Biology subjects

Gaultier, C.

Publications and source records attributed to Gaultier, C..

5 recordsLinked to original sources

bioRxiv2026

Mechanism-Specific Speech Encoding Failures in Auditory Neuropathy: A Computational Phenotyping Framework

AO_SCPLOWBSTRACTC_SCPLOWAuditory nerve disorders, including auditory neuropathy spectrum disorders (ANSD), show distorted patterns of auditory nerve activity despite preserved spectral analysis of sound in the cochlea, producing impaired speech recognition despite normal auditory sensitivity. Distinct pathophysiological mechanisms affecting auditory-nerve activity have been identified in animal models, but current clinical speech tests were not designed to distinguish among them, because they average performance across phoneme categories, collapsing mechanism-specific confusion patterns into a single intelligibility score. Using computational modeling of auditory nerve responses, we simulated four candidate mechanisms and showed that their encoding disruptions cascade into systematic, phoneme-specific recognition failures: brief consonants were severely degraded while sustained vowels were preserved, and each mechanism produced a distinct confusion pattern. Models trained on ANSD-degraded signals developed compensation strategies that generalized to healthy signals, while the reverse did not, and noise training that benefited healthy models harmed ANSD models, mirroring real-world listening difficulty. Because simulation fixes the generating mechanism by construction, we could then measure directly how much mechanism-specific information each behavioral representation preserves. Aggregate word scoring discarded most of the information retained in the full confusion matrix, yet a handful of targeted phonetic contrasts recovered the mechanism. Simulation uniquely enables this analysis because the underlying mechanism is known, a property currently unavailable in patient datasets. Rather than offering direct diagnosis from behavior alone, the framework quantifies what aggregate scoring destroys and identifies the contrasts that best separate mechanisms, a principled route toward phonetically efficient tests that recover mechanistic information current scoring discards.

neuroscience↗

bioRxiv2025

Robust Decoding of Speech Acoustics from EEG: Going Beyond the Amplitude Envelope

ObjectiveDuring speech perception, properties of the acoustic stimulus can be reconstructed from the listeners brain using methods such as electroencephalography (EEG). Most studies employ the amplitude envelope as a target for decoding; however, speech acoustics can be characterised on multiple dimensions, including as spectral descriptors. The current study assesses how robustly an extended acoustic feature set can be decoded from EEG under varying levels of intelligibility and acoustic clarity. ApproachAnalysis was conducted using EEG from 38 young adults who heard intelligible and non-intelligible speech that was either unprocessed or spectrally degraded using vocoding. We extracted a set of acoustic features which, alongside the envelope, characterised instantaneous properties of the speech spectrum (e.g., spectral slope) or spectral change over time (e.g., spectral flux). We establish the robustness of feature decoding by employing multiple model architectures and, in the case of linear decoders, by standardising decoding accuracy (Pearsons r) using randomly permuted surrogate data. Main resultsLinear models yielded the highest r relative to non-linear models. However, the separate decoder architectures produced a similar pattern of results across features and experimental conditions. After converting r values to Z-scores scaled by random data, we observed substantive differences in the noise floor between features. Decoding accuracy significantly varies by spectral degradation and speech intelligibility for some features, but such differences are reduced in the most robustly decoded features. This suggests acoustic feature reconstruction is primarily driven by generalised auditory processing. SignificanceOur results demonstrate that linear decoders perform comparably to non-linear decoders in capturing the EEG response to speech acoustic properties beyond the amplitude envelope, with the reconstructive accuracy of some features also associated with understanding and spectral clarity. This sheds light on how sound properties are differentially represented by the brain and shows potential for clinical applications moving forward.

neuroscience↗

bioRxiv2022

A high-throughput sequencing approach identifies immunotherapeutic targets for bacterial meningitis in neonates

