CE37 - Neurosciences intégratives et cognitives

Association de l’imagerie motrice et de la stimulation musculaire pour favoriser la plasticité nerveuse pendant l’immobilisation d’un membre – MIMS

Combinaison de l'imagerie motrice et de la stimulation musculaire (MIMS) pour favoriser la plasticité neuromusculaire pendant l'immobilisation d'un membre

Full or partial body immobilization is used to acutely model muscle disuse. An acute injury often leads to a period of immobilization of the injured limb, resulting in drastic impairments of neural and muscular factors. The present project propose to developp a method that can prevent the important decline in motor function following limb immobilization, both at muscle and nervous levels.

Fighting the motor impairement after limb immobilization

For decades, limiting the several motor impairments that follow limb immobilization has been a major preoccupation for health care systems. The challenge for rehabilitation after an injury lays in the inability to move the involved limb, while it is recommended to start to exercise as soon as possible to prevent severe deconditioning. Several methods were proposed to reduce the force loss induced by prolonged immobilization. For example, neuromuscular electrical stimulation (NMES) that consists of evoking contractions by applying an electrical current over the muscles via surface electrodes, has been shown to provide significant results. While important effects are acknowledged on the nervous system (mainly spinal and corticospinal networks), this method is however mainly dedicated to counteract the muscle impairments (atrophy, decrease of contractile properties, etc.). On the opposite, the use of motor imagery (MI) that consists of asking participants to mentally simulate actions without actually performing them, was also shown to reduce the force loss induced by limb immobilization, but mainly by acting over central component (cerebral network, corticospinal pathway, spinal excitability, etc). <br />The novelty of the present project lies in the combination of those two methods: muscle stimulation and mental training. Subsequently, this project seeks to propose such a combined approach to maximize the effect of rehabilitation programs from central to peripheral aspects. By gathering two fields of research, i.e. neurosciences and physiology, and associating cutting-edge techniques from those fields such as cerebral imaging and muscle ultrasonography, this project intends to draw a clear picture of the whole neuromuscular system deconditioning. Indeed, while many studies focused on either brain function, by using cerebral imagery, or muscle function, by using intracellular physiology techniques (biopsies), to date no study fully investigated the brain-to-muscle system as a whole. Particularly, the involvement of the nervous networks linking both central and peripheral levels, i.e. the medullar network, remains unknown. Accordingly, this project will aim at deciphering corticospinal and spinal networks plasticity during prolonged limb disuse and its adaptation to combined NMES and MI rehabilitation programs. The main objectives of the project are threefold:<br />Objective 1: further analyzing the corticospinal mechanisms of motor impairments following limb immobilization<br />Objective 2: determining the dose-effect response of MI and NMES on the whole neuromuscular system<br />Objective 3: assessing neuromuscular plasticity during combined MI and NMES applied to the immobilized limb.

A set of preliminary experiments is necessary to determine the several parameters to apply in both NMES and MI. Therefore, each modality will firstly be studied separately, followed by a combination of both. The acute effect of NMES or MI will be assessed in order to determine the optimal dose that would be suitable in a chronic approach. Particularly, we will assess neuromuscular fatigue before and after single sessions of NMES differing in current characteristics (current types and duration) and MI (number of repetitions, etc.). Then, the main part of the project is constructed in a randomized design with several trained groups. The population studied will be young and healthy participants. Particular care will be taken to have gender-balanced groups to assess sex differences in the data.

Mental Imagery Task
The participants will first have to answer a questionnaire, the Movement Imagery Questionnaire 3rd version, or MIQ-3f, recently validated in French (Robin et al. 2020), to determine the imagery capacity of each individual. After having actually tested the isometric contraction of the hand with the device (grip force transducer, ADInstruments, Sydney, Australia), the participants will be instructed to imagine squeezing the Hand Grip as tightly as possible and to feel the sensations associated with the contraction, without actually developing any contraction (kinesthetic modality). Each imagined trial, lasting 5 seconds, will be preceded by two oral instructions given by the experimenter: «get ready«, «go«, and interrupted by a «stop« signal. The physiological signals recorded live will determine whether the participant is not involuntarily contracting the muscles. Each imaging session will last 20 minutes and will involve 4 sets of 25 imagined contractions. Each 5-second imagined contraction will be followed by a 5-second rest period. Between each series, one minute of rest will be observed. This type of session, in terms of duration and number of contractions, is what is classically performed in mental training protocols (Paravlic et al. 2018) and recommended in clinical practice (Malouin and Richards 2010).

