Biology subjects

Legrand, N.

Publications and source records attributed to Legrand, N..

7 recordsLinked to original sources

bioRxiv2026

Cardiac belief updating from volatile physiological afferents

Cardiac interoception is commonly assessed by comparing subjective estimates of heart rate with physiological measurements. But beliefs can easily obscure these measures, such that they cannot readily distinguish sensitivity to afferent signals from the influence of prior expectations; this ultimately challenges the notion that behaviours under these tasks could reflect interoceptive processes at all. Here, we develop a computational framework that uses naturally occurring heart rate variability to quantify how strongly perceptual beliefs are updated by physiological evidence. We formalise interoception as weighted Bayesian updating under the joint influence of expectations and afferents, and derive a new measure, cardiac interoceptive sensitivity, that quantifies the extent to which beliefs move with incoming signals. Applying this to the largest Heart Rate Discrimination dataset to date (n=549), a task providing robust estimates of cardiac beliefs, we find that sensitivity is weak in the healthy population, but shows large interindividual differences, with 43% of the participants exhibiting behaviours at least minimally compatible with interoceptive processing. These findings challenge the interpretation of conventional measures of cardiac interoception. They also introduce a new framework to relate bodily signals that cannot be controlled experimentally to external signals that can, laying a computational foundation for embodied psychophysics.

neuroscience↗

bioRxiv2021

The Respiratory Resistance Sensitivity Task: An Automated Method for Quantifying Respiratory Interoception and Metacognition

The ability to sense, monitor, and control respiration - e.g., respiratory interoception (henceforth, respiroception) is a core homeostatic ability. Beyond the regulation of gas exchange, enhanced awareness of respiratory sensations is directly related to psychiatric symptoms such as panic and anxiety. Indeed, chronic breathlessness (dyspnea) is associated with a fourfold increase in the risk of developing depression and anxiety, and the regulation of the breath is a key aspect of many mindfulness-based approaches to the treatment of mental illness. Physiologically speaking, the ability to accurately monitor respiratory sensations is important for optimizing cardiorespiratory function during athletic exertion, and can be a key indicator of illness. Given the important role of respiroception in mental and physical health, it is unsurprising that there is increased interest in the quantification of respiratory psychophysiology across different perceptual and metacognitive levels of the psychological hierarchy. Compared to other more popular modalities of interoception, such as in the cardiac domain, there are relatively few methods available for measuring aspects of respiroception. Existing inspiratory loading tasks are difficult to administer and frequently require expensive medical equipment, or offer poor granularity in their quantification of respiratory-related perceptual ability. To facilitate the study of respiroception, we here present a new, fully automated and computer-controlled apparatus and psychophysiological method, which can flexibly and easily measure respiratory-related interoceptive sensitivity, bias and metacognition, in as little as 30 minutes of testing, using easy to make 3D printable parts.

neuroscience↗

bioRxiv2021

Nafamostat-interferon-alpha combination suppresses SARS-CoV-2 infection in vitro and in vivo

SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here, we address these challenges by combining Pegasys (IFNa) and nafamostat to effectively suppress SARS-CoV-2 infection in cell culture and hamsters. Our results indicate that Serpin E1 is an important mediator of the antiviral activity of IFNa and that both Serpin E1 and camostat can target the same cellular factor TMPRSS2, which plays a critical role in viral replication. The low doses of the drugs in combination may have several clinical advantages, including fewer adverse events and improved patient outcome. Thus, our study may provide a proactive solution for the ongoing pandemic and potential future coronavirus outbreaks, which is still urgently required in many parts of the world.

microbiology↗

bioRxiv2021

The heart rate discrimination task: a psychophysical method to estimate the accuracy and precision of interoceptive beliefs

Interoception - the physiological sense of our inner bodies - has risen to the forefront of psychological and psychiatric research. Much of this research utilizes tasks that attempt to measure the ability to accurately detect cardiac signals. Unfortunately, these approaches are confounded by well-known issues limiting their validity and interpretation. At the core of this controversy is the role of subjective beliefs about the heart rate in confounding measures of interoceptive accuracy. Here, we recast these beliefs as an important part of the causal machinery of interoception, and offer a novel psychophysical "heart rate discrimination" method to estimate their accuracy and precision. By applying this task in 223 healthy participants, we demonstrate that cardiac interoceptive beliefs are more biased, less precise, and are associated with poorer metacognitive insight relative to an exteroceptive control condition. Our task, provided as an open-source python package, offers a robust approach to quantifying cardiac beliefs. HighlightsO_LICurrent interoception tasks conflate cardiac beliefs with accuracy. C_LIO_LIWe introduce a Bayesian method for estimating cardiac belief accuracy and precision. C_LIO_LIIndividuals underestimate their heart rate by -7 BPM (95% CI [-8.6 -5.3]) on average. C_LIO_LICardiac beliefs are associated with reduced precision and metacognitive insight. C_LIO_LIThe task and modelling tools are provided in the Python Cardioception Package. C_LI

neuroscience↗

bioRxiv2020

Emotional Metacognition: Stimulus Valence Modulates Cardiac Arousal and Metamemory

