Submitted by Maike Costa (maiksebas@gmail.com) on 2017-07-12T13:33:58Z No. of bitstreams: 1 arquivototal.pdf: 4697101 bytes, checksum: 4db6e787d30a0d774624fb6125ec1c29 (MD5) / Made available in DSpace on 2017-07-12T13:33:58Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 4697101 bytes, checksum: 4db6e787d30a0d774624fb6125ec1c29 (MD5) Previous issue date: 2015-12-28 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / This thesis aimed to verify the neurobiological bases of human values. As specific objectives, we sought to: 1) verify, via meta-analysis, the average effect size of studies using transcranial direct-current stimulation (tDCS) and their effect on behavior; 2) verify whether Neuromodulatory effects via non-invasive transcranial stimulation alter scores on implicit measures of human values; 3) check whether the neuromodulation produces behavioral changes; and 4) verify if the scores on implicit measures of human values, after stimulation, correlate with the behavioral variables. To this end, four studies were carried out. Study 1 aimed to carry out a systematic review and a meta-analysis on studies of transcranial direct-current stimulation (tDCS) in the region of the dorsolateral prefrontal cortex (DLPFC) and temporoparietal junction (JTP) and their effects on social variables. A total of 2814 articles were found, among them 17 studies were selected, which demonstrated the lack of research linking brain areas and social variables. It was also possible to observe a low effect size (r = -0.07). In turn, Study 2 aimed to build and knowing evidences of factor validity and criterion, and the internal consistency of the behavioral dispositions scale. The study included 352 people, mostly female, with a mean age of 28.2 years. It performed a principal components analysis setting the extraction of six factors, considering only the four items with higher saturation in each factor. Thus, the scale factor validity has been confirmed, and the final measurement consisted of 24 items. Moreover, it proved scale’s discriminant and convergent validity with alphas greater than 0.69 to all factors. Studies 3 and 4 were experimental, using the neuromodulation of non-invasive nature (Transcranial Direct Current Stimulation). In Study 3 we sought to determine whether neuromodulatory effects of the dorsolateral prefrontal cortex (DLPFC) imply a change in the implicit normative and excitement subfunctions scores as well as the related behavioral task (Balloon Analog Risk Task). The study included 45 people, and 64.4% were female and the mean age was 26.9 years, who answered: Single Categorie IAT for Human Values (SC-IAT-values) computerized version, Basic Values Questionnaire (Gouveia, 2003) and Behavioral Dispositional Questionnaire. Analysis of variance allowed verifying a negative relationship between the DLPFC and excitement values, i.e., the inhibition of this area had an effect on these values and subsequent behavior. In fact, the neuromodulation effect was observed to both implicit [F (2) = 4.22; p <0.05] and the behavioral level [F (2) = 3.23; p < 0.05]. In Study 4 aimed verifying that the temporoparietal junction Neuromodulatory effects imply a change in the implicit normative and excitement subfunctions scores as well as the related behavioral task (Balloon Analog Risk Task). The study included 45 people, being 66.7% female and the mean age was 25.5 years, who answered the same measures of the previous study. A variance analysis verified a relationship between the temporoparietal junction and normative values [F (2) = 3.84; p <0.05]; behavioral measure also showed significant differences [F (2) = 3.48; p <0.05], indicating the effect of stimulation. Finally, it is expected that the results presented and discussed in this thesis can contribute to the academic community, specifically in the field of social neuroscience, social psychology and cognitive psychology. / A presente tese teve como objetivo geral verificar as bases neurobiológicas dos valores humanos. Como objetivos específicos, buscou-se: 1) verificar, via metanálise, o tamanho de efeito médio dos estudos que usam estimulação transcraniana por corrente contínua (ETCC) e seu efeito no comportamento; 2) verificar se efeitos neuromodulatórios via estimulações transcranianas não-invasivas alteram os escores nas medidas implícitas dos valores humanos; 3) verificar se a neuromodulação produz alterações comportamentais; e 4) verificar se os escores nas medidas implícitas dos valores humanos, pós estimulação, correlacionam-se com as variáveis comportamentais. Para tanto, quatro estudos foram realizados. O Estudo 1 teve como objetivo realizar uma revisão sistemática e metanálise acerca dos estudos sobre estimulação transcraniana por corrente contínua (ETCC) na região do córtex pré-frontal dorsolateral (CPFDL) e junção temporoparietal (JTP) e seus efeitos em variáveis sociais. De um total de 2814 artigos, 17 estudos foram selecionados, os quais demonstraram a carência de pesquisas relacionando as áreas cerebrais e as variáveis sociais. Também foi possível observar um baixo tamanho de efeito (r = -0,07). Já o Estudo 2 teve como objetivo construir e conhecer evidências de validade