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Reduced White Matter Integrity and Deficits in Neuropsychological Functioning in Adults With Autism Spectrum Disorder.

ABSTRACT: Autism spectrum disorder (ASD) is currently viewed as a disorder of cortical systems connectivity, with a heavy emphasis being on the structural integrity of white matter tracts. However, the majority of the literature to date has focused on children with ASD. Understanding the integrity of white matter tracts in adults may help reveal the nature of ASD pathology in adulthood and the potential contributors to cognitive impairment. This study examined white matter water diffusion using diffusion tensor imaging in relation to neuropsychological measures of cognition in a sample of 45 adults with ASD compared to 20 age, gender, and full-scale-IQ-matched healthy volunteers. Tract-based spatial statistics were used to assess differences in diffusion along white matter tracts between groups using permutation testing. The following neuropsychological measures of cognition were assessed: processing speed, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Results indicated that fractional anisotropy (FA) was significantly reduced in adults with ASD in the anterior thalamic radiation (P = 0.022) and the right cingulum (P = 0.008). All neuropsychological measures were worse in the ASD group, but none of the measures significantly correlated with reduced FA in either tract in the adults with ASD or in the healthy volunteers. Together, this indicates that the tracts that are the most impacted in autism may not be (at least directly) responsible for the behavioral deficits in ASD. Autism Res 2020, 13: 702-714. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: White matter tracts are the data cables in the brain that efficiently transfer information, and damage to these tracts could be the cause for the abnormal behaviors that are associated with autism. We found that two long-range tracts (the anterior thalamic radiation and the cingulum) were both impaired in autism but were not directly related to the impairments in behavior. This suggests that the abnormal tracts and behavior are the effects of another underlying mechanism.

SUBMITTER: Haigh SM

PROVIDER: S-EPMC8237714 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:There has been increasing evidence of White Matter (WM) microstructural disintegrity and connectome disruption in Autism Spectrum Disorder (ASD). We evaluated the effects of age on WM microstructure by examining Diffusion Tensor Imaging (DTI) metrics and connectome Edge Density (ED) in a large dataset of ASD and control patients from different age cohorts. N = 583 subjects from four studies from the National Database of Autism Research were included, representing four different age groups: (1) A Longitudinal MRI Study of Infants at Risk of Autism [infants, median age: 7 (interquartile range 1) months, n = 155], (2) Biomarkers of Autism at 12 months [toddlers, 32 (11)m, n = 102], (3) Multimodal Developmental Neurogenetics of Females with ASD [adolescents, 13.1 (5.3) years, n = 230], (4) Atypical Late Neurodevelopment in Autism [young adults, 19.1 (10.7)y, n = 96]. For each subject, we created Fractional Anisotropy (FA), Mean- (MD), Radial- (RD), and Axial Diffusivity (AD) maps as well as ED maps. We performed voxel-wise and tract-based analyses to assess the effects of age, ASD diagnosis and sex on DTI metrics and connectome ED. We also optimized, trained, tested, and validated different combinations of machine learning classifiers and dimensionality reduction algorithms for prediction of ASD diagnoses based on tract-based DTI and ED metrics. There is an age-dependent increase in FA and a decline in MD and RD across WM tracts in all four age cohorts, as well as an ED increase in toddlers and adolescents. After correction for age and sex, we found an ASD-related decrease in FA and ED only in adolescents and young adults, but not in infants or toddlers. While DTI abnormalities were mostly limited to the corpus callosum, connectomes showed a more widespread ASD-related decrease in ED. Finally, the best performing machine-leaning classification model achieved an area under the receiver operating curve of 0.70 in an independent validation cohort. Our results suggest that ASD-related WM microstructural disintegrity becomes evident in adolescents and young adults-but not in infants and toddlers. The ASD-related decrease in ED demonstrates a more widespread involvement of the connectome than DTI metrics, with the most striking differences being localized in the corpus callosum.

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Reduced White Matter Integrity and Deficits in Neuropsychological Functioning in Adults With Autism Spectrum Disorder.

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