Caractérisation des mécanismes neurophysiologiques qui sous-tendent la préparation de mouvements avec et sans douleur associée : études en stimulation magnétique transcrânienne et mesures comportementales

Introduction : La préparation motrice est un processus complexe, à l’interface entre les aspects cognitifs et moteurs, au cours duquel différentes étapes vont se déployer, permettant de définir les paramètres du mouvement qui sera exécuté par la suite. Lorsqu’un mouvement génère systématiquement de la douleur, notre organisme est capable d’anticiper cette douleur liée au mouvement afin d’établir des stratégies de protection. Il a été montré dans de précédentes études qu’en présence de douleur, des changements spécifiques d’activité musculaire en fonction du rôle agoniste/antagoniste du muscle permettent de protéger le membre douloureux pendant l’exécution du mouvement. Toutefois, les mécanismes neurophysiologiques qui sous-tendent l’anticipation de la douleur pendant la préparation motrice demeurent largement inconnus. L’objectif général de la thèse est de mieux comprendre les mécanismes neurophysiologiques qui sous-tendent la préparation de mouvements avec et sans douleur associée. Méthode : Une revue systématique (étude 1) a été réalisée afin de synthétiser les études qui ont investigué la préparation motrice en mesurant les changements de temps de réaction induits par une stimulation cérébrale non-invasive chez des participants en santé, offrant l’opportunité d’évaluer la contribution causale d’une région corticale lors de la préparation motrice. Puis, la stimulation magnétique transcrânienne (TMS) a été utilisée dans deux études pour mesurer l’excitabilité corticospinale de muscles proximaux du bras lors d’une tâche de pointage de cibles avec indiçage. Dans l’étude 2, les potentiels évoqués moteurs (MEPs) et les mouvements évoqués par la TMS ont été mesurés sur le biceps et le triceps à plusieurs intervalles de temps avant l’exécution de flexions et d’extensions du coude réalisées sans douleur, afin de caractériser les changements d’excitabilité corticospinale associés à la préparation motrice. Dans l’étude 3, des stimulations nociceptives ont été appliquées pendant l’exécution de flexions ou d’extensions auprès de deux groupes de participants et les MEPs ont été mesurés sur le biceps pendant la préparation motrice. Des mesures comportementales (temps de réaction et pics de vitesse) ont également été réalisées afin d’évaluer les phases d’initiation et de réalisation du mouvement. Résultats : Les résultats obtenus dans l’étude 1 supportent l’implication fonctionnelle de cinq régions corticales (le cortex préfrontal dorsolatéral, le cortex pariétal postérieur, l’aire motrice supplémentaire, le cortex pré-moteur dorsal et le cortex moteur primaire), intégrées dans un réseau fronto-pariétal, dans plusieurs composantes de la préparation motrice allant des aspects attentionnels jusqu’aux aspects moteurs. Les résultats de l’étude 2 ont révélé une asymétrie dans la réponse corticospinale entre les muscles fléchisseur et extenseur du coude de même que des différences entre la préparation de mouvements de flexion et d’extension du coude. Les résultats de l’étude 3 ont mis en évidence que pour la direction associée à la douleur, l’excitabilité corticospinale du biceps est supérieure avant une extension (contexte antagoniste) qu’avant une flexion (contexte agoniste). De plus, les participants mettent plus de temps à initier le mouvement associé à la douleur, mais le réalisent ensuite plus vite. Conclusion : Les résultats de la thèse ont permis de révéler le rôle primordial du but de l’acte moteur sur les processus qui opèrent pendant la préparation motrice. En effet, les corrélats corticaux qui sous-tendent la préparation motrice diffèrent selon le mouvement préparé. De plus, la réponse corticospinale des muscles fléchisseur et extenseur du coude varie selon la direction du mouvement préparé et l’intervalle de stimulation au cours de la préparation. Enfin, l’anticipation d’une douleur associée à un mouvement affecte l’excitabilité corticospinale mesurée lors de la préparation motrice. Ces derniers résultats ont par ailleurs confirmé les prédictions de la théorie d’adaptation du contrôle moteur en présence de douleur qui suggère la mise en place de stratégies de protection se reflétant à travers une augmentation de l’excitabilité corticospinale du muscle antagoniste et à l’inverse une diminution du muscle agoniste au mouvement douloureux.Introduction: Motor preparation is a complex process at the interplay between cognitive and motor aspects, during which multiple steps occur and allow to define the parameters of the upcoming movement. When a movement generates pain repeatedly, the central nervous system should eventually be able to anticipate movement-related pain and establish self-protective strategies during motor preparation in order to avoid pain or to minimize its harmful consequences. It has been previously shown that when pain occurs during movement execution, specific changes occur in the muscular activity depending on the role of the agonist/antagonist muscle that protect the painful limb. However, the mechanisms in the origins the effects of pain anticipation during motor preparation remain poorly understood. The main objective of this thesis is to better understand neurophysiological mechanisms that underlie motor preparation with and without associated pain. Methods: A systematic review (study 1) was performed in order to synthetize studies that have investigated motor preparation by measuring changes in reaction time, induced by non-invasive brain stimulation in healthy participants. This offered an opportunity to evaluate the causal contribution of a given cortical region during motor preparation. Then, transcranial magnetic stimulation (TMS) was used in two studies in order to evaluate corticospinal excitability changes in proximal arm muscles during a pre-cued reaching task. In study 2, motor evoked potentials (MEPs) and TMS-evoked movements have been measured in the biceps and the triceps at various time intervals prior to elbow flexion and extension, when executed without pain. This aimed at characterizing corticospinal excitability changes associated with motor preparation. In study 3, nociceptive stimulations were applied during the execution of flexion or extension for two experimental groups and MEPs were measured in the biceps during motor preparation. Behavioral measures (reaction time and peaks of velocity) were also measured to assess the phases of initiation and execution of the movement. Results: Results obtained in study 1 support a functional implication of five cortical regions (dorsolateral prefrontal cortex, posterior parietal cortex, supplementary motor area, dorsal premotor cortex and primary motor cortex), integrated in a fronto-parietal network, in various components of motor preparation ranging from attentional to motor aspects. The results of study 2 reveal an asymmetry in the corticospinal output between flexor and extensor muscles of the elbow as well as differences in the preparation of flexion and elbow extension movements. The results of study 3 show that corticospinal excitability of the biceps is greater before extension (antagonistic context) than before flexion (agonist context) for the direction associated with pain. In addition, participants take longer to initiate the movement associated with pain, but then realize it faster. Conclusion: The results obtained in this thesis have revealed the prominent role of the motor goal on the processes which operate during motor preparation. Indeed, the cortical correlates underlying motor preparation differ according to the type of movement prepared. In addition, corticospinal output for elbow flexor and extensor muscles varies according to the direction of the prepared movement and the stimulation interval during the preparation phase. Finally, pain anticipation affects corticospinal excitability measured during motor preparation. These latest results have also confirmed and extended what the motor control adaptation theory forecast, suggesting the implementation of protective strategies reflected through an increase in the corticospinal excitability of the antagonist muscle and conversely through a decrease of the agonist muscle to the painful movement

