An investigation of age-related neuropathophysiology in autism spectrum disorder using fixel-based analysis of corpus callosum white matter micro- and macrostructure

Background Corpus callosum anomalies are commonly noted in autism spectrum disorder (ASD). Given the complexity of its microstructural architecture, with crossing fibers projecting throughout, we applied fixel-based analysis to probe white matter micro- and macrostructure within this region. As ASD is a neurodevelopmental condition with noted abnormalities in brain growth, age was also investigated. Methods Data for participants with (N=54) and without (N=50) ASD, aged 5-34 years, were obtained from the Autism Brain Imaging Data Exchange-II (ABIDE-II). Within each site, indices of fiber density (FD), fiber cross-section (FC), and combined fiber density and cross-section (FDC) were compared between those groups. Results Young adolescents with ASD (age = 11.19 ± 7.54) showed reduced macroscopic FC and FDC compared to age-matched neurotypical controls (age = 10.04 ± 4.40). Reduced FD and FDC was noted in a marginally older ASD (age 13.87 ± 3.15) cohort compared to matched controls (age = 13.85 ± 2.90). Among the oldest cohorts, a non-significant trend indicated reduced FD in older adolescents/young adults with ASD (age = 17.07 ± 3.56) compared to controls (age = 16.55 ± 2.95). There was a positive correlation between age and callosal mean FC and FDC in the youngest cohort. When stratified by diagnosis, this finding remained only for the ASD sample. Conclusion White matter aberration appears greatest among younger ASD cohorts. In older adolescents and young adults, less of the corpus callosum seems affected. This supports the suggestion that some early neuropathophysiological indicators in ASD may dissipate with age.