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. 2013 Aug 2;3:106-14.
doi: 10.1016/j.nicl.2013.07.007. eCollection 2013.

White Matter Microstructure Correlates With Autism Trait Severity in a Combined Clinical-Control Sample of High-Functioning Adults

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Free PMC article

White Matter Microstructure Correlates With Autism Trait Severity in a Combined Clinical-Control Sample of High-Functioning Adults

Clare R Gibbard et al. Neuroimage Clin. .
Free PMC article

Abstract

Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in tracts involved in emotion processing in autism spectrum disorder (ASD), but little is known regarding the nature and distribution of WM anomalies in relation to ASD trait severity in adults. Increasing evidence suggests that ASD occurs at the extreme of a distribution of social abilities. We aimed to examine WM microstructure as a potential marker for ASD symptom severity in a combined clinical-neurotypical population. SIENAX was used to estimate whole brain volume. Tract-based spatial statistics (TBSS) was used to provide a voxel-wise comparison of WM microstructure in 50 high-functioning young adults: 25 ASD and 25 neurotypical. The severity of ASD traits was measured by autism quotient (AQ); we examined regressions between DTI markers of WM microstructure and ASD trait severity. Cognitive abilities, measured by intelligence quotient, were well-matched between the groups and were controlled in all analyses. There were no significant group differences in whole brain volume. TBSS showed widespread regions of significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in ASD compared with controls. Linear regression analyses in the combined sample showed that average whole WM skeleton FA was negatively influenced by AQ (p = 0.004), whilst MD and RD were positively related to AQ (p = 0.002; p = 0.001). Regression slopes were similar within both groups and strongest for AQ social, communication and attention switching scores. In conclusion, similar regression characteristics were found between WM microstructure and ASD trait severity in a combined sample of ASD and neurotypical adults. WM anomalies were relatively more severe in the clinically diagnosed sample. Both findings suggest that there is a dimensional relationship between WM microstructure and severity of ASD traits from neurotypical subjects through to clinical ASD, with reduced coherence of WM associated with greater ASD symptoms. General cognitive abilities were independent of the relationship between WM indices and ASD traits.

Keywords: Autism quotient; Autism spectrum disorder; Diffusion tensor imaging; Tract-based spatial statistics; White matter.

Figures

Fig. 1
Fig. 1
Axial slices of the cohort's mean white matter skeleton (green) overlaid with (A) red clusters depicting white matter voxels with significantly lower fractional anisotropy (FA) in subjects with autism spectrum disorder (ASD) compared to healthy controls (p < 0.05; FWE-corrected). Tracts in all major lobes of the cerebrum (frontal, parietal, occipital and temporal lobes) and the corpus callosum connecting the two brain hemispheres are affected. (B and C) Blue clusters showing regions with significantly higher mean diffusivity (MD) (B) and radial diffusivity (RD) (C) in ASD compared to controls (p < 0.05; FWE-corrected). Similarly to the FA results, the clusters are widespread throughout the cerebrum. There were no significant differences in axial diffusivity (AD) between the two groups. TBSS fill was used for visualisation. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 2
Fig. 2
Scatter plots showing results of linear regression controlling for age, gender, full-scale intelligence quotient (IQ) and whole brain volume. Red squares denote participants diagnosed with an autism spectrum disorder (ASD); blue triangles represent neurotypical controls. Grey shading shows the standard error of the fit. (A) A significant negative relationship between autism quotient (AQ) and fractional anisotropy (FA) (t = − 3.04; p = 0.004) in addition to significant positive relationships for AQ with (B) mean diffusivity (MD) (t = 3.24; p = 0.002) and (C) radial diffusivity (RD) (t = 3.42; p = 0.001). (D) There was a weak positive influence of AQ on axial diffusivity (AD) (t = 1.52; p = 0.14). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 3
Fig. 3
Plots of the regression slopes between the DTI metrics and AQ across all participants (purple circle), and within ASD (red square) and neurotypical control (blue triangle) groups separately. All regressions controlled for age, gender, full-scale intelligence quotient (IQ) and whole brain volume. Points represent the value of the regression slope; lines show the 95% confidence interval of the fit. The plots show greater variance in the separate groups, particularly the ASD group. Slopes were similar for regression in the combined sample in comparison to regressions in the separate groups, particularly for MD and AD. Slopes for FA and RD were more different, but model comparison showed no significant difference in the fits (all p > 0.24). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 4
Fig. 4
Axial slices of the group white matter skeleton (green) overlaid with blue clusters showing white matter voxels in which autism quotient (AQ) is positively related (p < 0.05; FWE-corrected) with (A) mean diffusivity (MD) widespread through the left hemisphere and bilaterally in the occipital lobe and (B) with radial diffusivity (RD) in voxels of the left hemisphere forming part of the left superior longitudinal fasciculus (SLF). There were no significant relationships between AQ and fractional anisotropy (FA) or axial diffusivity (AD). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

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