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

Abstract

Background: 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, often revealing reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in white matter. Methods: 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 publication year, participant characteristics (age, sex, IQ), and laterality moderate the magnitude of the estimated differences. Our analysis included 881 effect sizes from 66 studies (NASD = 2231, NTD = 1856; Mage = 2–50 years) across 12 white matter tracts. Results: We found a significant moderate summary effect size for FA in nine tracts (corpus callosum, corticospinal tract, thalamic radiation, arcuate fasciculus, inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF], uncinate fasciculus, cingulum; Hedges’ g = −0.30 to −0.50), suggesting that individuals with ASD have lower FA compared to TD controls. Additionally, we found a significant moderate-to-large summary effect size for MD in eight tracts (corpus callosum, corona radiata, corticospinal tract, arcuate fasciculus, IFOF, ILF, SLF, uncinate fasciculus; Hedges’ g = 0.29 to 0.97), suggesting that individuals with ASD have higher MD compared to TD controls. Furthermore, moderators demonstrated tract- and metric-specific effects. Conclusions: Our findings highlight the complex, multidimensional nature of white matter microstructure alterations observed in ASD.