White matter compromise in autism? Differentiating motion confounds from true differences in diffusion tensor imaging.

Common findings from diffusion tensor imaging (DTI) in autism spectrum disorder (ASD) include reduced fractional anisotropy (FA), and increased mean and radial diffusivity (MD, RD) of white matter tracts. However, findings may be confounded by head motion. We examined how group-level motion matching affects DTI comparisons between ASD and typically developing (TD) groups. We included 57 ASD and 50 TD participants, comparing three subsets at increasing levels of motion-matching stringency: full sample (FS); quality-controlled (QC); and quantitatively-matched (QM). Groups were compared on diffusivity measures using Tract-Based Spatial Statistics (TBSS) and probabilistic tractography. Two methods for estimating diffusivity were compared: dti-fit and restore. TBSS: In set FS, FA was reduced in the ASD compared to the TD group throughout the right hemisphere. This effect was less extensive in set QC and absent in set QM. However, effect sizes remained stable or increased with better quality-control in some regions. Tractography: In set QM, MD was significantly higher in ASD overall and RD was higher in bilateral ILF. Effects were more robust in QM than in FS or QC sets. Effect sizes in several tracts increased with stringent quality matching. Restore improved tensor estimates, with some increases in effect sizes, but did not fully compensate for reduced quality. Findings suggest that some previously reported DTI findings for ASD may have been confounded by motion. However, effects in the tightly matched subset indicate that tract-specific anomalies probably do exist in ASD. Our results highlight the need for careful quality-control and motion-matching. Autism Res 2017, 10: 1606-1620.