Biology subjects

Mouraux, A.

Publications and source records attributed to Mouraux, A..

13 recordsLinked to original sources

bioRxiv2025

Interindividual variations in peak alpha frequency do not predict the magnitude or extent of secondary hyperalgesia induced by high-frequency stimulation

BackgroundPrevious studies have shown an association between interindividual variations in the frequency of alpha-band EEG oscillations such as estimates of peak alpha frequency (PAF) and pain sensitivity. Whether differences in PAF also influence the susceptibility to develop central sensitization (CS) is unknown. ObjectiveThis study aimed to determine if the PAF of vision- and sensorimotor-related alpha-band activity is associated with the magnitude and extent of secondary mechanical hyperalgesia induced by high-frequency stimulation (HFS) of the skin, a surrogate marker of CS. MethodsThe EEG was recorded in 32 healthy participants at rest during eyes open and eyes closed conditions, and during bilateral finger movements. Two methods were used to isolate vision- and sensorimotor-related alpha-band activity based on sensitivity to eye closure and movement: one based on an independent component analysis, the other on spectral subtraction. PAF was assessed using a center-of-gravity approach or the Fitting Oscillations and One-Over-F (FOOOF) method, accounting for the aperiodic EEG component. HFS was applied to the right forearm, and pinprick sensitivity was assessed at both forearms, before and 40 minutes after HFS. ResultsNeither sensorimotor-nor vision-related PAF were significantly correlated with the magnitude or extent of HFS-induced secondary hyperalgesia. Interestingly, at the non-sensitized forearm, participants with a higher vision-related PAF exhibited greater habituation to pinprick stimuli, suggesting that variations in PAF may relate to variations in sensory habituation. ConclusionInterindividual variations of PAF were not significantly associated with the susceptibility to develop HFS-induced secondary hyperalgesia. New and NoteworthyUsing several methods to estimate vision- and sensorimotor-related peak alpha frequency (PAF) in the EEG frequency spectrum, we found no significant association between interindividual variations in PAF and the susceptibility to develop secondary hyperalgesia following high-frequency stimulation (HFS) of the skin in healthy participants.

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bioRxiv2025

Aligned representation of visual and tactile motion directions in hMT+/V5 and fronto- parietal regions

Moving events on the skin can be perceived through vision and touch. How does the brain create a unified multisensory representation of motion directions initially acquired in different coordinate systems? We show that the middle occipito-temporal region (hMT+/V5), along with a fronto-parietal network, encodes visual and tactile directions using a common external frame of reference independent of body posture. We characterized brain activity using fMRI in participants exposed to directional visual and tactile motion stimuli across different hand postures. We demonstrate that individually and functionally defined hMT+/V5 shows univariate preference for both visual and tactile motion and encodes motion directions across hand postures. Unlike somatosensory regions, information about tactile directions was enhanced in right hMT+/V5 when mapped using an external as compared to a somatotopic frame of reference. Crossmodal decoding showed that tactile directions defined in an external frame of reference, but not a somatotopic one, align with the representation of visual directions in the right hMT+/V5 (both in MT and MST). A whole brain searchlight group analysis confirmed these individually defined regions-of-interest results and extended the presence of an aligned visual-tactile code for directional motion in external space to the parietal and frontal cortex. Our findings reveal a brain network involving hMT+/V5 that encodes motion directions in vision and touch using a common external frame of reference.

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bioRxiv2025

Electrical Spinal Imaging (ESI): Analysing spinal cord activity with non-invasive, high-resolution mapping

