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Recognition memory for details of musical phrases (discrimination between targets and similar lures) improves for up to 15 s following the presentation of a target, during continuous listening to the ongoing piece. This is attributable to binding of stimulus features during that time interval. The ongoing-listening paradigm is an ecologically valid approach for investigating short-term memory, but previous studies made use of relatively mechanical MIDI-produced stimuli. The present study assessed whether expressive performances would modulate the previously reported finding. Given that expressive performances introduced slight differences between initially presented targets and their target-test items, expressive performance could make the task more difficult overall than did the previously used mechanical renderings. However, results revealed an even stronger improvement for the expressive pieces than for the mechanical pieces. The pattern of results was observed for participants varying in their level of musical experience, though the difference between expressive and mechanical conditions was more pronounced for the less-experienced participants. Overall, our study showed that the memory improvement phenomenon extends to more realistic musical material, which includes expressive timing characteristics of live performance.

Alterations in the voltage-gated sodium channel Nav.1.1 are implicated in various neurological disorders, including epilepsy, Alzheimer’s disease, and autism spectrum disorders. Previous studies suggest that the reduction of Nav1.1 expression leads to a decrease of fast spiking activity in inhibitory neurons. Because interneurons (INs) play a critical role in the temporal organization of neuronal discharge, we hypothesize that Nav1.1 dysfunction will negatively impact neuronal coordination in vivo. Using shRNA interference, we induced a focal Nav1.1 knock-down (KD) in the dorsal region of the right hippocampus of adult rats. Focal, unilateral Nav1.1 KD decreases the performance in a spatial novelty recognition task and the firing rate in INs, but not in pyramidal cells. It reduced theta/gamma coupling of hippocampal oscillations and induced a shift in pyramidal cell theta phase preference. Nav1.1 KD degraded spatial accuracy and temporal coding properties of place cells, such as theta phase precession and compression of ongoing sequences. Aken together, these data demonstrate that a deficit in Nav1.1 alters the temporal coordination of neuronal firing in CA1 and impairs behaviors that rely on the integrity of this network. They highlight the potential contribution of local inhibition in neuronal coordination and its impact on behavior in pathological conditions.

Purpose Spring-assisted cranioplasty is performed to correct the long and narrow head shape of children with sagittal synostosis. Such corrective surgery involves osteotomies and the placement of spring-like distractors, which gradually expand to widen the skull until removal about 4 months later. Due to its dynamic nature, associations between surgical parameters and post-operative 3D head shape features are difficult to comprehend. The current study aimed at applying population-based statistical shape modelling to gain insight into how the choice of surgical parameters such as craniotomy size and spring positioning affects post-surgical head shape. Methods Twenty consecutive patients with sagittal synostosis who underwent spring-assisted cranioplasty at Great Ormond Street Hospital for Children (London, UK) were prospectively recruited. Using a nonparametric statistical modelling technique based on mathematical currents, a 3D head shape template was computed from surface head scans of sagittal patients after spring removal. Partial least squares (PLS) regression was employed to quantify and visualise trends of localised head shape changes associated with the surgical parameters recorded during spring insertion: anterior–posterior and lateral craniotomy dimensions, anterior spring position and distance between anterior and posterior springs. Results Bivariate correlations between surgical parameters and corresponding PLS shape vectors demonstrated that anterior–posterior (Pearson’s \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$r=0.64, p=0.002$$\end{document}r=0.64,p=0.002) and lateral craniotomy dimensions (Spearman’s \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\rho =0.67, p

BACKGROUND: Aortic arch reconstruction after hypoplastic left heart syndrome (HLHS) palliation can vary widely in shape and dimensions between patients. Arch morphology alone may affect cardiac function and outcome. We sought to uncover the relationship of arch three-dimensional shape features with functional and short-term outcome data after total cavopulmonary connection (TCPC).METHODS: Aortic arch shape models of 37 patients with HLHS (age, 2.89 ± 0.99 years) were reconstructed from magnetic resonance data before TCPC completion. A novel, validated statistical shape analysis method was used to compute a three-dimensional anatomic mean shape from the cohort and calculate the deformation vectors of the mean shape toward each patient's specific anatomy. From these deformations, three-dimensional shape features most related to ventricular ejection fraction, indexed end-diastolic volume, and superior cavopulmonary pressure were extracted by partial least-square regression analysis. Shape patterns relating to intensive care unit and hospital lengths of stay after TCPC were assessed.RESULTS: Distinct deformation patterns, which result in an acutely mismatched aortic root and ascending aorta, and a gothic-like transverse arch, correlated with increased indexed end-diastolic volume and higher superior cavopulmonary pressure but not with ejection fraction. Specific arch morphology with pronounced transverse arch and descending aorta mismatch also correlated with longer intensive care unit and hospital lengths of stay after TCPC completion.CONCLUSIONS: Independent of hemodynamically important arch obstruction, altered aortic morphology in HLHS patients appears to have important associations with higher superior cavopulmonary pressure and with short-term outcomes after TCPC completion as highlighted by statistical shape analysis, which could act as adjunct to risk assessment in HLHS.

