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International audience; Myotonic dystrophy type 1 (DM1) is a severe neuromuscular disease mediated by a toxic gain of function of mutant RNAs. The neuropsychological manifestations affect multiple domains of cognition and behavior, but their etiology remains elusive. Transgenic DMSXL mice carry the DM1 mutation, show behavioral abnormalities, and express low levels of GLT1, a critical regulator of glutamate concentration in the synaptic cleft. However, the impact of glutamate homeostasis on neurotransmission in DM1 remains unknown. We confirmed reduced glutamate uptake in the DMSXL hippocampus. Patch clamp recordings in hippocampal slices revealed increased amplitude of tonic glutamate currents in DMSXL CA1 pyramidal neurons and DG granule cells, likely mediated by higher levels of ambient glutamate. Unexpectedly, extracellular GABA levels and tonic current were also elevated in DMSXL mice. Finally, we found evidence of synaptic dysfunction in DMSXL mice, suggestive of abnormal short-term plasticity, illustrated by an altered LTP time course in DG and in CA1. Synaptic dysfunction was accompanied by RNA foci accumulation in localized areas of the hippocampus and by the mis-splicing of candidate genes with relevant functions in neurotransmission. Molecular and functional changes triggered by toxic RNA may induce synaptic abnormalities in restricted brain areas that favor neuronal dysfunction.

International audience; Planet Earth is becoming increasingly difficult for large animal species to inhabit. Yet, these species are of major importance for the functioning of the biosphere and their progressive disappearance is accompanied by profound negative alterations of ecosystems1 (Supplemental information). To implement effective conservation measures, it is essential to have a detailed knowledge of the biology of these species. Here, we show that the hippopotamus Hippopotamus amphibius, an iconic African megaherbivore for which little is known about social communication, uses vocal recognition to manage relationships between territorial groups. We conducted playback experiments on groups of hippos and observed their response to vocalizations from an individual of the same group (familiar), a group from the same lake (neighbor) and a distant group (stranger). We found that stranger vocalizations induced a stronger behavioral reaction than the other two stimuli. In addition to showing that hippos are able to identify categories of conspecifics based on vocal signatures, our study demonstrates that hippo groups are territorial entities that behave less aggressively toward their neighbors than toward strangers. These new behavioral data suggest that habituation playbacks prior to conservation translocation operations may help reduce the risk of conflict between individuals that have never seen each other.

Correspondence.; International audience; In reply to the correspondence “A combination of sectional micro-anatomy and micro-stereoscopic anatomy is an improved micro-dissection method” by Jing-Zhan Wu and Chun-Hai Tang: We agree with the authors that it is important to collect data using diverse techniques (two and three dimensional) for the best possible understanding of a species' brain structure.The authors speak of “discrepancies,” especially concerning the shape and size of cerebral ventricles, between their study (Wu et al. 2021) conducted on 40-day-old (juvenile) rabbits and our study on 4-day-old (newborn) rabbits (Schneider et al. 2018). They also mention differences observed in the brain of adult rabbits studied by Shek et al. (1986). These are differences, not “discrepancies”, and they are not surprising because the brain changes shape during development, especially in the size and shape of the ventricles (e.g. Scelsi et al. 2020). These same changes occur in rabbits. Most importantly, shortly after birth, the brain of the newborn rabbit changes very rapidly – indeed, we observed clear differences between neonates (0-day-old) (Schneider et al. 2016) and 4-day-old rabbit pups (Schneider et al. 2018). Therefore, it is important that Wu et al. 2021 compare literature describing brain sections of 40-day-old rabbits, or extend their own studies to the brain of 4-day-old rabbit pups, to get a clear understanding of any differences observed. Such differences might not be due to different techniques.

International audience; Background: Peripheral inflammation is associated with impaired prognosis in schizophrenia (SZ). Highly sensitive C-reactive protein (hs-CRP) is the most used inflammatory biomarker in daily practice. However, no consensual cut-off has been determined to date to discriminate patients with peripheral inflammation from those without.Aims: To determine if patients with peripheral inflammation between 1 and 3 mg/L had poorer outcomes compared to those with undetectable CRP ( 1 mg/L is a reliable marker to detect peripheral inflammation in patients with schizophrenia.

Pain intensity has been reported to fluctuate during the day in some experimental and clinical conditions, but the mechanisms underlying these fluctuations are unknown. Although the circadian timing system is known to regulate a wide range of physiological functions, its implication in pain regulation is largely unknown. Using highly controlled laboratory constant-routine conditions, we show that pain sensitivity is rhythmic over the 24 h and strongly controlled by the endogenous circadian timing system. We found that the circadian component of pain sensitivity can be modelled with a sinusoidal function, with a maximum in the middle of the night and a minimum in the afternoon. We also found a weak homeostatic control of pain sensitivity, with a linear increase over the 34 h of prolonged wakefulness, which slowly builds up with sleep pressure. Using mathematical modelling, we describe that the circadian system accounts for ∼80% of the full magnitude of pain sensitivity over the 24 h, and that sleep-related processes account for only ∼20%. Overall, our data reveal the neurobiological mechanisms involved in driving the rhythmicity of pain perception in humans. We show that pain sensitivity is controlled by two superimposed processes: a strong circadian component and a modest homeostatic sleep-related component. Our findings highlight the need to consider time of day in pain assessment, and indicate that personalized circadian medicine may be a promising approach to pain management.

Since the end of the 1970s, cochlear implants have been gradually acknowledged as a conventional method for the rehabilitation of deafness which significantly improves quality of life. Nowadays, people with profound hearing loss can recover or have access to hearing. Every year in France, approximately 1,000 people benefit from a cochlear implantation. However, great disparities persist and there is a "continuous spectrum" of performances in implanted patients, ranging from total failure to the restoration of a near-normal speech comprehension. Several physiological and technical factors help to explain some of the variability in the results. In this work we investigated the effect of the bioelectric interaction between the electrodes and the cochlear cells as well as the impact of the sound coding strategy in the understanding of speech in noise. A first study evaluates, with a general point of view, the understanding of speech in noise, function of the coding strategy with or without channel selection. We used two approaches; a direct evaluation with cochlear implant patients and a simulation study with normal-hearing subjects. In both populations, a difference was observed in favor of the strategy without channel selection. Thus, under the most common signal-to-noise ratio conditions, delivering information from all channels can lead to better recognition percentages than with a selection strategy. The second study introduces the problem of channel interaction. The aim of this study is to evaluate the understanding of speech in noise to the setting of a channel selection strategy and the phenomenon of interaction. Once again, we set up a simulation protocol with normal-hearing subjects and a protocol with cochlear implants. On one hand, we measured the understanding of speech in noise as a function of the number of selected channels, and on the other hand, we evaluated the degree of interaction by measuring frequency selectivity. The part concerning cochlear implant patients is still ongoing and we need to collect data from a larger number of subjects. The part with normal-hearing subjects is finished and it gives us a first approach of what we can expect with the implanted patients. The results of this part show a threshold effect at which performance decreases. Furthermore, by varying the interaction, an intra-subject correlation was observed between frequency selectivity and speech comprehension., Depuis la fin des années 70, l’implant cochléaire a progressivement pris sa place dans les moyens classiques de réhabilitation des surdités profondes neurosensorielles. C’est ainsi que des personnes atteintes de déficience auditive profonde, retrouvent ou acquièrent l’accès à une audition utile, améliorant dans des proportions remarquables, leur qualité de vie. Environ 1 000 personnes en bénéficient chaque année en France. Cependant de grandes disparités persistent et il existe un « spectre continu » des performances chez les patients implantés qui vont de l’échec total à la restauration d’une compréhension de la parole quasi normale. Plusieurs facteurs physiologiques et techniques permettent d’expliquer une partie de la variabilité des résultats. Dans ce travail nous nous sommes intéressés à l’effet de l’interaction bioélectrique entre les électrodes et les cellules cochléaires ainsi qu’à l’impact de la stratégie de codage du son dans la compréhension de la parole dans le bruit. Une première étude évalue de façon générale la compréhension de la parole dans le bruit en fonction de la stratégie de codage avec et sans sélection de canaux. Pour cela nous avons utilisé deux approches ; une évaluation directe avec des patients implantés cochléaires et une étude en simulation avec des sujets normoentendants. Dans les deux populations, une différence a été observée en faveur de la stratégie sans sélection des canaux. Ainsi, dans les conditions de rapport signal sur bruit les plus courantes, délivrer l’information de l’ensemble des canaux peut conduire à de meilleurs pourcentages de reconnaissance qu'une stratégie de sélection. La seconde étude introduit la problématique de l’interaction. Le but de cette étude est de mettre en relation la compréhension de la parole dans le bruit avec le réglage d’une stratégie à sélection de canaux et le phénomène d’interaction. À nouveau, nous avons mis en place un protocole en simulation avec des sujets normoentendants et un protocole avec des implantés cochléaires. D’une part, nous avons mesuré la compréhension de la parole dans le bruit en fonction du nombre de canaux sélectionnés et d’autre part nous avons évalué le degré d’interaction par une mesure de la sélectivité fréquentielle. La partie concernant les patients implantés cochléaires est toujours en cours et nous nous employons à recueillir des données chez un nombre plus élevé de sujets. La partie avec les sujets normoentendants est terminée et elle nous donne une première approche de ce que nous pouvons attendre avec les implantés. Les résultats de cette partie montrent un effet de seuil à partir duquel les performances diminuent. De plus, en faisant varier l’interaction, il a été observé une corrélation intra-sujet entre la sélectivité fréquentielle et la compréhension de la parole.

In fish, most hormonal productions of the pituitary gland display daily and/or seasonal rhythmic patterns under control by upstream regulators, including internal biological clocks. The pineal hormone melatonin, one main output of the clocks, acts at different levels of the neuroendocrine axis. Melatonin rhythmic production is synchronized mainly by photoperiod and temperature. Here we aimed at better understanding the role melatonin plays in regulating the pituitary hormonal productions in a species of scientific and economical interest, the euryhaline European sea bass Dicentrarchus labrax. We investigated the seasonal variations in mRNA abundance of pituitary hormones in two groups of fish raised one in sea water (SW fish), and one in brackish water (BW fish). The mRNA abundance of three melatonin receptors was also studied in the SW fish. Finally, we investigated the in vitro effects of melatonin or analogs on the mRNA abundance of pituitary hormones at two times of the year and after adaptation to different salinities. We found that (1) the reproductive hormones displayed similar mRNA seasonal profiles regardless of the fish origin, while (2) the other hormones exhibited different patterns in the SW vs. the BW fish. (3) The melatonin receptors mRNA abundance displayed seasonal variations in the SW fish. (4) Melatonin affected mRNA abundance of most of the pituitary hormones in vitro; (5) the responses to melatonin depended on its concentration, the month investigated and the salinity at which the fish were previously adapted. Our results suggest that the productions of the pituitary are a response to multiple factors from internal and external origin including melatonin. The variety of the responses described might reflect a high plasticity of the pituitary in a fish that faces multiple external conditions along its life characterized by marked daily and seasonal changes in photoperiod, temperature and salinity.

