Flexible nonlinear modeling reveals age-related differences in resting-state functional brain connectivity in autistic males from childhood to mid-adulthood.

Publication date: Apr 15, 2025

Divergent age-related functional brain connectivity in autism spectrum disorder (ASD) has been observed using resting-state fMRI, although the specific findings are inconsistent across studies. Common statistical regression approaches that fit identical models across functional brain networks may contribute to these inconsistencies. Relationships among functional networks have been reported to follow unique nonlinear developmental trajectories, suggesting the need for flexible modeling. Here we apply generalized additive models (GAMs) to flexibly adapt to distinct network trajectories and simultaneously describe divergent age-related changes from childhood into mid-adulthood in ASD. 1107 males, aged 5-40, from the ABIDE I & II cross-sectional datasets were analyzed. Functional connectivity was extracted using a network-based template. Connectivity values were harmonized using COMBAT-GAM. Connectivity-age relationships were assessed with thin-plate spline GAMs. Post-hoc analyses defined the age-ranges of divergent aging in ASD. Typically developing (TD) and ASD groups shared 15 brain connections that significantly changed with age (FDR-corrected p 

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Concepts Keywords
Autism Age-related
Males Autism
Nonlinear Cross-sectional
Td fMRI
Functional connectivity
Generalized additive model

Semantics

Type Source Name
disease MESH autism spectrum disorder
pathway REACTOME Reproduction
disease MESH Autism
drug DRUGBANK Esomeprazole
drug DRUGBANK Factor IX Complex (Human)
drug DRUGBANK Oxygen
drug DRUGBANK Ademetionine
pathway REACTOME Release
drug DRUGBANK Gold
drug DRUGBANK Indoleacetic acid
drug DRUGBANK D-Alanine
drug DRUGBANK Coenzyme M
disease MESH tic
drug DRUGBANK Alpha-Linolenic Acid
disease MESH abnormalities
drug DRUGBANK Guanosine
drug DRUGBANK Zolmitriptan
drug DRUGBANK Serine
disease MESH psychosis
disease MESH uncertainty
disease MESH anxiety
disease MESH Attention Deficit Hyperactivity disorder

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