A Prospective Evaluation of Infant Cerebellar-Cerebral Functional Connectivity in Relation to Behavioral Development in Autism Spectrum Disorder

IBIS Network, Zoë W. Hawks, Alexandre Todorov, Natasha Marrus, Tomoyuki Nishino, Muhamed Talovic, Mary Beth Nebel, Jessica B. Girault, Savannah Davis, Scott Marek, Benjamin A. Seitzman, Adam T. Eggebrecht, Jed Elison, Stephen Dager, Matthew W. Mosconi, Lawrence Tychsen, Abraham Z. Snyder, Kelly Botteron, Annette Estes, Alan EvansGuido Gerig, Heather C. Hazlett, Robert C. McKinstry, Juhi Pandey, Robert T. Schultz, Martin Styner, Jason J. Wolff, Lonnie Zwaigenbaum, Lori Markson, Steven E. Petersen, John N. Constantino, Desirée A. White, Joseph Piven, John R. Pruett

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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 magnetic resonance imaging 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 network (FPN; subserves error signaling in support of EBL) and cerebellar–default mode network (DMN; broadly implicated in ASD) connections. Cerebellar-FPN functional connectivity was used as a proxy for EBL, and cerebellar-DMN functional connectivity provided a comparative foil. Data-driven functional connectivity magnetic resonance imaging 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. Functional connectivity magnetic resonance imaging 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.

Original languageEnglish
Pages (from-to)149-161
Number of pages13
JournalBiological Psychiatry Global Open Science
Volume3
Issue number1
DOIs
StatePublished - Jan 2023

Keywords

  • Autism
  • Cerebellum
  • Development
  • Error-based learning
  • Functional connectivity
  • Infancy

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