In Vivo Evidence of Reduced Integrity of the Gray-White Matter Boundary in Autism Spectrum Disorder

Abstract

Atypical cortical organization and reduced integrity of the gray-white matter boundary have been reported by postmortem studies in individuals with autism spectrum disorder (ASD). However, there are no in vivo studies that examine these particular features of cortical organization in ASD. Hence, we used structural magnetic resonance imaging to examine differences in tissue contrast between gray and white matter in 98 adults with ASD and 98 typically developing controls, to test the hypothesis that individuals with ASD have significantly reduced tissue contrast. More specifically, we examined contrast as a percentage between gray and white matter tissue signal intensities (GWPC) sampled at the gray-white matter boundary, and across different cortical layers. We found that individuals with ASD had significantly reduced GWPC in several clusters throughout the cortex (cluster, P < 0.05). As expected, these reductions were greatest when tissue intensities were sampled close to gray-white matter interface, which indicates a less distinct gray-white matter boundary in ASD. Our in vivo findings of reduced GWPC in ASD are therefore consistent with prior postmortem findings of a less well-defined gray-white matter boundary in ASD. Taken together, these results indicate that GWPC might be utilized as an in vivo proxy measure of atypical cortical microstructural organization in future studies.

Keywords: ASD; FreeSurfer; MRI; imaging; lamination.

Figure 1.

Gray and white matter signal intensity sampling procedure. (A) Gray and white matter signal intensity sampling points are shown for one 2D coronal slice. (B) WMIs (red line) were sampled at an absolute distance of 1 mm subjacent to the white matter surface (i.e. gray–white matter boundary). GMI signals (blue to yellow lines) were measured at projection fractions representing a percentage of the total orthogonal distance from the white matter surface to the outer pial surface starting at the white matter surface up to 60% into the cortical sheet at 10% intervals.

Figure 2.

Regions of decreased gray-to-white matter signal intensity percent contrast (GWPC) in ASD. Individuals with ASD showed significantly decreased GWPC (RFT, P < 0.5), indicating less definition between gray and white matter, in several regions highlighted in blue including 1) the posterior-cingulate cortex, 2) fronto-temporal and fronto-parietal regions, as well as 3) the bilateral fusiform and entorhinal cortex. The spatial and statistical extent of these differences was greatest when tissue intensities were sampled at the gray–white matter boundary and decreased along with increasing projection fractions (superscript a) into the cortical sheet. See Table 2 for statistical details.

Figure 3.

Regional differences in gray (GMI) and white matter (WMI) signal intensities in ASD. Individuals with ASD showed no significant differences in WMI (RFT, P < 0.5) measured at 1 mm subjacent to the gray–white matter boundary (superscript a) nor tissue intensities measured at the boundary. Significantly increased GMI (RFT, P < 0.5) was observed across all projection fractions (superscript b) within the cortical sheet in ASD participants. The statistical and spatial extent of these increases in GMI were most evident at the 30% projection fraction and incorporated 1) the bilateral anterior temporal lobes and the left middle temporal gyrus, 2) the right temporo-parietal junction, and 3) the bilateral fusiform and entorhinal cortex. See Table 2 for statistical details.