xls file data for: "Modulation of corticospinal output in agonist and antagonist proximal arm muscles during motor preparation"

Summary PLOS ONE data : " Modulation of corticospinal output in agonist and antagonist proximal arm muscles during motor preparation " (2017

New insight on the role of late indirect‐wave pathway underlying theta‐burst stimulation‐induced plasticity

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The recruitment of indirect waves within primary motor cortex during motor imagery: A directional transcranial magnetic stimulation study

International audienceMotor imagery (MI) refers to the mental simulation of an action without overt movement. While numerous transcranial magnetic stimulation (TMS) studies provided evidence for a modulation of corticospinal excitability and intracortical inhibition during MI, the neural signature within the primary motor cortex is not clearly established. In the current study, we used directional TMS to probe the modulation of the excitability of early and late indirect waves (I-waves) generating pathways during MI. Corticospinal responses evoked by TMS with posterior–anterior (PA) and anterior–posterior (AP) current flow within the primary motor cortex evoke preferentially early and late I-waves, respectively. Seventeen participants were instructed to stay at rest or to imagine maximal isometric contractions of the right flexor carpi radialis. We demonstrated that the increase of corticospinal excitability during MI is greater with PA than AP orientation. By using paired-pulse stimulations, we confirmed that short-interval intracortical inhibition (SICI) increased during MI in comparison to rest with PA orientation, whereas we found that it decreased with AP orientation. Overall, these results indicate that the pathways recruited by PA and AP orientations that generate early and late I-waves are differentially modulated by MI

The Oscillatory Nature of Movement Initiation

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The recruitment of indirect waves within primary motor cortex during motor imagery: A directional transcranial magnetic stimulation study

International audienceMotor imagery (MI) refers to the mental simulation of an action without overt movement. While numerous transcranial magnetic stimulation (TMS) studies provided evidence for a modulation of corticospinal excitability and intracortical inhibition during MI, the neural signature within the primary motor cortex is not clearly established. In the current study, we used directional TMS to probe the modulation of the excitability of early and late indirect waves (I-waves) generating pathways during MI. Corticospinal responses evoked by TMS with posterior–anterior (PA) and anterior–posterior (AP) current flow within the primary motor cortex evoke preferentially early and late I-waves, respectively. Seventeen participants were instructed to stay at rest or to imagine maximal isometric contractions of the right flexor carpi radialis. We demonstrated that the increase of corticospinal excitability during MI is greater with PA than AP orientation. By using paired-pulse stimulations, we confirmed that short-interval intracortical inhibition (SICI) increased during MI in comparison to rest with PA orientation, whereas we found that it decreased with AP orientation. Overall, these results indicate that the pathways recruited by PA and AP orientations that generate early and late I-waves are differentially modulated by MI