Apparently balanced chromosomal rearrangements (ABCRs) which include translocations, insertions, inversions, and complex rearrangements are rare events. Without affecting the phenotype in most cases, they can cause pairing abnormalities during meiosis and result in the formation of unbalanced gametes which can lead to pregnancy termination. Additionally, 6% of patients with translocations, 9% of patients with inversions, and 23% of patients with complex rearrangement have a phenotype resulting from cryptic imbalance or breakpoint pathology such as gene disruption or dysregulation by a position effect. Indeed, in addition to the genomic sequence, genes expression is also determined by epigenetic factors. DNA is wrapped around histones, forming chromatin. These histones can undergo post-translational modifications modulating chromatin compaction. Chromatin is also structured within the nucleus, in a hierarchical three-dimensional architecture. Indeed, chromatin is organized in chromosomal territories, in chromosomal compartments, in topologically associated domains and in chromatin loops. The organization of the genome can be disrupted by ABCRs, which can induce changes in gene expression and lead to the development of neurodevelopmental disorders. We have studied the effect of these ABCRs on the nucleus. To do this, we performed an expression study of TCF4 gene to study expression abnormalities by disruption of different transcription start sites. Then we determined by three-dimensional fluorescence in situ hybridization the radial position ratio of loci involved in ABCRs. Finally, we characterized by karyotype, fluorescence in situ hybridization, chromosomal micro-array analysis and whole genome sequencing the chromoanagenesis of six families in which an asymptomatic parent transmitted, in an unbalanced way, a chromosomal rearrangement to its child, to understand the pairing of abnormal chromosomes during meiosis. We have shown that chromosomal rearrangements disturbed cells, both during interphase and meiosis. They cause repercussions on the genomic sequence, by disrupting genes or their regulatory elements. Moreover, a patient's phenotype may be different depending on the transcription start site which is impacted by chromosomal rearrangement. In fact, patients with a proximal chromosomal rearrangement of TCF4 gene, involving the first transcription initiation sites, have a moderate phenotype. Chromosomal rearrangements also have repercussions on the spatial organization of chromatin. The radial position ratios of loci involved in translocations or inversions can be modified. The relocation of the derivatives can then influence the phenotype of the patients by modifying their environment. In meiosis, chromoanagenesis disturbed the pairing of homologous chromosomes which form complex figures with regions of asynapsis. This can lead to the formation of imbalanced gametes. As this recombination is random and unpredictable, prenatal diagnosis is recommended for these families., Les remaniements de structure chromosomique apparemment équilibrés (RCAE), qui comprennent les translocations, les insertions, les inversions et les remaniements complexes sont des évènements rares. Sans conséquence sur le phénotype dans la majorité des cas, ils peuvent entrainer des anomalies d’appariement au moment de la méiose et résulter à la formation de gamètes déséquilibrés pouvant mener à des interruptions de grossesse. De plus, 6% des patients avec translocations, 9% des patients avec inversions et 23% des patients avec un remaniement complexe présente un phénotype pouvant résulter d’un déséquilibre cryptique ou d’une pathologie du point de cassure comme une interruption de gène ou une dysrégulation par un effet de position. En effet, outre la séquence génomique, l’expression des gènes est également déterminée par des facteurs épigénétiques. L’ADN est enroulé autour d’histones, formant ainsi la chromatine. Ces histones peuvent subir des modifications post-traductionnelles modulant la compaction de la chromatine. La chromatine est également structurée au sein du noyau, formant une architecture tridimensionnelle hiérarchisée. Ainsi, la chromatine est organisée en territoires chromosomiques, puis en compartiments chromosomiques, en domaines associés topologiquement et en boucles chromatiniennes. L’organisation du génome peut être perturbée par les RCAE, ce qui peut induire une modification de l’expression génique et entrainer l’apparition de troubles du neurodéveloppement. Nous avons étudié l’effet de ces RCAE sur le noyau. Pour cela, nous avons réalisé une étude d’expression du gène TCF4 afin d’étudier des anomalies d’expression par interruption de différents sites d’initiation de la transcription. Puis nous avons déterminer par hybridation in situ en fluorescence en trois dimensions le ratio de position radiale de loci impliqués dans des RCAE. Enfin nous avons caractérisé par caryotype, hybridation in situ en fluorescence, analyse chromosomique sur puce à ADN et séquençage du génome entier les chromoanagenesis de six familles dans lesquelles un parent asymptomatique a transmis, de manière déséquilibrée, un remaniement chromosomique à sa descendance afin d’appréhender l’appariement des chromosomes anormaux pendant la méiose. Nous avons montré que les remaniements chromosomiques perturbent les cellules, tant au moment de l’interphase que lors de la méiose. Ils entraînent des répercussions au niveau de la séquence génomique, en interrompant des gènes ou leurs éléments régulateurs. De plus, le phénotype d’un patient peut être différent en fonction du site d’initiation de la transcription qui est impacté par un remaniement chromosomique. En effet les patients présentant un remaniement chromosomique proximal du gène TCF4, impliquant les premiers sites d’initiation de la transcription, présentent un phénotype modéré. Les remaniements chromosomiques ont également des répercussions au niveau de l’organisation spatiale de la chromatine. Les ratios de position radiale des loci impliqués dans des translocations ou des inversions, peuvent être modifiés. La relocalisation des dérivés peut alors avoir un effet sur le phénotype des patients en modifiant leur environnement. Lors de la méiose, les chromoanagenesis perturbent l’appariement des chromosomes homologues qui forment alors des figures complexes avec des régions d’asynapsis. Cela peut mener à la formation de gamètes déséquilibrés. Cette recombinaison étant aléatoire et imprévisible, le dépistage prénatal est recommandé pour ces familles.

While the relationship between hearing loss and cognitive decline is now accepted, the influence of hearing rehabilitation on cognitive decline is not yet clearly established. In order to explore more precisely the link between auditory rehabilitation and auditory cognition, we propose an analysis of the listening cognitive effort. It’s also essential to take into account the listening effort in the daily life of patients with hearing aids, and when performing intelligibility tasks in noise, in order to better understand the cognitive load generated by hearing loss and its implication during the auditory rehabilitation by hearing aids. The aim of this work was therefore to better understand the interrelationships between auditory rehabilitation by hearing aids and the cognitive effort of listening to hearing-impaired patients, by providing various cognitive aspects such as short-term memory. The benefit of hearing aids can be measured using well-known objectives measures such as tonal and vocal audiometric gain or even the measurement of the hearing-aid daily use. But these measures take little account of the involvement of cognitive factors. Conversely, a subjective evaluation by means of questionnaires makes it possible to focus on the patient's daily hearing habits and their hearing abilities during the situations they encounter the most frequently. After a presentation of the various questionnaires used in hearing care, we propose the validation of a French version of a hearing aid satisfaction questionnaire (Satisfaction with Amplification in Daily Living from Cox & Alexander) and the development of a new questionnaire aimed at exploring the musical habits of patients fitted with a hearing aid. Then, we will present the creation and validation of an Extended Effort Assessment Scale, from Alhanbali’s Effort assessment scale, and its interrelations with the Speech Spatial Qualities of Hearing Scale. Finally, after a review of different tools for measuring cognitive abilities adapted to the patient with hearing aids, we will present the results of a pilot study on the link between short-term memory, cognitive ability, listening effort and intelligibility in noise in the hearing-aid wearer. The French version of the SADL, validated in 150 patients, showed good internal consistency and results comparable to those of the international literature. The listening effort questionnaire in daily life was validated in a population of nearly 500 patients, and showed specific links with hearing aids, with listening effort depending more on the hearing aid experience and the age of their current hearing aid, as well as their hearing loss. We have shown that this questionnaire is more sensitive to fitting problems, and allows exploration of additional aspects compared to the hearing abilities questionnaire. Finally, an evaluation of the link between speech in noise and cognitive abilities has shown the feasibility of innovative hearing tests implemented on tablets in hearing care professional centers, and has highlighted the importance of short-term memory. verbal and musical in the perception of speech in cocktail party noise. The use of these new tools for assessing the patient's needs and the benefit of the hearing aid, taking into account their hearing and cognitive abilities, as well as their everyday communication situations, represents a new source of essential information to adapt the best hearing aid fitting to the patient's needs., Si la relation entre perte auditive et déclin cognitif est admise, le bénéfice de la réhabilitation auditive sur le déclin cognitif n’est pour le moment pas encore clairement établi. Afin d’explorer plus finement le lien entre réhabilitation auditive et cognition auditive, nous proposons une analyse sous l’angle de l’effort cognitif d’écoute. En effet, la prise en compte de cet effort d’écoute dans le quotidien des patients appareillés, et lors de réalisation de tâches d’intelligibilité dans le bruit, est indispensable pour mieux cerner la charge cognitive engendrée par la perte auditive et son implication dans le bénéfice de l’appareillage ressenti par le patient. L’objet de ce travail consiste donc à mieux comprendre les interrelations entre réhabilitation auditive par appareillage auditif et effort cognitif d’écoute de patients malentendants, en intégrant différents aspects cognitifs comme la mémoire à court terme. Le bénéfice rendu par les aides auditives peut être mesuré grâce à des indicateurs objectifs bien connus tels que le gain prothétique tonal et vocal ou encore la mesure du temps de port des aides auditives. Mais ces indicateurs rendent peu compte de l’implication des facteurs cognitifs. À l’inverse, une évaluation subjective par le biais de questionnaires permet de s’intéresser aux habitudes auditives quotidiennes du patient et à leurs capacités auditives lors des situations de communication qu’ils rencontrent le plus fréquemment. Après une présentation des différents questionnaires utilisés en audioprothèse, nous proposons la validation d’une version française du questionnaire de satisfaction vis-à-vis de l’appareillage auditif (SADL de Cox & Alexander) et l’élaboration d’un nouveau questionnaire s’intéressant à l’écoute musicale des patients appareillés. Puis, nous présenterons la création et validation d’un questionnaire d’effort cognitif d’écoute (Extended Effort Assessment Scale) et à ses interrelations avec un questionnaire d’habilités auditives (Speech Spatial Qualities of hearing scale). Enfin, après une revue des différents outils de mesure des capacités cognitives adaptés au patient appareillé, nous présenterons les résultats d’une étude pilote sur le lien entre mémoire à court terme, capacité cognitive, effort d’écoute et intelligibilité dans le bruit chez le patient appareillé. La version française du SADL, validée chez 150 patients, a montré une bonne cohérence interne et des résultats comparables à ceux de la littérature internationale. Le questionnaire d’effort d’écoute dans la vie quotidienne a été validé dans une population de près de 500 patients, et a montré des liens spécifiques avec l’appareillage auditif, avec un effort d’écoute dépendant plus de l’expérience d’appareillage des patients et de l’âge de leur aide auditive actuelle, que de leur perte auditive. Nous avons montré que ce questionnaire est plus sensible aux problèmes d’appareillage, et permet d’explorer des aspects complémentaires par rapport au questionnaire d’habiletés auditives. Enfin, une évaluation du lien entre intelligibilité dans le bruit et capacités cognitives a permis de montrer la faisabilité de tests auditifs novateurs implémentés sur tablette en cabinet d’audioprothèse, et a permis la mise en évidence de l’importance de la mémoire à court terme verbale et musicale dans la perception de la parole dans un bruit de voix mélangées. L’utilisation de ces nouveaux outils d’évaluation des besoins du patient et du bénéfice de l’aide auditive, en prenant en compte ses capacités auditives, cognitives, ainsi que ses situations de communication de la vie quotidienne, représente une nouvelle source d’informations indispensables pour adapter au mieux le réglage de l’aide auditive aux besoins du patient.

International audience; Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant hereditary neurodegenerative disease caused by the expansion of a CAG-repeat in the ataxin-7 (ATXN7) gene, usually characterized by progressive cerebellar ataxia and retinal dystrophy. We report the case of a 45-year-old woman presenting with a rapid-onset amyotrophic lateral sclerosis (ALS) phenotype associated with a 39-CAG-repeat expansion in ATXN7. This patient had neither ataxia nor retinal dystrophy, but she had an oculomotor cerebellar syndrome and a family history suggestive of SCA7. In SCA7, shorter expansions may be associated with less severe and incomplete clinical phenotypes, which could explain the patient's phenotype. Unknown genetic and environmental factors may also influence the patient's phenotype. We suggest that a pathological expansion in ATXN7 should be considered in cases of ALS-like phenotype, particularly when associated with oculomotor abnormalities or a family history of ataxia or blindness.

