Abstract
Previous studies using diffusion tensor imaging (DTI) to investigate white matter (WM) structural connectivity have suggested widespread, although inconsistent WM alterations in autism spectrum disorder (ASD), such as greater reductions in fractional anisotropy (FA). However, findings may lack generalizability because: (a) most have focused solely on the ASD male brain phenotype, and not sex‐differences in WM integrity; (b) many lack stringent and transparent data quality control such as controlling for head motion in analysis. This study addressed both issues by using Tract‐Based Spatial Statistics (TBSS) to separately compare WM differences in 81 ASD (56 male, 25 female; 4–21 years old) and 39 typically developing (TD; 23 males, 16 females; 5–18 years old) children and young people, carefully group‐matched on sex, age, cognitive abilities, and head motion. ASD males and females were also matched on autism symptom severity. Two independent‐raters completed a multistep scan quality assurance to remove images that were significantly distorted by motion artifacts before analysis. ASD females exhibited significant widespread reductions in FA compared to TD females, suggesting altered WM integrity. In contrast, no significant localized or widespread WM differences were found between ASD and TD males. This study highlights the importance of data quality control in DTI, and outlines important sex‐differences in WM alterations in ASD females. Future studies can explore the extent to which neural structural differences might underlie sex‐differences in ASD behavioral phenotype, and guide clinical interventions to be tailored toward the unique needs of ASD females and males. Autism Res 2019, 12: 1472–1483. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.Lay SummaryPrevious Diffusion Tensor Imaging (DTI) studies have found atypical brain structural connectivity in males with autism, although findings are inconclusive in females with autism. To investigate potential sex‐differences, we studied males and females with and without autism who showed a similar level of head movement during their brain scan. We found that females with autism had widespread atypical neural connectivity than females without autism, although not in males, highlighting sex‐differences.
Highlights
Diffusion tensor imaging (DTI) along with other structural and functional imaging techniques, have increasingly been used to provide evidence that the neural phenotype of autism spectrum disorder (ASD) includes alterations in structural connectivity
This aligns with the notion of controlling for the effect of head motion highlighted by Koldewyn et al [2014], in which typically developing (TD) and ASD participants were matched by head motion and samples with much excessive head motion were not included in analyses
We did not observe any significant increases in fractional anisotropy (FA) across any fiber tracts in females with ASD when compared to TD females
Summary
Diffusion tensor imaging (DTI) along with other structural and functional imaging techniques, have increasingly been used to provide evidence that the neural phenotype of autism spectrum disorder (ASD) includes alterations in structural connectivity. These researchers were able to ameliorate this effect by controlling for head motion in their analysis [Yendiki et al, 2014] These studies suggest that data quality, suboptimal group matching, and head motion create major discrepancies in which specific tracts are identified as being affected in individuals with autism. The present study aims to evaluate sex differences in WM between individuals with ASD and their TD peers, while stringently controlling for data quality and matching for confounding variables known to produce artifact findings and false positive errors This aligns with the notion of controlling for the effect of head motion highlighted by Koldewyn et al [2014], in which TD and ASD participants were matched by head motion and samples with much excessive head motion were not included in analyses. The study challenges previous research that reports significant differences in WM tracts in the ASD group by analyzing males and females as separate groups to capture any evident sex differences
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