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Faivre, N.

Publications and source records attributed to Faivre, N..

At least 19 recordsLinked to original sources

Supramodal Coding of Detection and Confidence in the Human Cortex

Perception is inherently multisensory, yet it remains unclear whether the brain detects stimuli and evaluates confidence in these detections using circuits shared across senses or circuits specific to each modality. Prior evidence is limited: scalp electrophysiology cannot localize where a shared code operates, whereas functional imaging cannot resolve its timing. We recorded intracranial activity (stereoelectroencephalography) in eight patients with epilepsy who performed a near-threshold audiovisual detection task in which they reported, on each trial, whether a visual, auditory, or audiovisual stimulus was present and rated their confidence, both overall and separately for each modality. Analyzing high-gamma activity at the single-channel and region-of-interest levels, we found that stimulus detection involved a broadly distributed, largely supramodal set of cortical regions responding regardless of modality, including the insula, dorsomedial prefrontal cortex, and superior temporal gyrus. Multivariate decoders trained to distinguish detected from undetected stimuli in one modality generalized to the other modality, indicating a shared detection code within these regions. Confidence relied on a more mixed architecture but was also substantially supramodal. Finally, the auditory cortex encoded confidence information about its non-preferred (visual) modality, with a similar effect in the visual cortex for auditory confidence, suggesting that the involvement of sensory cortices in confidence is not confined to its preferred input.

neuroscience↗

Dual human lung models reveal compartment-specific activity of anti-tuberculosis drugs and host-directed therapies

Tuberculosis (TB) remains a major global health challenge that requires new therapeutic strategies to improve drug efficacy, shorten treatment duration, prevent drug resistance, and limit Mycobacterium tuberculosis (Mtb) persistence. Here, we established complementary in vitro human lung models integrating alveolar macrophage-like (AML) cells and airway air-liquid interface (ALI) cultures to evaluate standard-of-care antibiotics, host-directed therapies, and virulence-targeting agents. AMLs recapitulated key morphological, transcriptional, and functional features of primary alveolar macrophages, including a CD16+ immunoregulatory phenotype highly permissive to Mtb infection. In parallel, ALI cultures maintained epithelial barrier integrity and secretory functions, allowing apical Mtb infection, drug penetration analysis, and inflammatory profiling. Benchmarking of standard-of-care antibiotics revealed compartment-specific activity: isoniazid, rifampicin, and moxifloxacin were effective in both systems, while pyrazinamide was active only in AMLs. Anti-inflammatory host-directed therapies such as ibuprofen and doramapimod selectively reduced cytokine production without affecting bacterial load. Together, this dual-platform system offers a physiologically relevant and scalable model to assess antimicrobial efficacy and host modulation across distinct pulmonary niches, bridging the gap between conventional macrophage assays and the complex human lung.

immunology↗

Presence Hallucination Induction through Robotically Mediated Somatomotor Conflicts: a pooled analysis of 26 experiments

Hallucinations are significant symptoms in psychiatric and neurodegenerative diseases, that may indicate advanced disease progression or worse disease forms. They are also frequent in healthy individuals, especially elderly or bereaved. Despite their relevance, studying hallucinations in controlled laboratory conditions remains challenging given the limited procedures inducing clinically relevant hallucinations. We have previously developed a robotics-based protocol capable of inducing a specific clinically relevant hallucination, presence hallucination (PH), in both healthy individuals and patients. Using this approach, we have systematically investigated the sensitivity and intensity of PH-induction, as well as its effects on various sensory, behavioral and cognitive aspects. In the present study, we pooled individual-participant data from 26 in-house experiments (totaling 580 individuals) and conducted a Bayesian analysis to estimate effects and moderators of PH-induction. PH-induction was reliably induced with a medium effect-size, and individuals with schizotypal traits were more sensitive. Furthermore, we identified that PH-induction may not strongly depend on altered agency, but found a synergistic relationship between passivity and induced PH. Collectively these results elucidate the role of somatomotor processes in aberrant own body perceptions, advance understanding of psychosis, and provide powerful statistical priors for future studies.

neuroscience↗

Lipid-mediated GPR32 signaling reprograms macrophage metabolism to impair anti-tuberculous immunity

