Axonal deficits in young adults with High Functioning Autism and their impact on processing speed

• White matter microstructure is altered in young adults with High Functioning Autism.
• We report decreased Axonal Water Fraction and intra-axonal diffusivity.
• Changes in these DKI metrics are consistent with axonal deficits.
• Alterations in axonal diffusion metrics correlate with reduced processing speed.
• DKI may yield promising biomarkers for autism diagnosis and characterization.

Microstructural white matter deficits in Autism Spectrum Disorders (ASD) have been suggested by both histological findings and Diffusion Tensor Imaging (DTI) studies, which show reduced fractional anisotropy (FA) and increased mean diffusivity (MD). However, imaging reports are generally not consistent across studies and the underlying physiological causes of the reported differences in FA and MD remain poorly understood. In this study, we sought to further characterize white matter deficits in ASD by employing an advanced diffusion imaging method, the Diffusional Kurtosis Imaging (DKI), and a two-compartment diffusion model of white matter. This model differentially describes intra- and extra-axonal white matter compartments using Axonal Water Fraction (faxon) a measure reflecting axonal caliber and density, and compartment-specific diffusivity measures. Diagnostic utility of these measures and associations with processing speed performance were also examined. Comparative studies were conducted in 16 young male adults with High Functioning Autism (HFA) and 17 typically developing control participants (TDC). Significantly decreased faxon was observed in HFA compared to the control group in most of the major white matter tracts, including the corpus callosum, cortico-spinal tracts, and superior longitudinal, inferior longitudinal and inferior fronto-occipital fasciculi. Intra-axonal diffusivity (Daxon) was also found to be reduced in some of these regions. Decreased axial extra-axonal diffusivity (ADextra) was noted in the genu of the corpus callosum. Reduced processing speed significantly correlated with decreased faxon and Daxon in several tracts. faxon of the left cortico-spinal tract and superior longitudinal fasciculi showed good accuracy in discriminating the HFA and TDC groups. In conclusion, these findings suggest altered axonal microstructure in young adults with HFA which is associated with reduced processing speed. Compartment-specific diffusion metrics appear to improve specificity and sensitivity to white matter deficits in this population.