Evaluation of cortico-spinal excitability of the upper limb deficit after stroke : the contribution of transcranial magnetic stimulation

Le déficit moteur du membre supérieur résultant d’un accident vasculaire cérébral (AVC) limite certaines activités fonctionnelles, notamment la préhension. L’objectif de cette thèse est de déterminer quels paramètres acquis en Stimulation Magnétique Transcrânienne (TMS) permettent de mieux comprendre les mécanismes impliqués dans la parésie du membre supérieur (MS) après AVC. Les deux études reposent sur une cohorte de 40 patients présentant un déficit moteur du MS suite à un AVC ischémique en phases subaiguë et chronique. La première étude vise à déterminer les corrélations existant entre les différents paramètres électrophysiologiques extraits de la courbe de recrutement qui reflètent la fonction de la voie cortico-spinale. La mesure de l’amplitude des potentiels évoqués moteurs (PEM) recueillis à une seule intensité de stimulation semble suffisante pour appréhender la fonction de cette voie motrice chez des sujets sains et chez des patients victimes d’un AVC. La seconde étude vise à identifier les facteurs explicatifs de la parésie du MS persistant après un AVC à partir d’une évaluation multimodale regroupant des données cliniques, des données acquises en TMS et des données d’imagerie structurelle et fonctionnelle. Les résultats montrent que le seuil moteur est la seule variable indépendante retenue et explique environ 50% de la variance de la fonction motrice. Les travaux présentés dans cette thèse soulignent l’importance de l’acquisition de deux paramètres couramment recueillis en TMS : l’amplitude des PEM et le seuil moteur. Davantage que l’intégrité structurelle du faisceau cortico-spinal, le seuil moteur explique la fonction motrice résiduelle du MS.Upper limb motor deficits resulting from a stroke can limit certain activities of daily living, notably grasping movements. The goal of this thesis is to determine which parameters acquired with Transcranial Magnetic Stimulation (TMS) best unravel the mechanisms implicated in upper limb (UL) motor deficits after stroke. The two studies presented in this doctoral work are based on a cohort of 40 patients suffering from UL motor deficits following ischemic stroke in the subacute and chronic phases. The first study aims to determine the correlations between different electrophysiological variables extracted from input-output curves and other parameters reflecting the function of the corticospinal tract (CST). The amplitude of motor evoked potentials (MEPs) measured at a single intensity seem sufficient to capture the function of the CST both in healthy subjects and stroke patients. The second study aims to identify factors capable of explaining the severity of UL deficits following stroke using a multimodal evaluation comprising clinical and TMS data as well as structural and functional neuroimaging data. The results show that the resting motor threshold (rMT) independently explains around 50% of the variance in motor function. This thesis highlights the importance of two parameters commonly acquired in TMS: the amplitude of MEPs and the rMT. An important result of this work is the rMT’s ability to independently explain residual UL motor function beyond the structural integrity of the CST. The rMT may therefore be used as a stratification factor or as a secondary efficacy outcome marker in interventional studies aiming to optimize post-stroke motor recovery

Évaluation de l’excitabilité cortico-spinale dans le déficit moteur du membre supérieur après AVC : l’apport de la stimulation magnétique transcrânienne

