Mapping Along-Tract Commissural and Association White Matter Microstructural Differences in Autistic Children and Young Adults

Previous diffusion magnetic resonance imaging (dMRI) research has indicated altered white matter microstructure in autism, but the implicated regions are inconsistent across studies. Such prior work has largely used conventional dMRI analysis methods, including the traditional microstructure model, diffusion tensor imaging (DTI). However, these methods are limited in their ability to precisely map microstructural differences and accurately resolve complex fiber configurations. In our study, we investigated white matter microstructure alterations in autism using the refined along-tract analytic approach, BUndle ANalytics (BUAN), with both an advanced microstructure model, the tensor distribution function (TDF) and DTI. We analyzed dMRI data from 365 autistic and neurotypical participants (5-24 years; 34% female) from 10 cohorts to examine commissural and association tracts. Autism was associated with lower fractional anisotropy and higher diffusivity in localized portions of nearly every commissural and association tract examined; these tracts inter-connected a wide range of brain regions, including frontal, temporal, parietal, and occipital regions. Taken together, BUAN and TDF allow robust and spatially precise mapping of microstructural properties in autism. Our findings rigorously demonstrate that white matter microstructure alterations in autism may be greater within specific regions of individual tracts, and that the implicated tracts are distributed across the brain.