The spinal cord is the key bridge between the brain and the body. However, scientific understanding of healthy spinal cord function has historically been limited because noninvasive measures of its neural activity have proven exceptionally challenging. In this work, we describe a novel recording and analysis approach to obtain non-invasive, high-resolution images of the electrical activity of the spinal cord in humans (Electrical Spinal Imaging, ESI). ESI is analytically simple, easy to implement, and data-driven: it does not involve template-based strategies prone to produce spurious signals. Using this approach we provide a detailed description and physiological characterization of the spatiotemporal dynamics of the peripheral, spinal and cortical activity elicited by somatosensory stimulation. We also demonstrate that attention modulates post-synaptic activity at spinal cord level. Our method has enabled four new insights regarding spinal cord activity. (1) We identified three distinct responses in the time domain: sP9, sN13 and sP22. (2) The sP9 is a traveling wave reflecting the afferent volley entering the spinal cord through the dorsal root. (3) In contrast, the sN13 and sP22 reflect segmental post-synaptic activity. (4) While the sP9 response is first seen on the dorsal electrodes ipsilateral to the stimulated side, the sN13 and sP22 were not lateralised with respect to the side of stimulation. (5) Unimodal attention strongly modulates the amplitude of the sP22, but not that of the sP9 and sN13 components. The proposed method offers critical insights into the spatiotemporal dynamics of somatosensory processing within the spinal cord, paving the way for precise non-invasive functional monitoring of the spinal cord in basic and clinical neurophysiology.

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bioRxiv2024

Evidence of interplays between the vascular and nociceptive systems revealed by changes in capsaicin pain caused by limb position change

This experiment aimed at confirming our incidental observation that, when capsaicin is applied on the volar forearm, raising the arm to a vertical position leads to a dramatic increase in capsaicin-evoked pain and to explore possible underlying mechanisms. Twenty healthy volunteers received a 2% capsaicin patch on one forearm and a vehicle patch on the other. Patches were kept in place for 60 minutes. The sensation caused by the patch was assessed repeatedly -in resting position and when the arm was raised vertically-before, during and after patch application. In addition, capsaicin-induced secondary hyperalgesia was assessed using mechanical pinprick stimuli. Half of the participants were seated upright while the other half were lying supine, to assess whether the effect of limb position was due to gravity. After a few minutes of patch application, raising the capsaicin treated arm (but not the vehicle treated arm) led to a strong increase of the pain experienced at the patch. This effect of raising the arm did not differ between participants in the supine and seated groups and is therefore likely related to the position of the arm relative to the ground (gravity) rather than to the body. Mechanical secondary hyperalgesia and the arm raising effect were strongly decorrelated at the last time point after patch removal, indicating different underlying mechanisms. Our results indicate that capsaicin-evoked pain can be strongly modulated by limb posture and that this effect may be caused by an interplay between vascular and nociceptive systems.

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bioRxiv2024

Exploration of the EEG response to periodic thermal and vibrotactile stimuli

Under certain conditions, a stimulus applied at a given frequency will lead to a periodic variation of neural activity at the same frequency. Taking advantage of this periodicity, it is possible to tag this response in the EEG frequency spectrum. Frequency tagging of sustained periodic noxious heat stimuli led to the recording of phase-locked and non-phase-locked responses whose functional significance remains unclear. This study aimed at assessing whether such responses can also be recorded during the repetitive presentation of brief innocuous cold, noxious heat and vibrotactile stimuli. Comparison between the responses obtained with different stimulation modalities should inform us on the nature of the neural processes underlying these responses (modality aspecific, somatosensory, thermosensory, nociceptive). Comparison between upper and lower limb stimulation should inform us on the somatotopic organization of these responses and, therefore, on their potential sources. Based on our results, on one hand, trains of brief innocuous cold, noxious heat and vibrations can elicit phase-locked and non-phase-locked responses which appear highly similar to those evoked by sustained periodic noxious heat stimuli when frequency tagged. On the other hand, when analysed in the time domain or using time-frequency decomposition, these responses appeared highly similar to those that can be recorded following isolated brief noxious heat or tactile stimuli. These responses consisted in phase-locked activity corresponding to the vertex potential, thought to reflect modality non-specific attentional processes, and in an alpha-to-beta ERD originating in the S1/M1 area contralateral to the stimulated hand, probably reflecting non-specific somatosensory activity.

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bioRxiv2022

Non-invasive multi-channel electrophysiology of the human spinal cord - assessing somatosensory processing from periphery to cortex

The spinal cord is of fundamental importance for integrative processing in brain-body communication, yet routine non-invasive recordings in humans are hindered by vast methodological challenges. Here we overcome these challenges by developing an easy-to-use electrophysiological approach based on high-density multi-channel spinal recordings combined with multivariate spatial-filtering analyses. These advances enable a spatiotemporal characterization of spinal cord responses and demonstrate a sensitivity that permits assessing even single-trial responses. To furthermore enable the study of integrative processing along the neural processing hierarchy in somatosensation, we expand this approach by simultaneous peripheral, spinal and cortical recordings and provide direct evidence that bottom-up integrative processing occurs already within the spinal cord and thus after the first synaptic relay in the central nervous system. Finally, we demonstrate the versatility of this approach by providing non-invasive recordings of nociceptive spinal cord responses during heat-pain stimulation. Beyond establishing a new window on human spinal cord function at millisecond timescale, this work provides the foundation to study brain-body communication in its entirety in health and disease.

