Dataset Information

Regional Alterations in Cortical Sulcal Depth in Living Fetuses with Down Syndrome.

ABSTRACT: Down syndrome (DS) is the most common genetic cause of developmental disabilities. Advanced analysis of brain magnetic resonance imaging (MRI) has been used to find brain abnormalities and their relationship to neurocognitive impairments in children and adolescents with DS. Because genetic factors affect brain development in early fetal life, there is a growing interest in analyzing brains from living fetuses with DS. In this study, we investigated regional sulcal folding depth as well as global cortical gyrification from fetal brain MRIs. Nine fetuses with DS (29.1 ± 4.24 gestational weeks [mean ± standard deviation]) were compared with 17 typically developing [TD] fetuses (28.4 ± 3.44). Fetuses with DS showed lower whole-brain average sulcal depths and gyrification index than TD fetuses. Significant decreases in sulcal depth were found in bilateral Sylvian fissures and right central and parieto-occipital sulci. On the other hand, significantly increased sulcal depth was shown in the left superior temporal sulcus, which is related to atypical hemispheric asymmetry of cortical folding. Moreover, these group differences increased as gestation progressed. This study demonstrates that regional sulcal depth is a sensitive marker for detecting alterations of cortical development in DS during fetal life, which may be associated with later neurocognitive impairment.

SUBMITTER: Yun HJ

PROVIDER: S-EPMC7786357 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Regional Alterations in Cortical Sulcal Depth in Living Fetuses with Down Syndrome.

Yun Hyuk Jin HJ Perez Juan David Ruiz JDR Sosa Patricia P Valdés J Alejandro JA Madan Neel N Kitano Rie R Akiyama Shizuko S Skotko Brian G BG Feldman Henry A HA Bianchi Diana W DW Grant P Ellen PE Tarui Tomo T Im Kiho K

Cerebral cortex (New York, N.Y. : 1991) 20210101 2

Down syndrome (DS) is the most common genetic cause of developmental disabilities. Advanced analysis of brain magnetic resonance imaging (MRI) has been used to find brain abnormalities and their relationship to neurocognitive impairments in children and adolescents with DS. Because genetic factors affect brain development in early fetal life, there is a growing interest in analyzing brains from living fetuses with DS. In this study, we investigated regional sulcal folding depth as well as global ...[more]

PMID: 32940649

Similar Datasets

Project description:ObjectiveTissue abnormalities in focal epilepsy may extend beyond the presumed focus. The underlying pathophysiology of these broader changes is unclear, and it is not known whether they result from ongoing disease processes or treatment-related side effects, or whether they emerge earlier. Few studies have focused on the period of onset for most focal epilepsies, childhood. Fewer still have utilized quantitative magnetic resonance imaging (MRI), which may provide a more sensitive and interpretable measure of tissue microstructural change. Here, we aimed to determine common spatial modes of changes in cortical architecture in children with heterogeneous drug-resistant focal epilepsy and, secondarily, whether changes were related to disease severity.MethodsTo assess cortical microstructure, quantitative T1 and T2 relaxometry (qT1 and qT2) was measured in 43 children with drug-resistant focal epilepsy (age range = 4-18 years) and 46 typically developing children (age range = 2-18 years). We assessed depth-dependent qT1 and qT2 values across the neocortex, as well as their gradient of change across cortical depths. We also determined whether global changes seen in group analyses were driven by focal pathologies in individual patients. Finally, as a proof-of-concept, we trained a classifier using qT1 and qT2 gradient maps from patients with radiologically defined abnormalities (MRI positive) and healthy controls, and tested whether this could classify patients without reported radiological abnormalities (MRI negative).ResultsWe uncovered depth-dependent qT1 and qT2 increases in widespread cortical areas in patients, likely representing microstructural alterations in myelin or gliosis. Changes did not correlate with disease severity measures, suggesting they may represent antecedent neurobiological alterations. Using a classifier trained with MRI-positive patients and controls, sensitivity was 71.4% at 89.4% specificity on held-out MRI-negative patients.SignificanceThese findings suggest the presence of a potential imaging endophenotype of focal epilepsy, detectable irrespective of radiologically identified abnormalities.

Project description:Introduction: Down syndrome (DS) is a genetic disorder with an extra copy of chromosome 21 and DS remains one of the most common causes of intellectual disabilities in humans. All DS patients have Alzheimer's disease (AD)-like neuropathological changes including accumulation of plaques and tangles by their 40s, much earlier than the onset of such neuropathological changes in AD patients. Due to the lack of human samples and appropriate techniques, our understanding of DS neuropathology during brain development or before the clinical onset of the disease remains largely unexplored at the cellular and molecular levels. Methods: We used induced pluripotent stem cell (iPSC) and iPSC-derived 3D cortical organoids to model Alzheimer's disease in Down syndrome and explore the earliest cellular and molecular changes during DS fetal brain development. Results: We report that DS iPSCs have a decreased growth rate than control iPSCs due to a decreased cell proliferation. DS iPSC-derived cortical organoids have a much higher immunoreactivity of amyloid beta (Aß) antibodies and a significantly higher amount of amyloid plaques than control organoids. Although Elisa results did not detect a difference of Aß40 and Aß42 level between the two groups, the ratio of Aß42/Aß40 in the detergent-insoluble fraction of DS organoids was significantly higher than control organoids. Furthermore, an increased Tau phosphorylation (pTau S396) in DS organoids was confirmed by immunostaining and Western blot. Elisa data demonstrated that the ratio of insoluble Tau/total Tau in DS organoids was significantly higher than control organoids. Conclusion: DS iPSC-derived cortical organoids mimic AD-like pathophysiologyical phenotype in vitro, including abnormal Aß and insoluble Tau accumulation. The molecular neuropathologic signature of AD is present in DS much earlier than predicted, even in early fetal brain development, illustrating the notion that brain organoids maybe a good model to study early neurodegenerative conditions.

Dataset Information

Regional Alterations in Cortical Sulcal Depth in Living Fetuses with Down Syndrome.

Publications

Regional Alterations in Cortical Sulcal Depth in Living Fetuses with Down Syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets