Two-dimensional analysis of the supragranular layers in autism spectrum disorder

Neurons in the supragranular layers of the human cerebral cortex play an important role in long-range cortico-cortical connections. Alterations to these layers are of special interest in autism spectrum disorder (ASD) as they could play a significant role in altered connectivity between distal regions of cortex. The present study isolated sampling boxes through the use of an automated boundary identification technique. A two-dimensional analysis of the Nissl-stained tissue was then performed to examine whether differences in cell size and number are present in ASD tissue. The analysis focused on layers II and III of association cortex sampled from frontal (BA9), temporal (BA21), and parietal (BA7) regions. In previous studies, both BA9 and BA21 have been linked to alterations in cortical connectivity in ASD. Aside from the expected differences between cortical layers and regions, data analysis revealed that ASD tissue possessed a higher density of cells, the magnitude of which was layer dependent, and that the cell profiles were of a smaller size. The results of this study suggest that cellular abnormalities with respect to cell size and number are present in multiple areas of association cortex, specifically within layers that are involved in long-range connectivity. Additionally, the results comport with previous findings of altered cortical minicolumns in frontal and temporal areas and further suggest that similar irregularities may also be present in parietal areas.