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bioRxiv2022

Exploring the properties of the left angular gyrus using TMS-evoked potentials

The angular gyrus (AG) is involved in multiple cognitive processes and its structural alterations are commonly observed in many neuropsychiatric syndromes. Since changes in excitability may precede structural changes and clinical symptoms, there is a need for diagnostic tools assessing the functional state of hub brain regions like the AG. The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) can provide such functional readouts by probing the brain response to direct stimulation. This study aimed to characterize TMS-evoked potentials (TEP) elicited by AG stimulation, determine optimal stimulation parameters, and identify TEP biomarkers of AG function. We recorded AG-TEPs in 19 subjects using four TMS orientations and three intensities and compared TEP spatiotemporal features using topographic dissimilarity and microstate analyses. Additionally, we explored the relationship between AG-TEP topography and TMS-evoked muscular activity. Our results showed topographic variability in AG-TEP components P25, N45, and N75. The P25 topography was sensitive to TMS orientation, while the topography of N45 and N75 was highly dependent on both coil orientation and intensity. Interestingly, we found that TMS-evoked muscular activity was also dependent on both these parameters and strongly related to the occurrence of a specific topographic pattern, which therefore possibly corresponds to the somatosensory brain response to muscle contraction. We conclude that the early AG-TEP component P25 likely reflects neural processes triggered by direct AG activation and could provide an index of local excitability. Later components N45 and N75 must be interpreted with caution as they may primarily reflect peripherally evoked activity.

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bioRxiv2022

Evaluation of GABAAR-mediated inhibition in the human brain using TMS-evoked potentials

GABAA receptor (GABAAR) - mediated inhibition participates in the control of cortical excitability, and its impairment likely contributes to the pathologic excitability changes that have been associated with multiple neurological disorders. Therefore, there is a need for its direct evaluation in the human brain, and the combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) might represent the optimal tool. TMS-evoked brain potentials (TEPs) capture the spread of activity across the stimulated brain network, and since this process at least partially depends on the GABAAR-mediated inhibition, TEPs may constitute relevant biomarkers of local GABAAergic function. Here, we aimed to assess the effect of GABAARs activation using TEPs, and to identify TEP components that are sensitive to the state of GABAAergic inhibition. In 20 healthy subjects, we recorded TEPs evoked by sub- and supra-threshold stimulation of the primary motor cortex (M1), motor-evoked potentials (MEPs) and resting-state EEG (RS-EEG). GABAARs were activated (1) pharmacologically by oral administration of alprazolam compared to placebo within each subject, and (2) physiologically using a sub-threshold conditioning stimulus to characterize the effect of short-latency intracortical inhibition (SICI). In supra-threshold TEPs, alprazolam suppressed the amplitude of components N17, N100 and P180, and increased component N45. The pharmacological modulation of N17 correlated with the change observed in MEPs and with the alprazolam-induced increase of lower {beta}-band RS-EEG. Only a reduction of N100 and P180 was found in sub-threshold TEPs. TEP SICI manifested as a reduction of N17, P60 and N100, and its effect on N17 correlated with the alprazolam-induced N17 suppression and {beta} increase. Our results indicate that N17 of supra-threshold TEPs could serve as a non-invasive biomarker of local cortical excitability reflecting the state of GABAAR-mediated inhibition in the sensorimotor network. Furthermore, the alprazolam-induced increase of {beta}-band oscillations possibly corresponds to the increased inhibitory neurotransmission within this network.