Our everyday listening environment is a complex acoustic mixture that needs to be processed and filtered in order to access relevant auditory information. Cognitive resources are then required for the selective processing of a particular sound stream, and simultaneous filtering of irrelevant information. The engagement of these cognitive resources to understand an auditory message, leads to listening effort, especially in noisy environments. Listening effort has been investigated in the last two decades, using a large panel of methods. The work of this thesis aims at bringing new insights on the investigation of listening effort, first with the use of pupillometry, then based on the complementarity of different measures (subjective, behavioral and objective). A methodological investigation was first conducted on pupillometry data recorded during a word-in-noise task, among older hearing-impaired patients, with and without hearing-aids. Several analysis methods were compared, including different normalization techniques, baseline periods, and baseline durations. While the different normalization methods and baseline durations showed similar results, the choice of the baseline period turned out to have a crucial influence on conclusions. Indeed, anticipatory, pre-stimulus cognitive processes, such as attention mobilization were observed on pupil dilation when the baseline period was the most anterior, relative to the stimulus onset. The differences in pupil dilation were observed even at perfect intelligibility, highlighting the relevance of pupillometry as an objective measure of listening effort. The second axis of this work focused on the results of empirical studies in which several measures, including pupillometry, were concurrently used to assess listening effort. Empirical studies were conducted (1) in older hearing-impaired patients using subjective measures of effort and pupillometry during a word-in-noise task, (2) in normal-hearing young adults using pupillometry and sclap electroencephalography during a discrimination in noise task. The lack of correlation between self-assessed difficulty of the task and pupil responses in hearing-impaired listeners, suggests that the two measures address different aspects of effortful listening. Pupil responses allowed for the observation of anticipation processes, even at perfect intelligibility, while subjective measures described the overall perceived effort during the task. In normal-hearing young adults, the modulations of the cortical responses observed thanks to electroencephalography, were linked to the processing of the stimulation and the inhibition of the irrelevant sound source during discrimination. Pupillary responses, recorded simultaneously, brought information on participants' arousal state during the task. Results of both studies then suggest that the different measures complement each other, and that their combination can help for the understanding of the different cognitive processes involved during effortful listening. Overall, this PhD work brings insights on the use and processing of the pupillometric signal to explore listening effort. It also underlines the relevance of the use of pupillometry and its contribution for the study of listening effort, among distinct populations. Finally, it shows the complementarity of subjective and objective measures during the assessment of listening effort, supporting the idea that it is a multidimensional construct., Notre environnement sonore quotidien est un mélange acoustique complexe, qui doit être traité et filtré, pour accéder aux informations auditives pertinentes. Les processus simultanés de sélection d'un son en particulier et d'inhibition de l'information non pertinente, nécessitent donc des ressources cognitives. Le déploiement de ces ressources pour comprendre un message sonore induit donc un effort d'écoute, et plus particulièrement dans les environnements bruyants. Depuis deux décennies, l'effort d'écoute a été étudié via un important panel de méthodes. Le travail de cette thèse a pour but d'apporter de nouvelles perspectives à l'étude de l'effort d'écoute, dans un premier temps par l'utilisation de la pupillométrie, puis en s'appuyant la complémentarité de différentes mesures (subjectives, comportementales et objectives). Une étude méthodologique a d'abord été menée sur les données de pupillométrie enregistrées pendant une tâche de reconnaissance de mots dans le bruit, chez des patients âgés malentendants, avec ou sans leur aide auditive. Plusieurs méthodes d'analyse ont été comparées, dont différentes techniques de normalisation, périodes de ligne de base et durées de ligne de base. Alors que les différentes méthodes de normalisation ainsi que durées de ligne de base ont donné des résultats similaires, le choix de la période de ligne de base a eu une influence déterminante sur les conclusions de l'étude. En effet, des processus cognitifs d'anticipation, liés à la mobilisation de l'attention avant la présentation des stimuli, ont pu être observés sur la dilatation pupillaire, lorsque la période de ligne de base était la plus antérieure à la présentation des mots. Ces différences de dilatation pupillaire ont pu être observées même lorsque l'intelligibilité était parfaite, soulignant la pertinence de la pupillométrie comme mesure objective de l'effort d'écoute. Le deuxième axe de cette thèse se concentre sur les résultats d'études empiriques, dans lesquelles plusieurs mesures permettant d’appréhender l’effort d’écoute, dont la pupillométrie, ont été conjointement utilisées. Les études empiriques ont été menées (1) chez les patients âgés malentendants en utilisant des mesures subjectives de l'effort d'écoute et la pupillométrie pendant une tâche de reconnaissance de mots dans le bruit, (2) chez les jeunes adultes normo-entendants en utilisant la pupillométrie et l'électroencéphalographie de scalp pendant une tâche de discrimination dans le bruit. L'absence de corrélation entre les scores d'auto-évaluation de difficulté de la tâche et les réponses pupillaires chez les patients malentendants suggère que les deux mesures évaluent différents aspects de l'effort d'écoute. Les réponses pupillaires permettent d'observer des processus d'anticipation, alors que les mesures subjectives décrivent l'effort global perçu pendant la tâche. Chez les jeunes adultes normo-entendants, les modulations des réponses corticales observées grâce à l'électroencéphalographie, étaient liées au traitement de la stimulation et à l'inhibition de la source sonore non pertinente pendant la discrimination. Les réponses pupillaires, enregistrées simultanément, ont apporté des informations concernant l'état de vigilance des participants pendant la tâche. Les résultats de ces deux études suggèrent donc que les différentes mesures se complémentent, et que leur combinaison aide à la compréhension des divers processus cognitifs impliqués dans l'effort d'écoute. Dans l'ensemble, ce travail de doctorat apporte de nouvelles connaissances sur l'utilisation et le traitement du signal de pupillométrie. Il souligne également la pertinence et les contributions de la pupillométrie dans l'étude de l'effort d'écoute. Enfin, il montre la complémentarité des mesures objectives et subjectives dans l'étude de l'effort d'écoute, appuyant l'hypothèse que l'effort d'écoute est multidimensionnel.

International audience; Background: Patient suicide (PS) is known to be a frequent and challenging occupational hazard for mental health professionals. No study previously explored the prevalence and impact of PS in a large sample of French psychiatrists.Method: A national web-based survey was performed between September and December 2019 to assess (a) the prevalence of the exposure to PS, (b) the emotional, traumatic and professional impacts of PS, and (c) the perceived support in the aftermath of PS in French psychiatrists. Participants were contacted through email to answer the online 62-item questionnaire, including a measure of traumatic impact through the Impact of Event Scale-Revised. Emotional and professional impacts and perceived support were assessed through dedicated items.Results: A total of 764 psychiatrists fully completed the survey. Of them, 87.3% reported an exposure to PS and 13.7% reported PTSD symptoms afterward. Guilt, sadness and shock were the most frequent emotions. Among the exposed psychiatrists, 15.1% have temporarily considered changing their career path. The most emotionally distressing PS occurred during their ten first years of practice or during residency. A total of 37.1% of respondents felt unsupported and 50.4% reported that no team meeting had been organized in the aftermath. The feeling of responsibility for the death was strongly associated with negative impacts.Conclusion: Our results entail considerations to prevent negative mental health outcomes in psychiatrists after PS. Notably, our results advocate for the implementation of educational programs during psychiatric residency and postvention programs in healthcare settings to effectively help psychiatrists in dealing with PS.

Recently, a new generation of devices have been developed to record neural activity simultaneously from hundreds of electrodes with a very high spatial density, both forin vitroandin vivoapplications. While these advances enable to record from many more cells, they also challenge the already complicated process of spike sorting (i.e., extracting isolated single-neuron activity from extracellular signals). In this work, we used synthetic ground-truth recordings with controlled levels of correlations among neurons to quantitatively benchmark the performance of state-of-the-art spike sorters focusing specifically on spike collisions. Our results show that while modern template-matching-based algorithms are more accurate than density-based approaches, all methods, to some extent, failed to detect synchronous spike events of neurons with similar extracellular signals. Interestingly, the performance of the sorters is not largely affected by the spiking activity in the recordings, with respect to average firing rates and spike-train correlation levels. Since the performances of all modern spike sorting algorithms can be affected as function of the activity of the recorded neurons, scientific claims on correlations and synchrony should be carefully assessed based on the analysis provided in this paper.

International audience; Unlike the acoustic features of calls, the temporal patterns of call usage in nonhuman primates are highly flexible. Our recent studies suggest that vocal patterns and species social needs coevolved. Different patterns, for example calling alone by producing one or several calls in a sequence or interacting vocally with more or less call overlap, may serve different functions. Vocal turn-taking in particular may be key to understanding the possible link between vocal behavior and social life. Turn-taking is used flexibly in many primate species, notably during affiliative encounters, and follows social and temporal rules that evoke similarities with human conversations. We tested the influence of caller characteristics and production context on the vocal behavior of a captive group of 15 chimpanzees using 48h30 of scan and focal sampling. 84% of the 516 recorded utterances were isolated calls. When there were vocal interactions, overlapping calls prevailed (63%), mostly involving adult males pant-hooting. Chimpanzees mostly produced calls in series, and the higher-ranked the caller, the faster the speed of call delivery. The social importance of consecutive calling was supported by a higher rate of audience reaction when the number of calls increased, suggesting strategic use of message redundancy. However, social integration, age, and sex weakly influenced call rates and interaction patterns. Although this study concerns a single study group, the rarity of turn-taking supports findings for wild chimpanzees. Why chimpanzees do not display this vocal behavior, which is commonly observed in primates, including other apes, is still puzzling.

Background Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation. Methods We evaluated the effect of chest X-rays from diagnostic medical procedures in a dataset composed of 1552 BC cases identified through French family cancer clinics and 1363 unrelated controls. Participants reported their history of X-ray exposures in a detailed questionnaire and were tested for 113 DNA repair genes. Logistic regression and multinomial logistic regression models were used to assess the association with BC. Results Chest X-ray exposure doubled BC risk. A 3% increased BC risk per additional exposure was observed. Being 20 years old or younger at first exposure or being exposed before first full-term pregnancy did not seem to modify this risk. Birth after 1960 or carrying a rare likely deleterious coding variant in a DNA repair gene other than BRCA1/2 modified the effect of chest X-ray exposure. Conclusion Ever/never chest X-ray exposure increases BC risk 2-fold regardless of age at first exposure and, by up to 5-fold when carrying 3 or more rare variants in a DNA repair gene. Further studies are needed to evaluate other DNA repair genes or variants to identify those which could modify radiation sensitivity. Identification of subpopulations that are more or less susceptible to ionizing radiation is important and potentially clinically relevant.

International audience; Refractive errors are common, especially in children and adolescents, leading to global health issues, academic implications and economic costs. Circadian rhythm and sleep habits may play a role. The study included 1130 children from the EDEN birth-cohort. Data were collected through parental questionnaires at age 2 and 5 for sleep duration and timing, and at age 5 for refractive error. At 5 years, 20.4% were prescribed glasses (2% for myopia, 11.9% for hyperopia and 6.8% for unknown reason). Children slept on average (SD) 11h05/night (± 30 min) and 10h49/night (± 48 min) at age 2 and 5, respectively. Average bedtime and midsleep was 8.36 pm (± 30 min), 2.06 am (± 36 min), and 8.54 pm (± 30 min), 2.06 am (± 24 min) at age 2 and 5, respectively. A U-shaped association was observed between sleep duration at age 2 and eyeglass prescription at age 5. Later midsleep and bedtime at age 2 were associated with an increased risk of eyeglass prescription at age 5. Associations became borderline significant after adjustment for confounding factors. Sleep duration and timing at age 2 were associated with subsequent refractive errors in preschoolers from general population. Sleep hygiene might be a target for refractive errors prevention.

International audience; Aims: Metabolic Syndrome (MetS) is a major health epidemic of Western countries and patients with schizophrenia is a particularly vulnerable population due to lifestyle, mental illness and treatment factors. However, we lack prospective data to guide prevention. The aim of our study is then to determine MetS incidence and predictors in schizophrenia.Method: Participants were recruited in 10 expert centers at a national level and followed-up for 3 years. MetS was defined according to the International Diabetes Federation criteria. Inverse probability weighting methods were used to correct for attrition bias.Results: Among the 512 participants followed-up for 3 years, 77.9% had at least one metabolic disturbance. 27.5% were identified with MetS at baseline and excluded from the analyses. Among the rest of participants (N = 371, mean aged 31.2 (SD = 9.1) years, with mean illness duration of 10.0 (SD = 7.6) years and 273 (73.6%) men), MetS incidence was 20.8% at 3 years and raised to 23.6% in tobacco smokers, 29.4% in participants receiving antidepressant prescription at baseline and 42.0% for those with 2 disturbed metabolic disturbances at baseline. Our multivariate analyses confirmed tobacco smoking and antidepressant consumption as independent predictors of MetS onset (adjusted odds ratios (aOR) = 3.82 [1.27-11.45], p = 0.016, and aOR = 3.50 [1.26-9.70], p = 0.0158). Antidepressant prescription predicted more specifically increased lipid disturbances and paroxetine was associated with the highest risk of MetS onset.Conclusion: These results are an alarm call to prioritize MetS prevention and research in schizophrenia. We have listed interventions that should be actively promoted in clinical practice.

