Pre-movement changes in sensorimotor beta oscillations predict motor adaptation drive

International audienceBeta frequency oscillations in scalp electroencephalography (EEG) recordings over the primary motor cortex have been associated with the preparation and execution of voluntary movements. Here, we test whether changes in beta frequency are related to the preparation of adapted movements in human, and whether such effects generalise to other species (cat). Eleven healthy adult humans performed a joystick visuomotor adaptation task. Beta (15-25 Hz) scalp EEG signals recorded over the motor cortex during a pre-movement preparatory phase were, on average, significantly reduced in amplitude during early adaptation trials compared to baseline, late adaptation, or aftereffect trials. The changes in beta were not related to measurements of reaction time or reach duration. We also recorded local field potential (LFP) activity within the primary motor cortex of three cats during a prism visuomotor adaptation task. Analysis of these signals revealed similar reductions in motor cortical LFP beta frequencies during early adaptation. This effect was present when controlling for any influence of the reaction time and reach duration. Overall, the results are consistent with a reduction in pre-movement beta oscillations predicting an increase in adaptive drive in upcoming task performance when motor errors are largest in magnitude and the rate of adaptation is greatest

Neurophysiological correlates of preparation for action measured by electroencephalography

The optimal performance of an action depends to a great extend on the ability of a person to prepare in advance the appropriate kinetic and kinematic parameters at a specific point in time in order to meet the demands of a given situation and to foresee its consequences to the surrounding environment. In the research presented in this thesis, I employed high-density electroencephalography in order to study the neural processes underlying preparation for action. A typical way for studying preparation for action in neuroscience is to divide it in temporal preparation (when to respond) and event preparation (what response to make). In Chapter 2, we identified electrophysiological signs of implicit temporal preparation in a task where such preparation was not essential for the performance of the task. Electrophysiological traces of implicit timing were found in lateral premotor, parietal as well as occipital cortices. In Chapter 3, explicit temporal preparation was assessed by comparing anticipatory and reactive responses to periodically or randomly applied external loads, respectively. Higher (pre)motor preparatory activity was recorded in the former case, which resulted in lower post-load motor cortex activation and consequently to lower long-latency reflex amplitude. Event preparation was the theme of Chapter 4, where we introduced a new method for studying (at the source level) the generator mechanisms of lateralized potentials related to response selection, through the interaction with steady-state somatosensory responses. Finally, in Chapter 5 we provided evidence for the existence of concurrent and mutually inhibiting representations of multiple movement options in premotor and primary motor areas.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Uncovering the neurophysiology of mood, motivation and behavioral symptoms in Parkinson’s disease through intracranial recordings

Neuropsychiatric mood and motivation symptoms (depression, anxiety, apathy, impulse control disorders) in Parkinson’s disease (PD) are highly disabling, difficult to treat and exacerbated by current medications and deep brain stimulation therapies. High-resolution intracranial recording techniques have the potential to undercover the network dysfunction and cognitive processes that drive these symptoms, towards a principled re-tuning of circuits. We highlight intracranial recording as a valuable tool for mapping and desegregating neural networks and their contribution to mood, motivation and behavioral symptoms, via the ability to dissect multiplexed overlapping spatial and temporal neural components. This technique can be powerfully combined with behavioral paradigms and emerging computational techniques to model underlying latent behavioral states. We review the literature of intracranial recording studies investigating mood, motivation and behavioral symptomatology with reference to 1) emotional processing, 2) executive control 3) subjective valuation (reward & cost evaluation) 4) motor control and 5) learning and updating. This reveals associations between different frequency specific network activities and underlying cognitive processes of reward decision making and action control. If validated, these signals represent potential computational biomarkers of motivational and behavioural states and could lead to principled therapy development for mood, motivation and behavioral symptoms in PD

L’étude de la contribution des mécanismes dépendants de la répétition aux processus de consolidation des mémoires motrices dans le cortex moteur primaire et de la manifestation électrophysiologique du traitement des récompenses monétaires au-dessus des aires cérébrales motrices

