Biology subjects

Picard, M.-E.

Publications and source records attributed to Picard, M.-E..

6 recordsLinked to original sources

bioRxiv2026

From language to pain: brain-behavior representations of hypnotic verbal suggestions for pain modulation

Language can shape pain by conveying conceptual information about future somatosensory experiences. However, how verbal input is encoded in the brain and how these representations are later implemented during pain modulation remains unclear. We used a standardized hypnotic procedure with fMRI to test how verbal suggestions of hypoalgesia and hyperalgesia (vs neutral control) modulate pain. We quantified convergent neural responses across individuals during both suggestion encoding and pain processing, using inter-subject correlation and multivoxel pattern similarity approaches, respectively, and related these measures to individual differences in hypnotic suggestibility using representational similarity analysis. More suggestible individuals showed similar temporal dynamics in language-related regions during encoding and more similar hypoalgesia-specific patterns in the left parahippocampal gyrus (PHG) during pain. In contrast, lower suggestibility was associated with convergent responses in sensorimotor and monitoring systems across phases, demonstrating different neural implementation in individuals less successful in converting suggestions into hypoalgesia. These findings identify the PHG as a key region linking the effect of verbal suggestions to subsequent pain relief and show that hypnotic suggestibility structures how neural dynamics during language processing translate into altered pain experiences. This study offers a mechanistic lens for understanding how medical hypnosis and language-based therapies influence pain.

neuroscience↗

bioRxiv2026

Epistasis limits but does not prevent the transfer of mutation-drug resistance mapping across 600 million years of fungal evolution

Whether different pathogens acquire resistance to antimicrobials through the same mutations is a major question in evolution and microbiology. Most antifungal drugs are used to treat infections caused by multiple fungal species, many of which have diverged for millions of years. If the evolution of resistance was to converge onto the same set of mutations across species, knowing the mechanism of resistance in one would allow us to predict and track it in others. The extent of this convergence remains unknown due to the lack of systematic data on resistance mutations. Here, we quantify the conservation of resistance mutations in the cytosine deaminase (CD), a protein responsible for resistance to flucytosine, one of the oldest antifungal drugs. By comparing the crystal structures of this enzyme through 600 My of evolution, we show that the CD structure is highly conserved. We compared the full CD mutational resistance spectrum of resistance from an ascomycete and a basidiomycete. We found that resistance mutations in one ortholog can be used to predict resistance in the other at a high level of accuracy. However, because of epistasis, around 10% of mutations have distinct effects in the two orthologs, which imposes an upper limit to the transferability of the knowledge of resistance mutations from one species to another. Using biochemical assays and by structural characterization of several mutants, we identify distinct mechanisms of epistasis, one important being that the local physiochemical environment of some position has evolved in a way that makes the same substitutions destabilizing or entirely inactivating in an ortholog-specific manner. Our results show that resistance mutations can be conserved in fungi across hundreds of millions of years of evolution but that epistasis eventually limits the accuracy of these predictions.

microbiology↗

bioRxiv2026

Facing pain is effortful: key role of the supplementary motor area and anterior midcingulate cortex

Pain captures attention and interferes with executive and motor processes. In the presence of pain, increasing effort may represent a compensatory mechanism to counteract pain-related disruption and maintain task performance. In this preregistered fMRI study, we investigated neural mechanisms underlying preserved task performance during pain and increased perceived effort. Forty right-handed participants performed a visuomotor force-matching task consisting of isometric handgrip contractions at a low and high force levels under individually calibrated painful or non-painful thermal stimulation. Thermal stimulation was applied to the left forearm, and participants rated the intensity of perceived effort after each isometric contraction. Maintaining task performance under pain was associated with increased perceived effort and recruited brain regions involved in pain modulation and cognitive control. Region-of-interest analysis showed perceived effort was consistently linked to decreased anterior midcingulate cortex activity, whereas supplementary motor area contributions varied depending on its role in motor execution or pain processing. Across experimental condition, motor, pain-modulatory and cognitive-control regions were associated with effort perception. Independently of condition, effort perception was modulated by ventromedial prefrontal cortex and ventral striatum. These findings indicate that effort perception is a complex phenomenon reflecting brain activity within areas involved in motor, executive and valuation processes. Significance StatementThis study advances our understanding of the neural mechanisms underlying task performance under pain and increased effort perception. Brain activity was measured during a visuomotor force-matching task performed in the presence or absence of pain. By contrasting task-related activity between painful and non-painful conditions, we identified regions associated with cognitive control and pain modulation involved in preserving task performance under pain. By correlating activity in regions of interest with ratings of perceived effort, we demonstrated the involvement of the supplementary motor area and midcingulate cortex in effort perception. These findings suggest that additional neural resources are recruited to maintain performance during pain and that the supplementary motor area and midcingulate cortex contribute to heightening the effort experienced.

