Biology subjects

Lefebvre, S.

Publications and source records attributed to Lefebvre, S..

8 recordsLinked to original sources

bioRxiv2026

A touch that lingers: synchronized patting strengthens neural tracking of auditory rhythm in newborns

Rhythmic auditory stimulation in early life rarely occurs in isolation. Caregivers naturally combine singing and speech with rhythmic touch, rocking, and visual cues. Newborns are sensitive to auditory rhythm from birth, yet little is known about how temporally aligned information across sensory modalities shapes the neural encoding of auditory rhythmic structure. Here, we tested whether rhythmic touch can alter how the newborn brain tracks an ongoing auditory signal beyond the period of tactile stimulation. We recorded high-density electroencephalography from full-term newborns (N = 40), 1-3 days after birth, while they were exposed to recorded French lullabies presented either alone or accompanied by gentle patting synchronized with the metrically strong beat. Patting was delivered intermittently, allowing us to compare neural responses to lullabies across conditions, notably during periods without concurrent tactile stimulation. We quantified neural tracking of the lullabies using brain-stimulus coherence and temporal response function modeling. Newborns' neural activity synchronized with the rhythmic structure of the lullabies at frequencies corresponding to both the beat and the metrically accented strong beat. Critically, neural tracking was stronger when the lullabies had been accompanied by synchronized touch than when they were presented alone, and this enhancement persisted during subsequent periods in which no touch was delivered. Although rhythmic touch enhanced tracking in newborns with both weaker and stronger auditory-only tracking, there was a larger gain in those who initially showed weaker auditory tracking. Together, our findings reveal that the newborn brain exploits rhythmic touch to strengthen its encoding of auditory rhythm, and that this benefit outlasts the touch itself. This provides neural evidence that patting an infant in time with a song, a caregiving practice shared across cultures, does more than simply provide a tactile stimulation. It shapes how the newborn brain encodes the song's rhythm.

neuroscience↗

bioRxiv2023

In vivo expansion of gene-targeted hepatocytes through transient inhibition of an essential gene

Homology Directed Repair (HDR)-based genome editing is an approach that could permanently correct a broad range of genetic diseases. However, its utility is limited by inefficient and imprecise DNA repair mechanisms in terminally differentiated tissues. Here, we tested "Repair Drive", a novel method for improving targeted gene insertion in the liver by selectively expanding correctly repaired hepatocytes in vivo. Our system consists of transient conditioning of the liver by knocking down an essential gene, and delivery of an untargetable version of the essential gene in cis with a therapeutic transgene. We show that Repair Drive dramatically increases the percentage of correctly targeted hepatocytes, up to 25%. This resulted in a five-fold increased expression of a therapeutic transgene. Repair Drive was well-tolerated and did not induce toxicity or tumorigenesis in long term follow up. This approach will broaden the range of liver diseases that can be treated with somatic genome editing.

genetics↗

bioRxiv2022

Robust and durable prophylactic protection conferred by RNA interference in preclinical models of SARS-CoV-2

RNA interference is a natural antiviral mechanism that could be harnessed to combat SARS-CoV-2 infection by targeting and destroying the viral genome. We screened lipophilic small-interfering RNA (siRNA) conjugates targeting highly conserved regions of the SARS-CoV-2 genome and identified leads targeting outside of the spike-encoding region capable of achieving [≥]3-log viral reduction. Serial passaging studies demonstrated that a two-siRNA combination prevented development of resistance compared to a single-siRNA approach. A two-siRNA combination delivered intranasally protected Syrian hamsters from weight loss and lung pathology by viral infection upon prophylactic administration but not following onset of infection. Together, the data support potential utility of RNAi as a prophylactic approach to limit SARS-CoV-2 infection that may help combat emergent variants, complement existing interventions, or protect populations where vaccines are less effective. Most importantly, this strategy has implications for developing medicines that may be valuable in protecting against future coronavirus pandemics.

pharmacology and toxicology↗

bioRxiv2021

Individual growth models support the quantification of isotope incorporation rate, trophic discrimination and their interactions

Two large but independent bodies of literature exist on two essential components of the dynamics of isotopic incorporation: the isotopic incorporation rate ({lambda}) and the trophic discrimination factor ({Delta}). Understanding the magnitude of these two parameters and the factors that shape them is fundamental to interpret the results of ecological studies that rely on stable isotopes. {lambda} scales allometrically with body mass among species and depends on growth within species. Both are often assumed to be constant and independent of each other but evidence accumulates that might be linked and to vary with growth. We built and analyzed a model (IsoDyn) that connects individual growth and isotopic incorporation of nitrogen into whole body and muscle tissues. The model can assume a variety of individual growth patterns including exponential or asymptotic growths. {lambda} depends on the rate of body mass gains which scales allometrically with body mass. {Delta} is a dynamic response variable that depends partly on the ratio between fluxes of gains and losses and covaries negatively with {lambda}. The model can be parameterized either from existing large databases of animal growth models or directly from experimental results. The model was applied to experimental results on three ectotherms and one endotherm and compared to the results of the simpler and widely used time model. IsoDyn model gave a better fit with relatively little calibration. IsoDyn clarifies and expands the interpretation of isotopic incorporation data.

ecology↗

bioRxiv2020

Sensing of endogenous nucleic acids by ZBP1 induces keratinocyte necroptosis and skin inflammation

