Dans les suites d'un accident vasculaire moteur (AVC), il existe une réorganisation des cartes de représentation corticale des territoires musculaires pouvant intéresser aussi bien le cortex moteur primaire (CMP) que le cortex prémoteur (CPM) de l'hémisphère cérébral atteint. La contribution de ces deux aires à la plasticité corticale post-AVC est loin d'être bien définie. Notre objectif était d'étudier les modifications de cartographie corticale motrice, notamment au niveau du CMP et du CPM, et leur implication dans la récupération fonctionnelle post-AVC. Dans ce but nous avons utilisé une technique de stimulation magnétique transcrânienne (SMT) guidée par l'imagerie (neuronaviguée). Les limites anatomiques des aires corticales et l'existence de repères anatomiques fiables dans différentes régions d'intérêts ont été définies dans un premier temps. Puis nous avons établi la cartographie normale des représentations corticales motrices dans un groupe de sujets sains, notamment au moyen de cartes « probabilistes » d'obtention de réponses motrices à la SMT qui prennent en compte les variabilités interindividuelles. Nous avons ensuite étudié les modifications de ces représentations dans un groupe de patients ayant des séquelles de lésion vasculaire des régions corticales motrices. Enfin, nous avons effectué un travail prospectif de suivi cartographique d'un groupe de patients ayant présenté un AVC moteur. Dans cette dernière partie, l'analyse des données cliniques et de SMT obtenues à la phase aigüe et à trois mois de l'AVC nous a permis de caractériser les modifications anatomo-fonctionnelles corticales qui accompagnent la régression du déficit moteur, supportant en particulier le rôle central du CMP de l'hémisphère lésé. En conclusion, nous proposons des modèles d'organisation neuronale expliquant le fonctionnement du cortex moteur chez le sujet sain ainsi que la récupération motrice après une lésion partielle du CMP. / Following stroke, reorganization of the motor cortical maps takes places and involves both the primary motor cortex (M1) and the premotor cortex (PMC) on the affected hemisphere. The relative contribution of each of these two cortical areas in the process of post-stroke plasticity and motor recovery remains uncertain. The present project was designed to study the cortical changes that follow a motor stroke, namely those involving M1 and the PMC, and their implications for motor recovery. For this purpose we used MRI-guided (neuronavigated) transcranial magnetic stimulation (TMS). First, we defined the anatomical limits of the cortical areas and the reliable cortical landmarks within each region of interest. We then defined a normal motor map in a group of healthy subjects. Our “probabilistic” map was based on the probability of obtaining motor responses in a given area and therefore accounted for inter-subject variability of motor representations. Thereafter we studied the modifications of the motor cortical representations in a group of patients having recovered from a motor stroke. Finally, we prospectively followed a group of patients presenting with a motor stroke. By comparing the neurophysiological and clinical data at admission and three months later, we were able to characterize the anatomo-functional cortical changes that accompany motor recovery following stroke. Our results are consistent with a major role of M1 in motor recovery. To conclude, we propose a model of how the motor cortex works in healthy subjects and during post-stroke recovery process.

