavioral development in autism
Publication TypeJournal Article
Year of Publication2021
AuthorsHawks, ZW, Todorov, A, Marrus, N, Nishino, T, Talovic, M, Nebel, MBeth, Girault, JB, Davis, S, Marek, S, Seitzman, BA, Eggebrecht, AT, Elison, J, Dager, S, Mosconi, MW, Tychsen, L, Snyder, AZ, Botteron, K, Estes, A, Evans, A, Gerig, G, Hazlett, HC, McKinstry, RC, Pandey, J, Schultz, R, Styner, M, Wolff, JJ, Zwaigenbaum, L, Markson, L, Petersen, SE, Constantino, JN, White, DA, Piven, J, Pruett, J
JournalBiological Psychiatry Global Open Science
KeywordsAutism, Cerebellum, development, error-based learning, functional connectivity, infancy

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed based on social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar pathology contributes causally to ASD by disrupting error-based learning (EBL) during infancy. The present study represents the first test of this theory in a prospective infant sample, with potential implications for ASD detection. Methods Data from the Infant Brain Imaging Study (n=94, 68 male) were used to examine 6-month cerebellar functional connectivity (fcMRI) in relation to later (12/24-month) ASD-associated behaviors and outcomes. Hypothesis-driven univariate analyses and machine learning-based predictive tests examined cerebellar-frontoparietal (FPN; subserves error signaling in support of EBL) and cerebellar-default mode (DMN; broadly implicated in ASD) network connections. Cerebellar-FPN functional connectivity was used as a proxy for EBL, and cerebellar-DMN functional connectivity provided a comparative foil. Data-driven fcMRI enrichment examined brain-wide behavioral associations, with post-hoc tests of cerebellar connections. Results Cerebellar-FPN and cerebellar-DMN connections did not demonstrate associations with ASD. fcMRI enrichment identified 6-month correlates of later ASD-associated behaviors in networks of a priori interest (FPN, DMN), as well as in cingulo-opercular (also implicated in error signaling) and medial visual networks. Post-hoc tests did not suggest a role for cerebellar connections. Conclusions We failed to identify cerebellar functional connectivity-based contributions to ASD. However, we observed prospective correlates of ASD-associated behaviors in networks that support EBL. Future studies may replicate and extend network-level positive results, and tests of the cerebellum may investigate brain-behavior associations at different developmental stages and/or using different neuroimaging modalities.