Biology subjects

Hamel, R.

Publications and source records attributed to Hamel, R..

12 recordsLinked to original sources

bioRxiv2026

Optimizing Intermittent Theta-Burst Stimulation: The Effects of Pulse Parameters on Corticospinal Excitability

Objective. Intermittent theta burst stimulation (iTBS) is a repetitive transcranial magnetic stimulation (rTMS) protocol used in clinical settings to alleviate symptoms of psychiatric disorders. Although the pulse parameters currently used in iTBS have remained unchanged since the first treatments, recent controllable TMS devices allow for the personalization of pulse shape and duration, opening the possibility of testing the efficacy of other pulse parameters in modulating corticospinal excitability (CSE). Methods. In a repeated-measures design, changes in CSE were induced by the administration of iTBS over the left primary motor cortex under three different conditions: long bidirectional pulse (L-Bi), long quasi-unidirectional pulse (L-QU), and a control short quasi-unidirectional pulse (S-QU). We assessed TMS-induced motor evoked potentials before and up to 70 minutes after iTBS. We hypothesized that L-QU pulses would induce greater facilitation than other conditions. Results. A mixed linear model showed that all conditions induced increased MEPs compared to baseline. However, the L-Bi pulse led to a larger and more sustained MEP increase than both unidirectional pulses, while the S-QU pulse appeared less effective in modulating CSE. We observed large within- and between-subject variability in responsiveness to the iTBS protocols. Conclusion. These results suggest that L-Bi pulses in iTBS protocols are more potent than unidirectional pulses in inducing CSE changes in the cortex of healthy adults. The individual variability in response to iTBS and the potential clinical relevance of these findings are discussed.

neuroscience↗

bioRxiv2026

Timecourse of corticospinal excitability for observed action: evidence of early suppression followed by return to baseline without facilitation

IntroductionAction observation modulates corticospinal excitability, with most previous studies indicating an increase in excitability in the muscles involved in the observed movement. In addition, previous work suggests that modulation of corticospinal excitability could be specific to the timing of the stimulation, muscle, and direction of movement. Here we examined the influence of these factors on corticospinal excitability. MethodParticipants observed stimuli presenting a static hand, followed by an image of the endpoint of an index/little finger abduction movement. Transcranial magnetic stimulation was delivered at time points from 100-800ms after movement onset. Stimuli were presented in various orientations to study possible effects of anatomical positioning and movement direction, compared relative to the control condition of a static hand. ResultsCorticospinal excitability was lower at early timings (100-400ms), before rising to a plateau at later timings (500-800ms) which did not differ from the static hand condition. This facilitation was muscle-specific, with higher excitability for the muscle involved in the observed movement. By contrast, the relative direction of movement did not influence corticospinal excitability. DiscussionThese results replicate the time-dependent modulation of corticospinal excitability induced by action observation; however, we argue that simply interpreting such effects as an increase in excitability may be overly simplistic. In line with previous studies, we argue that the choice of control condition used during action observation studies may be critical to the overall direction of effects.