Abstract : The present thesis seeks to provide insights into the contribution of the two major learning mechanisms driving motor memory consolidation in the primary motor cortex (M1): repetition-dependent and reward-based learning mechanisms. However, because evidence remains scarce on this last learning mechanism, the study of the neural manifestation of reward processing in motor areas was investigated. More specifically, the first scientific contribution presented in this thesis sought to address the contribution of repetition-dependent mechanisms to motor memory consolidation in M1. As such, the first project used single-pulse transcranial magnetic stimulation (TMS) to interfere with M1 activity as participants executed newly learned motor behaviors during a performance asymptote. Results revealed that motor memory formation in M1 was initiated when behaviors were repeating, suggesting that repetition-dependent mechanisms contributed to retention in M1. The second scientific contribution sought to use scalp electroencephalography (EEG) recordings to investigate the electrophysiological manifestations of reward processing over cortical motor areas. Overall, results revealed that increases in beta-band power (20-30 Hz) over contralateral motor electrodes are modulated by reward processing. Although these results did not allow specifically addressing the contribution of reward-based learning mechanisms to consolidation in M1, they nonetheless provide the plausible neural substrates involved in this learning mechanism. The discussion first sought to integrate these two projects and second to provide an overview of the future perspectives that the two projects have led to. Overall, the proposed research projects mainly revolve around the demonstration of the associations– even maybe causality – between motor memory consolidation in M1, reward processing, beta-band power and dopaminergic activity. Throughout the discussion, working hypotheses as well as the methodological means to test them – ranging from non-invasive brain stimulation to electroencephalography recordings and even to the study of interindividual variations in the expression of dopamine-related genes – are outlined.Le présent mémoire cherche à fournir un aperçu des mécanismes neurophysiologiques qui sous-tendent les deux mécanismes principaux d’apprentissage impliqués dans la consolidation des mémoires motrices dans le cortex moteur primaire (M1). Bien que le modèle cellulaire le plus accepté pour la formation des mémoires motrices soit la potentialisation à long-terme (long-term potentiation, en anglais), la littérature suggère que les mécanismes d’apprentissage qui initient le stockage synaptique des mémoires motrices dépendent de la plasticité Hebienne (i.e., répétitions dans les mouvements) et des récompenses vécues pendant l’acquisition d’une nouvelle habileté motrice. La première contribution scientifique du présent mémoire aborde la contribution des mécanismes Hebbiens d’apprentissage à la consolidation des mémoires motrices dans le M1. Dans ce premier projet, la stimulation magnétique transcrânienne (SMT) a été utilisée pour interférer avec l’activité neuronale du M1 lorsque les participants acquéraient et exécutaient de nouveaux comportements moteurs pendant l’atteinte d’un plateau de performance (i.e., répétitions dans les mouvements). Les résultats démontrent que la formation des mémoires motrices dans le M1 est initiée lorsque les comportements moteurs sont de plus en plus répétés, ce qui suggère que le stockage synaptique des mémoires motrices dans M1 est dépendant de la répétition des comportements pendant l’acquisition. Le deuxième projet scientifique a cherché à mettre en lumière la contribution des régions motrices au traitement des récompenses dans un contexte moteur en utilisant l’enregistrement d’activités électroencéphalographiques. Entre autres, suite à l’octroi d’une récompense, les résultats démontrent une augmentation de la puissance spectrale dans la bande de fréquences bêta (20-30 Hz) des électrodes motrices contralatérales à la main utilisée pendant la tâche motrice. Dans l’ensemble, bien que ce deuxième projet ne puisse statuer sur la contribution spécifique du M1 dans la consolidation des mémoires motrices sur la base des récompenses vécues pendant l’acquisition, les résultats qui en émergent pourraient être un reflet des substrats neuronaux impliqués dans ce mécanisme d’apprentissage. Dans un premier temps, la discussion intègre ces deux contributions et, dans un deuxième temps, donne un aperçu des perspectives futures de recherche qui émanent de ces deux contributions scientifiques. Globalement, les hypothèses de recherche suggérées se concentrent principalement autour de la démonstration d’une association ou d’un lien causal entre la formation des mémoires motrices dans le M1, le traitement de récompenses, les réponses spectrales en bêta ainsi que l’activité dopaminergique. Au travers de la discussion, les hypothèses spécifiques ainsi que les moyens méthodologiques pour les tester – qui vont des techniques de stimulation cérébrale non invasives à l’enregistrement d’activité électroencéphalographique et même jusqu’à l’étude des variations génétiques interindividuelles dans l’expression des gènes régulant l’activité dopaminergique – sont décrits

Investigating cerebellar modulation of premotor inhibitory control during motor adaptation