BackgroundWorldwide, Escherichia coli is the leading cause of neonatal Gram-negative bacterial meningitis, but full understanding of the pathogenesis of this disease is not yet achieved. Moreover, to date, no vaccine is available against bacterial neonatal meningitis. MethodsHere, we used Transposon Sequencing of saturated banks of mutants (TnSeq) to evaluate E. coli K1 genetic fitness in murine neonatal meningitis. We identified E. coli K1 genes encoding for factors important for systemic dissemination and brain infection, and focused on products with a likely outer-membrane or extra-cellular localization, as these are potential vaccine candidates. We used in vitro and in vivo models to study the efficacy of active and passive immunization. ResultsWe selected for further study the conserved surface polysaccharide Poly-{beta}-(1-6)-N-Acetyl Glucosamine (PNAG), as a strong candidate for vaccine development. We found that PNAG was a virulence factor in our animal model. We showed that both passive and active immunization successfully prevented and/or treated meningitis caused by E. coli K1 in neonatal mice. We found an excellent opsonophagocytic killing activity of the antibodies to PNAG and in vitro these antibodies were also able to decrease binding, invasion and crossing of E. coli K1 through two blood brain barrier cell lines. Finally, to reinforce the potential of PNAG as a vaccine candidate in bacterial neonatal meningitis, we demonstrated that Group B Streptococcus, the main cause of neonatal meningitis in developed countries, also produced PNAG and that antibodies to PNAG could protect in vitro and in vivo against this major neonatal pathogen. InterpretationAltogether, these results indicate the utility of a high-throughput DNA sequencing method to identify potential immunotherapy targets for a pathogen, including in this study a potential broad-spectrum target for prevention of neonatal bacterial infections. FundingsANR Seq-N-Vaq, Charles Hood Foundation, Hearst Foundation. Groupe Pasteur Mutualite

microbiology↗

bioRxiv2020

Bacterial inhibition of CD8+ T-cells mediated cell death promotes neuroinvasion and within-host persistence

Central nervous system infections are amongst the most severe1,2, yet the mechanisms by which pathogens access the brain remain poorly understood. The model microorganism Listeria monocytogenes (Lm) is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest central nervous system infections3,4. While immunosuppression is a well-established host risk factor for neurolisteriosis3,5, little is known regarding the bacterial factors underlying Lm neuroinvasion. We have developed a clinically-relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains6 inoculated in a humanized mouse model of infection7, and we show that the bacterial protein InlB protects infected monocytes from CD8+ T-cells Fas-mediated cell death, in a c-Met/PI3-kinase/FLIP-dependent manner. This blockade of anti-Lm specific cellular immune response lengthens infected monocytes lifespan, favoring Lm transfer from infected monocytes to the brain. The intracellular niche created by InlB-mediated cell-autonomous immunosuppression also promotes Lm fecal shedding, accounting for its selection as a Lm core virulence gene. Here, we have uncovered an unanticipated specific mechanism by which a bacterial pathogen confers to the cells it infects an increased lifespan by rendering them resistant to cell-mediated immunity. This promotes Lm within-host persistence and dissemination to the central nervous system, and transmission.

immunology↗

bioRxiv2018

Cooption of antagonistic RNA-binding proteins establishes cell hierarchy in Drosophila neuro-developmental tumors

The mechanisms that govern the hierarchical organization of tumors are still poorly understood, especially in highly heterogeneous neural cancers. Previously, we had shown that aggressive neural tumors can be induced upon dedifferentiation of susceptible intermediate progenitors produced during early development (Narbonne-Reveau et al., 2016). Using clonal analysis, stochastic modelling and single-cell transcriptomics, we now find that such tumors rapidly become heterogeneous, containing progenitors with different proliferative potentials. We demonstrate that tumor heterogeneity emerges from the deregulated transition between two antagonistic RNA-binding proteins, Imp and Syncrip, that switch neural progenitors from a default self-renewing to a differentiation-prone state during development. Consequently, aberrant maintenance of Imp confers a cancer stem cell-like identity as Imp+ progenitors sustain tumor growth while being able to continuously generate Syncrip+ progenitors. The latter exhibit limited self-renewal likely due to Syncrip-mediated metabolic exhaustion. This study provides an example of how a subverted developmental transition establishes a hierarchical tumor.

developmental biology↗