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.

BackgroundThe corpus callosum is implicated in the pathophysiology of autism spectrum disorder (ASD). However, specific structural deficits and underlying mechanisms are yet to be well defined.MethodsWe employed diffusional kurtosis imaging (DKI) metrics to characterize white matter properties within five discrete segments of the corpus callosum in 17 typically developing (TD) adults and 16 age-matched participants with ASD without co-occurring intellectual disability (ID). The DKI metrics included axonal water fraction (faxon) and intra-axonal diffusivity (Daxon), which reflect axonal density and caliber, and extra-axonal radial (RDextra) and axial (ADextra) diffusivities, which reflect myelination and microstructural organization of the extracellular space. The relationships between DKI metrics and processing speed, a cognitive feature known to be impaired in ASD, were also examined.ResultsASD group had significantly decreased callosal faxon and Daxon (p = .01 and p = .045), particularly in the midbody, isthmus, and splenium. Regression analysis showed that variation in DKI metrics, primarily in the mid and posterior callosal regions explained up to 70.7% of the variance in processing speed scores for TD (p = .001) but not for ASD (p > .05).ConclusionDecreased DKI metrics suggested that ASD may be associated with axonal deficits such as reduced axonal caliber and density in the corpus callosum, especially in the mid and posterior callosal areas. These data suggest that impaired interhemispheric connectivity may contribute to decreased processing speed in ASD participants.Electronic supplementary materialThe online version of this article (10.1186/s13229-018-0245-1) contains supplementary material, which is available to authorized users.

Prior ex vivo histological postmortem studies of autism spectrum disorder (ASD) have shown gray matter microstructural abnormalities, however, in vivo examination of gray matter microstructure in ASD has remained scarce due to the relative lack of non-invasive methods to assess it. The aim of this work was to evaluate the feasibility of employing diffusional kurtosis imaging (DKI) to describe gray matter abnormalities in ASD in vivo. DKI data were examined for 16 male participants with a diagnosis of ASD and IQ>80 and 17 age- and IQ-matched male typically developing (TD) young adults 18–25 years old. Mean (MK), axial (AK), radial (RK) kurtosis and mean diffusivity (MD) metrics were calculated for lobar and sub-lobar regions of interest. Significantly decreased MK, RK, and MD were found in ASD compared to TD participants in the frontal and temporal lobes and several sub-lobar regions previously associated with ASD pathology. In ASD participants, decreased kurtosis in gray matter ROIs correlated with increased repetitive and restricted behaviors and poor social interaction symptoms. Decreased kurtosis in ASD may reflect a pathology associated with a less restrictive microstructural environment such as decreased neuronal density and size, atypically sized cortical columns, or limited dendritic arborizations.

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