Upper limb motor deficits resulting from a stroke can limit certain activities of daily living, notably grasping movements. The goal of this thesis is to determine which parameters acquired with Transcranial Magnetic Stimulation (TMS) best unravel the mechanisms implicated in upper limb (UL) motor deficits after stroke. The two studies presented in this doctoral work are based on a cohort of 40 patients suffering from UL motor deficits following ischemic stroke in the subacute and chronic phases. The first study aims to determine the correlations between different electrophysiological variables extracted from input-output curves and other parameters reflecting the function of the corticospinal tract (CST). The amplitude of motor evoked potentials (MEPs) measured at a single intensity seem sufficient to capture the function of the CST both in healthy subjects and stroke patients. The second study aims to identify factors capable of explaining the severity of UL deficits following stroke using a multimodal evaluation comprising clinical and TMS data as well as structural and functional neuroimaging data. The results show that the resting motor threshold (rMT) independently explains around 50% of the variance in motor function. This thesis highlights the importance of two parameters commonly acquired in TMS: the amplitude of MEPs and the rMT. An important result of this work is the rMT’s ability to independently explain residual UL motor function beyond the structural integrity of the CST. The rMT may therefore be used as a stratification factor or as a secondary efficacy outcome marker in interventional studies aiming to optimize post-stroke motor recovery.Le déficit moteur du membre supérieur résultant d’un accident vasculaire cérébral (AVC) limite certaines activités fonctionnelles, notamment la préhension. L’objectif de cette thèse est de déterminer quels paramètres acquis en Stimulation Magnétique Transcrânienne (TMS) permettent de mieux comprendre les mécanismes impliqués dans la parésie du membre supérieur (MS) après AVC. Les deux études reposent sur une cohorte de 40 patients présentant un déficit moteur du MS suite à un AVC ischémique en phases subaiguë et chronique. La première étude vise à déterminer les corrélations existant entre les différents paramètres électrophysiologiques extraits de la courbe de recrutement qui reflètent la fonction de la voie cortico-spinale. La mesure de l’amplitude des potentiels évoqués moteurs (PEM) recueillis à une seule intensité de stimulation semble suffisante pour appréhender la fonction de cette voie motrice chez des sujets sains et chez des patients victimes d’un AVC. La seconde étude vise à identifier les facteurs explicatifs de la parésie du MS persistant après un AVC à partir d’une évaluation multimodale regroupant des données cliniques, des données acquises en TMS et des données d’imagerie structurelle et fonctionnelle. Les résultats montrent que le seuil moteur est la seule variable indépendante retenue et explique environ 50% de la variance de la fonction motrice. Les travaux présentés dans cette thèse soulignent l’importance de l’acquisition de deux paramètres couramment recueillis en TMS : l’amplitude des PEM et le seuil moteur. Davantage que l’intégrité structurelle du faisceau cortico-spinal, le seuil moteur explique la fonction motrice résiduelle du MS

Cerebello-Cortical Differences in Effective Connectivity of the Dominant and Non-dominant Hand during a Visuomotor Paradigm of Grip Force Control

International audienceStructural and functional differences are known to exist within the cortical sensorimotor networks with respect to the dominant vs. non-dominant hand. Similarly, the cerebellum, a key structure in the sensorimotor network with its cerebello-cortical connections, has been reported to respond differently when using the dominant vs. non-dominant hand. Several groups have already investigated causal interactions during diverse motor paradigms using effective connectivity but few have studied the larger visuomotor network, including key structures such as the parietal cortex and the cerebellum, with both hands. Moreover, the effect of force level on such interactions is still unclear. We therefore sought to determine the hemispheric asymmetries in the cerebello-cortical sensorimotor network in right-handers at two force levels (5% and 10% maximum voluntary contraction) for both hands. Cerebello-cortical modulations were investigated in 28 healthy, right-handed volunteers by determining the effective connectivity during a visuomotor task at two force levels under fMRI. A network was built consisting of the left and right primary motor (M1), ventral premotor (PMv) and posterior parietal cortices (PPC), in addition to the supplementary motor area (SMA), and the ipsilateral cerebellum (Cer) to the hand performing the motor task. Task performance (precision of isometric grip force tracking) did not differ between hands, nor did task-related activations in the sensorimotor areas apart from the contralateral primary motor cortex. However, during visuomotor control of the non-dominant hand, connectivity analysis revealed causal modulations between (i) the ipsilateral cerebellum and SMA, and (ii) the ipsilatearl cerebellum and contralateral PPC, which was not the case when using the dominant hand. These cerebello-cortical modulations for the non-dominant hand were Moulton et al. Cerebello-Cortical Effective Connectivity in Right-Handers more present at the higher of the two force levels. We conclude that precision force generation executed with the non-dominant hand, compared to the dominant hand, may require enhanced cerebello-cortical interaction to ensure equivalent left-right task performance

Closed-Loop Control of the Centre of Pressure in Post-Stroke Patients With Balance Impairments

