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


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.

SUBMITTER: Hawks ZW 

PROVIDER: S-EPMC9874081 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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

Hawks Zoë W ZW   Todorov Alexandre A   Marrus Natasha N   Nishino Tomoyuki T   Talovic Muhamed M   Nebel Mary Beth MB   Girault Jessica B JB   Davis Savannah S   Marek Scott S   Seitzman Benjamin A BA   Eggebrecht Adam T AT   Elison Jed J   Dager Stephen S   Mosconi Matthew W MW   Tychsen Lawrence L   Snyder Abraham Z AZ   Botteron Kelly K   Estes Annette A   Evans Alan A   Gerig Guido G   Hazlett Heather C HC   McKinstry Robert C RC   Pandey Juhi J   Schultz Robert T RT   Styner Martin M   Wolff Jason J JJ   Zwaigenbaum Lonnie L   Markson Lori L   Petersen Steven E SE   Constantino John N JN   White Desirée A DA   Piven Joseph J   Pruett John R JR  

Biological psychiatry global open science 20211216 1


<h4>Background</h4>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.<h4>Methods</h4>Data from the Infant Brain Imaging Stud  ...[more]

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