Evidence of wide-spread white matter compromise in children and adults with autism: a large-scale diffusion imaging study using repository data

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Authors

Otto, Stephanie Rene

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2021

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Thesis

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Autism Spectrum Disorder , Biomarker , Connectivity , Diffusion MRI , Tract Based Spatial Statistics , White Matter

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Abstract

Autism Spectrum Disorder (ASD) pathology involves multiple distributed neural networks. Abnormal white matter (WM) connectivity has been implicated as being responsible for perturbed neural functioning across distributed networks. Much of the existing research surrounding WM connectivity in ASD has primarily focused on children, while little is known about the anatomical and behavioral profile across the lifespan into adulthood. The present study used diffusion tensor imaging (DTI) to explore the degree to which WM connectivity is abnormal in ASD in a large sample of children and adults. Diffusion MRI data was acquired from the ABIDE II repository, Carnegie Mellon University, and the University of Pittsburgh. In total, we analyzed 336 subjects (199 ASD, 137 IQ-matched neurotypical (NT) controls). All data were collected on a 3‑Tesla scanner. Tract Based Spatial Statistics (TBSS) was performed using FMRIB’s FSL software. Due to the nested nature of the data, linear mixed-effects modeling was used to examine if there were group differences in diffusion measures between individuals with ASD and NT controls while controlling for several covariates (age, IQ, motion, brain volume). Individuals with ASD exhibited poorer overall diffusion, even after controlling for age, motion and IQ. Compared to NT controls, individuals with ASD showed decreased fractional anisotropy (FA), increased mean diffusivity (MD) and increased radial diffusivity (RD). Together, these results suggest that WM compromise begins early in ASD and persists throughout adulthood. Due to the nonlinear and dynamic nature of brain development in ASD, it is difficult to isolate aberrant changes in WM connectivity that might be a direct result of ASD. Focusing more efforts on adults with ASD may give researchers a better understanding of which of these changes in diffusion are sustained beyond development and maturation. Our findings highlight the need for longitudinal studies to better understand how age-related changes in WM diffusion properties may relate to the behavioral profile often seen in ASD across the lifespan.

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