Introdução: Níveis elevados de ansiedade têm sido associados com intensidade e comportamento da dor em pacientes com dores aguda e crônica. Foi observado, em indíviduos com síndrome dolorosa miofascial (SDM), que o estresse e a ansiedade aumentam a predisposição para o desenvolvimento de pontos-gatilhos miofasciais. Adicionalmente a isto, existe a tendência do indivíduo experimentar emoções negativas em situações de estresse (neuroticismo), característica de personalidade associada ao traço de personalidade, que pode influenciar negativamente na experiência de dor. Indivíduos com alta ansiedade-traço são geralmente hipersensíveis a estímulos e psicologicamente mais reativos. É concebível supôr a coexistência de alteração na excitabilidade cortical, entre dor crônica e ansiedade nestes pacientes. Para melhorar a compreensão dos mecanismos centrais relacionados à ansiedade e à dor crônica, avaliou-se os parâmetros de excitabilidade cortical, usando estimulação magnética transcraniana (EMT), pulso único e pareado. Nossa hipótese é que a excitabilidade corticoespinhal seja modulada pela ansiedade favorecendo a perda de influxo inibitório descendente. Objetivos: O presente estudo teve como objetivo responder a três perguntas relacionadas à síndrome dolorosa miofascial (SDM): 1) A excitabilidade do córtex motor está relacionada com a ansiedade-traço? 2) A ansiedade-traço modula alterações da excitabilidade corticoespinhal, após dor evocada pelo Quantitative Sensory Testing (QST)? 3) A ansiedade-traço prevê resposta à dor evocada pelo QST, se receber simultaneamente um estímulo heterotópico [Conditioned Pain Modulation (CPM)]? Pacientes e métodos: Foram incluídas mulheres com SDM (n = 47) e controles saudáveis (n = 11), com idade entre 19 e 65 anos. A excitabilidade do córtex motor foi avaliada pela EMT, e a ansiedade foi avaliada com base no Inventário de Ansiedade Traço-Estado (IDATE). A incapacidade relacionada à dor foi avaliada pelo perfil da escala de dor crônica para a população brasileira (B:PCP:S), e as medidas psicofísicas da dor foram medidas pelo QST e CPM. Resultados: Nas pacientes, a ansiedade-traço foi positivamente correlacionada com a facilitação intracortical (FIC) no baseline e após a dor evocada pelo QST (β = 0,05 e β = 0,04, respectivamente) e negativamente relacionada com o período de silêncio cortical (PSC) no baseline e após a dor evocada pelo QST (β = -1,17 e β = -1,23, respectivamente) (P <0,05 para todas as comparações). Após dor evocada pelo QST, a incapacidade relacionada à dor crônica foi positivamente correlacionada com a FIC (β = 0,02) (P <0,05). Os escores de dor durante o CPM foram positivamente correlacionados com a ansiedadetraço, quando a incapacidade relacionada à dor crônica foi igualmente alta (β = 0,39, P = 0,02). A excitabilidade cortical das controles saudáveis permaneceu inalterada após o QST. Conclusões: Estes resultados sugerem que, na SDM, o desequilíbrio entre os sistemas excitatórios e inibitórios descendentes do trato corticoespinhal está associado concomitantemente a maiores níveis de ansiedade-traço e maiores níveis de incapacidade funcional ocasionados pela dor crônica. / Background: High levels of anxiety have been associated with the intensity and pain behavior in patients with acute and chronic pain. It was observed that in subjects with myofascial pain (SDM), stress and anxiety syndrome increase the predisposition for the development of myofascial trigger points. In addition to this, there is a tendency of individuals to experience negative emotions in stressful situations (neuroticism), personality characteristic associated with trait personality that may negatively influence in the experience of pain. Individuals with higher trait anxiety are usually hypersensitive to stimuli and more psychologically reactive. It is conceivable to assume the co-existence of change in cortical excitability, chronic pain and anxiety, in these patients. To improve the understanding of the central mechanisms related to anxiety and chronic pain, we assessed cortical excitability parameters by single and paired pulse transcranial magnetic stimulation (TMS). We hypothesize that corticospinal excitability is modulated by anxiety favoring loss of descendent inhibitory influx. Objectives: This study aimed to answer three questions related to chronic myofascial pain syndrome (MPS): 1) Is the motor cortex excitability, as assessed by transcranial magnetic stimulation parameters (TMS), related to state-trait anxiety? 2) Does anxiety modulate corticospinal excitability changes after evoked pain by Quantitative Sensory Testing (QST)? 3) Does the state-trait anxiety predict the response to pain evoked by QST if simultaneously receiving a heterotopic stimulus [Conditional Pain Modulation (CPM)]? Patient and methods: We included females with chronic MPS (n=47) and healthy controls (n=11), aged from 19 to 65 years. Motor cortex excitability was assessed by TMS, and anxiety was assessed based on the State-Trait Anxiety Inventory. The disability related to pain (DRP) was assessed by the Profile of Chronic Pain scale for the Brazilian population (B:PCP:S), and the psychophysical pain measurements were measured by the QST and CPM. Results: In patients, trait-anxiety was positively correlated to intracortical facilitation (ICF) at baseline and after QST evoked pain (β= 0.05 and β= 0.04, respectively) and negatively correlated to the cortical silent period (CSP) (β= -1.17 and β= -1.23, respectively) (P <0.05 for all comparisons). After QST evoked pain, the DRP was positively correlated to ICF (β= 0.02) (P<0.05). Pain scores during CPM were positively correlated with trait-anxiety when it was concurrently with high DRP (β= 0.39; P= 0.02). Controls’cortical excitability remained unchanged after QST. Conclusions: These findings suggest that, in chronic MPS, the imbalance between excitatory and inhibitory descending systems of the corticospinal tract is associated with higher trait-anxiety concurrent with higher DRP.