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bioRxiv2022

Confidence of probabilistic predictions modulates the cortical response to pain

Pain typically evolves over time and the brain needs to learn this temporal evolution to predict how pain is likely to change in the future and orient behavior. This process is termed temporal statistical learning (TSL). Recently, it has been shown that TSL for pain sequences can be achieved using optimal Bayesian inference, which is encoded in somatosensory processing regions. Here, we investigate whether the confidence of these probabilistic predictions modulates the EEG response to noxious stimuli, using a TSL task. Confidence measures the uncertainty about the probabilistic prediction, irrespective of its actual outcome. Bayesian models dictate that the confidence about probabilistic predictions should be integrated with incoming inputs and weight learning, such that it modulates the early components of the EEG responses to noxious stimuli, and this should be captured by a negative correlation: when confidence is higher, the early neural responses are smaller as the brain relies more on expectations/predictions and less on sensory inputs (and vice versa). We show that participants were able to predict the sequence transition probabilities using Bayesian inference, with some forgetting. Then, we find that the confidence of these probabilistic predictions was negatively associated with the amplitude of the N2 and P2 components of the Vertex Potential: the more confident were participants about their predictions, the smaller was the Vertex Potential. These results confirm key predictions of a Bayesian learning model and clarify the functional significance of the early EEG responses to nociceptive stimuli, as being implicated in confidence-weighted statistical learning. SIGNIFICANCEThe functional significance of EEG responses to pain has long been debated because of their dramatic variability. This study indicates that such variability can be partly related to the confidence of probabilistic predictions emerging from sequences of pain inputs. The confidence of pain predictions is negatively associated with the cortical EEG responses to pain. This indicates that the brain relies less on sensory inputs when confidence is higher and shows us that confidence-weighted statistical learning modulates the cortical response to pain.

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bioRxiv2021

Trial by trial, machine learning approach identifies temporally discrete Aδ- and C-fibre mediated laser evoked potentials that predict pain behaviour in rats.

Laser evoked potentials (LEPs) - the EEG response to temporally-discrete thermal stimuli - are commonly used in experimental pain studies in humans. Such stimuli selectively activate nociceptors and produce EEG features which correlate with pain intensity. The rodent LEP has been proposed to be a translational biomarker of nociception and pain, however its validity has been questioned because of reported differences in the classes of nociceptive fibres mediating the response. Here we use a machine learning, trial by trial analysis approach on wavelet-denoised LEPs generated by stimulation of the plantar hindpaw of rats. The LEP amplitude was more strongly related to behavioural response than to laser stimulus energy. A simple decision tree classifier using LEP features was able to predict behavioural responses with 73% accuracy. An examination of the features used by the classifier showed that mutually exclusive short and long latency LEP peaks were clearly seen in single-trial data, yet were not evident in grand average data pooled from multiple trials. This bimodal distribution of LEP latencies was mirrored in the paw withdrawal latencies which were preceded and predicted by the LEP responses. The proportion of short latency events was increased after intradermal application of high dose capsaicin (to defunctionalise TRPV1 expressing nociceptors), suggesting they were mediated by A{delta}-fibres (specifically AMH-I). These findings demonstrate that both C- and A{delta}-fibres contribute to rodent LEPs and concomitant behavioural responses, providing a real-time assay of specific fibre function in conscious animals. Single-trial analysis approaches can improve the utility of LEPs as a translatable biomarker of pain.

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bioRxiv2018

Central sensitization increases the pupil dilation elicited by mechanical pinprick stimulation

High frequency electrical stimulation (HFS) of skin nociceptors triggers central sensitization, manifested as increased pinprick sensitivity of the skin surrounding the site at which HFS was applied. The aim of the present study was to compare the effects of HFS on pupil dilation and brain responses elicited by pinprick stimulation delivered in the area of increased pinprick sensitivity. In fourteen healthy volunteers HFS was applied to one of the two forearms. Before and twenty minutes after applying HFS, mechanical pinprick stimuli (64 mN and 96 mN) were delivered to the area surrounding the site at which HFS was applied as well as the contralateral control arm. During pinprick stimulation both the pupil size and electroencephalogram were recorded. HFS induced a clear and comparable increase in pinprick sensitivity for both the 64 and 96 mN stimulation intensity. Both pinprick stimulation intensities elicited a greater pupil dilation response when delivered to the area of increased pinprick sensitivity. However, this greater pupil dilation response was larger for the 64 mN compared to the 96 mN stimulation intensity. A similar pattern was observed for the negative wave of the pinprick-evoked brain potentials (PEPs), however, the increase was not significant for the 96 mN and showed only a trend towards significance for the 64 mN. These results show that there is a correspondence between the increase in pupil dilation and the increase in PEPs, but that pupil size is a more sensitive measure for detecting the effects of central sensitization than PEPs.

