AIM The aim of this study was to identify the immediate effects on cortical excitability and grip control of a short intervention of EMG-triggered neuromuscular electrical stimulation, compared to voluntary activation of the finger flexor muscles, in people with chronic stroke. STUDY DESIGN This experimental study used a within-subject design with experimental and control interventions. PARTICIPANTS Fifteen people with chronic stroke participated in the study. INTERVENTION Participants performed a simple force tracking task with or without EMG-triggered neuromuscular electrical stimulation of the finger flexor muscles. MAIN OUTCOME MEASURES Cortical excitability was measured by single and paired-pulse transcranial magnetic stimulation. Multi-digit grip control accuracy was measured during ramp and sine wave force tracking tasks. Maximal grip strength was measured before and after each intervention to monitor muscle fatigue. RESULTS No significant increases in cortico-motor excitability were found. Intracortical inhibition significantly increased following the EMG-triggered neuromuscular electrical stimulation intervention immediately post-intervention (t = 2.466, p = .036), and at 10 minutes post-intervention (t = 2.45, p = .04). Accuracy during one component of the force tracking tasks significantly improved (F(1, 14) = 4.701, p = .048), following both EMG-triggered neuromuscular electrical stimulation and voluntary activation interventions. Maximal grip strength reduced significantly following both interventions, after the assessment of cortical excitability (F(1, 8) = 9.197, p = .16), and grip control (F(1, 14) = 9.026, p = .009). CONCLUSIONS EMG-triggered neuromuscular electrical stimulation during short duration force tracking training does not increase cortical excitability in participants with chronic stroke. Short duration force tracking training both with and without EMG-triggered neuromuscular electrical stimulation leads to improvements in training-specific aspects of grip control in people with chronic stroke.

AIM The aim of this study was to identify the immediate effects on cortical excitability and grip control of a short intervention of EMG-triggered neuromuscular electrical stimulation, compared to voluntary activation of the finger flexor muscles, in people with chronic stroke. STUDY DESIGN This experimental study used a within-subject design with experimental and control interventions. PARTICIPANTS Fifteen people with chronic stroke participated in the study. INTERVENTION Participants performed a simple force tracking task with or without EMG-triggered neuromuscular electrical stimulation of the finger flexor muscles. MAIN OUTCOME MEASURES Cortical excitability was measured by single and paired-pulse transcranial magnetic stimulation. Multi-digit grip control accuracy was measured during ramp and sine wave force tracking tasks. Maximal grip strength was measured before and after each intervention to monitor muscle fatigue. RESULTS No significant increases in cortico-motor excitability were found. Intracortical inhibition significantly increased following the EMG-triggered neuromuscular electrical stimulation intervention immediately post-intervention (t = 2.466, p = .036), and at 10 minutes post-intervention (t = 2.45, p = .04). Accuracy during one component of the force tracking tasks significantly improved (F(1, 14) = 4.701, p = .048), following both EMG-triggered neuromuscular electrical stimulation and voluntary activation interventions. Maximal grip strength reduced significantly following both interventions, after the assessment of cortical excitability (F(1, 8) = 9.197, p = .16), and grip control (F(1, 14) = 9.026, p = .009). CONCLUSIONS EMG-triggered neuromuscular electrical stimulation during short duration force tracking training does not increase cortical excitability in participants with chronic stroke. Short duration force tracking training both with and without EMG-triggered neuromuscular electrical stimulation leads to improvements in training-specific aspects of grip control in people with chronic stroke.

The human central nervous system (CNS) is capable of significant architectural and physiological reorganization in response to environmental stimuli. Novel sensorimotor experiences stimulate neuronal networks to modify their intrinsic excitability and spatial connectivity within and between CNS structures. Early learning-induced adaptations in the primary motor cortex are thought to serve as a priming stimulus for long term CNS reorganization underlying long-lasting changes in motor skill. Recent animal and human studies suggest that whole body exercise and core temperature elevation as systemic stressors also recruit activity-dependent processes that prime the motor cortex, cerebellum, and hippocampus to process sensorimotor stimuli from the environment, enhancing overall CNS learning and performance. A primary goal of rehabilitation specialists is to evaluate and design activity-based intervention strategies that induce or enhance beneficial neuroplastic processes across the lifespan. As such, an investgation of the influence of physical, non-pharmacological interventions on cortical excitability, motor learning, and cognitive function provide the central theme of this dissertation. The first study investigated the effects of a visually-guided motor learning task on motor cortex excitability at rest and during voluntary activation measured via transcranical magnetic stimulation (TMS). Motor learning significantly increased resting cortical excitability that was not accompanied by changes in excitability as a function of voluntary muscle activation. The cortical silent period, a measure of inhibition, increased after learning and was associated with the magnitude of learning at low activation. These findings suggest that separate excitatory and inhibitory mechanisms may influence motor output as a function of learning success. The following studies investigated the influence of systemic whole-body thermal stress on motor cortex excitability, motor learning and cognitive performance. We established the reliability of a novel TMS cortical mapping procedure to study neurophysiological responses after whole-body heat stress. Heat stress significantly potentiated motor cortex excitability, though acute motor learning and cognitive test performance did not differ between subjects receiving heat stress and control subjects. Future research is needed to delineate the potential of whole body heat stress as a therapeutic modality to influence central nervous system plasticity and performance.

