Widespread alterations in white matter microstructure in autism: A multilevel meta-analysis

Disrupted brain connectivity is central to understanding the neurobiological basis of autism spectrum disorder (ASD). Diffusion tensor imaging (DTI) has been extensively used to study brain microstructure in ASD, which often reveals reduced fractional anisotropy (FA) and increased mean diffusivity (MD), indicating altered microstructural integrity.

We conducted a multivariate random-effects meta-analysis with a multilevel structure to evaluate the extent to which FA and MD measures of white matter microstructure are altered in individuals with ASD compared to typically developing (TD) individuals, as well as how participant characteristics and laterality moderate the magnitude of the estimated differences. Our analysis included 680 effect sizes from 59 studies (N _ASD = 1,750, N _TD = 1,484; M _age = 2-50 years) across 11 white matter tracts.

We found a significant moderate summary effect size for FA in eight tracts (corpus callosum, corticospinal tract, thalamic radiation, arcuate fasciculus, inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF], and uncinate fasciculus; Hedges' g = -0.40 to -0.59), suggesting that individuals with ASD have lower FA values in these tracts compared to TD controls. Additionally, we found a significant moderate-to-large summary effect size for MD in six tracts (corpus callosum, corona radiata, arcuate fasciculus, IFOF, ILF, and SLF; Hedges' g = 0.32 to 1.09), suggesting that individuals with ASD have higher MD values in these tracts compared to TD controls. Furthermore, moderators demonstrated tract- and metric-specific effects.

Participants were primarily male, and the age range excludes later adulthood when white matter deterioration becomes more evident. Therefore, our findings are limited in generalizing to females and may not be applicable across the entire lifespan.

Collectively, our findings highlight the complex and multidimensional nature of white matter alterations observed in ASD.