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

Abstract

Scientific abstract Background 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. Methods We included 57 ASD and 50 TD participants, comparing 3 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. Results 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. Conclusions Findings suggest that some previously reported DTI findings for ASD may have been confounded by motion. However, effects in 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.

Development of frontoparietal connectivity predicts longitudinal symptom changes in young people with autism spectrum disorder

“…Across both time samples, the ASD group did not exhibit significant differences in the connectome compared with TDC, which is inconsistent with the earlier findings of diffuse white matter disruption 29 . Given the careful quality control for DSI data and tight motion-matching in the current data, as well as comparable sample sizes and high-functioning cohorts with earlier studies 29 , this finding might suggest that motion confounds have inflated previously reported white matter differences in ASD at the group level 30 . The present null finding in a diagnostic effect may also highlight the advantage of performing a longitudinal analysis to capture variance across the diagnostic groups with regards to differences in their developmental trajectories.…”

Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder

“…First, although a wealth of functional, EEG, and DTI data suggest disrupted connectivity in ASD [20, 69], the validity of these findings is sometimes questioned. Head motion artifact in particular has been proposed as the cause of group difference in ASD versus typically developing control DTI studies [70–73], as FA is known to substantial decrease with DWI slice-level motion artifact [74]. Here, we present longitudinal imaging data acquired in infants at high risk of ASD with a common genetic diagnosis over the period of early brain development.…”

A diffusion-weighted imaging tract-based spatial statistics study of autism spectrum disorder in preschool-aged children

“…Image artifacts associated with head motion are a significant confound in ASD research. Head motion has shown to be increased in ASD [72] and to significantly impact DWI results [73]. Accordingly, in addition to utilizing a noctoral sleep protocol [47] and state of the art within volume motion correction [68], we quantified head motion using the root-mean-square (RMS) displacement of both the mean absolute intervolume displacement with respect to the first image of each acquisition and the mean relative intervolume displacement between each preceding image in the sequence.…”