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), has evolved strategies to evade innate immunity and establish persistent infection. However, the mechanisms by which M. tuberculosis reprograms human macrophage metabolism remain incompletely defined. Tuberculous pleural effusion (TB-PE), a common extrapulmonary manifestation that frequently coexists with pulmonary TB, offers a unique, clinically relevant immunometabolic window into the TB microenvironment. Here, using patient-derived TB-PE samples, we demonstrate that this microenvironment induces a metabolic state in human macrophages that compromises their antimicrobial function. Lipidomic analysis identified an enrichment of the specialized pro-resolving mediator Resolvin D5 (RvD5), which signals through GPR32 to suppress macrophage microbicidal activity. The acellular fraction of TB-PE was sufficient to induce RvD5 secretion by monocytes, correlating with increased expression of RvD5 biosynthetic enzymes in pleural monocytes from TB patients. Mechanistically, RvD5-GPR32 signaling inhibited glycolysis without promoting oxidative phosphorylation, reducing HIF-1 activity and impairing intracellular M. tuberculosis control. HIF-1 stabilization restored antimicrobial function. These findings uncover the RvD5-GPR32-HIF-1 axis as a mechanism of metabolic immune suppression and a potential target for host-directed TB therapy. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/663524v3_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@64feceorg.highwire.dtl.DTLVardef@948ab0org.highwire.dtl.DTLVardef@1d387forg.highwire.dtl.DTLVardef@682f72_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Leaky evidence accumulation accounts for perceptual confidence and subjective duration

Perceptual consciousness is defined as the subjective experience associated with the processing of sensory cues from the environment. Subjective experience unfolds over time and is accompanied by a sense of confidence, yet the mechanisms underlying these two properties remain elusive. Here, we propose a computational mechanism that accounts not only for the onset of subjective experience but also its subjective duration and associated feeling of confidence. Our model assumes that a percept becomes conscious when an ongoing, leaky accumulation of sensory evidence surpasses a perceptual threshold and stops being conscious when it falls back below the threshold due to leakage. Crucially, this perceptual threshold can be lower than the decision threshold for reporting the percept. Moreover, our model derives confidence in accurately detecting sensory evidence from the maximum reached by the evidence accumulation process following stimulus onset. We conducted a preregistered study in which three distinct models of evidence accumulation were fitted to behavioral reports of detection, confidence, and subjective duration during a face detection task under temporal uncertainty. The leaky evidence accumulation model accounted for the observed behavioral data best and outperformed alternative models without leakage. In a follow-up experiment, we investigated the impact of leakage adaptation on detection and subjective duration. We found that changes in leakage induced by contextual variations of face duration influenced both detection rates and subjective duration, as predicted by our model. Altogether, our findings suggest that leaky evidence accumulation is a suitable candidate mechanism to explain qualitative aspects of subjective experience, including subjective duration and feelings of confidence.

neuroscience↗

Motor Equivalence in Motor Awareness

Motor awareness (MA) describes the level of conscious access we have to the details of our movements and as such is critical to the feeling of control we maintain over our actions (sense of agency). Although our movements rely on specific sensorimotor transformations as well as distinct reference frames for the active body part, or effector, numerous studies report spatiotemporal thresholds of MA that are comparable across different effectors and tasks as well as supramodal. However, this has not been tested directly and there is currently no direct empirical support for effector-independent MA nor a description of a potentially shared underlying mechanisms. We therefore designed a goal-directed reaching paradigm that participants performed once with their upper-limbs, using a joystick, and once with their full body, by leaning and thereby displacing their center-of-mass. We assessed both MA and corrective movements for sensorimotor mismatches by providing either veridical feedback or introducing random spatial deviations. We hypothesized that changes in motor compensation and awareness, across effectors, with and without a concurrent cognitive load, would follow the same pattern of behavior if they relied on a shared underlying mechanism. Our results lend support for such an effector-independent mechanism, as we observed that MA was comparable across effectors: i) in un-deviated control trials with and without cognitive load, ii) in converging trials where the direction of the deviation corresponded to the direction of the target location, and iii) based on strongly correlated psychometric MA thresholds across effectors. At the same time, data from diverging trials, where the direction of the deviation opposed the direction of the target location, indicate that in case of conflicting information and increased kinematic task demands MA draws on effector-specific sensorimotor information, corresponding to performance differences between hand and full body movements observed in baseline blind-reaching versus visually guided reaching. Overall, our findings provide a direct link between low-level sensorimotor transformations and abstract motor representations and their role in MA, consolidating a gap in conceptual frameworks of the sense of agency.

animal behavior and cognition↗

Inhibition of glycolysis in tuberculosis-mediated metabolic rewiring reduces HIV-1 spread across macrophages