A Lesão Medular incompleta (LMi) é uma condição gerada por processos lesionais que afetam parcialmente a integridade da medula espinhal, ocasionando comprometimento na função sensório-motora devido ao declínio do funcionamento das vias medulares. Tal comprometimento impacta diretamente em aspectos físicos, psicológicos e sociais, com consequente redução da qualidade de vida e da independência funcional. Dessa forma, uma reabilitação efetiva requer a redução dos danos ocasionados ela LMi e, portanto, depende de técnicas capazes de favorecer a neuroplasticidade dos circuitos medulares remanescentes. A Estimulação Magnética Transcraniana repetitiva (EMTr) de alta frequência é uma técnica capaz de induzir aumento na excitabilidade do córtex motor primário, trato córtico-espinhal e medula espinhal, facilitando o desenvolvimento da conectividade responsável pela melhora sensório-motora e funcional. Objetivou-se avaliar os efeitos da EMTr de alta frequência aplicada sobre a área dos membros inferiores em M1 na função sensório-motora e nos níveis de espasticidade em indivíduos com LMi crônica. Esse estudo duplo-cego, placebo controlado avaliou quinze indivíduos com LMi crônica (35.3 ± 7.9 anos, média ± desvio padrão) incluídos sequencialmente em cinco sessões de EMTr placebo e cinco sessões de EMTr ativa à 5Hz, separadas por um período de repouso de uma semana. Avaliações clínicas foram feitas antes e depois de da EMTr placebo e ativa. Foram observadas mudanças estatisticamente significativas nos escores motores do International Standards for Neurological Classification of Spinal Cord Injury Patients/Padrões Internacionais para Classificação Neurológica de Pacientes com Lesão Medular (ISNCSCI) (T(1, 14) = 5.359, P < 0.001), as quais foram acompanhadas de tamanhos de efeito clinicamente significativos. A sensibilidade superficial avaliada pelo ISNCSCI também apresentou mudanças estatisticamente significativas nos escores após EMTr ativa (T(1, 14) = 2.223, P < 0.043). Não foram observadas mudanças nos níveis de espasticidade. Nenhum participante relatou efeitos adversos graves, com exceção de dor de cabeça transitória após algumas sessões. O presente estudo encontrou mudanças estatísticas e clinicas consistentes na função sensório-motora em indivíduos com LMi crônica após EMTr ativa. Dessa forma, essa técnica pode ser uma forma efetiva de reabilitação em indivíduos com LMi / Incomplete Spinal Cord Injury (iSCI) is a condition generated by lesional processes that partially affect the integrity of the spinal cord, causing impairment in the sensorimotor function due to the decline in the functioning of the spinal cord. Such impairment directly impacts on physical, psychological and social aspects, with consequent reduction of quality of life and functional independence. Thus, effective rehabilitation requires the reduction of the damage caused by iSCI and, therefore, depends on techniques capable of favoring the neuroplasticity of the remaining medullary circuits. High frequency repetitive transcranial magnetic stimulation (rTMS) is a technique capable of inducing increased excitability of the primary motor cortex, corticospinal tract and spinal cord, facilitating the development of connectivity responsible for sensorimotor and functional improvement . The objective of this study was to evaluate the effects of high frequency applied rTMS on the lower limbs area in M1 on sensorimotor function and on spasticity levels in individuals with chronic iSCI. This double-blind, placebo-controlled study evaluated fifteen subjects with chronic iSCI (35.3 ± 7.9 years, mean ± standard deviation) included sequentially in five placebo rTMS sessions and five sessions of active rTMS at 5Hz