A Longitudinal Study of White Matter Development in Relation to Changes in Autism Severity Across Early Childhood

Abstract Background Cross-sectional diffusion-weighted MRI studies suggest that young autistic children have alterations in white matter structure that differ from older autistic individuals. However, it is unclear if these differences result from atypical neurodevelopment or sampling differences between young and older cohorts. Furthermore, the relationship between altered white matter development and longitudinal changes in autism symptoms is unknown. Methods Using longitudinal diffusion-weighted MRI acquired over 2-3 timepoints between the ages of approximately 2.5-7 years in 125 children with autism and 69 typically developing controls, we directly tested the hypothesis that individuals with autism have atypical white matter development across childhood. Additionally, we sought to determine whether changes in white matter diffusion parameters were associated with longitudinal changes in autism severity. Results Children with autism were found to have slower development of fractional anisotropy (FA) in the cingulum bundle, superior longitudinal fasciculus, internal capsule, and splenium of the corpus callosum. Furthermore, in the sagittal stratum, autistic individuals who increased in severity over time had a slower developmental trajectory of FA compared to individuals who decreased in severity. In the uncinate fasciculus individuals who decreased in severity also had greater increases in FA with age. Conclusions These longitudinal findings indicate that previously reported differences in diffusion-weighted MRI measures between younger and older autism cohorts are attributable to an atypical developmental trajectory of white matter. Differences in white matter development between individuals who increased, remained stable, or decreased in autism severity suggest that these functional differences are associated with fiber development in the autistic brain.