Neuromuscular stimulation
The NMES will be delivered by a Digitimer stimulator (model DS7AH, Hertfordshire, UK). Two rectangular electrodes (5 x 10 cm, Compex Medical SA) will be placed over forearm muscles’ bellies, more exactly on the brachium (cathode) and on the motor point (anode), which will be searched by means of a pen electrode to locate the motor point. The stimulation intensity will be adjusted to obtain an initial force level equal to 20% of the maximum voluntary force. Subjects will be asked to relax (control of forearm muscles’ activity by electromyography) during the contractions in order to avoid from any contribution of the voluntary command. Force will be recorded continuously during stimulation.

First preliminary study
In the first phase of the project, a study was conducted to investigate the neuromuscular and cardiovascular responses to a motor imagery (MI) session, performed under different conditions. Indeed, it is recognized that the context in which MI is performed can favorably or unfavorably limit its effects. Here, the question was whether the MI of leg muscle contractions should be performed standing or sitting. The standing position has the advantage of pre-activating the leg muscles unconsciously (the standing posture being managed involuntarily), making it easy to perform a mental task. Thanks to the help of partners who took part punctually in this protocol for the needs of the study, we were able to quickly set up this protocol. Indeed, for the needs of the study, we worked with researchers of the laboratory EA3920 «PRONOSTICAL MARKERS AND REGULATORY FACTORS OF CARDIAC AND VASCULAR PATHOLOGIES«, of the University of Franche-Comté, who carried out all the cardiovascular and metabolic analysis. The members of the MIMS project, such as the principal investigator (S. GROSPRETRE), Philippe GIMENEZ and Dr. Uros MARUSIC from Slovenia, specialist in the analysis of the effects of mental imagery and posture, have been involved since this first study. A group of healthy subjects was recruited to participate in two MI sessions in the laboratory, one sitting and one standing. We showed that in standing condition, the effects of MI were exacerbated on the neuromuscular system of the lower limbs, but also on the autonomic nervous system (heart rate, O2 gas exchange, etc). Thus, the presence of muscular pre-activation (such as that observed in simple standing posture), seems to exacerbate the effects of MI, not only on the motor system, but also on the cardiovascular system. This protocol could be initiated quickly at the launch of the ANR MIMS project because the required material was already available in the laboratory and the requests for ethics committee had been made upstream. This work was published in the journal FRONTIERS IN PHYSIOLOGY (Grosprêtre et al., 2021, Front Physiol, 12:762452. doi: 10.3389/fphys.2021.762452.). The outcome of this study is encouraging for the continuation of the project, as performing standing MI is not always possible if a limb is immobilized. Thus, in the continuation of the project, the muscular preactivation during the MI will be materialized by the electric muscular stimulation (NMES). This type of ergogenic stimulation, which represents an unconscious muscular activation as could be the maintenance of the standing posture, will be our model for the rest of the project.

The MIMS project will help me to put a first step in the clinical world, to progressively being able to work on some populations of patients. The methods implemented in the present projects would then be tested in real condition with patients with an immobilized limb, and in the future with other frailer populations such as post-stroke patients. My personal objective of this project is to strengthen and reinforce the relationships I had in past projects (during postdoctoral training), as well as to gather scientists from different scientific fields (neuroscience to muscle physiology) as well as from different practical field (from sports scientists to clinicians) and countries (France, Switzerland, Slovenia, USA). The logical continuation of this project is to extend the team by including other scientists and other countries to seek from international funding’s (European Research Council or Interreg France Switzerland funding). Incrementally, the success of the project should help in expanding the team to other fields, such as space and microgravity deconditioning effects. The two master’s degree students recruited in the present project would then be given the opportunity to pursue a PhD in my laboratory in the frame of other financial supports, in line with the perspective that the MIMS project will offer. The international collaborations established during the project would help to propel the PhD student hired for the present project to find a postdoctoral contract of quality in a foreign country.