Motor adaptation is marked by neurophysiological changes in the motor cortex; however, other regions of the motor network such as the cerebellum and premotor cortex also contribute to this process. Enhancing cerebellar activity has been shown to increase the rate of motor adaptation (Galea et al., 2011; Koch et al., 2020), though it is unclear which neurophysiological mechanisms contributing to adaptation are influenced by the cerebellum. Pre-movement beta event-related desynchronization (ß-ERD), which reflects a release of synchronized inhibitory control in the premotor cortex during movement planning, is one mechanism which may be modulated by the cerebellum through cerebellar-premotor cortical connections (Tzvi et al., 2020). I hypothesized that enhancing cerebellar activity with intermittent theta burst stimulation (iTBS) would improve participants’ adaptation rate, increase ß-ERD during motor adaptation, and that there would be a relationship between the task performance and the ß-ERD. Thirty-four participants were assigned to receive either active (A-iTBS) or sham cerebellar iTBS (S-iTBS). In the first study session participants completed a brief practice session on a visuomotor rotation task, with no rotation, to familiarize them with the task timing and joystick control of the cursor. Following practice, participants received active or sham iTBS. After ten minutes they completed training on the task, with a 45º rotation to the cursor movement. Participants returned to the lab 24 hours later for session 2, to perform the task again to get a measure for how much of the learned rotation had been retained. Angular error at peak velocity was the primary behavioural measure, which was the angular difference between the ideal trajectory of the cursor and the actual trajectory of the cursor at peak velocity in the movement. The primary neurophysiological measure was ß-ERD, the change in power in the ß band from rest to movement planning and was measured using electroencephalography (EEG). Results show a greater adaptation rate following active cerebellar iTBS, and an increase in ß-ERD compared to sham cerebellar iTBS. The divergence in ß-ERD change between groups is indicative of a cerebellar modulation of the motor cortical inhibitory control network. Interestingly, the enhanced release of inhibitory activity was not just present during the initial adaptation phase of training as predicted, but overall persisted across training. This finding may suggest that the effects of iTBS and the cerebellar influence on the premotor cortex were not specific to the adaptation period but persist through the entire training session. There was no difference between groups in the amount of the skill which was acquired during training or the amount of the skill which was retained between session 1 and session 2. Results from this study further our understanding of the connections between the cerebellum and the motor cortex as they relate to acquiring motor skills, as well as inform future skill training and rehabilitation protocols

L’adaptation visuomotrice implicite et ses contraintes

L’adaptation sensorimotrice réfère à la capacité de l’être humain d’ajuster de manière continue les commandes motrices des mouvements quotidiens pour interagir de façon efficace avec son environnement. Les défis sont nombreux, allant de l’acquisition ou de la perte de masse musculaire due à un programme de mise en forme, à l’ajustement de la force nécessaire pour effectuer des mouvements variés tels que soulever différents poids lors d’un entraînement, saisir une tasse de café le matin ou réaliser une frappe au soccer. Ces ajustements automatiques des commandes motrices garantissent la précision et l’efficacité des mouvements, conférant ainsi à l’adaptation sensorimotrice un rôle central dans le maintien d’une qualité de vie optimale. Le principal objectif de ce mémoire est d’explorer les fondements de l’adaptation sensorimotrice, en mettant l’accent sur les processus implicites qui sous-tendent les ajustements automatiques apportés aux commandes motrices des mouvements. Des études récentes ont mis en évidence une limite temporelle dans la capacité de ces processus implicites à s’adapter à une perturbation visuelle (interférence antérograde). Cette interférence antérograde temporelle se manifeste par une diminution de la capacité d’adaptation lorsque deux séances d’apprentissage se succèdent dans un court laps de temps. Les facteurs explicatifs de cette limite ont été attribués à un état réfractaire de la plasticité neuronale après une séance d’adaptation, ou encore à la présence de certains types d’essais entre les blocs d’apprentissage. Une approche pour élucider ces limites et les processus qui y sont associés consiste à identifier un marqueur neurophysiologique de l’adaptation sensorimotrice implicite. Un candidat potentiel est la synchronisation post-mouvement de la fréquence bêta, reconnue pour ses liens étroits avec les processus décisionnels menant à l’exécution des mouvements, ainsi qu’avec les mécanismes inhibiteurs neuronaux. De plus, plusieurs éléments suggèrent un lien entre une diminution de la synchronisation bêta post-mouvement et la présence de perturbations visuelles. Cependant, il reste à déterminer si ces observations s’appliquent à des perturbations purement implicites. L’objectif de ce mémoire est, dans un premier temps, d’évaluer si la synchronisation bêta post-mouvement est modulée par une exposition prolongée à des perturbations implicites. Dans cette optique, 32 participants ont été invités à deux séances en laboratoire au cours desquelles ils devaient exécuter des mouvements de pointage de cibles. Le premier bloc de chaque séance mettait en jeu de l’adaptation visuomotrice à des perturbations implicites lors de mouvements de pointage, tandis que le deuxième bloc utilisait un paradigme mettant de l’avant les biais post-rotation (représentatifs des processus implicites) mesurés alors que les participants devaient ignorer des perturbations stochastiques. Les résultats obtenus dans le premier bloc montrent que les participants se sont bien adaptés aux perturbations visuelles implicites. Cependant, ce volume d’adaptation vécu élevé n’est pas reflété par une diminution de la synchronisation bêta post-mouvement dans le deuxième bloc. Dans un deuxième temps, l’objectif est d’évaluer si l’exposition prolongée à une perturbation implicite limite la sensibilité subséquente à s’adapter lors de l’exposition à une nouvelle perturbation. Les résultats indiquent que ce type d’adaptation implicite n’affecte pas la sensibilité subséquente du système à s'adapter à des perturbations. L’interprétation principale avancée dans ce mémoire suggère que la PMBS serait représentative des processus explicites de l’adaptation sensorimotrice plutôt que des processus implicites. Une autre perspective d’interprétation est que l’absence d’une période réfractaire après le premier bloc d’adaptation implicite indique que la présence d’essais à l’aveugle entre les deux blocs d’adaptation implicites, comme observée dans d’autres études, pourrait potentiellement être la cause de l’interférence antérograde observée dans le deuxième bloc. En résumé, ce projet montre que, dans le cadre des paradigmes utilisés dans ce mémoire, l’exposition prolongée à des perturbations implicites n’influence pas l’activité β post-mouvement, et que l’interférence antérograde ne se manifeste que dans des contextes particuliers