Tuberculosis (TB) is a significant aggravating factor in individuals living with human immunodeficiency virus type 1 (HIV-1), the causative agent for acquired immunodeficiency syndrome (AIDS). Both Mycobacterium tuberculosis (Mtb), the bacterium responsible for TB, and HIV-1 target macrophages. Understanding how Mtb subverts these cells may facilitate the identification of new druggable targets. Here, we explored how TB can induce macrophages to form tunneling nanotubes (TNT), promoting HIV-1 spread. We found that TB triggers metabolic rewiring of macrophages, increasing their glycolytic ATP production. Using pharmacological inhibitors and glucose deprivation, we discovered that disrupting aerobic glycolysis significantly reduces HIV-1 exacerbation in these macrophages. Glycolysis is essential for tunneling nanotubes (TNT) formation, which facilitates viral transfer and cell-to-cell fusion and induces the expression of the sialoadhesin Siglec-1, enhancing both HIV-1 binding and TNT stabilization. Glycolysis did not exacerbate HIV-1 infection when TNT formation was pharmacologically prevented, indicating that higher metabolic activity is not sufficient per se to make macrophages more susceptible to HIV-1. Overall, these data might facilitate the development of targeted therapies aimed at inhibiting glycolytic activity in TB-induced immunomodulatory macrophages to ultimately halt HIV-1 dissemination in co-infected patients.

immunology↗

A functional overlap between evidence accumulation, confidence, and changes of mind in the pre-supplementary motor area and insula

Evidence accumulation models have proven to be powerful tools to explain the temporal dynamics of decisions, as well as their metacognitive components such as confidence judgments and changes of mind. However, it is still unclear how and where in the brain evidence accumulation leads to these two metacognitive components. To better understand the functional overlap between evidence accumulation, confidence, and changes of mind, we recorded intracranial high-gamma activity in patients with focal epilepsy while they reported the motion direction of a random dot kinetogram with a computer mouse, and estimated their confidence level. We found an anatomical overlap between the neural correlates of evidence accumulation, confidence, and changes of mind in the pre-supplementary motor area, as well as in the orbitofrontal, inferior frontal, and insular cortices. Both mouse-tracking behaviour and electrophysiological results were reproduced with a post-decisional evidence accumulation model. After characterising the temporal dynamics of decision-making with mouse-tracking and intracranial electrophysiology, we conclude that confidence and changes of mind result from evidence accumulation instantiated before the decision in the pre-supplementary motor area, and after the decision in the insula.

neuroscience↗

Cortical evidence accumulation for perceptual experience occurs irrespective of reports

Perceptual experience is a multi-faceted, dynamical process, tackled empirically through measures of stimulus detectability and confidence. To assess if stimulus detection and confidence can be explained by evidence accumulation, a form of sequential sampling of sensory evidence, we analyzed high-gamma activity from stereo-electroencephalographic data of 29 participants partaking in 3 pre-registered experiments. In an immediate-response experiment, individual channels and decoded multivariate latent variables in the visual, inferior frontal, and anterior insular cortices displayed functional markers of evidence accumulation. In two further experiments, this signal in the ventral visual cortex differentiated between (1) seen and unseen stimuli in delayed detection, (2) high and low intensity stimuli during passive viewing, and (3) levels of confidence when stimuli were seen. A computational model of leaky evidence accumulation successfully reproduced both behavioral and neural data. Overall, these results indicate that evidence accumulation explains key aspects of perceptual experience, encompassing both conscious access and monitoring.

neuroscience↗

Subcortical correlates of consciousness with human single neuron recordings

Subcortical brain structures such as the subthalamic nucleus or the thalamus are involved in regulating motor and cognitive behavior. However, their contribution to perceptual consciousness is still unclear, due to the inherent difficulties of recording subcortical neuronal activity in humans. Here, we asked neurological patients undergoing surgery for deep brain stimulation to detect weak vibrotactile stimuli applied on their hand while recording single neuron activity from the tip of a microelectrode. We isolated putative single neurons in the subthalamic nucleus and thalamus. A significant proportion of neurons modulated their activity while participants were expecting a stimulus. We found that the firing rate of 23% of these neurons differed between detected and undetected stimuli. Our results provide direct neurophysiological evidence of the involvement of the subthalamic nucleus and the thalamus for the detection of vibrotactile stimuli, thereby calling for a less cortico-centric view of the neural correlates of consciousness.

neuroscience↗

Robotically-induced auditory-verbal hallucinations: combining self-monitoring and strong perceptual priors