Emotion alters how we feel, see, and experience the world. In the domain of memory, the emotional valence and arousal of memorised stimuli can modulate both the acuity and content of episodic recall. However, no experiment has investigated whether arousal and valence also influence metacognition for memory (i.e., the process of self-monitoring memories). In a pre-registered study, we applied a novel psychophysiological design together with computational models of metacognition to assess the influence of stimulus valence and arousal on the sensitivity, bias, and efficiency of metamemory. To estimate the role of physiological arousal in mediating these effects, we recorded cardiac measures through pulse oximetry. We found that negative valence substantially decreased both memory performance and subjective confidence, in particular for low arousal words. Simultaneously, we found that emotional valence modulated both heart rate and heart-rate variability (HRV) during recognition memory. Exploratory trial-level analyses further revealed that subjective confidence was encoded in instantaneous heart-rate fluctuations and that this relationship was also modulated by emotional valence. Our results demonstrate that recognition memory and metacognition are influenced by the emotional valence of encoded items and that this correlation is in part related to cardiac activity.

neuroscience↗

bioRxiv2019

PPARβ/δ controls Mediator recruitment and transcription initiation

Repression of transcription by nuclear receptors involves NCOR and SMRT corepressor complexes, which harbour the deacetylase HDAC3 as a subunit. Both deacetylase-dependent and -independent repression mechanisms have been reported for these complexes. In the absence of ligands, the nuclear receptor PPAR{beta}/{delta} recruits NCOR and SMRT and represses expression of its canonical targets including the ANGPTL4 gene. Agonistic ligands cause corepressor dissociation and enable enhanced induction of transcription by coactivators. Vice versa, recently developed synthetic inverse agonists lead to augmented corepressor recruitment and repression that dominates over activating stimuli. Both basal repression of ANGPTL4 and reinforced repression elicited by inverse agonists are partially insensitive to HDAC inhibition. This raises the question of how PPAR{beta}/{delta} represses transcription mechanistically. Here, we show that the PPAR{beta}/{delta} inverse agonist PT-S264 impairs transcription initiation in human cells. Inverse agonist-bound PPAR{beta}/{delta} interferes with recruitment of Mediator, RNA polymerase II, and TFIIB, but not with recruitment of other basal transcription factors, to the ANGPTL4 promoter. We identify NCOR as the main ligand-dependent interactor of PPAR{beta}/{delta} in the presence of PT-S264. In PPAR{beta}/{delta} knockout cells, reconstitution with PPAR{beta}/{delta} mutants deficient in basal repression recruit less NCOR, SMRT, and HDAC3 to chromatin, concomitant with increased binding of RNA polymerase II. PT-S264 restores binding of NCOR, SMRT, and HDAC3, resulting in diminished polymerase II binding and transcriptional repression. In the presence of HDAC inhibitors, ligand-mediated repression of PPAR{beta}/{delta} target genes is only partially relieved. Our findings corroborate deacetylase-dependent and -independent repressive functions of HDAC3-containing complexes. Deacetylase-independent repression mediated by binding of inverse agonists to PPAR{beta}/{delta} involve NCOR/SMRT recruitment and interference with Mediator, TFIIB, and RNA polymerase II binding.

molecular biology↗

bioRxiv2018

Does the heart forget? Modulation of cardiac activity induced by inhibitory control over emotional memories

Effort to suppress past experiences from conscious awareness can lead to forgetting. It remains largely unknown whether emotions, including their physiological causes, are also impacted by such memory suppression. In two studies, we measured in healthy participants the aftereffect of suppressing negative memories on cardiac response. Results of Study 1 revealed that an efficient control of memories was associated with a long-term inhibition of the cardiac deceleration normally induced by disgusting stimuli. Attempts to suppress sad memories, on the opposite, aggravated cardiac response, an effect that was largely related to the inability to forget this specific material. In Study 2, we found using electroencephalography that a prominent neural marker of inhibitory control, a suppression of the 5-9 Hz frequency band, was related to the subsequent inhibition of the cardiac response. These results demonstrate that suppressing memories also influence the cardiac system, opening new avenues for treating intrusive memories.

neuroscience↗