International audience; Because the expression of pain in babies’ cries is based on universal acoustic features, it is assumed that adult listeners should be able to detect when a crying baby is experiencing pain. We report that detecting that a baby’s cry expresses pain actually requires learning through experience. Our psychoacoustic experiments reveal that adults with no experience of caring for babies are unable to identify whether a baby’s cry is a pain cry induced by vaccination or a mild discomfort cry recorded during a bath, even when they are familiar with the discomfort cries from this particular baby. In contrast, people with prior experience of babies — parents or professional caregivers — identify a familiar baby’s pain cries without having heard these cries before. Parents of very young children are even able to identify the pain cries of a baby who is completely unfamiliar to them. Exposure through caregiving and/or parenting thus shapes the auditory and cognitive abilities involved in decoding the information conveyed by the baby’s communication signals.

There is still a lack of robust data, acquired identically and reliably from tissues either surgically resected from patients with mesial temporal lobe epilepsy (mTLE) or collected in animal models, to answer the question of whether the degree of inflammation of the hippocampus differs between mTLE patients, and between epilepsy and epileptogenesis. Here, using highly calibrated RTqPCR, we show that neuroinflammatory marker expression was highly variable in the hippocampus and the amygdala of mTLE patients. This variability was not associated with gender, age, duration of epilepsy, seizure frequency, and anti-seizure drug treatments. In addition, it did not correlate between the two structures and was reduced when the inflammatory status was averaged between the two structures. We also show that brain tissue not frozen within minutes after resection had significantly decreased housekeeping gene transcript levels, precluding the possibility of using post-mortem tissues to assess physiological baseline transcript levels in the hippocampus. We thus used rat models of mTLE, induced by status epilepticus (SE), that have the advantage of providing access to physiological baseline values. They indisputably indicated that inflammation measured during the chronic phase of epilepsy was much lower than the explosive inflammation occurring after SE, and was only detected when epilepsy was associated with massive neurodegeneration and gliosis. Comparison between the inter-individual variability measured in patients and that established in all epileptic and control rats suggests that some mTLE patients may have very low inflammation in the hippocampus, close to control values. However, the observation of elevated inflammation in the amygdala of some patients indicates that inflammation should be studied not only at the epileptic hippocampus, but also in the associated brain structures in order to have a more integrated view of the degree of inflammation present in brain networks involved in mesial temporal lobe epilepsy.

Patients with drug-resistant epilepsy can experience respiratory alterations notably during seizures. The mechanisms underlying this long-term alteration of respiratory function remain unclear. This study aimed at determining in rats whether epilepsy is associated with alterations of both the respiratory function and brainstem serotonin (5-HT) system. Epilepsy was triggered by pilocarpine-induced status epilepticus in rats. 30-50% of epileptic (EPI) rats exhibited sharp decrease of oxygen consumption (SDOC), low metabolic rate of oxygen and slow regular ventilation; these rats were called EPI/SDOC+ rats. These alterations were only detected in rats with chronic epilepsy, independent of behavioral seizures, persisted over the time, and were not associated with death. In these rats, 5-HT fiber density in the nucleus tractus solitarius was below that of control and EPI/SDOC-rats. Both EPI/SDOC+ rats and DBA/2 mice presenting with fatal respiratory arrest following an audiogenic-induced seizure, a model of sudden and expected death in epilepsy, had increased transcript levels of tryptophan hydroxylase 2 (p

With the aim of designing a preclinical study evaluating an intracerebral cell-based therapy for stroke, an observational study was performed in the rat suture model of ischemic stroke. Objectives were threefold: (i) to characterize neurofunctional and imaging readouts in the first weeks following transient ischemic stroke, according to lesion subtype (hypothalamic, striatal, corticostriatal); (ii) to confirm that intracerebral administration does not negatively impact these readouts; and (iii) to calculate sample sizes for a future therapeutic trial using these readouts as endpoints. Our results suggested that the most relevant endpoints were side bias (staircase test) and axial diffusivity (AD) (diffusion tensor imaging). Hypothalamic-only lesions did not affect those parameters, which were close to normal. Side bias in striatal lesions reached near-normal levels within 2 weeks, while rats with corticostriatal lesions remained impaired until week 14. AD values were decreased at 4 days and increased at 5 weeks post-surgery, with a subtype gradient: hypothalamic < striatal < corticostriatal. Intracerebral administration did not impact these readouts. After sample size calculation (18-147 rats per group according to the endpoint considered), we conclude that a therapeutic trial based on both readouts would be feasible only in the framework of a multicenter trial.

Fraction knowledge is critical for the holistic development of mathematical knowledge. While fraction instruction typically begins in elementary school, children often encounter relational numerical concepts much earlier in their environment (e.g. sharing candies, varying the sweetness of a drink, baking muffins). A recently proposed theory, the Ratio Processing System (RPS) theory, posits that the understanding of symbolic fractions and non-symbolic relational magnitudes are fundamentally intertwined. However, research on the RPS theory and fraction learning interventions in the classroom are limited. In this dissertation, we examine both symbolic and non-symbolic relative magnitude processing from the perspectives of both cognitive neuroscience and educational game-based approach. First, performance accuracy on a match-to-sample task reveals individuals with varied mathematics skills to be perceptually sensitive to non-symbolic ratios but not to symbolic fractions. Second, univariate and multivariate analyses of neural activity patterns using a fMRI-adaptation paradigm suggest for an absence of overlapping brain activations for symbolic and non-symbolic magnitudes. Third, analyses of fifth grader’s fraction knowledge after playing a fraction educational game developed in the context of this thesis (Math Matthews Fractions) revealed that the game did not improve overall fraction skills above traditional classroom instruction. However, it was successful at improving decimal knowledge. The results of this thesis lead us to argue for fraction instruction focused on both perceptual methods as well as building connections between the multiple constructs of fractions. Future research holds great potential for examining fraction games that support teachers in building a holistic fraction understanding, rooted in the percept-concept links., La connaissance des fractions est essentielle au développement général des connaissances mathématiques. Bien que l'enseignement des fractions commence généralement à l'école primaire, les enfants rencontrent souvent des concepts liés aux fractions bien plus tôt dans leur environnement (par exemple, en partageant des bonbons, en variant le goût sucré d'une boisson, en préparant des muffins). Une théorie récemment proposée < the ratio processing system theory > postule que la compréhension des fractions et des rapports de grandeurs (i.e. ratio) sous forme non symbolique est fondamentalement liée. Cependant, les recherches sur la théorie RPS et les interventions d'apprentissage des fractions en classe sont limitées. Dans cette thèse, nous examinons le traitement de ratios, sous forme symbolique et non symbolique, du point de vue des neurosciences cognitives et de l'approche pédagogique basée sur le jeu. Tout d'abord, la précision de la performance dans une tâche d'appariement à l'échantillon révèle que des personnes ayant des compétences variées en mathématiques sont perceptivement sensibles aux ratios non symboliques mais pas aux ratios symboliques (i.e. les fractions). Deuxièmement, des analyses univariées et multivariées des schémas d'activité neuronale à l'aide d'un paradigme d'adaptation IRMf suggèrent l'absence de chevauchement des activations cérébrales pour les ratios symboliques et non symboliques. Troisièmement, des analyses de la compréhension des fractions chez les élèves de cinquième année, soit après l’utilisation d’un jeu en classe sur les fractions (Math Matthews Fractions), soit après un enseignement classique (sans jeu), ont révélé que le jeu n'a pas amélioré les compétences générales sur les fractions par rapport à l'enseignement classique (sans jeu). En revanche, il a amélioré la compréhension des nombres décimaux. Les résultats de cette thèse nous amènent à plaider en faveur d'un enseignement des fractions axé, d’une part sur des méthodes perceptives et d’autre part, sur la construction de liens entre les différents aspects des fractions. Les recherches futures offrent un grand potentiel pour l'étude de jeux sur les fractions qui aident les enseignants à développer, chez leurs élèves, une compréhension générale des fractions, enracinée dans les liens percept-concept.

While numerous transgenic mouse strains have been produced to model the formation of amyloid-β (Aβ) plaques in the brain, efficient methods for whole-brain 3D analysis of Aβ deposits are lacking. Moreover, standard immunohistochemistry performed on brain slices precludes any shape analysis of Aβ plaques. The present study shows how in-line (propagation-based) X-ray phase-contrast tomography (XPCT) combined with ethanol-induced brain sample dehydration enables hippocampus-wide detection and morphometric analysis of Aβ plaques. Performed in three distinct Alzheimer mouse strains, the proposed workflow identified differences in signal intensity and 3D shape parameters: 3xTg displayed a different type of Aβ plaques, with a larger volume and area, greater elongation, flatness and mean breadth, and more intense average signal than J20 and APP/PS1. As a label-free non-destructive technique, XPCT can be combined with standard immunohistochemistry. XPCT virtual histology could thus become instrumental in quantifying the 3D spreading and the morphological impact of seeding when studying prion-like properties of Aβ aggregates in animal models of Alzheimer’s disease. This is Part II of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part I shows how in-line XPCT enables 3D myelin mapping in the whole rodent brain and in human autopsy brain tissue.HighlightsX-ray phase-contrast tomography (XPCT) enables whole brain detection of Aβ plaquesMorphometric parameters of Aβ plaques may be readily retrieved from XPCT dataNew shape parameters were successfully extracted from three Alzheimer’s disease modelsA Fiji-based “biologist-friendly” analysis workflow is proposed and sharedXPCT is a powerful virtual histology tool that requires minimal sample preparationGraphical abstract

International audience; Inverted duplication deletion 8p [invdupdel(8p)] is a complex and rare chromosomal rearrangement that combines a distal deletion and an inverted interstitial duplication of the short arm of chromosome 8. Carrier patients usually have developmental delay and intellectual disability (ID), associated with various cerebral and extra-cerebral malformations. Invdupdel(8p) is the most common recurrent chromosomal rearrangement in ID patients with anomalies of the corpus callosum (AnCC). Only a minority of invdupdel(8p) cases reported in the literature to date had both brain cerebral imaging and chromosomal microarray (CMA) with precise breakpoints of the rearrangements, making genotype-phenotype correlation studies for AnCC difficult. In this study, we report the clinical, radiological, and molecular data from 36 new invdupdel(8p) cases including three fetuses and five individuals from the same family, with breakpoints characterized by CMA. Among those, 97% (n = 32/33) of patients presented with mild to severe developmental delay/ID and 34% had seizures with mean age of onset of 3.9 years (2 months-9 years). Moreover, out of the 24 patients with brain MRI and 3 fetuses with neuropathology analysis, 63% (n = 17/27) had AnCC. We review additional data from 99 previously published patients with invdupdel(8p) and compare data of 17 patients from the literature with both CMA analysis and brain imaging to refine genotype-phenotype correlations for AnCC. This led us to refine a region of 5.1 Mb common to duplications of patients with AnCC and discuss potential candidate genes within this region.

Background One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. Methods In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100–500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients’ symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment. Discussion The results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia. Trial registration ClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016

International audience; Congenital amusia is a neurodevelopmental disorder of music processing, which includes impaired pitch memory, associated to abnormalities in the right fronto-temporal network. Previous research has shown that tonal structures (as defined by the Western musical system) improve short-term memory performance for short tone sequences (in comparison to atonal versions) in non-musician listeners, but the tonal structures only benefited response times in amusic individuals. We here tested the potential benefit of tonal structures for short-term memory with more complex musical material. Congenital amusics and their matched nonmusician controls were required to indicate whether two excerpts were the same or different. Results confirmed impaired performance of amusic individuals in this short-term memory task. However, most importantly, both groups of participants showed better memory performance for tonal material than for atonal material. These results revealed that even amusics' impaired short-term memory for pitch shows classical characteristics of short-term memory, that is the mnemonic benefit of structure in the to-be-memorized material. The findings show that amusic individuals have acquired some implicit knowledge of regularities of their culture, allowing for implicit processing of tonal structures, which benefits to memory even for complex material.

