Download The dorsal anterior cingulate cortex ( BA32) in autism: an

Morphometric (tessellation) analysis reveals no quantifiable difference in
spatial arrangement of MAP2-immunolabelled neurons in BA32 (cortical
layers 5 and 6) in autism
Jason S. Dunham1, Eva M. Del Valle Suarez1, David P.L. Wiles2, Christoph
Schmitz3, Paul L. Gabbott1*, Payam Rezaie1*
1Neuropathology
and Functional Neurocytology Research Laboratories,
Department of Life Sciences, Faculty of Science, Open University, Milton Keynes,
UK; 2Media Cybernetics UK and Europe, Marlow, Buckinghamshire, UK;
3Department of Psychiatry and Neuropsychology, Maastricht University,
Netherlands. *Correspondence: [email protected]; [email protected].
Supported by: Autism Speaks (USA)
Abstract
Focal cortical dysplasia and laminar disorganisation are pathological features
associated with autism. Recent reports suggest neuronal numbers are reduced in
deeper cortical layers (fusiform gyrus and anterior cingulate). Changes affecting
neuronal arrangement in these layers would support early migratory disturbances
in autism. We analysed the spatial arrangement of MAP2+ neurons in layers 5-6
(L5/6) of the dorsal anterior cingulate cortex (BA32) using a novel tessellation
procedure based on the Voronoi method (1). Similar methods have previously
been applied to cases with epilepsy showing re-organisational dysplasia (2) and
microdysgenesis (3). Postmortem tissue from 8 autism cases (24.0 ± 5.3 years)
and 11 controls (28.1 ± 3.9 years) matched for age, gender and hemisphere, were
obtained via the Autism Tissue Program (USA) with LREC approval. A 1-in-4
series of sections were immunolabelled to detect MAP2+ neurons (clone HM2,
Sigma), and analysed using customised software (Image Pro Plus, Version 5) to
determine spatial ‘clustering’ of neurons. The tessellation programme defined the
midpoint between a ‘tagged’ neuron and its closest neighbour within a 2-D plane,
enabling calculation of coefficient of variation (CV) values of derived polygon
areas and mean distances between neighbouring neurons (1-3). L5-6 laminar
widths and mean percentage cortical depth values were also compared, but
showed no significant differences between cohorts. Total mean CV of polygon
areas, CV of polygon class sizes and mean point-to-point distances (between
nearest neighbouring neurons) did not differ significantly between groups. At least
two of the autism cases in this study showed evidence of focal neuronal crowding
and cortical dysplasia elsewhere within the cerebral cortex. However, tessellation
analysis failed to reveal any significant differences in spatial arrangements of
MAP2+ neurons within deeper cortical layers of BA32. Significant variation in
dysplastic features within brain areas and between affected individuals, if present,
could be masked when examining cohort/group effects.
References
1. Duyckaerts, C, Godefroy, G (2000) J Chem Neuroanatomy 20:83-92
2. Thom, M et al. (2009) J Neuropathol Exp Neurol 68:928-938
3. Eriksson, SF et al. (2003) J Neurosci Methods 128:151-157