separated by a washout period of one week. Clinical evaluations were done before and after the placebo and active rTMS. Statistically significant changes in the International Standards for Neurological Classification of Spinal Cord Injury Patients (ISNCSCI) motor scores (T (1, 14) = 5,359, P <0.001) were observed, which were accompanied by clinically significant effect sizes. The superficial sensitivity assessed by the ISNCSCI also showed statistically significant changes in the scores after active rTMS (T (1,14) = 2,223, P <0.043). No changes in spasticity were observed. No participant reported severe adverse events, except for transient headache after a few sessions. The present study found consistent statistical and clinical changes in sensorimotor function in individuals with chronic iSCI after active rTMS. Thus, this technique can be an effective form of rehabilitation in individuals with iSCI

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The main goal of the dissertation was to determine task-dependent modulation of corticospinal descending output. From this main goal, I conducted three different studies to determine how corticospinal output to muscles of the upper arm and hand changed as a function of the task demands. In study 1, I examined how a somatosensory-motor circuit changes when a muscle needs to be active in a task and found that this circuit may be dependent on the movement phase, type of afferent input, and the task demands. In study 2, I examined how this same somatosensory-motor circuit acts to both allow and prevent muscle activity before movement. I revealed that this somatosensory-motor circuit may function to prevent muscle activity when a muscle is not needed in a task and creates facilitation of corticospinal output when it needs to be active in a task. These effects, however, are dependent on the movement phase and the digit the muscle is controlling. Study 3 determined how corticospinal output is modulated to upper arm muscles when performing movements that required different combinations of segmental interactions to achieve the task successfully. Corticospinal output was increased when inertia and the BBC moment at a joint resisted the intended joint rotation and these effects were dependent on the muscle and movement phase. I propose a model of the connectivity between the primary motor and somatosensory cortices that would increase, modulate, or decrease corticospinal output to a muscle depending on its role in the task. The findings from this work provides information to guide future neural rehabilitative interventions for individuals who have movement disorders arising from altered somatosensory-motor processing such as Cerebellar Ataxia, Developmental Coordination Disorder, Focal Hand Dystonia, Parkinson’s disease, and stroke. / Dissertation / Doctor of Philosophy (PhD) / On a day to day basis, we perform a variety of movements without giving much thought to how complicated it is for our nervous system to perform said movements. There are many different areas of the brain that are responsible for controlling movement. This dissertation focuses on two key areas that are critical for movement performance, namely the primary motor and somatosensory cortices. The primary motor cortex is largely responsible for sending signals to the muscles to control movement, while the primary somatosensory cortex plays a crucial role in receiving and understanding sensory input from our body. The studies in this dissertation describe how these two areas of the brain communicate during finger and arm movements to produce or prevent muscle activity. This work has implications for individuals with disorders that impact their everyday movements.

