Abnormal cell patterning at the cortical gray–white matter boundary in autism spectrum disorders

Previous research on neuronal spacing and columnar organization indicates the presence of cell patterning alterations within the cerebral cortex of individuals with autism spectrum disorders (ASD). These patterning abnormalities include irregularities at the gray–white matter boundary and may implicate early neurodevelopmental events such as migration in altering cortical organization in ASD. The present study utilized a novel method to quantify the gray–white matter boundary in eight ASD and eight typically developing control subjects. Digital photomicrographs of the gray–white matter boundary were acquired from multiple positions within the superior temporal gyrus (BA21), dorsolateral frontal lobe (BA9), and dorsal parietal lobe (BA7) of each case. A sigmoid curve was fitted to the transition zone between layer VI and underlying white matter (subplate), and the slope of the resulting curve was used as a measure of the spatial extent of the transition zone. For all three cortical regions examined, ASD subjects showed “shallower” sigmoid curves compared to neurotypicals, indicating the presence of an indistinct boundary between cortical layer VI and the underlying white matter. These results may reflect the presence of supernumerary neurons beneath the cortical plate that could be the result of migration deficits or failed apoptosis in the subplate region. Furthermore, these findings raise questions regarding the validity of cortical measures that rely on gray–white matter parcellation, since an indistinct transition zone could lead to a misplaced cortical boundary and errors in both thickness and volume measures.

Research Highlights
► Utilized a novel method to quantify the cortical gray-white matter boundary in ASD.
► ASD cases showed a consistently less distinct gray-white matter boundary.
► The effect was present in all brain regions examined.
► The results have implications for neurodevelopment and MRI thresholding.