1. Grosprêtre, S., Marusic, U., Gimenez, P., Ennequin, G., Mourot, L., & Isacco, L. (2021). Stand Up to Excite the Spine: Neuromuscular, Autonomic, and Cardiometabolic Responses During Motor Imagery in Standing vs. Sitting Posture. Frontiers in Physiology, 12(November), 1–19. doi.org/10.3389/fphys.2021.762452

Il est admis que le manque d'activité physique entraîne une diminution importante de la fonction motrice. L'immobilisation complète ou partielle du corps est souvent utilisée pour modéliser cette perte de fonction musculaire. Une blessure conduit souvent à une période d'immobilisation du membre blessé, ce qui entraîne une altération drastique des facteurs neuraux et musculaires. Depuis des décennies, la limitation des différentes déficiences motrices qui suivent l'immobilisation d'un ou de plusieurs membres est une préoccupation majeure des systèmes de santé. Le défi de la réadaptation après une blessure réside dans l'incapacité à bouger le membre concerné, alors qu'il est recommandé de commencer à faire de l'exercice dès que possible pour éviter un déconditionnement sévère. Plusieurs méthodes sont alors possibles. Par exemple, la stimulation électrique neuromusculaire (NMES) qui consiste à provoquer des contractions en appliquant un courant électrique sur les muscles via des électrodes de surface, a montré des résultats significatifs. Si des effets importants sont reconnus sur le système nerveux (principalement les réseaux médullaires et corticospinaux), cette méthode est cependant principalement dédiée à contrer les déficiences musculaires (atrophie, diminution des propriétés contractiles, etc.). À l'inverse, l'utilisation de l'imagerie motrice (IM) qui consiste à demander aux participants de simuler mentalement des actions sans les réaliser réellement, s'est également avérée efficace pour réduire la perte de force induite par l'immobilisation des membres, mais principalement en agissant sur la composante centrale (réseau cérébral, voie corticospinale, excitabilité de la colonne vertébrale, etc).
La nouveauté du présent projet réside dans la combinaison de ces deux méthodes : la stimulation musculaire et l'entraînement mental. En regroupant deux domaines de recherche, à savoir les neurosciences et la physiologie, et en associant des techniques de pointe issues de ces domaines, telles que l'imagerie cérébrale et l'échographie musculaire, ce projet vise à dresser un tableau clair de l'ensemble du déconditionnement du système neuromusculaire. En effet, si de nombreuses études ont porté soit sur la fonction cérébrale, en utilisant l'imagerie cérébrale, soit sur la fonction musculaire, en utilisant des techniques de physiologie intracellulaire (biopsies), à ce jour, aucune étude n'a étudié de manière approfondie le système cerveau-muscle dans son ensemble. En particulier, l'implication des réseaux nerveux reliant les niveaux central et périphérique, c'est-à-dire le réseau médullaire, reste inconnue. En conséquence, ce projet visera à déchiffrer la plasticité des réseaux corticospinaux et spinaux lors de l'immobilisation prolongée d'un membre et son adaptation à des programmes de réadaptation combinés de NMES et d'IM.
Ce projet rassemble des scientifiques de France, de Suisse, des États-Unis et de Slovénie ainsi que de multiples domaines de recherche (cognition, neurophysiologie, physiologie). La durée du projet est prévue à 42 mois avec l'embauche d'un doctorant et de deux masters. Au-delà de l'aspect scientifique, ce projet est avant tout un moyen d'améliorer les premières phases des programmes de réhabilitation. Une partie non négligeable du projet est donc consacrée à la diffusion de ces travaux auprès d'un large public. Outre les congrès scientifiques destinés à la communauté scientifique, la diffusion de nos résultats auprès des cliniciens se fera par l'organisation d'ateliers de formation, d'abord pour les hôpitaux locaux puis au niveau national si le succès escompté est atteint. Enfin, une attention particulière sera accordée à l'élaboration d'un programme de communication durable à l'intention du public le plus large (c'est-à-dire le grand public), en mettant en place un site web avec de courts tutoriels sur différents supports (vidéos, notes explicatives, etc.).

Coordinateur du projet

Monsieur Sidney Grosprêtre (CULTURE, SPORT, SANTÉ, SOCIÉTÉ)

L'auteur de ce résumé est le coordinateur du projet, qui est responsable du contenu de ce résumé. L'ANR décline par conséquent toute responsabilité quant à son contenu.



Aide de l'ANR 181 375 euros
Début et durée du projet scientifique : novembre 2020 - 42 Mois

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