Frontal White Matter Tract Impairment In Autism Spectrum Disorders: A Diffusion Tensor Imaging Study Using Tract Based Spatial Statistics

Background:  

White matter overgrowth early in the course of illness may cause widespread developmental impairment of white matter tracts and functional underconnectivity, in autism spectrum disorders (ASD).

Diffusion tensor imaging (DTI) can infer properties of white matter micro-structure in vivo. Currently, DTI data informing the nature of white matter disturbance in ASD, is limited.

Objectives:  

To examine for the presence of widespread white matter disturbance in children and adolescents with ASD compared to controls, using DTI.

Methods:  

DTI scans were acquired for 19 children and adolescents with ASD (full scale IQ ≥ 70; 7-18 years; mean 12.3 ± 3) and 16 age and IQ matched controls (7-18 years; mean 12.5 ± 3) on a 3T Siemens Allegra head-dedicated MRI system.

Whole brain DTI values for fractional anisotropy, mean diffusivity, radial, and axial diffusivity values were extracted and age by group interaction effects examined.

Voxel-wise comparisons were performed using tract-based spatial statistics (TBSS) in: (i) ASD children and adolescents, and (ii) ASD children only (age ≤12), versus controls.

Results:  

Significant age by group interaction effects for whole-brain DTI indices in our total sample, were driven by differences among ASD and control children.

TBSS analysis of children and adolescents revealed no between-group differences for DTI indices. However, widespread increases in mean and radial diffusivity found in ASD children, prominently affected frontal white matter regions.

Follow-up analyses revealed particular impairment in white matter tracts linking frontal with parietal and temporal lobes, in ASD.

Conclusions:  

Our findings point to prominent disruption of frontal white matter in children with ASD. Unexpected, were widespread increases in radial diffusivity, a potential index of abnormal myelination.