Aberrant detection of endogenous nucleic acids by the immune system can cause inflammatory disease. The scaffold function of the signalling kinase RIPK1 limits spontaneous activation of the nucleic acid sensor ZBP1. Consequently, loss of RIPK1 in keratinocytes induces ZBP1-dependent necroptosis and skin inflammation. Whether nucleic acid sensing is required to activate ZBP1 in RIPK1 deficient conditions and which immune pathways are associated with skin disease remained open questions. Using knock-in mice with disrupted ZBP1 nucleic acid binding activity, we report that sensing of endogenous nucleic acids by ZBP1 is critical in driving skin pathology characterised by antiviral and IL-17 immune responses. Inducing ZBP1 expression by interferons triggers necroptosis in RIPK1-deficient keratinocytes and epidermis-specific deletion of MLKL prevents disease, demonstrating that cell-intrinsic events cause inflammation. These findings indicate that dysregulated sensing of endogenous nucleic acid by ZBP1 can drive inflammation and may contribute to the pathogenesis of IL-17-driven inflammatory skin conditions such as psoriasis. SummaryDevos, Tanghe et al. find that the recognition of endogenous nucleic acids by the nucleic acid sensor ZBP1 causes necroptosis of RIPK1-deficient keratinocytes. This process drives the development of an inflammatory skin disease characterised by an IL-17 immune response.

immunology↗

bioRxiv2019

Embodiment improves performance on an immersive brain computer interface in head-mounted virtual reality

Brain computer interfaces (BCI) can be used to provide individuals with neurofeedback of their own brain activity and train them to learn how to control their brain activity. Neurofeedback-based BCIs used for motor rehabilitation aim to close the loop between attempted motor commands and sensory feedback by providing supplemental sensory information when individuals successfully establish specific brain patterns. Existing neurofeedback-based BCIs have used a variety of displays to provide feedback, ranging from devices that provide a more immersive and compelling experience (e.g., head-mounted virtual reality (HMD-VR) or CAVE systems) to devices that are considered less immersive (e.g., computer screens). However, it is not clear whether more immersive systems (i.e., HMD-VR) improve neurofeedback performance compared to computer screens, and whether there are individual performance differences in HMD-VR versus screen-based neurofeedback. In this pilot experiment, we compared neurofeedback performance in HMD-VR versus on a computer screen in twelve healthy individuals. We also examined whether individual differences in presence or embodiment correlated with neurofeedback performance in either environment. Participants were asked to control a virtual right arm by imagining right hand movements. Real-time brain activity indicating motor imagery, which was measured via electroencephalography (EEG) as desynchronized sensorimotor rhythms (SMR; 8-24 Hz) in the left motor cortex, drove the movement of the virtual arm towards (increased SMR desynchronization) or away from (decreased SMR desynchronization) targets. Participants performed two blocks of 30 trials, one for each condition (Screen, HMD-VR), with the order of conditions counterbalanced across participants. After completing each block, participants were asked questions relating to their sense of presence and embodiment in each environment. We found that, while participants performance on the neurofeedback-based BCI task was similar between conditions, the participants reported levels of embodiment was significantly different between conditions. Specifically, participants experienced higher levels of embodiment in HMD-VR compared to the computer screen. We further found that reported levels of embodiment positively correlated with neurofeedback performance only in the HMD-VR condition. Overall, these preliminary results suggest that embodiment may improve performance on a neurofeedback-based BCI and that HMD-VR may increase embodiment during a neurofeedback-based BCI task compared to a standard computer screen.

neuroscience↗

bioRxiv2018

High-definition transcranial direct current stimulation over the dorsal premotor cortex reliably modulates motor network excitability

The effectiveness of transcranial direct current stimulation (tDCS) placed over the motor hotspot (thought to represent the primary motor cortex (M1)) to modulate motor network excitability is highly variable. The premotor cortex--particularly the dorsal premotor cortex (PMd)--may be a promising alternative target to more effectively modulate motor excitability, as it influences motor control across multiple pathways, one independent of M1 and one with direct, modulating connections to M1. This double-blind, placebo-controlled study aimed to differentially excite motor and premotor regions using high-definition tDCS (HD-tDCS) with concurrent functional magnetic resonance imaging (fMRI). HD-tDCS applied over either the motor hotspot or the premotor cortex demonstrated high inter-individual variability in changes on cortical motor excitability. However, HD-tDCS over the premotor cortex led to a higher number of responders and greater changes in local fMRI-based complexity than HD-tDCS over the motor hotspot. Furthermore, an analysis of individual motor hotspot anatomical locations revealed that, in more than half of the participants, the motor hotspot is not located over anatomical M1 boundaries, despite using a canonical definition of the motor hotspot. This heterogeneity in stimulation site may contribute to the variability of tDCS results. Altogether, these findings provide new considerations to enhance tDCS reliability.

neuroscience↗

bioRxiv2017

The Anatomical Tracings of Lesions After Stroke (ATLAS) Dataset - Release 1.1

Stroke is the leading cause of adult disability worldwide, with up to two-thirds of individuals experiencing long-term disabilities. Large-scale neuroimaging studies have shown promise in identifying robust biomarkers (e.g., measures of brain structure) of long-term stroke recovery following rehabilitation. However, analyzing large rehabilitation-related datasets is problematic due to barriers in accurate stroke lesion segmentation. Manually-traced lesions are currently the gold standard for lesion segmentation on T1-weighted MRIs, but are labor intensive and require anatomical expertise. While algorithms have been developed to automate this process, the results often lack accuracy. Newer algorithms that employ machine-learning techniques are promising, yet these require large training datasets to optimize performance. Here we present ATLAS (Anatomical Tracings of Lesions After Stroke), an open-source dataset of 304 T1-weighted MRIs with manually segmented lesions and metadata. This large, diverse dataset can be used to train and test lesion segmentation algorithms and provides a standardized dataset for comparing the performance of different segmentation methods. We hope ATLAS release 1.1 will be a useful resource to assess and improve the accuracy of current lesion segmentation methods.

neuroscience↗