Inducing hallucinations under controlled experimental conditions in non-hallucinating individuals represents a novel research avenue oriented towards understanding complex hallucinatory phenomena, avoiding confounds observed in patients. Auditory-verbal hallucinations (AVH) are one of the most common and distressing psychotic symptoms, whose etiology remains largely unknown. Two prominent accounts portray AVH either as a deficit in auditory-verbal self-monitoring, or as a result of overly strong perceptual priors. In order to test both theoretical models and evaluate their potential integration, we developed a robotic procedure able to induce self-monitoring perturbations (consisting of sensorimotor conflicts between poking movements and corresponding tactile feedback) and a perceptual prior associated with otherness sensations (i.e., feeling the presence of a non-existing another person). Here, in two independent studies, we show that this robotic procedure led to AVH-like phenomena in healthy individuals, which was further associated with delusional ideation. Specifically, a condition with stronger sensorimotor conflicts induced more AVH-like sensations (self-monitoring), while, in the otherness-related experimental condition, there were more AVH-like sensations when participants were detecting other-voice stimuli, compared to detecting self-voice stimuli (strong-priors). By demonstrating an experimental procedure able to induce AVH-like sensations in non-hallucinating individuals, we shed new light on AVH phenomenology, thereby integrating self-monitoring and strong-priors accounts.

neuroscience↗

Prior information differentially affects discrimination decisions and subjective confidence reports

According to Bayesian models, both decisions and confidence are based on the same precision-weighted integration of prior expectations ("priors") and incoming information ("likelihoods"). This assumes that priors are integrated optimally and equally in decisions and confidence, which has not been tested. In two experiments, we quantitatively assessed how priors inform both decisions and confidence. With a gamified dual-decision task we controlled the strength of priors and likelihoods to create pairs of conditions that were matched in posterior information, but differed on whether the prior or likelihood was more informative. We found that priors were underweighted in discrimination decisions, but used to a greater extent in confidence about those decisions, and this was not due to differences in processing time. With a Bayesian model we quantified the weighting parameters for the prior at both levels, and confirmed that priors are more optimally used in explicit confidence, even when underused in decisions.

neuroscience↗

Increased functional connectivity of the intraparietal sulcus underlies the attenuation of numerosity estimations for self-generated words

Previous studies have shown that self-generated stimuli in auditory, visual, and somatosensory domains are attenuated, producing decreased behavioral and neural responses compared to the same stimuli that are externally generated. Yet, whether such attenuation also occurs for higher-level cognitive functions beyond sensorimotor processing remains unknown. In this study, we assessed whether cognitive functions such as numerosity estimations are subject to attenuation. We designed a task allowing the controlled comparison of numerosity estimations for self (active condition) and externally (passive condition) generated words. Our behavioral results showed a larger underestimation of self-compared to externally-generated words, suggesting that numerosity estimations for self-generated words are attenuated. Moreover, the linear relationship between the reported and actual number of words was stronger for self-generated words, although the ability to track errors about numerosity estimations was similar across conditions. Neuroimaging results revealed that numerosity underestimation involved increased functional connectivity between the right intraparietal sulcus and an extended network (bilateral supplementary motor area, left inferior parietal lobule and left superior temporal gyrus) when estimating the number of self vs. externally generated words. We interpret our results in light of two models of attenuation and discuss their perceptual versus cognitive origins.

neuroscience↗

Sense of self impacts spatial navigation and hexadirectional coding in human entorhinal cortex

Grid cells in entorhinal cortex (EC) encode an individuals location in space and rely on environmental cues and self-motion cues derived from the individuals body. Body-derived signals are also primary signals for the sense of self and self-identification with a body. However, it is currently unknown whether self-identification impacts grid cells and spatial navigation. Integrating the online manipulation of bodily signals, to modulate self-identification, into a spatial navigation task and with an fMRI measure to detect grid cell-like representation (GCLR) in humans, we report improved spatial navigation performance and decreased GCLR in EC when participants navigated with enhanced self-identification. These changes were further associated with increased activity in posterior parietal and retrosplenial cortex. Modulating self-identification by controlling online body-derived signals during spatial navigation, these data link the sense of self to spatial navigation and to entorhinal grid cell-like activity within a distributed cortical spatial navigation system.

