Search bioRxiv⌕ Search

Biology subjects

Clerc, M.

Publications and source records attributed to Clerc, M..

5 recordsLinked to original sources

Attentional inhibition ability predicts neural representation during challenging auditory streaming

Focusing on a single source within a complex auditory scene is challenging. M/EEG-based auditory attention detection allows to detect which stream, within a set of multiple concurrent streams, an individual is attending to. The high inter-individual variability in the AAD performance is most often attributed to physiological factors and signal to noise ratio of neural data. Here we address the hypothesis that cognitive factors and in particular sustained attention, WM and attentional inhibition, may also partly explain the variability in AAD performance, because they support the cognitive processes required when listening to complex auditory scenes. Here, we chose a particularly challenging auditory scene, by presenting dichotically polyphonic classical piano excerpts lasting one minute each. Two different excerpts were presented simultaneously in each ear. Forty-one participants, with different degrees of musical expertise, listened to these complex auditory scenes focussing on one ear while we recorded the EEG. Participants also completed several tasks assessing executive functions. As expected, attended stimuli were better decoded than unattended stimuli. Importantly, attentional inhibition ability did explain around 10% of the reconstruction accuracy and around 8% of the classification accuracy. No other cognitive function was a significant predictor of reconstruction or of classification accuracies. No clear effect of musical expertise was found on reconstruction and classification performances. In conclusion, cognitive factors seem to impact the robustness of the auditory representation and hence the performance of neural based decoding approaches. Taking advantage of this relation could be useful to improve next-generation hearing aids.

neuroscience↗

Rearing environment persistently modulates the phenotype of mice

The phenotype of an organism results from its genotype and the influence of the environment throughout development. Even when using animals of the same genotype, independent studies may test animals of different phenotypes, resulting in poor replicability due to genotype-by-environment interactions 1-4. Thus, genetically defined strains of mice may respond differently to experimental treatments depending on their rearing environment 5. However, the extent of such phenotypic plasticity and its implications for the replicability of research findings have remained unknown. Here, we examined the extent to which common environmental differences between rearing facilities modulate the phenotype of genetically homogeneous (inbred) mice. We conducted a comprehensive multi-center study, where inbred mice from the same breeding stock were reared in five different facilities throughout early life and adolescence, before being transported to a single test laboratory. We found persistent effects of rearing facility on the composition and heterogeneity of the gut microbial community. These effects were paralleled by persistent differences in body weight and in the behavioural phenotype of the mice. Furthermore, we show that common variation among rearing facilities is strong enough to influence epigenetic patterns in neurons at the level of chromatin organization. We detected changes in chromatin organization in the regulatory regions of genes involved in nucleosome assembly, neuronal differentiation, synaptic plasticity and regulation of behavior. Our findings demonstrate that common environmental differences between rearing facilities may produce facility-specific phenotypes, from the molecular to the behavioural level. We expect our findings to stimulate further research into the mechanisms and drivers of these epigenetic changes mediated by the laboratory environment. Furthermore, they highlight an important limitation of inferences from single-laboratory studies and a need to account for the animals environmental background in study design to produce robust and replicable findings.

neuroscience↗

Supplemented nutrition increases immunity and drug efficacy in a natural host-helminth system

Gastrointestinal helminths are common parasites of humans, wildlife, and livestock, leading to chronic infections in large parts of the world. In humans, there is also an overlap in the incidence of malnutrition and helminth infections which can predispose individuals to higher infection burdens and reduced anthelmintic efficacy due to compromised immunity. This relationship has been well-studied in laboratory models by testing for the impact of dramatic reductions of specific nutrients on infection outcomes. However, much less is known about the benefits of whole-diet supplementation in natural host-helminth systems. We experimentally supplemented the diet of wood mice (Apodemus sylvaticus) and measured resistance to the gastrointestinal nematode Heligmosomoides polygyrus and anthelmintic treatment efficacy in both natural and captive populations. Supplemented wood mice were more resistant to H. polygyrus infection, cleared worms more efficiently after treatment, produced stronger general and parasite-specific antibody responses, and maintained better body condition. In addition, supplemented nutrition in conjunction with anthelminthic treatment significantly reduced H. polygyrus transmission potential. These large-scale improvements in condition and immunity of supplemented nutrition found in controlled and wild environments show the rapid and extensive benefits of a well-balanced diet and have important implications for using diet interventions to improve disease control programmes. Author SummaryGastrointestinal helminths are ubiquitous parasites which cause chronic infections and debilitating symptoms worldwide for human and animal populations alike. Efforts to control helminth infections rely primarily on deworming drugs. However, despite high availability and low cost of these drugs, reinfection is common and helminths remain a substantial problem in many areas of the world. One factor which contributes to the persistence of helminth infections is co-occurrence of malnutrition. Extensive work in model laboratory systems has shown that deficiencies in both macro- and micronutrients can impair host immune responses to helminth infections, but how this relationship translates to natural host-helminth systems and drug efficacy is still poorly understood. Here, we used a combination of experimental nutrition supplementation and deworming treatment in paired wood mouse populations in both wild and captive environments to determine the role of a well-balanced diet for infection control in a natural host-helminth system. We found that mice on a supplemented diet had lower burden of infection and increased drug efficacy, body condition, and immune responses. We also found that supplementation lowered transmission potential of hosts. These broad and rapid effects of increased nutrition quality have important implications for the benefits of diet interventions alongside deworming drugs.