Mechanical loading can modulate tissue plasticity and has potential applications in rehabilitation science and regenerative medicine. To safely and effectively introduce mechanical loads to human cells, tissues, and the entire body, we need to understand the optimal loading environment to promote growth and health. The purpose of this research was 1) to validate a limb vibration and compression system; 2) to determine the effect of limb vibration on neural excitability measured by sub-threshold TMS-conditioned H-reflexes and supra-threshold TMS; 3) to determine changes in center of pressure, muscle activity, and kinematics during a postural task following limb vibration; 4) to determine the effect of vibration on accuracy and long latency responses during a weight bearing visuomotor task. The major findings of this research are 1) the mechanical system presented in the manuscript can deliver limb vibration and compression reliably, accurate, and safely to human tissue; 2) sub-threshold cortical stimulation reduces the vibration-induced presynaptic inhibition of the H-reflex. This reduction cannot be attributed to an increase in cortical excitability during limb vibration because the MEP remains unchanged with limb vibration; 3) limb vibration altered the soleus and tibialis EMG activity during a postural control task. The vibration-induced increase in muscle activity was associated with unchanged center of pressure variability and reduced center of pressure complexity; 4) healthy individuals were able to accommodate extraneous afferent information due to the vibration interventions They maintained similar levels of accuracy of a visuomotor tracking task and unchanged long latency responses during an unexpected perturbation.

Although inhibitory cortical interneurons play a critical role in regulating brain excitability and function, the effects of stroke on these neurons is poorly understood. In particular, interneurons expressing vasoactive intestinal peptide (VIP) specialize in inhibiting other classes of inhibitory neurons, and thus serve to modulate cortical sensory processing. To understand how stroke affects this circuit, we imaged VIP neuron responses (using GCaMP6s) to low and high intensity forepaw stimulation, both before and after focal stroke in somatosensory cortex. Our data show that the fraction of forelimb responsive VIP interneurons and their response fidelity (defined as a cell’s number of responsive trials out of eight trials at a certain imaging week) was significantly reduced in the first week after stroke, especially when lower intensity forepaw stimulation was employed. The loss of responsiveness was most evident in highly active VIP neurons (defined by their level of responsiveness before stroke), whereas less active neurons were minimally affected. Of note, a small fraction of VIP neurons that were minimally active before stroke, became responsive afterwards suggesting that stroke may unmask sensory responses in some neurons. Although VIP responses to forepaw stimulation generally improved from 2-5 weeks recovery, the variance in response fidelity after stroke was comparatively high and therefore less predictable than that observed before stroke. Lastly, stroke related changes in response properties were restricted to within 400μm of the infarct border. These findings reveal the dynamic and resilient nature of VIP neurons and suggest that a sub-population of these cells are more apt to lose sensory responsiveness during the initial phase of stroke, whereas some minimally responsive cells are progressively recruited into the forelimb sensory circuit. Furthermore, stroke appears to disrupt the predictability of sensory-evoked responses in these cortical interneurons which could have important consequences for sensory perception. / Graduate / 2021-01-13

No description available.

