Patches of Disorganization in the Neocortex of Children with Autism
By R. Stoner, Maggie L Chow, Maureen P. Boyle, Susan Sunkin, P. Mouton, Subhojit Roy, A. Wynshaw-Boris, S. Colamarino, E. Lein, Eric Courchesne. New England Journal of Medicine, 2014
691 citations recorded by the source corpus.
Background Autism involves early brain overgrowth and dysfunction, which is most strongly evident in the prefrontal cortex. As assessed on pathological analysis, an excess of neurons in the prefrontal cortex among children with autism signals a disturbance in prenatal development and may be concomitant with abnormal cell type and laminar development. Methods To systematically examine neocortical architecture during the early years after the onset of autism, we used RNA in situ hybridization with a panel of layer- and cell-type– specific molecular markers to phenotype cortical microstructure. We assayed markers for neurons and glia, along with genes that have been implicated in the risk of autism, in prefrontal, temporal, and occipital neocortical tissue from postmortem samples obtained from children with autism and unaffected children between the ages of 2 and 15 years. Results We observed focal patches of abnormal laminar cytoarchitecture and cortical disorganization of neurons, but not glia, in prefrontal and temporal cortical tissue from 10 of 11 children with autism and from 1 of 11 unaffected children. We observed heterogeneity between cases with respect to cell types that were most abnormal in the patches and the layers that were most affected by the pathological features. No cortical layer was uniformly spared, with the clearest signs of abnormal expression in layers 4 and 5. Three-dimensional reconstruction of layer markers confirmed the focal geometry and size of patches. Conclusions In this small, explorative study, we found focal disruption of cortical laminar architecture in the cortexes of a majority of young children with autism. Our data support a probable dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages. (Funded by the Simons Foundation and others.)
Subfields: Cognitive Neuroscience, Developmental Neuroscience
View Paper: https://www.semanticscholar.org/paper/8535d93cf84e3202651e1f671a3c313ab1192d78
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Citations in the corpus
- Genome-wide prediction and functional characterization of the genetic basis of autism spectrum disorder (2016, result): “This finding is largely consistent with previous studies 16,18,30,31 , as well as recent findings on the possible role of callosal projection neurons 17 and on the neuropathology of autism brain 32 .”
- The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring (2016, background): “1, H and I); (ii) Cortical development starts approximately at E11 (20), which aligns well with the time points of potential fetal exposure to MIA (7); (iii) Disorganized cortex and focal patches of abnormal laminar cytoarchitecture have been found in the brains of ASD patients (21, 22); and (iv) MI”
- Brain organoids: advances, applications and challenges (2019, background): “Despite the difficulty in collecting human brain samples with consistent quality, analyses of these samples have continued to expand our knowledge of normal and diseased human brains (Calvet et al., 2016; Hansen et al., 2010; Moore et al., 2017; Nowakowski et al., 2016; Ozair et al., 2018; Pollen et”