Even though we perceive the space surrounding us as a cartesian continuum, the region of space near the body where physical interactions with the environment take place is a special region, termed peripersonal space (PPS). PPS was first defined on the basis of neurons properties recorded in the monkey in specific premotor and parietal brain regions. More recently, a putative homologous network has been identified in humans using functional Magnetic Resonance Imaging (fMRI). The representation of this space does not refer to a well-demarcated region with clear borders but is instead flexible allowing us to adapt our behavior depending on the context. In particular, the world of human and non-human animals is first and foremost a social world. In this social world, a comfort zone is necessary to regulate the distance between selves and others and thus avoid discomfort or even anxiety. Much less is known about this social dimension of PPS than about the physical, object-related function of PPS. In this context, my PhD work aimed first at bridging the gap between the properties recorded in the monkey’s individual neurons and the neuroimaging measure of the human premotor-parietal network. Second, it aimed at shedding new light on the social dimension of PPS, a topic that has largely been overlooked up to now although it is of utmost importance for all animals. To address these questions, I have developed protocols in virtual reality (VR) environment with a virtual reality headset or with a 3D projector in the MRI scanner because it allows for very precise manipulation and control of visual information at different distances from our body. To carry out my first objective, we used similar experimental procedures in both humans and monkeys to compare cerebral activity with fMRI. Through two tasks, where either real or virtual objects were presented at different distances (close and far) from the body, I identified an homologous premotor-parietal network underlying PPS representation in the two species. To carry out my second objective, I used a multiscale approach. Specifically, my goal was to understand how social information (emotional facial expressions) in our PPS affects our perceptual abilities, our physiological state using measures of pupil diameter and heart rate, and our brain activity using fMRI. At the behavioral level, my results showed that our visual discriminating abilities were improved when emotional faces were presented in PPS compared to the far space, even when retinal size was equated for close and far images. This improvement in perceptual abilities was accompanied by an increase in heart rate frequency, reflecting an arousing response when emotional faces were close to the body. Finally, at the neuronal level, I have identified an occipito-premotor-parietal network with increased activity in the presence of close compared to far emotional faces. Interestingly, my results also show that a common network encoded similarly social and non-social stimuli in PPS. In parallel to this work in heathy volunteers, I also established a direct link between unilateral medial-temporal lesions and a deficit in the regulation of appropriate social distances. In summary, my results demonstrate that social presence in PPS facilitates our behavioral performance, increases our level of arousal, and recruits a central premotor-parietal neural network regardless of the type of cue (social or non-social). Thus, a common neural network might allow a rapid response, that might be primary recruited in any situation occurring in our PPS and additional brain regions might come into play to fine tune our behavior depending on the context., Même si nous percevons l'espace qui nous entoure comme un continuum cartésien, la région de l'espace près du corps où se déroulent les interactions physiques avec l'environnement est une région spéciale, appelée espace péri-personnel (EPP). L’EPP a d'abord été défini sur la base des propriétés de neurones enregistrés chez le singe dans des régions cérébrales prémotrices et pariétales spécifiques. Plus récemment, un réseau homologue putatif a été identifié chez l'homme en utilisant l’IRMf. La représentation de cet espace ne fait pas référence à une région bien délimitée avec des frontières claires mais est au contraire flexible, nous permettant d'adapter notre comportement en fonction du contexte. En particulier, le monde des hommes et des singes est avant tout un monde social. Dans ce monde social, une zone de confort est nécessaire pour réguler la distance entre soi et les autres et ainsi éviter l'inconfort, voire l'anxiété. Cependant, on sait encore peu de choses sur cette dimension sociale de l’EPP comparé à celle liée aux objets. Dans ce contexte, mon travail de thèse visait d'abord à combler le fossé entre les propriétés enregistrées dans les neurones individuels du singe et les activités cérébrales identifiées en neuroimagerie du réseau prémoteur-pariétal humain. Deuxièmement, il visait à apporter un nouvel éclairage sur la dimension sociale de l’EPP, un sujet qui a été largement négligé jusqu'à présent alors qu'il est de la plus haute importance pour tous les animaux. Pour répondre à ces questions, j'ai développé des protocoles utilisant un environnement de réalité virtuelle (RV) permettant une manipulation et un contrôle très précis des informations visuelles à différentes distances de notre corps. Pour réaliser mon premier objectif, j’ai utilisé des procédures expérimentales similaires chez l'homme et le singe afin de comparer l'activité cérébrale en IRMf. À travers deux tâches, où des objets réels ou virtuels étaient présentés à différentes distances (proche et éloignée) du corps, j'ai identifié un réseau prémoteur-pariétal homologue sous-jacent à la représentation de l’EPP chez les deux espèces. Pour réaliser mon deuxième objectif, j'ai utilisé une approche multi-échelle. Plus précisément, mon objectif était de comprendre comment les informations sociales (expressions faciales émotionnelles) dans notre EPP affectent nos capacités de perception, notre état physiologique, et notre activité cérébrale. Au niveau comportemental, mes résultats ont montré que nos capacités de discrimination visuelle étaient améliorées lorsque les visages émotionnels étaient présentés dans l’EPP par rapport à l'espace lointain, même lorsque la taille rétinienne était similaire pour les images proches et lointaines. Cette amélioration des capacités perceptives s'accompagnait d'une augmentation de la fréquence cardiaque lorsque les visages émotionnels étaient proches du corps. Enfin, au niveau neuronal, j'ai identifié un réseau occipito-prémoteur-pariétal avec une activité accrue en présence de visages émotionnels proches par rapport aux visages lointains. Mes résultats montrent également qu'un réseau commun code de manière similaire des stimuli sociaux et non sociaux dans l’EPP. Parallèlement à ce travail réalisé chez des volontaires sains, j'ai également établi un lien direct entre des lésions unilatérales médio-temporales et un déficit dans la régulation appropriée des distances sociales. En résumé, mes résultats démontrent que la présence sociale dans l’EPP facilite nos performances comportementales, augmente notre niveau de vigilance et recrute un réseau neuronal prémoteur-pariétal central quelque soit le type d’information (sociale ou non sociale). Ainsi, un réseau neuronal commun permettrait une réponse rapide, qui pourrait être principalement recruté dans n’importe quelle situation se produisant dans notre EPP, et des régions cérébrales supplémentaires pourraient entrer en jeu afin d’affiner notre comportement en fonction du contexte.

International audience; In the last decade, two hypotheses, one on the evolution of animal vocal communication in general and the other on the origins of human language, have gained ground. The first hypothesis argues that the complexity of communication co-evolved with the complexity of sociality. Species forming larger groups with complex social networks have more elaborate vocal repertoires. The second hypothesis posits that the core of communication is represented not only by what can be expressed by an isolated caller, but also by the way that vocal interactions are structured, language being above all a social act. Primitive forms of conversational rules based on a vocal turn-taking principle are thought to exist in primates. To support and bring together these hypotheses, more comparative studies of socially diverse species at different levels of the primate phylogeny are needed. However, the majority of available studies focus on monkeys, primates that are distant from the human lineage. Great apes represent excellent candidates for such comparative studies because of their phylogenetic proximity to humans and their varied social lives. We propose that studying vocal turn-taking in apes could address several major gaps regarding the social relevance of vocal turn-taking and the evolutionary trajectory of this behaviour among anthropoids. Indeed, how the social structure of a species may influence the vocal interaction patterns observed among group members remains an open question. We gathered data from the literature as well as original unpublished data (where absent in the literature) on four great ape species: chimpanzees Pan troglodytes, bonobos Pan paniscus, western lowland gorillas Gorilla gorilla gorilla and Bornean orang-utans Pongo pygmaeus. We found no clear-cut relationship between classical social complexity metrics (e.g. number of group members, interaction rates) and vocal complexity parameters (e.g. repertoire size, call rates). Nevertheless, the nature of the society (i.e. group composition, diversity and valence of social bonds) and the type of vocal interaction patterns (isolated calling, call overlap, turn-taking-based vocal exchanges) do appear to be related. Isolated calling is the main vocal pattern found in the species with the smallest social networks (orang-utan), while the other species show vocal interactions that are structured according to temporal rules. A high proportion of overlapping vocalisations is found in the most competitive species (chimpanzee), while vocal turn-taking predominates in more tolerant bonobos and gorillas. Also, preferentially interacting individuals and call types used to interact are not randomly distributed. Vocal overlap ('chorusing') and vocal exchange ('conversing') appear as possible social strategies used to advertise/strengthen social bonds. Our analyses highlight that: (i) vocal turn-taking is also observed in non-human great apes, revealing universal rules for conversing that may be deeply rooted in the primate lineage; (ii) vocal interaction patterns match the species' social lifestyle; (iii) although limited to four species here, adopting a targeted comparative approach could help to identify the multiple and subtle factors underlying social and vocal complexity. We believe that vocal interaction patterns form the basis of a promising field of investigation that may ultimately improve our understanding of the socially driven evolution of communication.

International audience; Reorganization of the sensorimotor cortex following permanent (e.g., amputation) or temporary (e.g., local anaesthesia) deafferentation of the hand has revealed large-scale plastic changes between the hand and face representations that are accompanied by perceptual correlates. The physiological mechanisms underlying this reorganization remain poorly understood. The aim of this study was to investigate sensorimotor interactions between the face and hand using an afferent inhibition transcranial magnetic stimulation protocol in which the motor evoked potential elicited by the magnetic pulse is inhibited when it is preceded by an afferent stimulus. We hypothesized that if face and hand representations in the sensorimotor cortex are functionally coupled, then electrocutaneous stimulation of the face would inhibit hand muscle motor responses. In two separate experiments, we delivered an electrocutaneous stimulus to either the skin over the right upper lip (Experiment 1) or right cheek (Experiment 2) and recorded muscular activity from the right first dorsal interosseous. Both lip and cheek stimulation inhibited right first dorsal interosseous motor evoked potentials. To investigate the specificity of this effect, we conducted two additional experiments in which electrocutaneous stimulation was applied to either the right forearm (Experiment 3) or right upper arm (Experiment 4). Forearm and upper arm stimulation also significantly inhibited the right first dorsal interosseous motor evoked potentials, but this inhibition was less robust than the inhibition associated with face stimulation. These findings provide the first evidence for face-to-hand afferent inhibition.