fatorial e de critério, bem como da consistência interna da Escala de disposições comportamentais. Participaram deste estudo 352 pessoas, majoritariamente do sexo feminino, com média de idade de 28,2 anos. Por meio de Análise dos componentes principais e fixando a extração em seis fatores, considerando, unicamente, os quatro itens que mais saturavam em cada fator. Deste modo, a validade fatorial da escala foi corroborada, e a medida final constou de 24 itens. Ademais, pode-se comprovar validade convergente e discriminante da medida; os alfas de todos os fatores foram superiores a 0,69. Os Estudos 3 e 4 foram de caráter experimental, empregando a neuromodulação de caráter não-invasivo (Estimulação Transcraniana de Corrente Contínua). No Estudo 3 buscou-se verificar se efeitos neuromodulatórios do córtex pré-frontal dorsolateral (CPFDL) implicam em uma modificação nos escores implícitos das subfunções experimentação e normativa, bem como na tarefa comportamental relacionada (Balloon Analog Risk Task). Participaram deste estudo 45 pessoas, sendo a maioria do sexo feminino e com idade média de 26,9 anos, os quais responderam a: Single Categorie IAT de Valores Humanos (SC-IAT-Valores) versão computadorizada, Questionário de Valores Básicos (Gouveia, 2003) e Questionário de Disposições Comportamentais. Por meio de análises de variância foi possível verificar uma relação negativa entre o CPFDL e os valores de experimentação, isto é, a inibição desta área surtiu efeito em tais valores e nos comportamentos subsequentes. De fato, o efeito da neuromodulação foi observado tanto a nível implícito [F (2) = 4,22; p < 0,05] quanto a nível comportamental [F (2) = 3,23; p < 0,05]. No Estudo 4 buscou-se verificar se efeitos neuromodulatórios da junção temporoparietal implicam em uma modificação nos escores implícitos das subfunções experimentação e normativa, bem como na tarefa comportamental relacionada (Balloon Analog Risk Task). Participaram deste estudo 45 pessoas, a maioria do sexo feminino e com idade média de 25,5 anos, os quais responderam as mesmas medidas do estudo anterior. Por meio de análises de variância foi possível verificar uma relação entre a junção temporoparietal e os valores normativos [F (2) = 3,84; p < 0,05]; a medida comportamental também apresentou diferença significativa [F (2) = 3,48; p < 0,05], indicando o efeito da estimulação. Finalmente, espera-se que os resultados apresentados e discutidos nesta tese possam contribuir com a comunidade acadêmica, especificamente no âmbito da Neurociência social, Psicologia social e Psicologia cognitiva.

The diploma thesis deals with the topic of neurocognitive changes in schizophrenia and the possibility of non-pharmacological interventions. It first summarizes current knowledge about schizophrenia, in connection with interdisciplinary overlaps enabling orientation in the topic. The thesis describes the individual cognitive disorders that are part of the disease. The main focus of the work is to inform about the possibilities of cognitive remediation. We focus on cognitive training and transcranial direct current stimulation in more detail. In particular, the use of stimulation methods has not yet been described in Czech literature. The work should thus contribute to the mapping of this issue. The theoretical part is followed by an empirical presentation of the results of our pilot study. In the study, we use a quantitative-qualitative methodology to map objective and subjective changes in cognitive functions before and after the application of stimulation and cognitive training in patients with schizophrenia. We included 9 patients who met the entry criteria. The results of the quantitative part did not reveal significant changes after the application of active tDCS stimulation in combination with cognitive training. The qualitative part of the study described subjectively perceived changes and...

The diploma thesis deals with the topic of neurocognitive changes in schizophrenia and the possibility of non-pharmacological interventions. It first summarizes current knowledge about schizophrenia, in connection with interdisciplinary overlaps enabling orientation in the topic. The thesis describes the individual cognitive disorders that are part of the disease. The main focus of the work is to inform about the possibilities of cognitive remediation. We focus on cognitive training and transcranial direct current stimulation in more detail. In particular, the use of stimulation methods has not yet been described in Czech literature. The work should thus contribute to the mapping of this issue. The theoretical part is followed by an empirical presentation of the results of our pilot study. In the study, we use a quantitative-qualitative methodology to map objective and subjective changes in cognitive functions before and after the application of stimulation and cognitive training in patients with schizophrenia. We included 9 patients who met the entry criteria. The results of the quantitative part did not reveal significant changes after the application of active tDCS stimulation in combination with cognitive training. The qualitative part of the study described subjectively perceived changes and...