Notre travail a porté : 1) sur l'étude des modifications d'excitabilité corticale au cours du traitement des poussées de sclérose en plaques (SEP) et de l'évolution naturelle des formes progressives de SEP ; 2) sur la caractérisation du tremblement d'action, fréquemment observé dans le cadre de cette maladie et qui constitue une importante source de handicap. Ceci a conduit à la réalisation de 5 études. La première étude a démontré que l'amélioration rapide des performances motrices observées à la suite du traitement de poussées de SEP par une corticothérapie administrée en flash quotidien sur plusieurs jours, s'accompagnait de modifications significatives d'excitabilité corticale étudiée par stimulation magnétique transcrânienne. Ces modifications portaient sur la balance d'influences GABAergiques et glutamatergiques au sein du cortex moteur. Cette augmentation d'excitabilité survient bien avant toute possibilité de remyélinisation ou de régénérescence axonale et constitue donc une amélioration fonctionnelle induite par le traitement. Dans la deuxième étude, différents paramètres d'excitabilité corticale ont été suivis sur un an chez des patients présentant une forme progressive de SEP, traitée ou non traitée. Cette étude a mis en évidence une diminution de l'inhibition intracorticale et une augmentation du seuil moteur au repos chez les patients non traités, accompagnant une augmentation des scores cliniques de handicap. En revanche, les patients traités restaient stables, aussi bien sur le plan neurophysiologique que clinique. Ces résultats montrent que l'évolution de la SEP progressive est associée à une altération globale et évolutive de l'excitabilité du cortex moteur, portant aussi bien sur les neurones pyramidaux que sur les circuits de contrôle inhibiteur, probablement liée à l'aggravation de la perte neuronale au fil du temps. Nos résultats montrent également que différents types de traitement immunomodulateur peuvent arrêter ce cours évolutif. Dans une troisième étude, nous avons caractérisé l'existence d'un tremblement chez 32 patients atteints de SEP au moyen d'enregistrements électromyographiques et accélérométriques réalisés au membre supérieur. Ces enregistrements n'ont permis de confirmer l'existence d'un véritable tremblement que chez un seul patient. L'étude neurophysiologique concomitante de circuits de contrôle cérébelleux et protubérantiels a permis de montrer que la plupart des aspects cliniques de tremblement dans la SEP ne révélait en fait qu'un pseudo-tremblement lié en grande partie à des dysfonctions cérébelleuses. Nos deux dernières études ont permis de préciser ce résultat, au moyen d'une analyse du signal électromyographique et accélérométrique par décomposition modale empirique associée à une transformée de Hilbert-Huang. Cette méthode d'analyse apparaît valide et performante pour caractériser les tremblements et pseudo-tremblements survenant dans la SEP et les distinguer d'autres types de tremblement, comme le tremblement essentiel. / Our work focused on: 1) the study of cortical excitability changes in the treatment of multiple sclerosis (MS) relapses and the natural history of progressive forms of MS; 2) the characterization of action tremor, which is frequently observed in the course of the disease and is a major source of disability. This has led to the realization of five studies. The first study demonstrated that a rapid improvement in motor performance can be observed following treatment of MS relapses by intravenous corticosteroids administered daily over several days, accompanied by significant changes in cortical excitability parameters studied by transcranial magnetic stimulation techniques. These changes focused on the balance between GABAergic and glutamatergic influences in the motor cortex. An increase in cortical excitability occurs well before any possibility of remyelination or axonal regeneration, demonstrating a functional improvement induced by the treatment. In the second study, different parameters of cortical excitability were followed over one year in patients with progressive MS, treated or untreated. This study showed a decrease of intracortical inhibition and increased motor threshold at rest in untreated patients, accompanying a worsening of clinical disability scores. In contrast, treated patients remained stable, both on clinical and neurophysiological parameters. These results show that the evolution of progressive MS is associated with a global and progressive impairment of motor cortex excitability, concerning both pyramidal neurons on inhibitory control circuits, probably due to the progression of cortical neuronal loss over time. Our results also showed that different types of immunomodulatory therapy can stop this evolutionary course. In a third study, we characterized the existence of action tremor in 32 MS patients using electromyographic and accelerometer recordings in the upper limb. These recordings confirmed the existence of a real tremor in only one patient. Concomitant neurophysiological study of cerebellar and pontine circuits of control showed that most of the clinical aspects of tremor in MS in fact revealed a pseudo-tremor largely due to cerebellar dysfunctions. Our last two studies have clarified this result by means of an analysis of the electromyographic and accelerometer signal using empirical mode decomposition associated with Hilbert-Huang transform. This method of analysis appears valid and effective to characterize tremor or pseudo-tremor occurring in MS patients and to distinguish them from other types of tremor, such as essential tremor.