Forty years have passed since the coining of the term "peripersonal space" (PPS), that region of space in which our daily life takes place, in which we can interact with the objects and people around us. The first studies of the electrophysiological literature of this spatial representation have observed in specific regions of the macaque’s brain the existence of multisensory neurons capable of encoding tactile, visual and / or auditory stimuli according to their distance from specific parts of the body. These bi- or trimodal neurons, indeed, show tactile receptive fields centered on a specific part of the body, such as the face or hand, and visual and / or auditory receptive fields overlapping spatially with the formers. In this way, the same neurons are able to respond to tactile, visual and auditory stimulations delivered on or close to a specific body-part. Furthermore, these multisensory receptive fields are "anchored" to each other: the movement of the monkey's hand involves a coherent displacement not only of the tactile receptive fields, but also of the visual ones. This body-part centered reference frame of the coding of multisensory stimuli within PPS allows to keep the information relating to the position of the different parts of the body and surrounding objects always updated, with the aim of planning and implementing effective actions. Neurophysiological and behavioral studies on patients suffering from extinction and neglect following brain lesions of the right hemisphere have allowed to highlight, even in humans, the existence and modularity of the PPS. Subsequent neuroimaging studies have brought support to this evidence, highlighting a network of fronto-parietal and subcortical regions capable of coding multi-modal stimulations according to their distance from the body. The functions of this spatial representation are manifold: mediate the relationship between the perception of external stimuli and the execution of goal-directed actions, monitoring the space around the body in order to identify potential threats and implement defensive reactions, organize and manage the space between us and others in case of different types of social interaction and allow us to identify ourselves with our body, giving it a localization in space. However, despite the great scientific interest that this region of space has elicited over the past forty years, a direct comparison of its neural underpinnings in non-human primates and humans is still missing. For this reason, in the first chapter of this doctoral dissertation we will report the results of an fMRI study, conducted on human and macaque participants, which investigated the neural response patterns to stimulations close to or far from different body-parts, minimizing the differences among the experimental protocols used in the two species. For the first time PPS is tested in two different species but with the same experimental protocol, highlighting similarities and differences between the human and simian PPS circuit but also between the response patterns associated with the stimulation of different bodily districts. Starting from the second chapter we will instead focus our interest only on human participants, to try to shed light on a defining problem that has overlapped the concept of PPS representation to that of a second spatial representation: the arm reaching space (ARS). The latter, considered as the space around the body that we can reach by extending our arm, over time has often been used as a synonym for the PPS representation, leading to define PPS as ARS or to test the two spatial representations with the same experimental protocols. However, the different neural bases and the different characteristics of the encoding of stimuli within these two regions of space suggest their distinction. In chapter II, to this purpose, we will present a series of five behavioral experiments that investigated the differences and similarities between PPS and ARS .. [etc], Quarante ans exacts se sont écoulés depuis l'apparition du terme « espace péripersonnel » (EPP), cette région de l'espace dans laquelle notre vie quotidienne prend place, dans laquelle nous pouvons interagir avec les objets et les personnes qui nous entourent. Les premières études de la littérature électrophysiologique de cette représentation spatiale ont observé dans des régions spécifiques du cerveau des macaques l'existence de neurones multisensoriels capables de coder des stimuli tactiles, visuels et/ou auditifs en fonction de leur distance des parties spécifiques du corps. Ces neurones bi- ou trimodaux présentent en effet des champs récepteurs tactiles centrés sur une partie précise du corps, comme le visage ou la main, et des champs récepteurs visuels et/ou auditifs se superposant spatialement aux premiers. De cette façon, les mêmes neurones sont capables de répondre à des stimulations tactiles, visuelles et auditives délivrées sur ou à proximité d'une partie spécifique du corps. De plus, ces champs récepteurs multisensoriels sont « ancrés » les uns aux autres : le mouvement de la main du singe impliquait une mise à jour non seulement des champs récepteurs tactiles, mais aussi des champs visuels. Ce référentiel centré sur les parties du corps du codage des stimuli multisensoriels au sein de l’EPP nous permet de garder les informations relatives à la position des différentes parties du corps et des objets environnants toujours à jour, dans le but de planifier et de mettre en œuvre des actions efficaces. Des études neurophysiologiques et comportementales sur des patients souffrant d'extinction et sur des patients héminégligeant suite à des lésions cérébrales de l'hémisphère droit ont permis de mettre en évidence, même chez l'homme, l'existence et la modularité du PPS. Des études ultérieures en neuro-imagerie ont apporté un soutien à cette preuve, mettant en évidence un réseau de régions fronto-pariétales et sous-corticales capables de coder des stimulations multimodales en fonction de leur distance du corps. Les fonctions de cette représentation spatiale sont multiples : médiatiser la relation entre la perception de stimuli externes et l'exécution d'actions ciblées, la surveillance de l'espace autour du corps afin d'identifier les menaces potentielles et mettre en œuvre des réactions défensives, organiser et gérer l'espace entre nous et les autres dans le cas de différents types d'interactions sociales ou nous permettre de nous identifier à notre corps, en lui donnant une localisation dans l'espace. Cependant, malgré le grand intérêt scientifique que cette région de l'espace autour du corps a suscité au cours des quarante dernières années, une comparaison directe de ses fondements neuronaux chez les primates non humains et les humains fait toujours défaut. Pour cette raison, dans le premier chapitre de cette thèse de doctorat, nous rapporterons les résultats d'une étude IRMf, menée sur des participant·e·s humain·e·s et macaques, qui a identifié les patterns de réponse neuronale à des stimulations proches ou éloignées de différentes parties du corps, tout en essayant de minimiser les différences entre les protocoles expérimentaux utilisés chez les deux espèces. Pour la première fois le PPS est investigué chez deux espèces différentes mais avec le même protocole expérimental, mettant en évidence des similitudes et des différences entre le circuit PPS humain et simien, mais aussi entre les patterns de réponse associés à la stimulation de différents secteurs corporels. À partir du deuxième chapitre, nous concentrerons plutôt notre intérêt sur la représentation de l'EPP chez l’être humain, pour essayer de faire la lumière sur un problème de définition qui a confondu la représentation EPP avec l’espace atteignable (EA). Cette dernière, considérée comme l'espace autour du corps que l'on peut atteindre en étendant le bras, a souvent été utilisée au fil du temps comme synonyme de la représentation de l’EPP, conduisant à .. [etc]

International audience; Developmental aspects of auditory cognition were investigated in 5-to-10-year-old children (n = 100). Musical and verbal short-term memory (STM) were assessed by means of delayed matching-to-sample tasks (DMST) (comparison of two four-item sequences separated by a silent retention delay), with two levels of difficulty. For musical and verbal materials, children's performance increased from 5 years to about 7 years of age, then remained stable up to 10 years of age, with performance remaining inferior to performance of young adults. Children and adults performed better with verbal material than with musical material. To investigate auditory cognition beyond STM, we assessed speech-in-noise perception with a four-alternative forced-choice task with two conditions of phonological difficulty and two levels of cocktail-party noise intensity. Partial correlations, factoring out the effect of age, showed a significant link between musical STM and speech-in-noise perception in the condition with increased noise intensity. Our findings reveal that auditory STM improves over development with a critical phase around 6-7 years of age, yet these abilities appear to be still immature at 10 years. Musical and verbal STM might in particular share procedural and serial order processes. Furthermore, musical STM and the ability to perceive relevant speech signals in cocktail-party noise might rely on shared cognitive resources, possibly related to pitch encoding. To the best of our knowledge, this is the first time that auditory STM is assessed with the same paradigm for musical and verbal material during childhood, providing perspectives regarding diagnosis and remediation in developmental learning disorders.

International audience; Transfer learning for training brain-computer interface (BCI) decoding algorithms is useful to reduce the calibration time, increase the accuracy, reduce the risk of overfitting and allow the application of machine learning methods that require a large amount of data, such as deep neuronal networks. In this article we propose a transfer learning method inspired by recent advances in Riemannian geometry. The method aligns vectors in the tangent space of a source and a target data set by means of Procrustes Analysis. We apply the method on a publicly available P300-BCI database. We show that using our method it is possible to transfer information reusing data from other subjects. The classification accuracy we obtain, as compared to the state of art, shows a clear transmission of information using the transfer learning method.

International audience; Rhythm perception involves strong auditory-motor connections that can be enhanced with movement. However, it is unclear whether just seeing someone moving to a rhythm can enhance auditory-motor coupling, resulting in stronger entrainment. Rhythmic priming studies show that presenting regular rhythms before naturally spoken sentences can enhance grammaticality judgments compared to irregular rhythms or other baseline conditions. The current study investigated whether introducing a point-light figure moving in time with regular rhythms could enhance the rhythmic priming effect. Three experiments revealed that the addition of a visual cue did not benefit rhythmic priming in comparison to auditory conditions with a static image. In Experiment 1 (27 7-8-year-old children), grammaticality judgments were poorer after audiovisual regular rhythms (with a bouncing point-light figure) compared to auditory-only regular rhythms. In Experiments 2 (31 adults) and 3 (31 different adults), there was no difference in grammaticality judgments after audiovisual regular rhythms compared to auditory-only irregular rhythms for either a bouncing point-light figure (Experiment 2) or a swaying point-light figure (Experiment 3). Comparison of the observed performance with previous data suggested that the audiovisual component removed the regular prime benefit. These findings suggest that the visual cues used in this study do not enhance rhythmic priming and could hinder the effect by potentially creating a dual-task situation. In addition, individual differences in sensory-motor and social scales of music reward influenced the effect of the visual cue. Implications for future audiovisual experiments aiming to enhance beat processing, and the importance of individual differences will be discussed.

International audience; Recent theories and data suggest that adapted behavior involves economic computations during which multiple trade-offs between reward value, accuracy requirement, energy expenditure, and elapsing time are solved so as to obtain rewards as soon as possible while spending the least possible amount of energy. However, the relative impact of movement energy and duration costs on perceptual decision-making and movement initiation is poorly understood. Here, we tested 31 healthy subjects on a perceptual decision-making task in which they executed reaching movements to report probabilistic choices. In distinct blocks of trials, the reaching duration (“Time” condition) and energy (“Effort” condition) costs were independently varied compared to a “Reference” block, while decision difficulty was maintained similar at the block level. Participants also performed a simple delayed-reaching (DR) task aimed at estimating movement initiation duration in each motor condition. Results in that DR task show that long duration movements extended reaction times (RTs) in most subjects, whereas energy-consuming movements led to mixed effects on RTs. In the decision task, about half of the subjects decreased their decision durations (DDs) in the Time condition, while the impact of energy on DDs were again mixed across subjects. Decision accuracy was overall similar across motor conditions. These results indicate that movement duration and, to a lesser extent, energy expenditure, idiosyncratically affect perceptual decision-making and action initiation. We propose that subjects who shortened their choices in the time-consuming condition of the decision task did so to limit a drop of reward rate.

International audience; While recent advances in genetics make it possible to follow the genetic exchanges between populations and their phenotypic consequences, the impact of the genetic exchanges on the sensory perception of populations has yet to be explored. From this perspective, the present study investi- gated the consequences of African gene flow on odor perception in a Malagasy population with a predominantly East Asian genetic background. To this end, we combined psychophysical tests with genotype data of 235 individuals who were asked to smell the odorant molecule beta-ionone (βI). Results showed that in this population the ancestry of the OR5A1 gene significantly influences the ability to detect βI. At the individual level, African ancestry significantly protects against specific anosmia/hyposmia due to the higher frequency of the functional gene (OR ratios = 14, CI: 1.8–110, p-value = 0.012). At the population level, African introgression decreased the prevalence of specific anosmia/hyposmia to this odorous compound. Taken together, these findings validate the conjecture that in addition to cultural exchanges, genetic transfer may also influence the sensory perception of the population in contact.

International audience; Introduction: Patients with right stroke lesion have postural and balance disorders, including weight-bearing asymmetry, more pronounced than patients with left stroke lesion. Spatial cognition disorders post-stroke, such as misperceptions of subjective straight-ahead and subjective longitudinal body axis, are suspected to be involved in these postural and balance disorders. Prismatic adaptation has showed beneficial effects to reduce visuomotor disorders but also an expansion of effects on cognitive functions, including spatial cognition. Preliminary studies with a low level of evidence have suggested positive effects of prismatic adaptation on weight-bearing asymmetry and balance after stroke. The objective is to investigate the effects of this intervention on balance but also on postural disorders, subjective straight-ahead, longitudinal body axis and autonomy in patients with chronic right stroke lesion.Methods and analysis: In this multicentre randomised double-blind sham-controlled trial, we will include 28 patients aged from 18 to 80 years, with a first right supratentorial stroke lesion at chronic stage (≥12 months) and having a bearing ≥60% of body weight on the right lower limb. Participants will be randomly assigned to the experimental group (performing pointing tasks while wearing glasses shifting optical axis of 10 degrees towards the right side) or to the control group (performing the same procedure while wearing neutral glasses without optical deviation). All participants will receive a 20 min daily session for 2 weeks in addition to conventional rehabilitation. The primary outcome will be the balance measured using the Berg Balance Scale. Secondary outcomes will include weight-bearing asymmetry and parameters of body sway during static posturographic assessments, as well as lateropulsion (measured using the Scale for Contraversive Pushing), subjective straight-ahead, longitudinal body axis and autonomy (measured using the Barthel Index).Ethics and dissemination: The study has been approved by the ethical review board in France. Findings will be submitted to peer-reviewed journals relative to rehabilitation or stroke.Trial registration number: NCT03154138.

