Abstract
BackgroundPrevious 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.ResultsThe 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.ConclusionsThe 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.
Highlights
Previous reports indicate the presence of histological abnormalities in the brains of individuals with autism spectrum disorders (ASD) suggestive of a dysplastic process
Individuals were less well matched for sex, with two male ASD donors being paired with female neurotypical controls
Considering t as a function of y alone, mean cortical thickness was reduced in ASD in the vicinity of, and somewhat anterior to, the anterior commissure (AC) (Figure 2)
Summary
Previous reports indicate the presence of histological abnormalities in the brains of individuals with autism spectrum disorders (ASD) suggestive of a dysplastic process. Among the earliest reports of cortical abnormalities in autism was the claim made by Bauman and Kemper of indistinct lamination of the anterior cingulate gyrus in 5 out of their 6 cases [8] It was Bailey and colleagues who first emphasized the significance of abnormalities of the cerebral cortex in autism [5]. Hutsler and colleagues used thickness and lamination as proxy measurements for cortical organization when studying histological sections of eulaminate cortex (BA7, BA9, and BA21) in 8 autistic spectrum disorder individuals and an equal number of controls [10]. A later study using the same patient population evaluated the transition zone between the cortical gray and white matter by overlaying a sigmoid function in binary images [11] Their results indicated an indistinct boundary accounted, possibly, by the presence of supernumerary neurons beneath the cortical plate. Studies on whole brain serial sections by Wegiel and colleagues suggest that defects of neurogenesis and neuronal migration account for described dysplastic changes [13]
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