neuroscience↗

bioRxiv2025

Time-Dependent Facilitation of Homologous Actions

Unimanual actions can interfere with or facilitate similar actions performed with the opposite hand, especially when in close temporal proximity. Across three sequential button-press experiments, we tested how effector homology - anatomical similarity between fingers - and temporal delays between actions shape these effects. Specifically, we examined whether a priming action altered the reaction time (RT) of a subsequent action. Compared with unimanual RTs, we indexed slowing of the second actions RT as interference, and quickening as facilitation. Priming with homologous actions (e.g., index finger-index finger) produced interference at short intervals ([≤]200ms) but transitioned to facilitation at longer intervals ([≥]400ms). Priming with non-homologous actions (e.g., little finger-index finger) also produced interference at short intervals, but never resulted in facilitation. Critically, these patterns emerged whether the priming actions were performed with the opposite or the same hand, indicating that interference and facilitation do not depend on interhemispheric dynamics. Our results reveal a previously undocumented time-dependent shift from interference to facilitation that is specific to homologous actions, challenging models that explain the interference between parallel actions solely by competitive interhemispheric dynamics or central bottleneck processes. We propose that facilitation and interference flexibly coexist, and are shaped by effector homology and timing. These findings extend current models of bimanual coordination and highlight new opportunities for enhancing motor performance and neurorehabilitation. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/682693v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@20dc18org.highwire.dtl.DTLVardef@151ea4corg.highwire.dtl.DTLVardef@ed2547org.highwire.dtl.DTLVardef@12a9550_HPS_FORMAT_FIGEXP M_FIG A left-hand index finger press primed a subsequent right-hand index (homologous) or right-hand little finger (non-homologous) response at variable delays. For homologous actions (index-index), reaction times (RTs) quickened relative to unimanual single-press baseline for delays [≥]400ms, whereas for non-homologous actions (index-little), RTs slowed and gradually returned to baseline by ~600ms. This dissociation indicates that effector homology and timing dictate whether a preceding action facilitates or interferes with the execution of a subsequent one. C_FIG

neuroscience↗

bioRxiv2025

Evidence of Human adaptation for cluster 2 TMUV strain despite effective anti-viral responses.

Tembusu virus (TMUV) is an emerging Orthoflavivirus with potential zoonotic importance. To date, the biological differences among TMUV strains remain poorly understood. In this study, we compared the replication of a TMUV strain belonging to the cluster 1 and one belonging to the cluster 2 in human lung epithelial cells and further examined the replication characteristics of TMUV cluster 2 strain in both human and mosquito cell lines. The TMUV cluster 2 strain demonstrated a significant higher replication efficiency than the cluster 1 strain in human cells, indicating stronger adaptation to human-derived cells. Infection of human cells with the cluster 2 strain also induced robust innate immune response, including type I interferon and interferon-stimulated gene expression, associated with activation of the unfolded protein response via the PERK, and IRE1 pathways, reflecting an ER stress engagement. These findings suggest that TMUV cluster 2 strain exhibits enhanced replication capacity and more effectively modulates human host responses at the cellular level, underscoring its potential relevance in human health and the zoonotic risk it represents.

molecular biology↗

bioRxiv2025

Multiple orthoflaviviruses secrete sfRNA in mosquito saliva to promote transmission by inhibiting MDA5-mediated early interferon response

Numerous orthoflaviviruses transmitted through the bites of different mosquito species infect more than 500 million people annually. Skin infection at the bite site represents a critical and conserved step in transmission and a deeper understanding of this process will promote the design of broad-spectrum interventions to address diverse orthoflavivirus health threats. Here, we identify and characterize a transmission-enhancing viral factor in mosquito saliva that is shared across orthoflaviviruses. Saliva from West Nile virus-infected Culex and Zika virus-infected Aedes contains a viral non-coding RNA, subgenomic flaviviral RNA (sfRNA), within lipid vesicles distinct from virions. Higher concentration of sfRNA in infectious saliva positively correlates with infection intensity in human cells and skin explants. Early sfRNA delivery into transmission-relevant skin cell types and human skin explant demonstrate that sfRNA is responsible for the infection enhancement. Co-inoculation of sfRNA in a mouse model of transmission enhanced skin infection and worsened disease severity, supporting the role of salivary sfRNA as a transmission-enhancer. Mechanistically, salivary sfRNA attenuates early interferon response in human skin cells and skin explants by disrupting MDA5 signaling. Our results, derived from two distinct orthoflaviviruses and supported by prior studies, establish salivary sfRNA as a pan-orthoflavivirus transmission-enhancing factor driven by a conserved viral non-coding RNA.

immunology↗

bioRxiv2024

West Nile virus is transmitted within mosquito populations through infectious mosquito excreta

