White Matter Microstructural Alterations in Autism Localized with Bundle Analytics

ABSTRACT Previous diffusion magnetic resonance imaging research in autism has reported altered microstructure in the corpus callosum (CC), the major commissure connecting the two brain hemispheres. However, the CC consists of many fibers connecting various brain regions, and the precise localization of these differences in autism remains unclear. Additionally, the conventional diffusion tensor imaging (DTI) model cannot resolve complex fiber configurations and may miss subtle alterations. In this study, we investigated CC microstructure in 365 participants (5-25 years; 34.0% female; 195 with autism) from 10 sites/scanners by using a novel along-tract mapping method, BUndle ANalytics (BUAN), and advanced microstructure model, the tensor distribution function (TDF). Autism was associated with regionally specific reductions in white matter integrity and elevations in diffusivity. The TDF model detected CC microstructure differences more sensitively than DTI. Taken together, BUAN and TDF allow for precise and rigorous white matter analyses, enhancing the detection of subtle neural differences.