neuroscience↗

Sensorimotor hallucinationsin Parkinson's disease

Hallucinations in Parkinsons disease (PD) are one of the most disturbing non-motor symptoms, affect half of the patients, and constitute a major risk factor for adverse clinical outcomes such as psychosis and dementia. Here we report a robotics-based approach, enabling the induction of a specific clinically-relevant hallucination (presence hallucination, PH) under controlled experimental conditions and the characterization of a PD subgroup with enhanced sensorimotor sensitivity for such robot-induced PH. Using MR-compatible robotics in healthy participants and lesion network mapping analysis in neurological non-PD patients, we identify a fronto-temporal network that was associated with PH. This common PH-network was selectively disrupted in a new and independent sample of PD patients and predicted the presence of symptomatic PH. These robotics-neuroimaging findings determine the behavioral and neural mechanisms of PH and reveal pathological cortical sensorimotor processes of PH in PD, identifying a more severe form of PD associated with psychosis and cognitive decline.

neuroscience↗

Sensorimotor conflicts induce somatic passivity and louden quiet voices in healthy listeners

Sensorimotor conflicts are known to alter the perception of accompanying sensory signals and deficits in sensory attenuation have been observed in schizophrenia. In the auditory domain, self-generated tones or voices (compared to tones or voices presented passively or with sensorimotor delays) have been associated with changes in loudness perception and attenuated neural responses. It has been argued that for sensory signals to be attenuated, predicted and sensory consequences must have a consistent spatiotemporal relationship, between button presses and reafferent tactile signals, via predictive sensory signaling, a process altered in schizophrenia. Here, we investigated auditory sensory attenuation for a series of morphed voices while healthy participants applied sensorimotor stimulations that had no spatiotemporal relationship to the voice stimuli and that have been shown to induce mild psychosis-like phenomena. In two independent groups of participants, we report a loudening of silent voices and found this effect only during maximal sensorimotor conflicts (versus several control conditions). Importantly, conflicting sensorimotor stimulation also induced a mild psychosis-like state in the form of somatic passivity and participants who experienced stronger passivity lacked the sensorimotor loudening effect. We argue that this conflict-related sensorimotor loudness amplification may represent a reduction of auditory self-attenuation that is lacking in participants experiencing a concomitant mild psychosis-like state. We interpret our results within the framework of the comparator model of sensorimotor control, and discuss the implications of our findings regarding passivity experiences and hallucinations in schizophrenia.

neuroscience↗

Response-related signals increase confidence but not metacognitive performance

Confidence judgements are a central tool for research in metacognition. In a typical task, participants first perform perceptual (first-order) decisions and then rate their confidence in these decisions. The relationship between confidence and first-order accuracy is taken as measure of metacognitive performance. Confidence is often assumed to stem from decision-monitoring processes alone, but processes that co-occur with the first-order decision may also play a role in confidence formation. In fact, across a broad range of tasks, trials with quick reaction times to the first-order task are often judged with relatively higher confidence than those with slow responses. This robust finding suggests that confidence could be informed by a readout of reaction times in addition to decision-monitoring processes. To test this possibility, we assessed the contribution of response-related signals to confidence and, in particular, to metacognitive performance (i.e., a measure of the adequacy of these confidence judgements). In a factorial design, we measured the effect of making an overt (vs. covert) decision, as well as the effect of pairing a motor action to the stimulus about which the first-order decision is made. Against our expectations, we found no differences in overall confidence or metacognitive performance when first-order responses were covert as opposed to overt. Further, actions paired to visual stimuli presented led to higher confidence ratings, but did not affect metacognitive performance. These results suggest that some of the relationships between first-order decisional signals and confidence might indeed be correlational, and attributable to an upstream cognitive process, common to the two of them.

neuroscience↗

Sensorimotor conflicts alter perceptual and action monitoring

Bodily self-consciousness is defined as a set of prereflective representations of integrated bodily signals giving rise to self-identification, self-location and first-person perspective. While bodily self-consciousness is known to modulate perception, little is known about its influence on higher-level cognitive processes. Here, we manipulated bodily self-consciousness by applying sensorimotor conflicts while participants performed a perceptual task followed by confidence judgments. Results showed that sensorimotor conflicts altered perceptual monitoring by decreasing metacognitive performance. In a second experiment, we replicated this finding and extended our results by showing that sensorimotor conflicts also altered action monitoring, as measured implicitly through intentional binding. In a third experiment, we showed that effects on perceptual monitoring were induced specifically by sensorimotor conflicts related to the trunk and not to the hand. Taken together, our results suggest that bodily self-consciousness may serve as a scaffold for perceptual and action monitoring.

neuroscience↗