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bioRxiv2018

High frequency electrical stimulation induces a long-lasting enhancement of event-related potentials but does not change the perception elicited by intra-epidermal electrical stimuli delivered to the area of secondary mechanical hyperalgesia

High frequency electrical stimulation (HFS) of the skin induces increased pinprick sensitivity in the surrounding unconditioned skin (secondary hyperalgesia). Moreover, it has been shown that brief high intensity CO2 laser stimuli, activating both A{delta}- and C-fiber nociceptors, are perceived as more intense when delivered in the area of secondary hyperalgesia. To investigate the contribution of A-fiber nociceptors to secondary hyperalgesia the present study assessed if the perception and brain responses elicited by low-intensity intra-epidermal electrical stimulation (IES), a method preferentially activating A{delta}-fiber nociceptors, are increased in the area of secondary hyperalgesia. HFS was delivered to one of the two forearms of seventeen healthy volunteers. Mechanical pinprick stimulation and IES were delivered at both arms before HFS (T0), 20 minutes after HFS (T1) and 45 minutes after HFS (T2). In all participants, HFS induced an increase in pinprick perception at the HFS-treated arm, adjacent to the site of HFS. This increase was significant at both T1 and T2. HFS did not affect the percept elicited by IES, but did enhance the magnitude of the N2 wave of IES-evoked brain potentials, both at T1 and at T2. HFS induced a long-lasting enhancement of the N2 wave elicited by IES in the area of secondary hyperalgesia, indicating that HFS enhances the responsiveness of the central nervous system to nociceptive inputs conveyed by AMH-II nociceptors. However, we found no evidence that HFS affects the perception elicited by IES, which may suggest that AMH-II nociceptors do not contribute to HFS-induced secondary hyperalgesia.

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bioRxiv2017

Characterising the short-term habituation of event-related evoked potentials

Fast-rising sensory events evoke a series of functionally heterogeneous event-related potentials (ERPs). Stimulus repetition at 1 Hz is known to induce a strong habituation of the largest ERP responses, the vertex waves, which are elicited by stimuli regardless of their modality7, provided that they are salient and behaviourally-relevant. In contrast, the effect of stimulus repetition on the earlier sensor)7 components of ERls has been less explored, and the few existing results are inconsistent. To characterize how the different ERP waves habituate over time, we recorded the responses elicited by 60 identical somatosensory stimuli (activating either non-nociceptive A {beta} or nociceptive A5 afferents), delivered at 1 Hz to healthy human participants. We show that the well-described spatiotemporal sequence of lateralised and vertex ERP components elicited by the first stimulus of the series is largely preserved in the smaller-amplitude, habituated response elicited by the last stimuli of the series. We also found that the earlier lateralised sensory waves habituate across the 60 trials following the same decay function of the vertex waves: this decay function is characterised by a large drop at the first stimulus repetition followed by smaller decreases at subsequent repetitions. Interestingly, the same decay functions described the habituation of ERPs elicited by repeated non-nociceptive and nociceptive stimuli. This study provides a neurophysiological characterization of the effect of prolonged and repeated stimulation on the main components of somatosensory ERPs. It also demonstrates that both lateralised waves and vertex waves are obligator}7 components of ERPs elicited by non-nociceptive and nociceptive stimuli.\n\nSignificance statementOur results provide a functional characterization of the decay of the different ERP components when identical somatosensory (nociceptive and non-nociceptive) stimuli are repeated at 1Hz. East-rising stimuli elicit ERPs obligator)7 contributed by both early lateralised components and late vertex components, even when stimulus repetition minimizes stimulus relevance. This challenges the view that lateralised waves are not obligatorily elicited by nociceptive stimuli. Furthermore, the lateralised and vertex waves habituate to stimulus repetition following similar decay functions, which are unlikely explained in terms of fatigue or adaptation of skin receptors.

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