Movement training modulates the excitability in several cortical and subcortical areas. Compared to training with a single arm, movement training with both arms yields a greater increase in motor related cortical regions. A short-term session of bimanual training (BMT) enhances cortical activity of motor preparation and execution areas in both hemispheres. The underlying neural mechanisms for this increased activation with BMT are unclear, but may involve interhemispheric connections between homologous primary motor cortex (M1) representations and input from motor preparatory areas (i.e. dorsal premotor cortex (PMd)). Also, it is unclear how selective up-regulation or down-regulation of specific motor-related areas may contribute to changes in M1 excitability when combined with BMT. The work in this thesis investigated modulation of M1 excitability in terms of in-phase versus anti-phase BMT (Study #1), potentially up-regulating the left dorsal premotor cortex (lPMd) via iTBS before BMT (Study #2), theoretically down-regulating contralateral (right) M1 homologous representation before BMT (Study #3), and finally the potential intracortical and interhemispheric cortical adaptations in M1 bilaterally due to the same interventions as Study #2 (Study #4). For Study #1, it was hypothesized that in-phase BMT would lead to an increased excitability in M1. For Studies #2-4, it was hypothesized that modulation of motor-related areas would cause an increase in the excitability of left M1, and this modulation would be greater when combined with BMT. Study #1 found that in-phase, and not anti-phase BMT, lead to increase M1 excitability. Study #2 found that iTBS to lPMd followed by BMT caused a unique increase in M1 excitability, in terms of increased spatial extent and global MEP amplitude. Study #3 found that the combination of cTBS to right M1 with BMT caused greater excitability enhancements than either intervention alone. Finally, Study #4 found distinct modulations of cortical excitability within and across M1 bilaterally due to BMT, iTBS to lPMd and the combination of these interventions that involved long-interval inhibitory circuitry asymmetrically. Overall, this current work found that the modulation of remote cortical areas to M1 (i.e. lPMd and contralateral M1) in combination with movement training led to unique, and at times greater, excitability enhancements of M1 which could be advantageous in enhancing short-term plasticity in damaged M1.

No description available.

Résumé : L’interaction entre la douleur et le système moteur est bien connue en clinique et en réadaptation. Il est sans surprise que la douleur est un phénomène considérablement invalidant, affectant la qualité de vie de ceux et celles qui en souffrent. Toutefois, les bases neurophysiologiques qui sous-tendent cette interaction demeurent, encore aujourd’hui, mal comprises. Le but de la présente étude était de mieux comprendre les mécanismes corticaux impliqués dans l’interaction entre la douleur et le système moteur. Pour ce faire, une douleur expérimentale a été induite à l’aide d’une crème à base de capsaïcine au niveau de l’avant-bras gauche des participants. L'effet de la douleur sur la force des projections corticospinales ainsi que sur l’activité cérébrale a été mesuré à l’aide de la stimulation magnétique transcrânienne (TMS) et de l’électroencéphalographie (EEG), respectivement. L’analyse des données EEG a permis de révéler qu'en présence de douleur aiguë, il y a une augmentation de l’activité cérébrale au niveau du cuneus central (fréquence têta), du cortex dorsolatéral préfrontal gauche (fréquence alpha) ainsi que du cuneus gauche et de l'insula droite (toutes deux fréquence bêta), lorsque comparée à la condition initiale (sans douleur). Également, les analyses démontrent une augmentation de l'activité du cortex moteur primaire droit en présence de douleur, mais seulement chez les participants qui présentaient simultanément une diminution de leur force de projections corticales (mesurée avec la TMS t=4,45, p<0,05). Ces participants ont également montré une plus grande connectivité entre M1 et le cuneus que les participants dont la douleur n’a pas affecté la force des projections corticospinales (t=3,58, p<0,05). Ces résultats suggèrent qu’une douleur expérimentale induit, chez certains individus, une altération au niveau des forces de projections corticomotrices. Les connexions entre M1 et le cuneus seraient possiblement impliquées dans la survenue de ces changements corticomoteurs. / Abstract : The interaction between pain and the motor system is well-known in clinic. For instance, it is well documented that pain significantly complicates the rehabilitation of the patients. The aim of the present study was to better understand the cortical mechanisms underlying the interaction between pain and the motor system. Nineteen healthy adults participated in the study. The effect of pain (induced with a capsaicin cream) on brain activity and on the corticomotor system was assessed with electroencephalography (EEG) and transcranial magnetic stimulation (TMS), respectively. For EEG, 15 non-overlapping, 2-seconds artifacts were randomly selected for each participant. Intracranial source current density and functional connectivity was determined using sLORETA software. When participants experienced experimentally-induced inflammatory pain, their resting state brain activity increased significantly in the central cuneus (theta frequency), left dorsolateral prefrontal cortex (alpha frequency), and both left cuneus and right insula (beta frequency; all ts >3.66; all ps<0.01). A pain-evoked increase in the right primary motor cortex (M1) activity was also observed (beta frequency), but only among participants who showed a simultaneous reduction in the strength of the corticospinal projections (quantified using the recruitment curves obtained with TMS; t=4.45, p<0.05). These participants further showed greater beta motor-cuneus connectivity than participants for whom pain did not affect M1 somatotopy (t=3.58, p<0.05). These results suggest that pain-evoked increases in M1 beta power are intimately tied to alterations in corticospinal system. Moreover, we provide evidence that beta motor-cuneus connectivity is related to the corticomotor alterations induced by pain.