The primary aim of this thesis is to investigate the physiological effects of transcranial direct current stimulation (tDCS) as applied to the primary motor cortex (M1). This research was largely motivated by the need to understand the basic physiological changes of tDCS, in order to evaluate its use as a potential tool in recovery after stroke, as well as its more general applicability as a tool to modulate plasticity. The experiments in this thesis assess the ability of tDCS to modulate the primary motor cortex in healthy controls. The effects of tDCS on cortical GABA and motor resting state functional connectivity were measured with magnetic resonance spectroscopy (MRS) and resting functional MRI (fMRI). Anodal stimulation reduced GABA concentration and increased functional connectivity in the stimulated M1. Testing these changes within the same individuals demonstrated that the magnitude of changes do not correlate across subjects. Novel evidence on the timecourse of GABA change demonstrated that the reduction in GABA is most prominent in the 30-minute period after stimulation. To determine whether the tDCS-induced modulations in inhibition is restricted to the stimulated hemisphere or whether inhibitory changes could be observed in the nonstimulated M1, or in the interhemispheric connections between the M1s, transcranial magnetic stimulation (TMS) was used to measure intracortical inhibition in each M1 and interhemispheric inhibition and facilitation in the contralateral M1. There were no polarity-specifc effects on intracortical inhibition within either M1, and no changes in interhemispheric excitability from the stimulated to non-stimulated M1. Development of a two-voxel MRS method at ultra high field (7 Tesla) allowed for concurrent measurements of cortical neurotransmitters from both M1s with excellent spectral quality and GABA quantifcation. This method was used to demonstrate the timecourse of tDCS-induced changes in neurochemicals concurrently from both M1s. Anodal stimulation reduced GABA in both the anode-targeted and non-stimulated M1. Cathodal stimulation decreased GABA and glutamate in the non-stimulated M1, with no concurrent changes in the cathode-targeted M1. Bilateral stimulation reduced glutamate in both M1 with no change in GABA.

No description available.

Il y a une longue histoire derrière l’intérêt porté pour les rêves lucides –conscience de rêver pendant un rêve– datant de l’époque de la Grèce antique. La compréhension du rêve lucide a d’abord reposée sur des observations personnelles de certains individus ayant eux-mêmes expérimentés leurs propres rêves lucides. La découverte de l’inconscient, de même que celle du sommeil paradoxal (SP), a grandement contribué à l’essor du rêve lucide, qui a finalement constitué l’objet d’étude de plusieurs recherches empiriques, dont celles menées par le groupe de Stanford, qui est l’un des premiers à avoir évalué la capacité des rêveurs à signaler leurs rêves lucides à l’aide de différents mouvements du corps, en temps réel. Le rêve lucide est un phénomène prévalent, comprenant de nombreuses dimensions, allant de la conscience de soi jusqu’au contrôle sur le contenu du rêve. Certains auteurs ont également parlé du rêve lucide en tant qu’état mental hybride, combinant des caractéristiques des rêves survenant en SP et d’autres caractéristiques propres à l’éveil. De plus, il s’avère que les individus rapportant des rêves lucides fréquemment présentent des caractéristiques psychologiques particulières, sans compter les corrélats physiologiques mesurables qui ont également été associés aux rêves lucides, de même que des corrélats neurophysiologiques. Certains auteurs se sont questionnés sur les différentes façons d’induire des rêves lucides en sommeil. Les techniques proposées sont nombreuses et diversifiées, allant des techniques comportementales aux techniques de stimulation électrique. À cet effet, deux études ont utilisé la stimulation transcrânienne par courant direct (tDCS) (Stumbrys, Erlacher, & Schredl, 2013) et alternatif (tACS) (Voss et al., 2014) dans les régions frontales pendant le SP, montrant une association entre l’augmentation de la conscience de soi dans les rêves et l’activité gamma fronto-temporale. Toutefois, ces études renferment plusieurs faiblesses méthodologiques. Nous avons donc tenté de reproduire ces résultats considérables en appliquant la tACS en SP dans les régions frontales pendant 2.5 min à une fréquence de 40 Hz lors de siestes matinales –favorisant des périodes riches en SP– et en utilisant des tests statistiques plus conservateurs ainsi que des mouvements oculaires pour signaler la lucidité. Pour s’y faire, nous avons recruté 33 sujets dans une étude randomisée à simple aveugle dans laquelle la tACS a été appliquée (STIM) ou non (SHAM) en SP. Les sujets ont été réveillés 3 min après la fin de la STIM ou du SHAM pour répondre à un journal de rêves et une échelle évaluant