Stimulating the Healthy Brain to Investigate Neural Correlates of Motor Preparation: A Systematic Review

Objective. Noninvasive brain stimulation techniques can be used to selectively increase or decrease the excitability of a cortical region, providing a unique opportunity to assess the causal contribution of that region to the process being assessed. The objective of this paper is to systematically examine studies investigating changes in reaction time induced by noninvasive brain stimulation in healthy participants during movement preparation. Methods. A systematic review of the literature was performed in the PubMed, MEDLINE, EMBASE, PsycINFO, and Web of science databases. A combination of keywords related to motor preparation, associated behavioral outcomes, and noninvasive brain stimulation methods was used. Results. Twenty-seven studies were included, and systematic data extraction and quality assessment were performed. Reaction time results were transformed in standardised mean difference and graphically pooled in forest plots depending on the targeted cortical area and the type of stimulation. Conclusions. Despite methodological heterogeneity among studies, results support a functional implication of five cortical regions (dorsolateral prefrontal cortex, posterior parietal cortex, supplementary motor area, dorsal premotor cortex, and primary motor cortex), integrated into a frontoparietal network, in various components of motor preparation ranging from attentional to motor aspects

Exploring cortico-cortical interactions during action preparation by means of dual-coil transcranial magnetic stimulation: A systematic review

International audienceAction preparation is characterized by a set of complex and distributed processes that occur in multiple brain areas. Interestingly, dual-coil transcranial magnetic stimulation (TMS) is a relevant technique to probe effective connectivity between cortical areas, with a high temporal resolution. In the current systematic review, we aimed at providing a detailed picture of the cortico-cortical interactions underlying action preparation focusing on dualcoil TMS studies. We considered four theoretical processes (impulse control, action selection, movement initiation and action reprogramming) and one task modulator (movement complexity). The main findings highlight 1) the interplay between primary motor cortex (M1) and premotor, prefrontal and parietal cortices during action preparation, 2) the varying (facilitatory or inhibitory) cortico-cortical influence depending on the theoretical processes and the TMS timing, and 3) the key role of the supplementary motor area-M1 interactions that shape the preparation of simple and complex movements. These findings are of particular interest for clinical perspectives, with a need to better characterize functional connectivity deficiency in clinical population with altered action preparation

Influence of Voluntary Contraction Level, Test Stimulus Intensity and Normalization Procedures on the Evaluation of Short-Interval Intracortical Inhibition

Short-interval intracortical inhibition (SICI) represents an inhibitory phenomenon acting at the cortical level. However, SICI estimation is based on the amplitude of a motor-evoked potential (MEP), which depends on the discharge of spinal motoneurones and the generation of compound muscle action potential (M-wave). In this study, we underpin the importance of taking into account the proportion of spinal motoneurones that are activated or not when investigating the SICI of the right flexor carpi radialis (normalization with maximal M-wave (Mmax) and MEPtest, respectively), in 15 healthy subjects. We probed SICI changes according to various MEPtest amplitudes that were modulated actively (four levels of muscle contraction: rest, 10%, 20% and 30% of maximal voluntary contraction (MVC)) and passively (two intensities of test transcranial magnetic stimulation (TMS): 120 and 130% of motor thresholds). When normalized to MEPtest, SICI remained unchanged by stimulation intensity and only decreased at 30% of MVC when compared with rest. However, when normalized to Mmax, we provided the first evidence of a strong individual relationship between SICI and MEPtest, which was ultimately independent from experimental conditions (muscle states and TMS intensities). Under similar experimental conditions, it is thus possible to predict SICI individually from a specific level of corticospinal excitability in healthy subjects

Modulation of corticospinal excitability of trunk muscles in preparation of rapid arm movement

Many studies have described the dynamic modulation of corticospinal excitability of the prime movers during motor preparation. However although anticipatory postural adjustments (APA) are an inherent part of most voluntary movements, investigation of trunk muscle corticospinal excitability during motor preparation has been neglected in the literature. In the present study, the corticospinal excitability of the superficial multifidus (sMF) and rectus abdominis (RA) muscle has been assessed during the preparation of rapid arm flexions and extensions in fifteen participants. A Warning signal informed participants to prepare to move prior to a Go signal. Transcranial magnetic stimulation was applied during baseline and at 6 time intervals before (Delay period) or after (Motor execution period) the Go signal. Results revealed a significant inhibition of the amplitude of sMF motor-evoked potentials in both flexion and extension movements within the Delay period compared to baseline, while no significant modulation was observed for RA. During the Motor Execution period for arm extension, sMF displayed even more inhibition, along with a large and significant facilitation of RA. During the Motor execution period for arm flexion, sMF presented a trend toward larger motor-evoked potential amplitude compared to Delay period. These results suggest the existence of two concurrent mechanisms underlying motor preparation for APA: (i) before the Go signal, a nonspecific inhibitory mechanism for sMF, likely to preclude motor program release; (ii) after the Go signal, a task-specific modulation of corticospinal excitability consistent with the EMG pattern during the early phase of movement