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The anterior cingulate cortex in autism: heterogeneity of qualitative and quantitative cytoarchitectonic features suggests possible subgroups

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Abstract

Autism is a behaviorally defined disorder with deficits in social interaction, communication, atypical behaviors, and restricted areas of interest. Postmortem studies of the brain in autism have shown a broad spectrum of abnormalities in the cerebellum and neocortex, involving limbic regions such as anterior cingulate cortex (ACC, Brodmann’s area 24). Using stereological techniques, we analyzed quantitatively cytoarchitectonic subdomains of the ACC (areas 24a, b, c) with regard to cell packing density and cell size. Microscopic examination of the ACC was also done to identify any neuropathologies. Results showed a significant decrease in cell size in layers I–III and layers V–VI of area 24b and in cell packing density in layers V–VI of area 24c. Direct comparisons revealed irregular lamination in three of nine autism brains and increased density of neurons in the subcortical white matter in the remaining cases. Because previous studies have suggested that von Economo neurons (VENs) may be altered in autism, a preliminary study of their density and size was undertaken. VEN density did not differ between autism and control brains overall. However, among the nine autism cases, there were two subsets; three brains with significantly increased VEN density and the remaining six cases with reduced VEN density compared to controls. Collectively, the findings of this pilot study may reflect the known heterogeneity in individuals with autism and variations in clinical symptomotology. Further neuroanatomic analyses of the ACC, from carefully documented subjects with autism, could substantially expand our understanding of ACC functions and its role in autism.

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Acknowledgments

Tissue was provided by the Harvard Brain Bank Tissue Resource Center, the Autism Tissue Program and the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD. Supported by the National Institutes of Health Studies To Advance Autism Research and Treatment (NIH STAART) U54 MH66398 and National Institutes of Neurological Disorders and Stroke (NINDS) NS38975-01A1. We gratefully acknowledge Hillary Kaplan for her help with tissue processing, Dr. Michael Bowley for helpful discussions regarding stereological principles and design, Jerry Skefos for his expert technical assistance, and Dr. Ron Killiany for his statistical expertise.

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  1. Department of Anatomy and Neurobiology, Boston University School of Medicine, 72 East Concord Street, L-1004, Boston, MA, 02118, USA

    Marissa Leigh Simms, Thomas L. Kemper, Clare M. Timbie, Margaret L. Bauman & Gene J. Blatt

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  1. Marissa Leigh Simms
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Correspondence to Marissa Leigh Simms.

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Simms, M.L., Kemper, T.L., Timbie, C.M. et al. The anterior cingulate cortex in autism: heterogeneity of qualitative and quantitative cytoarchitectonic features suggests possible subgroups. Acta Neuropathol 118, 673–684 (2009). https://doi.org/10.1007/s00401-009-0568-2

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