Abnormal cell patterning at the cortical gray-white matter boundary in autism spectrum disorders
Psychology Department, University of Nevada, Reno, NV 89557, USA. Brain research
(Impact Factor: 2.84).
11/2010; 1360:138-46. DOI: 10.1016/j.brainres.2010.08.091
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.
Available from: Cornelie A Blok
- "Moreover, (selective) neuronal loss in several cortical regions often occurs in WMD . However, the layer of abnormal progenitor cells which do not reach the capacity to form myelin has been shown to be situated at the cortical grey-white matter boundaries , , which may change the intensity of the transition zone between cGM and WM, as is also reported in other abnormal cell patterning at the grey-white matter boundary , . We can only speculate that in our cohort of very preterm infants an indistinct transition of GM-to-abnormal white matter in those infants with WMD has led to overestimation of the grey volume measurements. "
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ABSTRACT: Increased levels of end-tidal carbon monoxide (ETCOc) in preterm infants during the first day of life are associated with oxidative stress, inflammatory processes and adverse neurodevelopmental outcome at 2 years of age. Therefore, we hypothesized that early ETCOc levels may also be associated with impaired growth of unmyelinated cerebral white matter.
From a cohort of 156 extremely and very preterm infants in which ETCOc was determined within 24 h after birth, in 36 infants 3D-MRI was performed at term-equivalent age to assess cerebral tissue volumes of important brain regions.
Linear regression analysis between cerebral ventricular volume, unmyelinated white matter/total brain volume-, and cortical grey matter/total brain volume-ratio and ETCOc showed a positive, negative and positive correlation, respectively. Multivariable analyses showed that solely ETCOc was positively related to cerebral ventricular volume and cortical grey matter/total brain volume ratio, and that solely ETCOc was inversely related to the unmyelinated white matter/total brain volume ratio, suggesting that increased levels of ETCOc, associated with oxidative stress and inflammation, were related with impaired growth of unmyelinated white matter.
Increased values of ETCOc, measured within the first 24 hours of life may be indicative of oxidative stress and inflammation in the immediate perinatal period, resulting in impaired growth of the vulnerable unmyelinated white matter of the preterm brain.
Available from: Daniel Dukes
- "Decreased gyrification, as observed in the present study, is highly suggestive of reduced cortical expansion during early brain development, a process that might differentially affect specific cortical regions. Neuropathological reports have pointed to abnormal cortical development in ASD, including a higher incidence of cortical dysgenesis, heterotopias and migration abnormalities (Avino and Hutsler, 2010; Wegiel et al., 2010). Further detailed examination revealed that one cell type affected by migration deficits in young children with ASD is von Economo neurons (Santos et al., 2011), which are spindle-shaped neurons thought to play a role in emotional function (Butti et al., 2013) that are located in the frontoinsular and cingulate cortices. "
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ABSTRACT: The structural correlates of functional dysconnectivity in autism spectrum disorders (ASD) have been seldom explored, despite the fact that altered functional connectivity is one of the most frequent neuropathological observations in the disorder. We analyzed cerebral morphometry and structural connectivity using multi-modal imaging for 11 children/adolescents with ASD and 11 matched controls. We estimated regional cortical and white matter volumes, as well as vertex-wise measures of cortical thickness and local Gyrification Index (lGI). Diffusion Tensor Images (DTI) were used to measure Fractional Anistropy and tractography estimates of short- and long-range connectivity. We observed four clusters of lGI reduction in patients with ASD, three were located in the right inferior frontal region extending to the inferior parietal lobe, and one was in the right medial parieto-occipital region. Reduced volume was found in the anterior corpus callosum, along with fewer inter-hemispheric frontal streamlines. Despite the spatial correspondence of decreased gyrification and reduced long connectivity, we did not observe any significant relationship between the two. However, a positive correlation between lGI and local connectivity was present in all four clusters in patients with ASD. Reduced gyrification in the inferior fronto-parietal and posterior medial cortical regions lends support for early-disrupted cortical growth in both the mirror neuron system and midline structures responsible for social cognition. Early impaired neurodevelopment in these regions may represent an initial substrate for altered maturation in the cerebral networks that support complex social skills. We also demonstrate that gyrification changes are related to connectivity. This supports the idea that an imbalance between short- and long-range white matter tracts not only impairs the integration of information from multiple neural systems, but also alters the shape of the brain early on in autism.
Available from: Nancy Minshew
- "What role they may play in adult brain function is unknown, although it is hypothesized that abnormal axonal connectivity during fetal life may cause, or be reflected by, abnormalities in the numbers and/or distribution of INs that persist into adulthood. The presence of excess INs in ASD could potentially be explained by either abnormal proliferation early in embryonic life or reduced developmental apoptosis in the later fetal/perinatal period (Chun and Shatz, 1989; Avino and Hutsler, 2010). Because the subplate is an early structure, the same frontal overgrowth causing excess radial glia/minicolumns and cortical neurons may also be responsible for (or related to) the production of excess subplate neurons. "
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ABSTRACT: Current theories concerning the cause of autism spectrum disorders (ASDs) have converged on the concept of abnormal development of brain connectivity. This concept is supported by accumulating evidence from functional imaging, diffusion tensor imaging, and high definition fiber tracking studies which suggest altered microstructure in the axonal tracts connecting cortical areas may underly many of the cognitive manifestations of ASD. Additionally, large-scale genomic studies implicate numerous gene candidates known or suspected to mediate neuritic outgrowth and axonal guidance in fetal and perinatal life. Neuropathological observations in postmortem ASD brain samples further support this model and include subtle disturbances of cortical lamination and subcortical axonal morphology. Of note is the relatively common finding of poor differentiation of the gray-white junction associated with an excess superficial white matter or "interstitial" neurons (INs). INs are thought to be remnants of the fetal subplate, a transient structure which plays a key role in the guidance and morphogenesis of thalamocortical and cortico-cortical connections and the organization of cortical columnar architecture. While not discounting the importance of synaptic dysfunction in the etiology of ASD, this paper will briefly review the cortical abnormalities and genetic evidence supporting a model of dysregulated axonal growth and guidance as key developmental processes underlying the clinical manifestations of ASD.
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