Understanding transmission routes of arboviruses is key to control their epidemiology and global health burden. Using West Nile virus and Culex mosquitoes, we tested whether arboviruses are transmitted through mosquito excreta. First, we determined the presence of infectious virions in excreta and quantified a high concentration of infectious units per excreta. Second, we showed that virion excretion starts early after oral infection and remains constant for a long period, regardless of mosquito infection level. These results highlight the infectiousness of excreta from infected mosquitoes. Third, we found that both larvae and pupae were susceptible to infection, although pupae were highly permissive. Forth, we established the proof-of-concept that immature mosqui-toes can be infected by infectious excreta, demonstrating a new excreta-mediated mode of transmission. Finally, by mathematically modelling excreta-mediated transmission in the field, we demonstrated its potential impact on arbovirus epidemiology. Our study uncovers a new route of transmission for arboviruses, unveiling mechanisms of viral maintenance in mosquito reservoirs and of vector species shift that contribute to zoonotic emergence.

zoology↗

bioRxiv2024

Mitochondrial reverse electron transport in myeloid cells perpetuates neuroinflammation

Sustained smouldering, or low grade, activation of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis (MS)1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate neuroinflammation is currently unknown. Using a multiomics approach, we identified a new molecular signature that perpetuates the activation of myeloid cells through mitochondrial complex II (CII) and I (CI) activity driving reverse electron transport (RET) and the production of reactive oxygen species (ROS). Blocking RET in pro-inflammatory myeloid cells protected the central nervous system (CNS) against neurotoxic damage and improved functional outcomes in animal disease models in vivo. Our data show that RET in myeloid cells is a potential new therapeutic target to foster neuroprotection in smouldering inflammatory CNS disorders3.

neuroscience↗

bioRxiv2023

Bilateral Intracortical Inhibition during Unilateral Motor Preparation and Sequence Learning

Motor sequence learning gradually quickens reaction time, suggesting that sequence learning alters motor preparation processes. Interestingly, evidence has shown that preparing sequence movements decreases short intracortical inhibition (SICI) in the contralateral motor cortex (M1), but also that sequence learning alters motor preparation processes in both the contralateral and ipsilateral M1s. Therefore, one possibility is that sequence learning alters the SICI decreases occurring during motor preparation in bilateral M1s. To examine this, two novel hypotheses were tested: unilateral sequence preparation would decrease SICI in bilateral M1s, and sequence learning would alter such bilateral SICI responses. Paired-pulse transcranial magnetic stimulation was delivered over the contralateral and ipsilateral M1s to assess SICI in an index finger muscle during the preparation of sequences initiated by either the right index or little finger. In the absence of sequence learning, SICI decreased in both the contralateral and ipsilateral M1s during the preparation of sequences initiated by the right index finger, suggesting that SICI decreases in bilateral M1s during unilateral motor preparation. As sequence learning progressed, SICI decreased in the contralateral M1 whilst it increased in the ipsilateral M1. Moreover, these bilateral SICI responses were observed at the onset of motor preparation, suggesting that sequence learning altered baseline SICI levels rather than the SICI decreases occurring during motor preparation per se. Altogether, these results suggest that SICI responses in bilateral M1s reflect two motor processes: an acute decrease of inhibition during motor preparation, and a cooperative but bidirectional shift of baseline inhibition levels as sequence learning progresses.

neuroscience↗

bioRxiv2023

Sub-Concussive Head Impacts From Heading Footballs Do Not Acutely Alter Brain Excitability As Compared to a Control Group

BackgroundRepeated sub-concussive head impacts are a growing brain health concern, but the possible mechanisms of trauma and plausible biomarkers remain elusive. One impediment is the lack of an experimental model to study the effects of sub-concussive head impacts on the brain. ObjectivesThis works objective was to provide an experimental model to study the acute effects of sub-concussive head impacts on the brain. To do so, this study aimed to replicate previous work from Di Virgilio et al. (2016) showing that head impacts from heading footballs acutely alter brain excitability by increasing corticomotor inhibition. MethodsScores from the Rivermead Post-Concussion Questionnaire and measurements of cortical silent period (CSP) duration - obtained using transcranial magnetic stimulation to assess corticomotor inhibition in the central nervous system - were taken before and after participants performed 20 football headings (Headings; n = 30) or control (Control; n = 30). ResultsThe results revealed increased headaches and dizziness symptoms in the Headings as compared to the Control group, revealing the qualitative experience of head impacts. The results then revealed that CSP duration similarly lengthened in both the Headings and Control groups, suggesting that head impacts did not cause the increased corticomotor inhibition. ConclusionsThe results show that head impacts from football headings did not acutely alter corticomotor inhibition as compared to a control group that did not experience head impacts, suggesting that excitability changes do not reflect acute sub-concussive brain injuries. Nonetheless, this work suggests that football headings can be used as an experimental model to study the effects of sub-concussive head impacts on brain health. Future work could use the present procedures to investigate additional biomarkers of brain injury.