Behavioural and neuronal correlates of sensory prioritization in the rat whisker system

Animals need to assess when to initiate actions based on uncertain sensory evidence. To formulate a response, decision making systems must prioritize extraction of neuronal signals that represent ecologically relevant events from signals that are behaviorally less relevant. This is commonly known as selective attention. The current thesis aims to investigate two simple forms of attention in rodents: sensory prioritization to a specific modality and temporal cueing. The rat whisker system is functionally efficient, and anatomically well characterized. We therefore utilize the whisker touch as a model sensory system to investigate the neuronal and behavioral correlates of attention in rats. We begin this thesis by designing a novel simple detection task that investigated whether rats dedicate attentional resources to the sensory modality in which a near-threshold event is more likely to occur. Detection of low-amplitude events is critical to survival, and to formulate a response, animals must extract minute neuronal signals from the sensory modality that is more likely to provide key information. We manipulated attention by controlling the likelihood with which a stimulus was presented from one of two modalities. In a whisker session, 80% of trials contained a brief vibration stimulus applied to whiskers and the remaining 20% of trials contained a brief change of luminance. These likelihoods were reversed in a visual session. When a stimulus was presented in the high-likelihood context, detection performance increased and was faster compared with the same stimulus presented in the low-likelihood context. Sensory prioritization was also reflected in neuronal activity in the vibrissal area of primary somatosensory cortex: single units responded differentially to a whisker vibration stimulus when presented with higher probability compared to the same stimulus when presented with lower probability. Neuronal activity in the vibrissal cortex displayed signatures of multiplicative gain control and enhanced response to vibration stimuli during the whisker session. In Chapter 3, we replicated these findings in a forced choice paradigm and extended the investigation from somatosensory/visual to the somatosensory/auditory. Attention was similarly manipulated by controlling likelihoods of stimulus presentation. Again, we observed improvements in detection performance and reaction time, as well as improvements in discrimination performance for stimuli presented in a high-likelihood context. The behavioral consequences of a forced choice compared to simple detection task are discussed. Finally, we developed a novel task that investigated whether rats were able to dedicate attentional resources in time. Operating with some finite quantity of attentional resources, by direct these resources at the expected time, animals would benefit from prioritizing processing based on temporal cues. We manipulated temporal cueing by presenting an auditory cue that preceded a target vibration stimulus in a subset of trials. On another subset, no auditory cue was presented. Presentations of these trials were of equal probability. Critically in this paradigm, the auditory cue provided temporal information but did not provide any spatial information about the location of the vibration stimulus. The auditory cue increased detection and discrimination performances and resulted in faster responses compared to trials in which the cue was absent. We observed neuronal signatures of temporal cuing in the vibrissal area of the primary somatosensory cortex. Single units showed enhanced response to the vibration stimulus during trials in which the stimulus was temporally expected. However, we did not observe signatures of multiplicative gain control in this paradigm. Instead, a decrease in baseline activity was observed that was phase locked to the onset of the auditory cue. In summary, this thesis presents two novel paradigms to study selective attention in rats in the form of sensory prioritization and temporal cueing. In addition, we investigate the neuronal correlates of selective attention in the vibrissal area of the primary somatosensory cortex. These series of experiments establish the rat as an alternative model organism to primates for studying attention

