Abnormal cell patterning at the cortical gray-white matter boundary in autism spectrum disorders
ABSTRACT Previous research on neuronal spacing and columnar organization indicates the presence of cell patterning alterations within the cerebral cortex of individuals with autism spectrum disorders (ASD). These patterning abnormalities include irregularities at the gray-white matter boundary and may implicate early neurodevelopmental events such as migration in altering cortical organization in ASD. The present study utilized a novel method to quantify the gray-white matter boundary in eight ASD and eight typically developing control subjects. Digital photomicrographs of the gray-white matter boundary were acquired from multiple positions within the superior temporal gyrus (BA21), dorsolateral frontal lobe (BA9), and dorsal parietal lobe (BA7) of each case. A sigmoid curve was fitted to the transition zone between layer VI and underlying white matter (subplate), and the slope of the resulting curve was used as a measure of the spatial extent of the transition zone. For all three cortical regions examined, ASD subjects showed "shallower" sigmoid curves compared to neurotypicals, indicating the presence of an indistinct boundary between cortical layer VI and the underlying white matter. These results may reflect the presence of supernumerary neurons beneath the cortical plate that could be the result of migration deficits or failed apoptosis in the subplate region. Furthermore, these findings raise questions regarding the validity of cortical measures that rely on gray-white matter parcellation, since an indistinct transition zone could lead to a misplaced cortical boundary and errors in both thickness and volume measures.
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ABSTRACT: Autism spectrum disorders (ASD) are characterized by impairments in social communication and restrictive, repetitive behaviors. While behavioral symptoms are well-documented, investigations into the neurobiological underpinnings of ASD have not resulted in firm biomarkers. Variability in findings across structural neuroimaging studies has contributed to difficulty in reliably characterizing the brain morphology of individuals with ASD. These inconsistencies may also arise from the heterogeneity of ASD, and wider age-range of participants included in MRI studies and in previous meta-analyses. To address this, the current study used coordinate-based anatomical likelihood estimation (ALE) analysis of 21 voxel-based morphometry (VBM) studies examining high-functioning individuals with ASD, resulting in a meta-analysis of 1055 participants (506 ASD, and 549 typically developing individuals). Results consisted of grey, white, and global differences in cortical matter between the groups. Modeled anatomical maps consisting of concentration, thickness, and volume metrics of grey and white matter revealed clusters suggesting age-related decreases in grey and white matter in parietal and inferior temporal regions of the brain in ASD, and age-related increases in grey matter in frontal and anterior-temporal regions. White matter alterations included fiber tracts thought to play key roles in information processing and sensory integration. Many current theories of pathobiology ASD suggest that the brains of individuals with ASD may have less-functional long-range (anterior-to-posterior) connections. Our findings of decreased cortical matter in parietal–temporal and occipital regions, and thickening in frontal cortices in older adults with ASD may entail altered cortical anatomy, and neurodevelopmental adaptations.11/2014; 7. DOI:10.1016/j.nicl.2014.11.004
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ABSTRACT: Autism spectrum disorder (ASD) is defined by impaired social interaction and communication accompanied by stereotyped behaviors and restricted interests. Although ASD is common, its genetic and clinical features are highly heterogeneous. A number of recent breakthroughs have dramatically advanced our understanding of ASD from the standpoint of human genetics and neuropathology. These studies highlight the period of fetal development and the processes of chromatin structure, synaptic function, and neuron-glial signaling. The initial efforts to systematically integrate findings of multiple levels of genomic data and studies of mouse models have yielded new clues regarding ASD pathophysiology. This early work points to an emerging convergence of disease mechanisms in this complex and etiologically heterogeneous disorder.
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ABSTRACT: Subplate neurons have an essential role in cortical circuit formation. They are among the earliest formed neurons of the cerebral cortex, are located at the junction of white and grey matter, and are necessary for correct thalamocortical axon ingrowth. Recent transcriptomic studies have provided opportunities for monitoring and modulating selected subpopulations of these cells. Analyses of mouse lines expressing reporter genes have demonstrated novel, extracortical subplate neurogenesis and have shown how subplate cells are integrated under the influence of sensory activity into cortical and extracortical circuits. Recent studies have revealed that the subplate is involved in neurosecretion and modification of the extracellular milieu.Nature reviews Neuroscience 02/2015; 16(3):133-46. DOI:10.1038/nrn3915 · 31.38 Impact Factor