Microstructural Covariance of White Matter in Autism Spectrum Disorder

Background: Brain imaging findings in children with autism spectrum disorder (ASD) suggest this condition is associated with altered white matter microstructure, which may lead to atypical brain “connectivity” (for a review, see Travers et al., 2012). Nevertheless, there is substantial heterogeneity in the behavioral phenotype of ASD, and it is unclear whether individuals with ASD have atypicalities of white matter microstructure that are localized to specific tracts. To assess this, one may examine how different white matter tracts relate to each other in typically developing (TD) individuals and then compare these patterns to those found in ASD. If white matter microstructural abnormalities are localized to specific tracts in ASD, then there will be atypicalities in the microstructural properties of these tracts in ASD than in typical development. Understanding specific white matter network “signatures” at group and individual levels may help us better determine meaningful classifications within the autism spectrum.

Objectives: We examined the extent to which the underlying white matter microstructure, as measured by diffusion tensor imaging (DTI), of each white matter tract related to that of each other white matter tract. We then compared the correlation matrix of diffusion coefficients of the ASD group to that of the TD group to determine the degree of similarity of the white matter tracts between each group. 

Methods: MRI Acquisition: Participants for this study consisted of 100 males with ASD and 57 age-matched TD males between 3 and 39 years of age. DTI data were acquired from each participant, images were corrected for distortion and head motion and maps of fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were calculated; only FA was used herein. Analysis: Mean FA from 48 major white matter tracts, as defined by the JHU ICBM-DTI-81 template, were extracted from each individual dataset. To examine the covariance of the microstructure of these white matter tracts between ASD and TD individuals, a matrix of the correlation between each of the 48 white matter tracts was generated for the ASD group and the TD group, separately. Box’s M-test was then used to examine whether these matrices were significantly different.   

Results: A gravitational plot of the organization of white matter microstructure of ASD and TD groups is depicted in Fig. 1. The correlation matrix of the ASD group was found to be significantly more widespread than the correlation matrix of the TD group (p = .027). 

Conclusions: Our results suggest that, at the group level, individuals with ASD have significantly less uniform white matter microstructure across multiple tracts of the brain compared to individuals with typical development. This suggests the possibility of more tract-specific white matter microstructure atypicalities in ASD. Future analyses will examine this white matter microstructural covariance at the individual level to determine possible biology-derived subgroups in ASD.