Biology subjects

Gruet, M.

Publications and source records attributed to Gruet, M..

5 recordsLinked to original sources

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↗

bioRxiv2026

Mental fatigue impairs cycling endurance performance and perception of effort, but not muscle activation

Mental fatigue is induced by prolonged engagement in cognitively demanding tasks and impairs endurance performance. The neuropsychophysiological mechanisms underlying this decreased performance remain unclear, with suggestion that mental fatigue may disrupt motor command and consequently muscle activation. We aimed to test this hypothesis in a repeated cross-over design study in which 18 participants completed two experimental sessions involving a time-to-task failure cycling test at 80% of peak power output. Each cycling task was preceded by 1h of a prolonged Stroop task (Stroop condition) or a neutral control task (Control condition). Mental fatigue was assessed using a visual analog scale anchored with "not fatigued at all" and "extremely fatigued. Perception of effort and surface electromyography from ten lower-limb muscles of the right leg were recorded at regular intervals during cycling. Mental fatigue was higher in the Stroop compared to the Control condition (p = .002). Endurance cycling time was shorter in the Stroop than in the Control condition (887 {+/-} 284 s vs. 999 {+/-} 379 s, respectively; -111 {+/-} 160 s, p = .009). No significant differences in electromyography parameters were observed between Stroop and Control conditions, for any muscle (p > .05). Perception of effort was higher in the Stroop condition from the onset of the cycling task (p = .006), and the rate of increase in perception of effort was significantly higher in the Stroop than Control condition (p = .031). Our findings do not support the hypothesis that mental fatigue alters motor control or increases central motor command, as no changes in muscle activation were detected. Conversely, our results reinforce the notion that prolonged cognitive engagement impairs endurance performance primarily through an increased perception of effort. Future research should consider combining surface electromyography with more sensitive neurophysiological techniques to investigate potential subtle changes in motor drive during dynamic, whole-body tasks under mental fatigue.

physiology↗

bioRxiv2025

Challenging the loss of complexity theory: insights from the neuromuscular system in chronic obstructive pulmonary disease

BackgroundAccording to the "loss of complexity" theory, aging and disease are expected to reduce complexity of physiological outputs, thereby limiting the systems adaptability. However, it remains unclear whether this concept applies to the neuromuscular system in people with chronic obstructive pulmonary disease (pwCOPD). This study aimed to challenge the loss of complexity hypothesis by assessing the regularity, as well as the steadiness and the accuracy, of force production during submaximal isometric contractions in pwCOPD compared to healthy individuals. MethodsSeventeen pwCOPD and seventeen age- and sex-matched healthy participants performed submaximal isometric contractions of the knee extensors at six target forces, ranging from 10 to 60% of their maximal voluntary contraction (MVC). Regularity of force signals was assessed using sample entropy (SampEn) and percentage of determinism (DET) from the recurrence quantification analysis. Steadiness and accuracy were quantified using the coefficient of variation (CV) and the root-mean-square error (RMSE), respectively. ResultsPwCOPD exhibited 26.5% lower MVC than healthy individuals. Despite this muscular weakness, no significant main effect of group or interaction effect (group x contraction intensity) was observed for SampEn, DET, CV and RMSE, suggesting a preserved force control in pwCOPD at all assessed force levels. ConclusionOur results indicate that the loss of complexity theory may not apply in moderate COPD, at least for the neuromuscular system. These findings suggest that neuromuscular alteration associated with COPD may not be sufficient to impair the complexity of force output, questioning the universality of the loss of complexity theory.

physiology↗

bioRxiv2024

RAS/PI3K pathway mutations sensitise epithelial ovarian cancer cells to a PARP/NAMPT inhibitor combination

The combination of PARP and NAMPT inhibitors (PARPi/NAMPTi) has been explored for the treatment of TNBC, Ewing Sarcoma and high grade serous carcinoma (HGSC). However, dose limiting toxicity has hampered NAMPTi in clinical trials. To maximise the therapeutic window, we set out to identify predictive genomic biomarkers. Bioinformatic analysis and screening of a panel of epithelial ovarian cancer (EOC) cell lines revealed that cells with RAS/PI3K pathway mutations were sensitive to the NAMPTi FK866. Activity of olaparib and FK866 was associated with a reduction in nicotinamide mononucleotide (NMN) and the PARP substrate nicotinamide adenine dinucleotide (NAD+), with coincident increases in ROS production, DNA damage and apoptosis induction. Caspase 3/7 activity was upregulated to a greater extent in RAS/PI3K mutant cell lines. Finally, the combination significantly reduced omental tumour weight and increased overall survival in mice injected with ID8 Trp53-/-;Pten-/- cells. This study highlights the potential of the PARPi/NAMPTi combination in RAS/PI3K pathway mutant EOC.

cancer biology↗

bioRxiv2023

Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma

Ovarian high-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian cancer with limited therapeutic options. In recent years, PARP inhibitors have demonstrated significant clinical benefits, especially in patients with BRCA1/2 mutations. However, acquired drug resistance and relapse is a major challenge. Therapies disrupting the spliceosome alter cancer transcriptomes and have shown potential to improve PARP inhibitor response. Indisulam (E7070) has been identified as a molecular glue that brings splicing factor RBM39 and DCAF15 E3 ubiquitin ligase in close proximity. Exposure to indisulam induces RBM39 proteasomal degradation through DCAF15-mediated polyubiquitination and subsequent RNA splicing defects. In this study, we demonstrate that loss of RBM39 induces splicing errors in DNA damage repair genes in ovarian cancer, leading to increased sensitivity to PARP inhibitors such as olaparib. Indisulam synergized with olaparib in multiple in vitro models of ovarian cancer regardless of PARP inhibitor sensitivity and improved olaparib response in mice bearing PARP inhibitor-resistant tumors. DCAF15 expression, but not BRCA1/2 mutational status, was essential for the synergy between indisulam and olaparib, suggesting that the combination therapy may benefit patients irrespective of their BRCA1/2 status. These findings demonstrate that combining RBM39 degraders and PARP inhibitors is a promising therapeutic approach to improving PARP inhibitor response in ovarian HGSC. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=74 SRC="FIGDIR/small/524417v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@4cccd5org.highwire.dtl.DTLVardef@1be34aorg.highwire.dtl.DTLVardef@e72b06org.highwire.dtl.DTLVardef@b9c89d_HPS_FORMAT_FIGEXP M_FIG C_FIG One Sentence SummaryWe identified a novel drug combination that may improve PARP inhibitor response and benefit a large group of ovarian cancer patients.

cancer biology↗