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A key feature of the fetal period is the rapid emergence of organised patterns of spontaneous brain activity. However, characterising this process in utero using functional MRI is inherently challenging and requires analytical methods which can capture the constituent developmental transformations. Here, we introduce a novel analytical framework, termed "maturational networks" (matnets), that achieves this by modelling functional networks as an emerging property of the developing brain. Compared to standard network analysis methods that assume consistent patterns of connectivity across development, our method incorporates age-related changes in connectivity directly into network estimation. We test its performance in a large neonatal sample, finding that the matnets approach characterises adult-like features of functional network architecture with a greater specificity than a standard group-ICA approach; for example, our approach is able to identify a nearly complete default mode network. In the in-utero brain, matnets enables us to reveal the richness of emerging functional connections and the hierarchy of their maturational relationships with remarkable anatomical specificity. We show that the associative areas play a central role within prenatal functional architecture, therefore indicating that functional connections of high-level associative areas start emerging prior to exposure to the extra-utero environment., (© 2023. The Author(s).)

An important step toward delivering an accurate connectome of the human brain is robust segmentation of 3D Magnetic Resonance Imaging (MRI) scans, which is particularly challenging when carried out on perinatal data. In this paper, we present an automated, deep learning-based pipeline for accurate segmentation of tissues from neonatal brain MRI and extend it by introducing an age prediction pathway. A major constraint to using deep learning techniques on developing brain data is the need to collect large numbers of ground truth labels. We therefore also investigate two practical approaches that can help alleviate the problem of label scarcity without loss of segmentation performance. First, we examine the efficiency of different strategies of distributing a limited budget of annotated 2D slices over 3D training images. In the second approach, we compare the segmentation performance of pre-trained models with different strategies of fine-tuning on a small subset of preterm infants. Our results indicate that distributing labels over a larger number of brain scans can improve segmentation performance. We also show that even partial fine-tuning can be superior in performance to a model trained from scratch, highlighting the relevance of transfer learning strategies under conditions of label scarcity. We illustrate our findings on large, publicly available T1- and T2-weighted MRI scans ( n = 709, range of ages at scan: 26-45 weeks) obtained retrospectively from the Developing Human Connectome Project (dHCP) cohort., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Richter and Fetit.)

Cardiovascular diseases are a public health concern; they remain the leading cause of morbidity and mortality in patients with type 2 diabetes. Phenotypic information available from retinal fundus images and clinical measurements, in addition to genomic data, can identify relevant biomarkers of cardiovascular health. In this study, we assessed whether such biomarkers stratified risks of major adverse cardiac events (MACE). A retrospective analysis was carried out on an extract from the Tayside GoDARTS bioresource of participants with type 2 diabetes (n = 3,891). A total of 519 features were incorporated, summarising morphometric properties of the retinal vasculature, various single nucleotide polymorphisms (SNPs), as well as routine clinical measurements. After imputing missing features, a predictive model was developed on a randomly sampled set (n = 2,918) using L1-regularised logistic regression (lasso). The model was evaluated on an independent set (n = 973) and its performance associated with overall hazard rate after censoring (log-rank p < 0.0001), suggesting that multimodal features were able to capture important knowledge for MACE risk assessment. We further showed through a bootstrap analysis that all three sources of information (retinal, genetic, routine clinical) offer robust signal. Particularly robust features included: tortuousity, width gradient, and branching point retinal groupings; SNPs known to be associated with blood pressure and cardiovascular phenotypic traits; age at imaging; clinical measurements such as blood pressure and high density lipoprotein. This novel approach could be used for fast and sensitive determination of future risks associated with MACE.

Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size., (© 2016 Martin et al.; Published by Cold Spring Harbor Laboratory Press.)