Mémoire de maîtrise présenté en vue de l'obtention de la maîtrise en psychologie (M. Sc) / L'humeur, en tant qu’élément central dans notre perception du monde, englobe diverses émotions et affecte grandement le bien-être mental et physiologique. Une régulation efficace de l'humeur est vitale pour un fonctionnement quotidien normal et tout dérèglement peut mener à des troubles psychologiques majeurs comme la dépression. Au niveau cérébral, le système de récompense, en particulier le cortex préfrontal dorsolatéral gauche (CPFdl) et ses projections dopaminergiques, joue un rôle central dans la régulation de l'humeur et du plaisir. De nombreuses recherches montrent maintenant que l’écoute de la musique influence notre humeur, en agissant sur le système de récompense. En outre, la stimulation magnétique transcrânienne répétitive excitatrice (SMTr) ciblant le CPFdl gauche a donné des résultats prometteurs en modifiant l'humeur et l'activité du système de récompense, ainsi qu'en modulant le plaisir perçu et la motivation pendant l'écoute de la musique en augmentant l'excitabilité et la plasticité corticales. Cependant, les études existantes sur l'impact de la SMTr sur l'humeur des personnes en bonne santé aboutissent à des résultats contradictoires, et l'effet conjoint de la SMTr et de la musique sur l'humeur reste inexploré. Cette étude vise donc à déterminer si la SMTr excitatrice peut augmenter les effets de la musique sur l'humeur chez des volontaires sains. Plus précisément, nous souhaitons valider l'impact de la musique, de la SMTr et de leur application combinée sur l'humeur des participants. Vingt-quatre participants ont suivi quatre sessions expérimentales, comprenant soit la SMTr seule, l’écoute de la musique seule, la SMTr associée à l’écoute de la musique, ou les conditions placebo/sham. L'humeur des participants a été évaluée à l'aide d'un questionnaire sur l'humeur et d'enregistrements de l'activité électrodermale (EDA) avant et après les stimuli. Les résultats ont révélé une amélioration significative de l'humeur générale et de l'humeur positive, ainsi qu'une diminution significative de l'humeur négative au cours de la séance de musique seule, ce qui indique l'efficacité de la musique en tant qu'intervention pour améliorer l'humeur. À l'inverse, la séance de SMTr seule a entraîné une diminution de l'humeur positive et une augmentation de l'humeur négative, ce qui suggère un effet négatif potentiel de la SMTr sur l'humeur. . Dans la session SMTr + musique, on a observé une tendance à l'amélioration de l'humeur, ce que nous interprétons comme le fait que l'application de la SMTr sur le CPFdl gauche a entrainé une baisse de l'humeur, tandis que l'écoute de la musique contrecarrait cet effet en induisant une humeur positive et en réduisant l'humeur négative.En conclusion, les résultats de cette étude soulignent le potentiel de la musique en tant qu'intervention visant à améliorer l'humeur. En outre, les résultats suggèrent que la SMTr excitatrice ciblant le CPFdl gauche peut entraîner une baisse de l'humeur. Il est nécessaire de poursuivre les recherches dans ce domaine, notamment en explorant d'autres combinaisons de stimuli, telles que la SMTr excitatrice sur le CPFdl droit associée à la musique, afin de mieux comprendre les mécanismes sous-jacents et d'optimiser l'utilisation de ces interventions pour la régulation de l'humeur. Ces recherches supplémentaires permettront de mieux comprendre la modulation de l'humeur et d'améliorer l'efficacité des interventions dans ce domaine. / Mood, as a central element in our perception of the world, encompasses a variety of emotions and greatly affects mental and physiological well-being. Effective mood regulation is vital for normal daily functioning, and any disruption can lead to major psychological disorders such as depression. At the cerebral level, the reward system, in particular, the left dorsolateral prefrontal cortex (DLPFC) and its dopaminergic projections, plays a central role in regulating mood and pleasure. A large body of research now shows that listening to music influences our mood, by affecting the reward system. In addition, excitatory repetitive transcranial magnetic stimulation (rTMS) targeting the left DLPFC has shown promising results in altering mood and the reward system activity, as well as modulating perceived pleasure and motivation during music listening by increasing cortical excitability and plasticity. However, existing studies on the impact of rTMS on mood in healthy individuals yield conflicting results, and the joint effect of rTMS and music on mood remains unexplored. This study aims to determine whether excitatory rTMS