ecology↗

The BUBR1 pseudokinase domain promotes efficient kinetochore PP2A-B56 recruitment to regulate spindle checkpoint silencing and chromosome alignment

The balance of phospho-signalling at outer-kinetochores during mitosis is critical for the accurate attachments between kinetochores and the mitotic spindle and timely exit from mitosis. In humans, a major player in determining this balance is the PP2A-B56 phosphatase which is recruited to the Kinase Attachment Regulatory Domain (KARD) of the Spindle Assembly Checkpoint protein Budding Uninhibited by Benzimidazole 1-related 1 (BUBR1) in a phospho-dependent manner. This event unleashes a rapid, switch-like phosphatase relay that reverses phosphorylation at the kinetochore, extinguishing the checkpoint and promoting anaphase entry. Here, we conclusively demonstrate that the pseudokinase domain of human BUBR1 lacks phosphotransfer activity and that it was maintained in vertebrates because it allosterically promotes KARD phosphorylation. Mutation or removal of this domain results in decreased PP2A-B56 recruitment to the outer kinetochore, attenuated checkpoint silencing and errors in chromosome alignment as a result of imbalance in Aurora B activity. We demonstrate that the functions of the BUBR1 pseudokinase and the BUB1 kinase domains are intertwined, providing an explanation for retention of the pseudokinase domain in certain eukaryotes.

cell biology↗

Learning 2-in-1: towards integrated EEG-fMRI-neurofeedback

Neurofeedback (NF) allows to exert self-regulation over specific aspects of ones own brain activity by returning information extracted in real-time from brain activity measures. These measures are usually acquired from a single modality, most commonly electroencephalography (EEG) or functional magnetic resonance imaging (fMRI). EEG-fMRI-neurofeedback (EEG-fMRI-NF) is a new approach that consists in providing a NF based simultaneously on EEG and fMRI signals. By exploiting the complementarity of these two modalities, EEG-fMRI-NF opens a new spectrum of possibilities for defining bimodal NF targets that could be more robust, flexible and effective than unimodal ones. Since EEG-fMRI-NF allows for a richer amount of information to be fed back, the question arises of how to represent the EEG and fMRI features simultaneously in order to allow the subject to achieve better self-regulation. In this work, we propose to represent EEG and fMRI features in a single bimodal feedback (integrated feedback). We introduce two integrated feedback strategies for EEG-fMRI-NF and compare their early effects on a motor imagery task with a between-group design. The BiDim group (n=10) was shown a two-dimensional (2D) feedback in which each dimension depicted the information from one modality. The UniDim group (n=10) was shown a one-dimensional (1D) feedback that integrated both types of information even further by merging them into one. Online fMRI activations were significantly higher in the UniDim group than in the BiDim group, which suggests that the 1D feedback is easier to control than the 2D feedback. However subjects from the BiDim group produced more specific BOLD activations with a notably stronger activation in the right superior parietal lobe (BiDim > UniDim, p < 0.001, uncorrected). These results suggest that the 2D feedback encourages subjects to explore their strategies to recruit more specific brain patterns. To summarize, our study shows that 1D and 2D integrated feedbacks are effective but also appear to be complementary and could therefore be used in a bimodal NF training program. Altogether, our study paves the way to novel integrated feedback strategies for the development of flexible and effective bimodal NF paradigms that fully exploits bimodal information and are adapted to clinical applications.

bioengineering↗