neuroscience↗

bioRxiv2023

The Neurochemical Mechanisms Underlying the Enhancing Effects of Rewards and Punishments on Motor Performance

Monetary rewards and punishments enhance motor performance and are associated with corticospinal excitability (CSE) increases within the motor cortex (M1) during movement preparation. However, such CSE changes have unclear origins; they could stem from increased glutamatergic (GLUTergic) facilitation and/or decreased type A gamma-aminobutyric acid (GABAA)-mediated inhibition within M1. To investigate this, paired-pulse transcranial magnetic stimulation was used to assess GLUTergic facilitation and GABAA inhibition within M1 whilst participants prepared to execute 4-element finger-press sequences. Behaviourally, rewards and punishments enhanced both reaction and movement times. Neurochemically, regardless of rewards or punishments, a digit-specific increase in GLUTergic facilitation and digit-unspecific decrease in GABAA inhibition occurred during preparation as movement onset approached. In parallel, both rewards and punishments non-specifically increased GLUTergic facilitation, but only rewards non-specifically decreased GABAA inhibition during preparation. This suggests that, to enhance performance, rewards both increase GLUTergic facilitation and decrease GABAA inhibition whilst punishments selectively increase GLUTergic facilitation. A control experiment revealed that such changes were not observed post-movement as participants processed reward and punishment feedback, indicating they were selective to movement preparation. Collectively, these results map the neurochemical changes in M1 by which incentives enhance motor performance.

neuroscience↗

bioRxiv2020

Time-resolved single-cell RNAseq profiling identifies a novel Fabp5-expressing subpopulation of inflammatory myeloid cells in chronic spinal cord injury

Innate immune responses following spinal cord injury (SCI) participate in early secondary pathogenesis and wound healing events. Here, we used time-resolved scRNAseq to map transcriptional profiles of SC tissue-resident and infiltrating myeloid cells post-SCI. Our work identifies a novel subpopulation of Fabp5+ inflammatory myeloid cells, comprising both resident and infiltrating cells and displaying a delayed cytotoxic profile at the lesion epicentre, which may serve as a target for future therapeutics.

neuroscience↗

bioRxiv2019

Characterization of human-iPSCs derived spinal motor neurons by single-cell RNA sequencing

Human induced pluripotent stem cells (iPSCs) offer the opportunity to generate specific cell types from healthy and diseased individuals, allowing the study of mechanisms of early human development, modelling a variety of human diseases, and facilitating the development of new therapeutics. Human iPSC-based applications are often limited by the variability among iPSC lines originating from a single donor, as well as the heterogeneity among specific cell types that can be derived from iPSCs. The ability to deeply phenotype different iPSC-derived cell types is therefore of primary importance to the successful and informative application of this technology. Here we describe a combination of motor neuron (MN) derivation and single-cell RNA sequencing approaches to generate and characterize specific MN subtypes obtained from human iPSCs. Our studies provide evidence for rapid and robust generation of MN progenitor cells that can give rise to a heterogenous population of brainstem and spinal cord MNs. Approximately 58% of human iPSC-derived MNs display molecular characteristics of lateral motor column MNs, [~]19% of induced MNs resemble hypaxial motor column MNs, while [~]6% of induced MNs have features of medial motor column MNs. The present study has the potential to improve our understanding of iPSC-derived MN subtype function and dysfunction, possibly leading to improved iPSC-based applications for the study of human MN biology and diseases.

neuroscience↗