Dunham, J.S.; Del Valle Suarez, E. M.; Wiles, D. P. L.; Schmitz, C.; Gabbott, P. L. and Rezaie, P.
The dorsal anterior cingulate cortex (BA32) in autism: Morphometric analyses of deep cortical layers and subcortical white matter.
In: The Emerging Neuroscience of Autism Spectrum Disorders: Etiologic Insights; Treatment Opportunities, 11-12 November 2010, San Diego, CA.
Introduction: The dorsal anterior cingulate cortex (BA32) is a region implicated in both social impairments and repetitive behaviors seen in Autism Spectrum Disorder (ASD). The neuropathological basis for these functional impairments is unclear. Cortical lamination progresses sequentially during mid-gestation, with layer 6 and then layer 5 populated by neurons. An investigation of cellular arrangement within these layers would provide insight into functional cortical circuitry in autism and highlight any significant early developmental disturbances.
Methods: A 1 in 4 series of 10m sections from BA32 obtained post-mortem from 8 cases with ASD (24.0 ± 5.3 years, range 5-45) and 11 age and gender-matched controls (28.1 ± 3.9 years, range 4-44), were stained with toluidine blue, immunolabeled with MAP2 and analysed using unbiased stereology (MicroBrightfield) to determine neuronal and glial cell densities in cortical layers 5, 6, subcortical white matter (WM) and total neuronal numbers (under 1mm2 cortex). Neuronal clustering and alignment were also determined using customised Voronoi tessellation and morphometric image analysis (Media Cybernetics).
Results: Mean WM glial cell density was 1.27 fold higher in ASD cases than controls (p=0.05), particularly high in the two oldest ASD cases (1.6-1.7 fold higher). Mean layer 5 and 6 neuronal and glial cell densities did not differ significantly between ASD and controls, although higher mean glial-to-neuronal ratios were found in ASD (L5:1.66; L6:1.88) compared to controls (L5:1.41; L6:1.54). Mean WM neuron densities were higher in ASD but did not reach statistical significance.
Discussion: This is the first stereological study of BA32 in ASD. Voronoi and morphometric analyses will be discussed. Increased WM glial density supports our previous findings, did not correlate with seizure activity, but could relate to altered functional connectivity and WM abnormalities reported in ASD. This work was supported by the Autism Tissue Program (US) and funded by Autism Speaks (US).
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