International audienceWhen a lightly touched surface is moved according to a closed-loop control law, it has been shown in young adults that the Centre of Pressure (CoP) can be displaced in a controllable way without the conscious cooperation of participants. In this closed-loop paradigm, the surface velocity was continuously adjusted according to the CoP position. Since the closed-loop control of the CoP does not require the participant's voluntary cooperation, it could be of interest for the development of innovative biofeedback devices in balance rehabilitation. Before anticipating the implementation of this closed-loop control paradigm with patients, it is necessary to establish its effects on people suffering from balance impairments. The aim of this study was to assess the effects of this CoP closed-loop control in post-stroke (PS) patients and aged-matched healthy controls. Efficacy of the closed-loop control for driving the patients' CoP was assessed using the saturation time and two scores computing the error between the predefined and the current CoP trajectories. 68% and 83% of the trials were considered as successful in patients and controls, respectively. The global tracking error of the closed-loop score was similar between the two groups. However, when examining the real CoP displacement from the starting position to the desired one, PS patients responded to the closed-loop control to a lesser extent than controls. These results, obtained in the same conditions for healthy and post-stroke individuals could be improved by tuning the closed-loop parameters according to individual characteristics. This study paves the road towards the development of involuntary/automatic biofeedback techniques in more ecological conditions

Redundancy Among Parameters Describing the Input-Output Relation of Motor Evoked Potentials in Healthy Subjects and Stroke Patients

International audienceBackground: Transcranial magnetic stimulation (TMS) is widely used to probe corticospinal excitability through Motor Evoked Potential (MEP) amplitude measurements. The input-output (I/O) curve is a sigmoid-shaped relation between the MEP amplitude at incremented TMS intensities. The aim of this study was to examine the relationships between seven parameters derived from the sigmoid function.Methods: Principal Component Analysis and Spearman's rank correlation matrices were used to determine if the seven I/O curve parameters capture similar or, conversely, different aspects of the corticospinal excitability in 24 healthy subjects and 40 stroke survivors with a hand motor impairment.Results: Maximum amplitude (MEPmax), peak slope, area under the I/O curve (AUC), and MEP amplitude recorded at 140% of the resting motor threshold showed strong linear relationships with each other (ρ > 0.72, p < 0.001). Results were found to be similar in healthy subjects and in both hemispheres of stroke patients. Our results did not support an added benefit of sampling entire I/O curves in both healthy subjects and stroke patients, with the exception of S50, the stimulus intensity needed to obtain half of MEPmax amplitude.Conclusions: This demonstrates that MEP elicited at a single stimulus intensity allows to capture the same characteristics of the corticospinal excitability as measured by the AUC, MEPmax and the peak slope, which may be of interest in both clinical and research settings. However, it is still necessary to plot I/O curves if an effect or a difference is expected at S50

Cerebello-Cortical Differences in Effective Connectivity of the Dominant and Non-dominant Hand during a Visuomotor Paradigm of Grip Force Control

Structural and functional differences are known to exist within the cortical sensorimotor networks with respect to the dominant vs. non-dominant hand. Similarly, the cerebellum, a key structure in the sensorimotor network with its cerebello-cortical connections, has been reported to respond differently when using the dominant vs. non-dominant hand. Several groups have already investigated causal interactions during diverse motor paradigms using effective connectivity but few have studied the larger visuomotor network, including key structures such as the parietal cortex and the cerebellum, with both hands. Moreover, the effect of force level on such interactions is still unclear. We therefore sought to determine the hemispheric asymmetries in the cerebello-cortical sensorimotor network in right-handers at two force levels (5% and 10% maximum voluntary contraction) for both hands. Cerebello-cortical modulations were investigated in 28 healthy, right-handed volunteers by determining the effective connectivity during a visuomotor task at two force levels under fMRI. A network was built consisting of the left and right primary motor (M1), ventral premotor (PMv) and posterior parietal cortices (PPC), in addition to the supplementary motor area (SMA), and the ipsilateral cerebellum (Cer) to the hand performing the motor task. Task performance (precision of isometric grip force tracking) did not differ between hands, nor did task-related activations in the sensorimotor areas apart from the contralateral primary motor cortex. However, during visuomotor control of the non-dominant hand, connectivity analysis revealed causal modulations between (i) the ipsilateral cerebellum and SMA, and (ii) the ipsilatearl cerebellum and contralateral PPC, which was not the case when using the dominant hand. These cerebello-cortical modulations for the non-dominant hand were more present at the higher of the two force levels. We conclude that precision force generation executed with the non-dominant hand, compared to the dominant hand, may require enhanced cerebello-cortical interaction to ensure equivalent left-right task performance