Objective To compare old patients hospitalized in ICU for respiratory distress due to COVID-19 with old patients hospitalized in ICU for a non-COVID-19-related reason in terms of autonomy and quality of life. Design Comparison of two prospective multi-centric studies. Setting This study was based on two prospective multi-centric studies, the Senior-COVID-Rea cohort (COVID-19-diagnosed ICU-admitted patients aged over 60) and the FRAGIREA cohort (ICU-admitted patients aged over 70). Patients We included herein the patients from both cohorts who had been evaluated at day 180 after admission (ADL score and quality of life). Interventions None. Measurements and main results A total of 93 COVID-19 patients and 185 control-ICU patients were included. Both groups were not balanced on age, body mass index, mechanical ventilation, length of ICU stay, and ADL and SAPS II scores. We modeled with ordered logistic regression the influence of COVID-19 on the quality of life and the ADL score. After adjustment on these factors, we observed COVID-19 patients were less likely to have a loss of usual activities (aOR [95% CI] 0.47 [0.23; 0.94]), a loss of mobility (aOR [95% CI] 0.30 [0.14; 0.63]), and a loss of ADL score (aOR [95% CI] 0.30 [0.14; 0.63]). On day 180, 52 (56%) COVID-19 patients presented signs of dyspnea, 37 (40%) still used analgesics, 17 (18%) used anxiolytics, and 14 (13%) used antidepressant. Conclusions COVID-19-related ICU stay was not associated with a lower quality of life or lower autonomy compared to non-COVID-19-related ICU stay.

International audience; Objectives: To evaluate the impact of nonviolent communication (NVC) training on five aspects of medical students' empathy skills using implicit and explicit measures. Methods: 312 third-year French medical students were randomly allocated to an intervention group (n = 123) or a control group (n = 189). The intervention group received 2.5 days of NVC training. For each group, empathy-related skills were measured implicitly using three cognitive tests (Visuo-Spatial Perspective Taking, Privileged Knowledge, Empathy for Pain evaluation) and explicitly using two self-rating questionnaires (Jefferson Scale of Physician Empathy, Empathy Quotient). Both groups completed tests and questionnaires before (pre-test) and three months after training (post-test). Responses were collected via online software, and data were analyzed using paired linear mixed models and Bayes Factors. Results: We found a significant increase in the Jefferson Scale of Physician Empathy (JSPE) score between pre-and post-tests in the intervention group compared to the control group (linear mixed models: 0.95 points [0.17, 1.73], t(158) = 2.39, p < 0.05), and an expected gender effect whereby females had higher JSPE scores (1.57 points [0.72, 2.42], t(262) =-3.62, p < 0.001). There was no interaction between these two factors. Conclusions: Our results show that brief training in nonviolent communication improves subjective empathy three months after training. These results are promising for the long-term effectiveness of NVC training on medical students' empathy and call for the introduction of NVC training in medical school. Further studies should investigate whether longer training will produce larger and longer-lasting benefits.

Tool use is a hallmark of human evolution. Beyond its sensorimotor components, whose complexity has been extensively investigated, tool use impacts cognition. Tool use requires integrating an external object as a body part and embedding its functional structure in the motor program. Additionally, it has been proposed that brain areas involved in language have exapted neural resources devoted to tool use. Accordingly, researchers have advanced the existence of similarities between the processes underlying tool use and language, in line with the similarities for action and language suggested by the embodied cognition models. Thus, this thesis aims to further characterize the shared neural resources and reciprocal behavioral links between tool use and language. In a first study, we used functional neuroimaging to test the existence of shared neural resources between tool use and two linguistic processes: phonology and semantics. For phonology, the participants performed a phonological identification task, whereas for semantics they underwent a semantic priming task with a lexical decision. Although tool use and phonology recruited contiguous regions in the inferior parietal lobe, no evidence for shared neural resources was found between those two functions. By contrast, multivariate analyses showed that the neural activity elicited by semantics was decoded within the tool-use neural network, in the left inferior frontal gyrus and the left occipitotemporal cortex. In a second study, we tested the existence of shared neural substrates for tool use and syntactic processing. The participants performed a syntactic comprehension task requiring to process syntactic structures of different complexity. Results showed tool use and complex syntax (i.e. object relatives) elicited neural activity anatomically co-localized within the basal ganglia. Multivariate analyses revealed similar spatial distributions of neural patterns prompted by tool use and object relative processing. Moreover, the shared neurofunctional resources are reflected behaviorally by cross-domain learning transfer: tool-use training significantly improves linguistic performance for complex syntax, and reciprocally, complex syntax training improves motor performance with the tool. No learning transfer was observed on language syntactic abilities if participants trained without the tool, nor on tool use if participants trained with simpler syntactic structures (i.e. subject relatives). Our findings show the existence of shared neural resources between tool use and language, pointing to the existence of a supramodal syntactic function shared between the motor and the language domains. More generally our work opens perspectives to develop learning or rehabilitation protocols taking advantage of the crossdomain learning transfer. From an evolutionary point of view, our results reinforce the hypothesis of a co-evolution between tool use and language, leading to shared neural resources for these two abilities., L’utilisation d’outil est le produit de l’évolution humaine. En plus de sa composante sensorimotrice, dont la complexité est désormais bien caractérisée, l’habileté à utiliser un outil impacte la cognition. En effet, l’utilisation d’outil requiert d’intégrer un objet externe comme une partie corporelle, tout en incluant sa structure fonctionnelle dans le programme moteur. D’autre part, il a été proposé que les aires cérébrales impliquées dans le langage aient exploité les ressources neuronales dédiées à l’outil. Ainsi, les chercheurs ont avancé l’hypothèse de similarités entre les processus sous-tendant l’utilisation d’outil d’une part et le langage de l’autre, en plus des similarités entre action et langage auparavant suggérées par les modèles de la cognition incarnée. Ainsi, cette thèse vise à caractériser les ressources neuronales partagées et les liens comportementaux réciproques entre l’utilisation d’outil et le langage. Dans une première étude, nous avons utilisé la neuroimagerie fonctionnelle pour tester l’existence de ressources neuronales partagées entre l’utilisation d’outil et deux fonctions langagières : la phonologie et la sémantique. Pour la phonologie, les participant.e.s devaient réaliser une tâche d’identification phonologique, tandis que pour la sémantique, une tâche d’amorçage sémantique avec décision lexicale était réalisée. Bien que l’utilisation d’outil et la phonologie recrutent des régions corticales contigües du lobule pariétal inférieur, aucune preuve n’a été trouvée en faveur de ressources neuronales partagées entre ces deux fonctions. Des analyses multivariées ont en revanche montré que l’activité neuronale induite par la sémantique est décodée au sein du réseau neuronal de l’utilisation d’outil et plus particulièrement dans le gyrus frontal inférieur gauche et le cortex occipitotemporal gauche. Dans une seconde étude, nous avons testé l’existence de ressources partagées pour l’utilisation d’outil et la fonction syntaxique. Les participant·e·s devaient réaliser une tâche de compréhension syntaxique impliquant des phrases relatives de complexité différente. Les résultats ont montré que l’utilisation d’outil et la syntaxe complexe (i.e. relatives objet) induisaient une activité neuronale anatomiquement co-localisée au sein des ganglions de la base. De plus, des analyses multivariées ont révélé une distribution spatiale similaire pour les patterns neuronaux induits par l’utilisation d’outil et le traitement des relatives objet. En conséquence, le partage de ces ressources neurofonctionnelles se reflète au niveau comportemental par un transfert d’apprentissage entre les deux domaines : l’entrainement à l’utilisation d’outil améliore la performance linguistique pour la syntaxe complexe et réciproquement, l’entrainement à la syntaxe complexe améliore la performance motrice avec l’outil. Aucun transfert d’apprentissage n’a été observé pour les habilités syntaxiques après un entrainement équivalent mais sans outil, ou bien pour l’utilisation d’outil après entrainement avec des structures syntaxiques plus simples (i.e. relatives sujet). Nos résultats démontrent l’existence de ressources partagées entre utilisation d’outil et langage et indiquent l’existence d’une fonction syntaxique supramodale dédiée aux domaines moteur et langagier. Plus généralement, nos travaux ouvrent des perspectives quant à la mise en place des protocoles d’apprentissage ou de réhabilitation interdomaine tirant profit du transfert d’apprentissage. Nos résultats confortent enfin l’hypothèse d’une coévolution entre l’habileté à utiliser un outil et le langage, ayant favorisé le partage de ressources neuronales communes pour ces deux habiletés.

OBJECTIVE: Brain state-dependent transcranial magnetic stimulation (TMS) requires real-time identification of cortical excitability states. Current state-of-the-art approaches deliver TMS during brain states shown to correlate with motor cortex (M1) excitability at the group level. Here, we hypothesized that machine learning classifiers could successfully discriminate between high and low M1 excitability states in individual subjects using power spectral features obtained from low-density electroencephalography (EEG) signals. METHODS: We analyzed a pre-existing publicly available dataset that delivered 600 single TMS pulses to the right M1 during EEG and electromyography (EMG) recordings. Personalized multivariate pattern classification was used to discriminate between brain states during which TMS evoked small and large motor-evoked potentials (MEPs). These brain states were labeled as low and high M1 excitability states, respectively. RESULTS: Personalized classifiers successfully discriminated between low and high M1 excitability states in every subject tested. MEPs elicited during classifier-predicted high excitability states were significantly larger than those elicited during classifier-predicted low excitability states in all subjects. Personalized classifiers trained using EEG features obtained immediately before each TMS pulse performed better than personalized classifiers trained using EEG features obtained from earlier time points. Personalized classifiers generalized weakly but significantly across subjects. CONCLUSION: Individual subjects exhibit unique brain activity patterns that correspond to low and high M1 excitability states. These patterns can be efficiently captured using power spectral features obtained from low-density EEG signals. Deploying individualized classifiers during brain state-dependent TMS may enable effective, fully personalized neuromodulation in the future.

