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Il est classiquement admis que le cortex moteur des primates est organisé topographiquement en lien avec le contrôle des différentes parties du corps. Il a également été suggéré que différentes zones de cette aires corticales pourraient être impliquées dans différents processus de préparation motrice. Suivant cette dernière hypothèse, cette thèse a pour objectif d’étudier les modulations spatiales et temporelles de l’activité neuronale du cortex moteur au cours de la préparation et de l’exécution de mouvements de saisie manuelle. Trois singes ont été entraînés à réaliser une tâche pré-indicée de saisie manuelle. Chez chaque animal, une matrice d’électrodes a été implantée chroniquement dans le cortex moteur. Dans une première étude, nous avons démontré que les modulations d’activité associées à différents processus préparatoires sont localisées dans différentes zones du cortex moteur. Ces zones seraient activées séquentiellement au cours de la préparation motrice suivant une alternance de phases de traitement stationnaire et de propagation dynamique. Dans une seconde étude, nous avons exploré les interactions neuronales par l’utilisation de la mesure de corrélation de variabilité (rsc) entre paires de neurones. Cette deuxième étude a fait ressortir 3 résultats principaux. Les valeurs de rsc sont plus élevées au cours de la préparation du mouvement que lors de son exécution. Elles diminuent avec la distance qui sépare les neurones. Elles sont plus importantes entre interneurones qu’entre neurones supposés pyramidaux. L’ensemble de ces observations ont été discutées en lien avec différentes modèles d’organisation spatiale des aires motrices corticales. / The motor cortex follows a somatotopic organization in which the different body parts are controlled by distinct cortical zones. It has also been proposed that different spatial zones of this cortical area could be involed in distinct processes of motor preparation. Following this latter hypothesis, the objective of this thesis is to study the spatio-temporal modulations of motor cortex activity during movement preparation and execution. Three monkeys have been trained in an instructed delayed reach-to-grasp task. In each animal, a multielectrode Utah array was chronically implanted in the motor cortex to explore the dynamic modulations of neural activity during task performance. In a first study, we demonstrated that the modulations of neural activity related to distinct processes of motor preparation occur at different cortical locations. These locations are activated sequentially during motor preparation through alternating phases of stationary processing and dynamic propagation. In a second study, we analysed the neural interactions using a measure of spike count correlation (rsc) between pair of neurons. We reported 3 main results. Correlations are higher during movement preparation than during execution. They decrease with the distance between neurons. Finally, they are higher bewteen putative interneurons than bewteen putative pyramidal neurones. All these observations are discussed in relation to several models of the spatial organization the motor cortex.

Thesis (Ph. D.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 129-138).

published_or_final_version / Human Performance / Doctoral / Doctor of Philosophy

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Thesis (Ph. D. in Psychology)--Vanderbilt University, May 2005. / Title from title screen. Includes bibliographical references.