can enhance the effects of music on mood in healthy volunteers. More specifically, we aim to validate the impact of music, rTMS, and their combined application on participants' mood. Twenty-four participants completed four experimental sessions, comprising either rTMS alone, listening to music alone, rTMS + music, or placebo/sham conditions. Participants' mood was assessed using a mood questionnaire and electrodermal activity (EDA) recordings before and after the stimuli. Results revealed a significant improvement in overall mood and positive mood, as well as a significant decrease in negative mood during the music-only session, indicating the effectiveness of music as a mood-enhancing intervention. Conversely, the rTMS session alone resulted in a decrease in positive mood and an increase in negative mood, suggesting a potential negative effect of rTMS on mood. In rTMS + music session, there was a trend in mood improvement, which we interpret as meaning that applying rTMS to the left DLPFC resulted in a decrease in the mood while listening to music counteracted this effect by inducing positive mood and reducing negative mood. In conclusion, the results of this study underline the potential of music as a mood-enhancing intervention. In addition, the results suggest that excitatory rTMS targeting the left DLPFC may lead to a decrease in mood. Further research in this area is necessary, including exploring alternative combinations of stimuli, such as excitatory rTMS on the right DLPFC in conjunction with music to better understand the underlying mechanisms and optimize the use of these interventions for mood regulation. This additional research will contribute to a more comprehensive understanding of mood modulation and enhance the effectiveness of interventions in this field.

Environ 300 millions de personnes dans le monde souffrent de dépression et environ 30% vont développer une dépression réfractaire. Une dépression est réfractaire quand deux traitements antidépresseurs ou plus échouent à améliorer la condition d’un patient. La stimulation magnétique transcrânienne (TMS) est un traitement sécuritaire et efficace de la dépression réfractaire. Son efficacité et sa tolérabilité ont été largement prouvées grâce à des études randomisées, des méta-analyses et des revues de littérature. Toutefois, jusqu’à présent, le traitement de la dépression réfractaire avec la TMS demeure sous-étudié avec des données en pratique clinique réelle. Pour répondre à cette lacune, nous avons conduit une analyse rétrospective des dossiers médicaux de patients dépressifs réfractaires ayant suivi un traitement de TMS à l’Unité de Neuromodulation Psychiatrique (UNP) du Centre Hospitalier de l’Université de Montréal (CHUM) entre janvier 2012 et mai 2022. Nous avons examiné l’efficacité et la tolérabilité de la TMS pour ces patients. De façon secondaire, nous avons vérifié si des caractéristiques cliniques des patients avant leur traitement de TMS pouvaient être associées avec l’amélioration de leurs symptômes dépressifs à la suite du traitement de TMS. Nous avons également vérifié si nos résultats étaient semblables à ceux retrouvés dans la littérature scientifique. Cette étude offrirait aux cliniciens une perspective réaliste de l’efficacité et de la tolérabilité de la TMS à une clinique de troisième ligne. / Around 300 million people worldwide suffer from depression and around 30% will develop treatment-resistant depression (TRD). Depression is treatment-resistant when two or more antidepressant treatments fail to improve a patient’s condition. Transcranial magnetic stimulation (TMS) is a safe and effective treatment for TRD. Its efficacy and tolerability have been widely demonstrated through randomized studies, meta-analyses, and literature reviews. However, to date, the treatment of TRD with TMS remains under-studied with evidence in real-world clinical practice. To address this gap, we conducted a retrospective chart review of TRD patients who had undergone TMS therapy at the Psychiatric Neuromodulation Unit (UNP) of the University of Montreal Hospital Center (CHUM) between January 2012 and May 2022. We examined the efficacy and tolerability of TMS for these patients. As a secondary measure, we examined whether baseline clinical characteristics of patients could be associated with the improvement of their depressive symptoms following TMS treatment. We also examined whether our results were similar to those found in the scientific literature. This study would provide clinicians with a realistic perspective on the efficacy and tolerability of TMS at a third-line clinic.

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