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. 2013 Oct 11:1:67.
doi: 10.1186/2051-5960-1-67.

Focal cortical dysplasias in autism spectrum disorders

Manuel F Casanova  1 , Ayman S El-Baz, Shweta S Kamat, Brynn A Dombroski, Fahmi Khalifa, Ahmed Elnakib, Ahmed Soliman, Anita Allison-McNutt, Andrew E Switala
Affiliations

Focal cortical dysplasias in autism spectrum disorders

Manuel F Casanova et al. Acta Neuropathol Commun. .

Abstract

Background: Previous reports indicate the presence of histological abnormalities in the brains of individuals with autism spectrum disorders (ASD) suggestive of a dysplastic process. In this study we identified areas of abnormal cortical thinning within the cerebral cortex of ASD individuals and examined the same for neuronal morphometric abnormalities by using computerized image analysis.

Results: The study analyzed celloidin-embedded and Nissl-stained serial full coronal brain sections of 7 autistic (ADI-R diagnosed) and 7 age/sex-matched neurotypicals. Sections were scanned and manually segmented before implementing an algorithm using Laplace's equation to measure cortical width. Identified areas were then subjected to analysis for neuronal morphometry. Results of our study indicate the presence within our ASD population of circumscribed foci of diminished cortical width that varied among affected individuals both in terms of location and overall size with the frontal lobes being particularly involved. Spatial statistic indicated a reduction in size of neurons within affected areas. Granulometry confirmed the presence of smaller pyramidal cells and suggested a concomitant reduction in the total number of interneurons.

Conclusions: The neuropathology is consistent with a diagnosis of focal cortical dysplasia (FCD). Results from the medical literature (e.g., heterotopias) and our own study suggest that the genesis of this cortical malformation seemingly resides in the heterochronic divisions of periventricular germinal cells. The end result is that during corticogenesis radially migrating neuroblasts (future pyramidal cells) are desynchronized in their development from those that follow a tangential route (interneurons). The possible presence of a pathological mechanism in common among different conditions expressing an autism-like phenotype argue in favor of considering ASD a "sequence" rather than a syndrome. Focal cortical dysplasias in ASD may serve to explain the high prevalence of seizures and sensory abnormalities in this patient population.

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Figures

Figure 1
Figure 1
Solution of the Laplace equation inside the cortical ribbon. The outer contour is the lamina I/lamina II boundary φ = –1 ; the inner contour is the white matter boundary φ = +1; and the midline is the equipotential φ = 0. Field lines are displayed spaced at 1 mm intervals along the midline.
Figure 2
Figure 2
Mean t in each brain section. The seven pairs are plotted individually, with measurements from the ASD donor indicated by triangles, and circles for the matched neurotypical donor. Note that the horizontal axis scale is not uniform. Average thickness for each slide is plotted with respect to the slide’s corresponding position in stereotaxic space. Six out of seven ASD patients showed diminutions within prefrontal cortex as defined by the AC.
Figure 3
Figure 3
Difference in t between the cerebral cortices of ASD and neurotypical donors with respect to position and curvature. The horizontal axis is the same as in Figure 2 (73 mm = frontal pole; 0 = anterior commissure; -106 mm = occipital pole). Regions where the cortex is narrower in ASD are colored blue, while regions where the cortex is wider are colored orange. Data were averaged across all seven pairs.
Figure 4
Figure 4
Box plots of estimated Boolean model parameters by lamina. The Boolean germ-grain model is completely characterized by three quantities: mean area and perimeter of the grain distribution, and intensity of the Poisson germ process.
Figure 5
Figure 5
Pattern spectrum by lamina, obtained by granulometry on segmented (binary) images. Bar height (y axis) is proportional to the total area of stained objects with sizes falling within each bin. The spectra were averaged bin-wise over the twelve narrow cortical regions of interest from two ASD cases and the twelve corresponding regions from matched control cases.
Figure 6
Figure 6
Coronal sections through the brain of an autistic patient. The overlay denotes those cortical areas showing abnormalities of cortical thickness. Towards both pole regions cortical thickness abnormalities preferentially affected the crest of gyri. Defects in cortical width tended to affect both crest and sulci of gyri in middle sections. Defects affecting crest of gyri were usually larger than those seen at the sulci of gyri. The y-coordinates are the normalized positions as in Figures 3 and 4.
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