Sensorimotor Processing in Post-Stroke Fatigue

Chronic pathological fatigue is a highly debilitating symptom with a significant impact on quality of life of stroke survivors. Despite its high prevalence, research into the mechanisms that underlie post-stroke fatigue is lacking. This thesis outlines how changes in cortical neurophysiology results in alterations in sensorimotor processing associated with the perception of effort and how prolonged experience of high effort can subsequently result in chronic pathological fatigue. I show that the perception of effort for what are usually low effort activities is altered in non-depressed, chronic stroke survivors with minimal physical impairment. Low effort voluntary contractions are perceived as more effortful in stroke survivors with high fatigue compared to those with low fatigue. Sensory attenuation, the ability to attend away from predictable sensory input, is thought to underlie altered effort perception. If one is unable to attend away from predictable sensory input associated with a voluntary movement, this will give rise to the perception of higher effort afforded to the movement. I show that stroke survivors with high fatigue do not show reduced sensory attenuation of sensory input arising from mechanoreceptors as quantified using a force matching task and suggest that high effort afforded to simple voluntary movements may be a result of reduced sensory attenuation of information arising from within the body, namely proprioceptive afferent information from the contracting muscle. Using TMS, I show that cortical excitability both at rest and during movement preparation is altered in stroke survivors with high fatigue and propose that cortical excitability reflects the degree of sensory attenuation at the level of the sensorimotor cortex. Finally, I show that neuromodulatory techniques such as transcranial direct current stimulation, are potential tools that can be used to reduce fatigue severity by potentially resetting cortical neurophysiology and reducing perceived effort. Overall, the data provides some evidence in support of the sensory attenuation model of fatigue and provides a novel insight into the mechanisms implicated in post- stroke fatigue

Neuroimaging of human motor control in real world scenarios: from lab to urban environment

The main goal of this research programme was to explore the neurophysiological correlates of human motor control in real-world scenarios and define mechanism-specific markers that could eventually be employed as targets of novel neurorehabilitation practice. As a result of recent developments in mobile technologies it is now possible to observe subjects' behaviour and monitor neurophysiological activity whilst they perform natural activities freely. Investigations in real-world scenarios would shed new light on mechanisms of human motor control previously not observed in laboratory settings and how they could be exploited to improve rehabilitative interventions for the neurologically impaired. This research programme was focussed on identifying cortical mechanisms involved in both upper- (i.e. reaching) and lower-limb (i.e. locomotion) motor control. Complementary results were obtained by the simultaneous recordings of kinematic, electromyographic and electrocorticographic signals. To study motor control of the upper-limb, a lab­based setup was developed, and the reaching movement of healthy young individuals was observed in both stable and unstable (i.e. external perturbation) situations. Robot-mediated force-field adaptation has the potential to be employed in rehabilitation practice to promote new skills learning and motor recovery. The muscular (i.e. intermuscular couplings) and neural (i.e. spontaneous oscillations and cortico­muscular couplings) indicators of the undergoing adaptation process were all symbolic of adaptive strategies employed during early stages of adaptation. The medial frontal, premotor and supplementary motor regions appeared to be the principal cortical regions promoting adaptive control and force modulation. To study locomotion control, a mobile setup was developed and daily life human activities (i.e. walking while conversing, walking while texting with a smartphone) were investigated outside the lab. Walking in hazardous environments or when simultaneously performing a secondary task has been demonstrated to be challenging for the neurologically impaired. Healthy young adults showed a reduced motor performance when walking in multitasking conditions, during which whole-brain and task-specific neural correlates were observed. Interestingly, the activity of the left posterior parietal cortex was predictive of the level of gait stability across individuals, suggesting a crucial role of this area in gait control and determination of subject specific motor capabilities. In summary, this research programme provided evidence on different cortical mechanisms operative during two specific scenarios for "real­world" motor behaviour in and outside the laboratory-setting in healthy subjects. The results suggested that identification of neuro-muscular indicators of specific motor control mechanisms could be exploited in future "real-world" rehabilitative practice