Abnormalities of cortical minicolumnar organization in the prefrontal lobes of autistic patients

Abstract

Recent functional imaging studies suggest deficits in connectivity between disparate and distant regions in the brains of autistic individuals. One possible explanation to these findings is the presence of modular abnormalities in the neocortex of autistic patients: a change in neuronal specialization within minicolumns that emphasizes short connecting fibers. In this study, we expand on previous findings by exploring the topography of minicolumnar abnormalities in autism. Our postmortem study included six patients with autism (DSM-IV-TR and ADI-R diagnosed) and six age-matched controls. Entire brain hemispheres were celloidin embedded, serially sectioned, and stained with gallocyanin. Digital photomicrographs of n = 9 cortical areas (including paralimbic, heteromodal association, unimodal association, and primary areas) obtained at high magnification were assembled into montages covering the entire cortical thickness. Stained cell somata were segmented from neuropil by thresholding. Computer image analysis clustered neurons into minicolumnar fragments. The full width of the image region nearest each fragment and the width of the cell-dense core of the fragment were estimated. The difference between these two quantities can be used as a measure of the peripheral neuropil space of minicolumns. We found an interaction of diagnosis and region for peripheral neuropil space (p = 0.041). Post hoc analysis revealed significant differences (p < 0.05) for the frontopolar region (area 10) and the anterior cingulate gyrus (area 24). The frontopolar cortex is involved in executive functions by implementing control over internally generated thoughts and relational integration (combination of multiple cognitive rules). The anterior cingulate gyrus is involved in the analysis of socially salient information, including the processing of familiar faces. Pathological findings in these areas may provide a correlate to some of the more salient manifestations of autism.