Diffusion-weighted imaging evidence of altered white matter development from late childhood to early adulthood in Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is thought to reflect disrupted development of brain connectivity characterized by white matter abnormalities and dyscoordination of activity across brain regions that give rise to core features. But there is little consensus about the nature, timing and location of white matter abnormalities as quantified with diffusion-weighted MRI. Inconsistent findings likely reflect small sample sizes, motion confounds and sample heterogeneity, particularly different age ranges across studies. We examined the microstructural integrity of major white matter tracts in relation to age in 38 high functioning ASD and 35 typically developing (TD) participants, aged 8-25, whose diffusion-weighted scans met strict data-quality criteria and survived group matching for motion. While there were no overall group differences in diffusion measures, the groups showed different relations with age. Only the TD group showed the expected positive correlations of fractional anisotropy with age. In parallel, axial diffusivity was unrelated to age in TD, but showed inverse correlations with age in ASD. Younger participants with ASD tended to have higher fractional anisotropy and axial diffusivity than their TD peers, while the opposite was true for older participants. Most of the affected tracts - cingulum bundle, inferior and superior longitudinal fasciculi - are association bundles related to cognitive, social and emotional functions that are abnormal in ASD. The manifestations of abnormal white matter development in ASD as measured by diffusion-weighted MRI depend on age and this may contribute to inconsistent findings across studies. We conclude that ASD is characterized by altered white matter development from childhood to early adulthood that may underlie abnormal brain function and contribute to core features.