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White Matter Abnormalities in Girls with Autism: A Tract-Based Spatial Statistics Study

Friday, May 12, 2017: 12:00 PM-1:40 PM
Golden Gate Ballroom (Marriott Marquis Hotel)
H. Turner1, J. Lei2, E. K. Lecarie1, D. Yang3,4, P. E. Ventola1, D. G. Sukhodolsky1, K. A. Pelphrey5 and R. J. Jou5, (1)Yale Child Study Center, New Haven, CT, (2)Centre for Applied Autism Research, University of Bath, Bath, United Kingdom, (3)Children's National Health System, Washington, DC, (4)Autism and Neurodevelopmental Disorders Institute, The George Washington University, Washington, DC, (5)Yale University, New Haven, CT
Background:

Many diffusion tensor imaging (DTI) studies implementing tract-based spatial statistics (TBSS) in samples consisting mainly of boys have shown widespread abnormalities in white matter (WM) microstructure in autism spectrum disorder (ASD). Even though girls make up a significant minority of individuals living with ASD, they are grossly understudied relative to boys, and few studies (if any) to date have implemented DTI with TBSS in the exclusive examination of ASD girls. While there is mounting evidence supporting differences in behavioral phenotype between girls and boys with ASD, much less is known about the neural phenotype in girls living with autism.

Objectives:

Characterize WM abnormalities in ASD girls in comparison to neurotypical (NT) girls using DTI.

Methods:

This study consisted of 46 girls: 26 ASD (Age: M = 9.22 y, SD = 4.18; Full-scale IQ: M = 96.79, SD = 21.15) and 20 NT (Age: M = 10.05 y, SD = 4.14; Full-scale IQ: M = 106.13, SD = 16.01). Participants underwent diffusion-weighted MRI (2.5mm3; 30 directions at b=1000s/mm2; 5 b=0; runs=3) on a 3T Siemens scanner. The best of three runs for each participant was selected for this preliminary analysis. All scans were pre-processed using FSL, including eddy current correction and estimation of the diffusion tensor, which enables calculation of the following WM microstructure metrics: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Voxel-wise group comparisons in WM microstructure were performed using TBSS which co-registers all diffusion data and generates an average WM skeleton on which statistical comparisons are made. Areas of significant difference were identified (p < 0.05 corrected for multiple comparisons across space) using Threshold-free Cluster Enhancement (TFCE).

Results:

There were no significant differences in age and IQ between groups. There were widespread regions of both right and left hemispheres in which MD was significantly elevated in ASD compared to NT. There were also widespread regions of both right and left hemispheres in which AD was significantly elevated in ASD compared to NT. All fiber types were represented, including association, commissure, and projection fibers. No other group comparisons reached significance; however, there was a trend towards significantly increased RD in the ASD group compared to NT.

Conclusions:

This study uses DTI and TBSS to show that ASD girls have WM abnormalities in comparison to NT girls, thus indicating that probands exhibit structural abnormalities in the brain. The pattern of abnormalities is similar to boys with respect to widespread involvement. In contrast, there appear to be some differences in which WM microstructure metrics are abnormal in girls with ASD, suggesting potential gender differences in neural phenotype.

See more of: Brain Structure (MRI, neuropathology)
See more of: Brain Structure (MRI, neuropathology)