neuroscience↗

bioRxiv2024

HEPN-AbiV is an RNase in the antiphage system AbiV

Prokaryotes and eukaryotes possess defense systems, which can be either innate or acquired, to protect against viral infections. At the bacterial population level, abortive infection (Abi) serves as an innate immune defense mechanism against phage invasion. The AbiV antiviral system is prevalent in several bacterial genomes and exhibits diverse characteristics in terms of gene composition and evolution. Our investigation into the Lactococcus AbiV system revealed a novel two-component system, abiV1 and abiV2, both of which are essential for its function as a type III toxin-antitoxin system. The toxin component AbiV (product of abiV1) is an RNase belonging to the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding) superfamily as it carries the consensus Rx4-6H motif. In vivo assays coupled with mass spectrometry showed that the lactococcal AbiV was expressed in the presence or absence of phages while in vitro experiments demonstrated that AbiV1 degraded ribosomal RNA but not mRNA. On the other hand, the antitoxin component (abiV2) was found to function as an RNA molecule that inhibited the nuclease activity of the AbiV1 toxin. The structural characterization of AbiV revealed that this RNase utilizes a large patch of positively charged area across the dimer to anchor RNA molecules. In addition, we showed that the AbiV N-terminal region (amino acids 1 to 23) is crucial for its RNase activity as a truncated AbiV lacking this segment adopted distinct conformational states incompatible with RNA binding. This study provided novel insights into the mode of action of the antiviral system AbiV.

biochemistry↗

bioRxiv2024

Compensatory mutations potentiate constructive neutral evolution by gene duplication

Protein functions generally depend on their assembly into complexes. During evolution, some complexes have transitioned from homomers encoded by a single gene to heteromers encoded by duplicate genes. This transition could occur without adaptive evolution through intermolecular compensatory mutations. Here, we experimentally duplicate and evolve an homodimeric enzyme to examine if and how this could happen. We identify hundreds of deleterious mutations that inactivate individual homodimers but produce functional enzymes when co-expressed as duplicated proteins that heterodimerize. The structure of one such heteromer reveals how both losses of function are buffered through the introduction of asymmetry in the complex that allows them to subfunctionalize. Constructive neutral evolution can thus occur by gene duplication followed by only one deleterious mutation per duplicate. One sentence summaryCompensatory deleterious mutations entangle gene duplicates

evolutionary biology↗

bioRxiv2023

Facial expression is a distinctive behavioural marker of pain processing in the brain

Pain is a private experience observable through various verbal and non-verbal behavioural manifestations, each of which may relate to different pain-related functions. Despite the importance of understanding the cerebral mechanisms underlying those manifestations, there is currently limited knowledge on the neural correlates of the facial expression of pain. In this functional magnetic resonance imaging (fMRI) study, noxious heat stimulation was applied in healthy volunteers and we tested if previously published brain signatures of pain were sensitive to pain expression. We then applied a multivariate pattern analysis to the fMRI data to predict the facial expression of pain. Results revealed the inability of previously developed pain neurosignatures to predict the facial expression of pain. We thus propose a Facial Expression of Pain Signature (FEPS) conveying distinctive information about the brain response to nociceptive stimulations with minimal or no overlap with other pain-relevant brain signatures associated with nociception, pain ratings, thermal pain aversiveness, or pain valuation. The FEPS may provide a distinctive functional characterization of the distributed cerebral response to nociceptive pain associated with the socio-communicative role of non-verbal pain expression. This underscores the complexity of pain phenomenology by reinforcing the view that neurosignatures conceived as biomarkers must be interpreted in relation to the specific pain manifestation(s) predicted and their underlying function(s). Future studies should explore other pain-relevant manifestations and assess the specificity of the FEPS against simulated pain expressions and other types of aversive or emotional states.

neuroscience↗