The study of motor cortex (dorsal premotor cortex and primary motor cortex) has been greatly aided by the development of a conceptual paradigm that has emerged over the past decade. In contrast to established frameworks, which view neural activity within motor cortex as a representation of particular movement parameters, the ‘dynamical systems paradigm’ posits that motor cortex is best understood via the low-dimensional neural processes that allow the generation of motor commands. This framework largely evolved from, and has been most successfully applied to, simple reaching tasks, where the sequential stages of movement generation are largely separated in time – motor cortex absorbs an input that specifies the identity of the upcoming reach, a second input initiates the movement, and strong, autonomous dynamics generate time-varying motor commands. However, while the dynamical systems paradigm has provided a useful scaffolding for interrogating motor cortex, our understanding of the mechanisms that generate movement is still evolving, and many questions remain unanswered. Prior work has established that the neural processes within motor cortex that generate descending commands are initiated by a large, condition-invariant input. But are movements made under different behavioral contexts initiated via the same mechanisms? Lesion studies suggest that the generation of so-called ‘self-initiated movements’ is uniquely dependent on the supplementary motor area (SMA), a premotor region immediately upstream of motor cortex. In contrast, SMA is thought to be less critical for generating externally-cued movements. To characterize the degree to which SMA is able to impact movement initiation across behavioral contexts, we trained two monkeys to make reaches that were either internally or externally cued. On a subset of trials, we disrupted activity within SMA via microstimulation and asked how this perturbation impacted the monkeys’ behavior. Surprisingly, we found that the effect of stimulation was largely preserved across contexts; the behavioral effects of stimulation could be explained by a simple model in which a context-invariant, time-varying kernel multiplicatively altered the odds of movement initiation. These results suggest that SMA is able to impact movement initiation across behavioral contexts. The question of how sequences of discrete actions are generated has been investigated for over one hundred years. It is commonly thought that once a given sequence (particularly a rapid sequence) becomes well-learned, individual actions that were once produced separately become ‘merged’, such that multiple actions are generated as a single, holistic unit. But what does it mean to generate multiple actions as a single unit? The dynamical systems paradigm offers the ability to translate this notion into specific predictions about the timing and structure of neural activity within motor cortex during sequence production. Importantly, it also offers predictions for the alternative hypothesis – that motor cortex generates the component actions of a sequence independently. To determine whether the production of rapid sequences requires motor cortex to merge multiple actions into a single ‘movement’, we trained monkeys to make sequences of two reaches. Surprisingly, we found that the same set of neural events are used to produce rapid sequences and isolated reaches. Rather than merging individual actions into a single unit, motor cortex generated rapid sequences by overlapping the neural activity related to reach preparation and execution. These results demonstrate that the performance of extremely fast, well-learned movement sequences does not require motor cortex to implement a sequence-specific strategy; the same neural motif that produces a simple reach can also generate movement sequences.

The human primary motor cortex (M1) undergoes structural and functional change throughout life by a process known as neuroplasticity. Techniques which artificially induce neuroplastic changes are seen as potential adjunct therapies for neurological conditions reliant on neuroplasticity for recovery of function. Unfortunately, the reported improvements in function when these techniques have been used in combination with regular rehabilitation have so far been inconsistent. One reason attributed to this is the large variability in effectiveness of these techniques in inducing neuroplastic change. This thesis has investigated factors influencing the effectiveness and reproducibility of neuroplasticity induction in human M1 using several experimental paradigms. The effectiveness and reproducibility of inducing neuroplasticity in human M1 using two variants of a paired associative stimulation (PAS) protocol was investigated in the first set of experiments (Chapter 2). Both protocols repeatedly paired a peripheral electrical stimulus to the median nerve of the left wrist with single-pulse transcranial magnetic stimulation (TMS) delivered 25 ms later to the contralateral M1. Neuroplastic changes were quantified by comparing the amplitude of the muscle evoked potential (MEP) recorded in abductor pollicis brevis (APB) muscle by suprathreshold TMS prior to and following PAS. With both protocols, neuroplasticity induction was more effective, and the responses across sessions more reproducible, if the experiments were performed in the afternoon compared to the morning. Subsequent experiments confirmed the time of day modulation of PAS-induced neuroplasticity by repeatedly testing twenty-five subjects on two separate occasions, once in the morning (8 am), and once in the evening (8 pm) (Chapter 3). Time of day was also shown to modulate GABAergic inhibition in M1. In a further set of experiments, a double-blind, placebo-controlled study demonstrated that artificially elevated circulating cortisol levels (with a single oral dose of hydrocortisone) inhibits PAS-induced neuroplasticity in the evening (8 pm), indicating that the time of day modulation of neuroplasticity induction with PAS is due, at least in part, to differences in circulating cortisol levels (Chapter 3). The cortical circuits that are modulated by PAS have also been shown to be important in motor learning. Therefore, the final set of experiments, described in Chapter 4, investigated whether motor-training-related changes in motor performance (and cortical excitability) following a ballistic motor training task are also modulated by time of day. Twenty-two subjects repeatedly abducted their left thumb with maximal acceleration for thirty minutes during two experimental sessions (morning (8 am) and evening (8 pm)) on separate occasions. Motor training improved motor performance, and increased cortical excitability, however these changes were independent of time of day. It may be that the motor training task and/or outcome measures used were not sufficiently sensitive to detect a subtle time of day effect of motor training on motor performance. Alternatively, the normally functioning motor system may be able to compensate for changes in cortical excitability to maintain optimal motor performance. These findings have important implications for therapies reliant on neuroplasticity for recovery of function, and indicate that rehabilitation may be most effective when circulating cortisol levels are low. / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2009