Altered white matter integrity and development in children with autism: a combined voxel-based morphometry and diffusion imaging study

Background: A combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism. Methods: Twenty children with autism (mean age=7±2.75 years old; age range: 4–14; 2 girls) and 22 matched normally developing children (mean age=7.68±2.03 years old; age range: 4–11; 2 girls) underwent magnetic resonance imaging (MRI). VBM was employed by applying the Template-o-Matic toolbox (TOM), a new approach which constructs the age-matched customized template for tissue segmentation. Also, the apparent diffusion coefficients (ADC) of water molecules were obtained from the analysis of DWI. Regions of interests (ROIs), standardized at 5 pixels, were placed in cortical lobes and corpus callosum on the non-diffusion weighted echo-planar images (b=0) and were then automatically transferred to the corresponding maps to obtain the ADC values. Results: Compared to normal children, individuals with autism had significantly: (1) increased white matter volumes in the right inferior frontal gyrus, the right fusiform gyrus, the left precentral and supplementary motor area and the left hippocampus, (2) increased gray matter volumes in the inferior temporal gyri bilaterally, the right inferior parietal cortex, the right superior occipital lobe and the left superior parietal lobule, and (3) decreased gray matter volumes in the right inferior frontal gyrus and the left supplementary motor area. Abnormally increased ADC values in the bilateral frontal cortex and in the left side of the genu of the corpus callosum were also reported in autism. Finally, age correlated negatively with lobar and callosal ADC measurements in individuals with autism, but not in children with normal development. Conclusions: These findings suggest cerebral dysconnectivity in the early phases of autism coupled with an altered white matter maturation trajectory during childhood potentially taking place in the frontal and parietal lobes, which may represent a neurodevelopmental marker of the disorder, possibly accounting for the cognitive and social deficits.