Normal aging is accompanied by cognitive and sensory deficits, including olfactory deficits, which affect the quality of life and health of elderly subjects. However, normal aging (independently of any degenerative pathology) is poorly explored and the cellular mechanisms underlying these deficits remain largely unknown. This lack of knowledge limits the care of elderly subjects as well as the development of remediation strategies to counteract olfactory and cognitive aging. The objectives of this thesis were first to improve the understanding of olfactory aging and the neural mechanisms underlying these deficits in mice, and second to improve the functioning of the aging brain. In a first study, we used the olfactory perceptual learning model to identify the cellular mechanisms underlying olfactory aging under basal and plasticity-requiring conditions. This learning improves discrimination between two perceptually similar odorants following repeated exposure to these odorants. In rodents, it requires the contribution of adult-born neurons in the olfactory bulb. We finely studied the kinetics of the appearance of olfactory perceptual learning deficits over the mouse lifespan (from 2 to 18 months) and revealed that the long-term retention of olfactory perceptual learning is impaired as early as 12 months of age, before the total loss of learning abilities at 18 months. These learning retention deficits are associated with an alteration of the structural plasticity of adult-born granule cells in the olfactory bulb. In a second study, we developed a remediation strategy to improve olfactory and cognitive aging, based on olfactory stimulation with a new odor every day (enrichment). These olfactory enrichment sessions were repeated throughout the life of the animal to allow the constitution of a cognitive reserve. This concept is associated in humans with a high level of cognitive stimulation and resistance to the deleterious effects of aging on cognitive performances and could be an effective strategy to promote better aging. Mice subjected to such olfactory enrichment displayed improved olfactory discrimination performance at late ages, as well as spatial memory and cognitive flexibility, indicating that the benefits of lifelong olfactory enrichment extend beyond the olfactory sphere and include broader cognitive benefits. At the cellular level, we did not observe any changes in adult neurogenesis in the olfactory bulb, a mechanism known to underlie olfactory learning and memory in the young adult. However, we revealed an increase in noradrenergic innervation that correlates with behavioral performances. Finally, we identified remodeling of brain networks implicated in behavioral tasks, which may underlie the improvement of cognitive performances in aged mice subjected to long-run olfactory enrichment. Overall, our data contribute to deepen our understanding of age-related alterations in brain plasticity mechanisms and their implication in learning and memory deficits. Moreover, this work proposes repeated olfactory enrichment throughout life as an effective strategy to promote better aging by improving not only olfactory, but also cognitive aging in general, inducing structural and functional remodeling in the brains of aged mice., Le vieillissement normal s’accompagne de déficits cognitifs et sensoriels, notamment olfactifs qui affectent la qualité de vie et la santé des individus âgés. Cependant, le vieillissement normal (indépendamment de toute pathologie dégénérative) reste peu étudié et les changements de la structure et du fonctionnement cérébraux qui sous-tendent ces déficits sont encore largement méconnus. Ce manque de connaissances limite la prise en charge des sujets âgés ainsi que le développement de stratégies de remédiation pour lutter contre le vieillissement olfactif et cognitif. Les objectifs de cette thèse étaient premièrement d’avancer dans la compréhension du vieillissement olfactif et des mécanismes neuronaux qui sous-tendent ces déficits chez la souris, puis dans un second temps, d’améliorer le fonctionnement du cerveau vieillissant. Dans une première étude, nous avons utilisé le modèle de l’apprentissage olfactif perceptif pour identifier des mécanismes cellulaires sous-tendant le vieillissement olfactif en conditions basales et dans des conditions sollicitant la plasticité. Cet apprentissage permet l’amélioration de la discrimination de deux odorants proches d’un point de vue perceptif, après une exposition répétée à ceux-ci. Chez le rongeur, il nécessite l'apport de nouveaux neurones dans le bulbe olfactif adulte. Nous avons étudié finement la cinétique d’apparition des déficits d’apprentissage olfactif perceptif au cours de la vie de la souris (de 2 à 18 mois) et révélé que la rétention à long terme de l’apprentissage olfactif perceptif est altérée dès l’âge de 12 mois, avant la perte totale des capacités d’apprentissage à 18 mois. Ces déficits de rétention sont associés à une altération de la plasticité structurale des nouveaux neurones granulaires du bulbe olfactif. Dans une deuxième étude, nous avons développé une stratégie de remédiation du vieillissement olfactif et cognitif, basée sur une stimulation olfactive avec une nouvelle odeur chaque jour (enrichissement). Des sessions d'enrichissement olfactif ont été répétées tout au long de la vie de l'animal afin de permettre la constitution d’une réserve cognitive. Ce concept est associé chez l’humain à un niveau de stimulation cognitive élevé et à une résistance face aux effets délétères du vieillissement sur les performances cognitives et pourrait constituer une stratégie efficace pour promouvoir le bien-vieillir. Les souris soumises à un tel enrichissement olfactif présentent de meilleures performances de discrimination olfactive à un âge avancé, ainsi que de mémoire spatiale et de flexibilité cognitive, indiquant que les bénéfices d'un enrichissement olfactif tout au long de la vie s’étendent au-delà de la sphère olfactive et incluent des bénéfices cognitifs plus larges. Au niveau cellulaire, nous n’avons pas observé de modifications de la neurogenèse adulte bulbaire, un mécanisme connu pour sous-tendre l’apprentissage et la mémoire olfactifs dans le bulbe olfactif jeune adulte. En revanche, nous révélons une augmentation de l’innervation noradrénergique qui corrèle avec les performances comportementales. Enfin, nous mettons en évidence des remaniements des réseaux cérébraux mis en jeu par les tâches comportementales, qui pourraient sous-tendre l’amélioration des performances cognitives chez les souris âgées soumises à l’enrichissement olfactif tout au long de la vie. Dans l’ensemble, nos données contribuent à approfondir notre connaissance des altérations des mécanismes de plasticité cérébrale liées au vieillissement et leur implication dans les déficits d’apprentissage et de mémoire. De plus, ce travail propose l’enrichissement olfactif répété tout au long de la vie comme une stratégie efficace de lutte contre le vieillissement non seulement olfactif, mais cognitif en général, induisant des remaniements structuraux et fonctionnels dans le cerveau des souris âgées.

International audience; An increased number of histaminergic neurons, identified by labeling histidine-decarboxylase (HDC) its synthesis enzyme, was unexpectedly found in patients with narcolepsy type 1 (NT1). In quest for enlightenment, we evaluate whether an increase in HDC cell number and expression level would be detected in mouse models of the disease, in order to provide proof of concepts reveling possible mechanisms of compensation for the loss of orexin neurons, and/or of induced expression as a consequence of local neuroinflammation, a state that likely accompanies NT1. To further explore the compensatory hypothesis, we also study the noradrenergic wake-promoting system. Immunohistochemistry for HDC, orexin, and melanin-concentrating hormone (MCH) was used to count neurons. Quantitative-PCR of HDC, orexin, MCH, and tyrosine-hydroxylase was performed to evaluate levels of mRNA expression in the hypothalamus or the dorsal pons. Both quantifications were achieved in genetic and neuroinflammatory models of narcolepsy with major orexin impairment, namely the orexin-deficient (Orex-KO) and orexin-hemagglutinin (Orex-HA) mice respectively. The number of HDC neurons and mRNA expression level were unchanged in Orex-KO mice compared to controls. Similarly, we found no change in tyrosine-hydroxylase mRNA expression in the dorsal pons between groups. Further, despite the presence of protracted local neuroinflammation as witnessed by the presence of reactive microglia, we found no change in the number of neurons nor the expression of HDC in Orex-HA mice compared to controls. Importantly, no correlation was found in all conditions between HDC and orexin. Our findings indicate that, in mice, the expression of histamine and noradrenalin, two wake-promoting systems, are not modulated by orexin level whether the lack of orexin is constitutive or induced at adult age, showing thus no compensation. They also show no recruitment of histamine by local neuroinflammation. Further studies will be needed to further define the role of histamine in the pathophysiology of NT1.

The present study explores the potential impact of peers' omnipresence at school on children's academic performance. We tested 99 fourth-graders either alone or with a classmate in a task involving both numeracy and literacy skills: numerosity comparison and phonological comparison. Ninety-seven college-aged young adults were also tested on the same task, either alone or with a familiar peer. Peer presence yielded a reaction time (RT) speedup in children, and this social facilitation was at least as important as that seen in adults. RT distribution analyses indicated that the presence of a familiar peer promotes the emergence of adult-like features in children. This included shorter and less variable reaction times (confirmed by an ex-Gaussian analysis), increased use of an optimal response strategy and, based on Ratcliff’s diffusion model, speeded up non decision (memory and/or motor) processes. Peer presence thus allowed children to, at least, narrow (for demanding phonological comparisons), and, at best, virtually fill in (for unchallenging numerosity comparisons) the developmental gap separating them from adult levels of performance. These findings confirm the influence of peer presence on skills relevant to education and lay the ground for exploring how the brain mechanisms mediating this fundamental social influence evolve during development.

Chunking mechanisms are central to several cognitive processes and notably to the acquisition of visuo-motor sequences. Individuals segment sequences into chunks of items to perform visuo-motor tasks more fluidly, rapidly, and accurately. However, the exact dynamics of chunking processes in the case of extended practice remain unclear. Using an operant conditioning device, eighteen Guinea baboons (Papio papio) produced a fixed sequence of nine movements during 1,000 trials by pointing to a moving target on a touch screen. Response times analyses revealed a specific chunking pattern of the sequence for each baboon. More importantly, we found that these patterns evolved during the course of the experiment, with chunks becoming progressively fewer and longer. We identified two chunk reorganization mechanisms: the recombination of preexisting chunks and the concatenation of two distinct chunks into a single one. These results provide new evidence on chunking mechanisms in sequence learning and challenge current models of associative and statistical learning.

Developmental Coordination Disorder (DCD) is a pathological condition characterized by impaired motor skills. Current theories advance that a deficit of the internal models is mainly responsible for DCD children’s altered behavior. Yet, accurate movement execution requires not only correct movement planning, but also integration of sensory feedback into body representation for action to update the state of the body. Here we advance and test the hypothesis that the plasticity of body representations is altered in DCD. To probe Body Representations (BR) plasticity, we submitted a well-established tool-use paradigm to seventeen DCD children, required to reach for an object with their hand before and after tool use, and compared their movement kinematics to that of a control group of Typically Developing (TD) peers. We also asked both groups to provide explicit estimates of their arm length. Results revealed that DCD children explicitly judged their arm shorter after tool use, similarly to their TD peers. Unlike them, though, DCD did not update their implicit BR estimate: kinematics showed that tool-use affected their peak amplitudes, but not their latencies. Remarkably, the kinematics of tool-use showed that the motor control of the tool was comparable between groups, both improving with practice, confirming that motor learning abilities are preserved in DCD. These findings indicate that the update of the BR for action is impaired in DCD, suggesting a novel deficit may contribute to this pathology. Further studies are needed to tease apart the possible role played by motor and body representations deficits in DCD.

International audience; Most recent research highlights how a specific form of causal understanding, namely technical reasoning, may support the increasing complexity of tools and techniques developed by humans over generations, i.e., the cumulative technological culture (CTC). Thus, investigating the neurocognitive foundations of technical reasoning is essential to comprehend the emergence of CTC in our lineage. Whereas functional neuroimaging evidence started to highlight the critical role of the area PF of the left inferior parietal cortex (IPC) in technical reasoning, no studies explored the links between the structural characteristics of such a brain region and technical reasoning skills. Therefore, in this study, we assessed participants’ technical-reasoning performance by using two ad-hoc psycho-technical tests; then, we extracted from participants’ 3 T T1-weighted magnetic-resonance brain images the cortical thickness (i.e., a volume-related measure which is associated with cognitive performance as reflecting the size, density, and arrangement of cells in a brain region) of all the IPC regions for both hemispheres. We found that the cortical thickness of the left area PF predicts participants’ technical-reasoning performance. Crucially, we reported no correlations between technical reasoning and the other IPC regions, possibly suggesting the specificity of the left area PF in generating technical knowledge. We discuss these findings from an evolutionary perspective, by speculating about how the evolution of parietal lobes may have supported the emergence of technical reasoning in our lineage.

A critical aspect of neuroscience is to establish whether and how brain networks evolved across primates. To date, most comparative studies have used resting-state functional magnetic resonance imaging (rs-fMRI) in anaesthetized nonhuman primates and in awake humans. However, anaesthesia strongly affects rs-fMRI signals. The present study investigated the impact of the awareness state (anaesthesia vs. awake) within the same group of macaque monkeys on the rs-fMRI functional connectivity organization of a well-characterized network in the human brain, the cingulo-frontal lateral network. Results in awake macaques show that rostral seeds in the cingulate sulcus exhibited stronger correlation strength with rostral compared to caudal lateral frontal cortical areas, while more caudal seeds displayed stronger correlation strength with caudal compared to anterior lateral frontal cortical areas. Critically, this inverse rostro-caudal functional gradient was abolished under anaesthesia. This study demonstrated a similar functional connectivity (FC) organization of the cingulo-frontal cortical network in awake macaque to that previously uncovered in the human brain pointing toward a preserved FC organization from macaque to human. However, it can only be observed in awake state suggesting that this network is sensitive to anaesthesia and warranting significant caution when comparing FC patterns across species under different states.

International audience; Daily activities can often be performed while listening to music, which could influence the ability to select relevant stimuli while ignoring distractors. Previous studies have established that the level of arousal of music (e.g., relaxing/stimulating) has the ability to modulate mood and affect the performance of cognitive tasks. The aim of this research was to explore the effect of relaxing and stimulating background music on selective attention. To this aim, 46 healthy adults performed a Stroop-type task in five different sound environments: relaxing music, stimulating music, relaxing music-matched noise, stimulating music-matched noise, and silence. Results showed that response times for incongruent and congruent trials as well as the Stroop interference effect were similar across conditions. Interestingly, results revealed a decreased error rate for congruent trials in the relaxing music condition as compared to the relaxing musicmatched noisecondition, and a similar tendency between relaxing music and stimulating musicmatched noise. Taken together, the absence of difference between background music and silence conditions suggest that they have similar effects on adult's selective attention capacities, while noise seems to have a detrimental impact, particularly when the task is easier cognitively. In conclusion, the type of sound stimulation in the environment seems to be a factor that can affect cognitive tasks performance.

International audience; Meeting Abstract 035