International audience; Primary microcephaly is a neurodevelopmental disorder that is caused by a reduction in brain size as a result of defects in the proliferation of neural progenitor cells during development. Mutations in genes encoding proteins that localize to the mitotic spindle and centrosomes have been implicated in the pathogenicity of primary microcephaly. In contrast, the contractile ring and midbody required for cytokinesis, the final stage of mitosis, have not previously been implicated by human genetics in the molecular mechanisms of this phenotype. Citron kinase (CIT) is a multi-domain protein that localizes to the cleavage furrow and midbody of mitotic cells, where it is required for the completion of cytokinesis. Rodent models of Cit deficiency highlighted the role of this gene in neurogenesis and microcephaly over a decade ago. Here, we identify recessively inherited pathogenic variants in CIT as the genetic basis of severe microcephaly and neonatal death. We present postmortem data showing that CIT is critical to building a normally sized human brain. Consistent with cytokinesis defects attributed to CIT, multinucleated neurons were observed throughout the cerebral cortex and cerebellum of an affected proband, expanding our understanding of mechanisms attributed to primary microcephaly.

Highlights • This paper presents a voxelwise atlas rating approach for computer-aided diagnosis. • The method relies on multiple atlas databases, but does not require annotated images. • The method reports an accuracy of 97.3%, which is higher than other state-of-the-art methods., Graphical abstract, Atlas-based analysis methods rely on the morphological similarity between the atlas and target images, and on the availability of labelled images. Problems can arise when the deformations introduced by pathologies affect the similarity between the atlas and a patient’s image. The aim of this work is to exploit the morphological dissimilarities between atlas databases and pathological images to diagnose the underlying clinical condition, while avoiding the dependence on labelled images. We propose a voxelwise atlas rating approach (VoxAR) relying on multiple atlas databases, each representing a particular condition. Using a local image similarity measure to assess the morphological similarity between the atlas and target images, a rating map displaying for each voxel the condition of the atlases most similar to the target is defined. The final diagnosis is established by assigning the condition of the database the most represented in the rating map. We applied the method to diagnose three different conditions associated with dextro-transposition of the great arteries, a congenital heart disease. The proposed approach outperforms other state-of-the-art methods using annotated images, with an accuracy of 97.3% when evaluated on a set of 60 whole heart MR images containing healthy and pathological subjects using cross validation.

The EuroBioBank (EBB) network (www.eurobiobank.org) is the first operating network of biobanks in Europe to provide human DNA, cell and tissue samples as a service to the scientific community conducting research on rare diseases (RDs). The EBB was established in 2001 to facilitate access to RD biospecimens and associated data; it obtained funding from the European Commission in 2002 (5th framework programme) and started operation in 2003. The set-up phase, during the EC funding period 2003-2006, established the basis for running the network; the following consolidation phase has seen the growth of the network through the joining of new partners, better network cohesion, improved coordination of activities, and the development of a quality-control system. During this phase the network participated in the EC-funded TREAT-NMD programme and was involved in planning of the European Biobanking and Biomolecular Resources Research Infrastructure. Recently, EBB became a partner of RD-Connect, an FP7 EU programme aimed at linking RD biobanks, registries, and bioinformatics data. Within RD-Connect, EBB contributes expertise, promotes high professional standards, and best practices in RD biobanking, is implementing integration with RD patient registries and 'omics' data, thus challenging the fragmentation of international cooperation on the field. EBB thanks EURORDIS for administrative support, Fondazione Telethon for administrative and financial support, the EC for providing funds (grants: FP5 EuroBioBank, contract N. 02769; FP6 TREAT-NMD, contract N. 036825; and FP7 RD-Connect, grant agreement N. 305444), and AFM for the vision of the network and for encouraging the network to get together. EBB gratefully acknowledges patients and collaborating clinicians/researchers for contributing samples and data to the network, and biobank staffs for running the EBB biobanks. The MRC support to the biobank in London and Newcastle is also gratefully acknowledged. Sí

International audience; We draw attention to a number of important considerations in the arguments about screening and outcome of intervention in children with autism and other developmental disorders. Autism screening in itself never provides a final clinical diagnosis, but may well identify developmental deviations indicative of autism-or of other developmental disorders-that should lead to referral for further clinical assessment. Decisions regarding population or clinic screening cannot be allowed to be based on the fact that prospective longitudinal RCT designs over decades could never be performed in complex developmental disorders. We propose an alternative approach. Early screening for autism and other developmental disorders is likely to be of high societal importance and should be promoted and rigorously evaluated.

International audience; We show that microinjecting cyclic GMP (cGMP) into unfertilized sea urchin eggs activates them by stimulating a rise in the intracellular free calcium ion concentration ([Ca21]i). The increase in [Ca21]i is similar in both magnitude and duration to the transient that activates the egg at fertilization. It is due to mobilization of calcium from intracellular stores but is not prevented by the inositol trisphosphate (InsP3) antagonist heparin. Furthermore, cGMP does not stimulate the eggs Na+/H+ antiport when the [Ca21]i transient is blocked by the calcium chelator bis-(O-aminophenoxy)-N,N,NN'-tetraacetic acid (BAPTA), suggesting that cGMP does not activate eggs by interacting with the their phosphoinositide signaling pathway. However, the [Ca21]i increase and activation are prevented in eggs in which the InsP3sensitive calcium stores have been emptied by the prior microinjection of the InsP3 analogue inositol 1,4,5-trisphosphorothioate. These data indicate that cGMP activates eggs by stimulating the release of calcium from an InsP3-sensitive calcium store via a novel, though unidentified, route independent of the InsP3 receptor.