le degré de lucidité contenu dans les rêves. Bien que plusieurs signaux de lucidité ont été observés, ces derniers se sont produits dans les deux conditions expérimentales, et ce, sans différence significative. L’auto-évaluation du contenu des rêves ne différait pas non plus entre les conditions. Par conséquent, les résultats de la présente étude ne permettent pas de conclure que la tACS appliquée à une fréquence de 40 Hz en SP engendre plus de rêves lucides signalés en temps réel, un plus grand nombre de rêves lucides tels que définis par la LuCiD Scale et des scores plus élevés aux facteurs de cette même échelle. Plusieurs considérations méthodologiques peuvent avoir jouer un rôle dans la production de rêves lucides en sommeil, tels que les critères de recrutement, la pratique des signaux de lucidité et les effets indirects de la tACS, et avoir masqué l’effet de la tACS, qui, dû à son effet sans doute minime, n’a peut-être pas été en mesure d’influencer significativement la production de rêves lucides. Somme toute, plusieurs sujets ont été en mesure de signaler ou de rapporter des rêves lucides dans le cadre de cette étude, ce pourquoi il serait intéressant d’étudier davantage les différentes applications des rêves lucides, autant dans le but d’accroitre nos connaissances sur les rêves et les théories de la conscience que pour développer de potentiels outils cliniques. / There is a long history of interest in lucid dreaming–the awareness of dreaming while dreaming–from the time of ancient Greece. The understanding of lucid dreaming was initially based on personal observations of certain individuals who had themselves experienced lucid dreams. Discovery of the unconscious, as well as rapid-eye-movement (REM) sleep, greatly contributed to the rise of interest in lucid dreaming, which finally became the object of several empirical studies. The Stanford group is one of the first to have conducted laboratory studies specifically on lucid dreams assessing, among other attributes, the ability of dreamers to signal their lucid dreams with different body movements in real-time. Lucid dreaming is a prevalent phenomenon, comprising many dimensions, ranging from self-awareness to control over dream content. Some authors have also described lucid dreaming as a hybrid mental state, mixing REM dreaming and wakefulness characteristics. Moreover, frequent lucid dreamers display certain psychological characteristics, such as high creativity, an internal locus of control, and increases in several cognitive functions. Lucid dreaming has measurable physiological and neurophysiological correlates. Some authors have speculated about the different ways to induce lucid dreams during sleep. The proposed techniques are many and varied, ranging from behavioral techniques to electrical stimulation techniques. Critically, two studies employing frontal transcranial direct (tDC) (Stumbrys et al., 2013) and alternating (tAC) current stimulation (Voss et al., 2014) during REM sleep, have shown an association between increased self-awareness in dreams and fronto-temporal gamma electroencephalographic activity. However, these studies suffer from several methodological weaknesses. We attempted to replicate these important findings using frontal tAC stimulation during morning, REM-rich naps, real-time signal verification and more appropriate conservative statistical tests. We recruited 33 subjects in a single-blind randomized group study in which tAC stimulation was applied (STIM) or not (SHAM) during the REM sleep of a morning nap. During the STIM condition, we applied frontal 40 Hz tAC stimulation during REM sleep for 2.5 min. Subjects were awakened 3 min after stimulation offset for dream reporting and administration of a scale to assess dream lucidity. Although several episodes of signal-verified dream consciousness were observed, these were equally frequent in SHAM and STIM conditions. Self-ratings of dream content also did not distinguish conditions. Therefore, the findings of the present study do not indicate that frontal gamma stimulation increases dreamed self-awareness as measured by real-time signal-verified lucid dreams and self-ratings of dreams. Several methodological considerations may have played a role in the negative findings, such as recruitment criteria, the eyes-closed practice signal and the indirect effects of tAC stimulation during the phosphene and sensation tests. The latter may have masked a real, albeit weak, tAC stimulation effect. Thus, many subjects were able to signal or report lucid dreams in this study, and this supports the notion that further study of lucid dreaming may lead to fruitful applications. Investigating lucid dreaming could be useful for increasing our knowledge of the physiological substrate of dreams, for clarifying theories of consciousness, and for developing potential clinical tools.

La sclérose en plaques est la maladie non tumorale du système nerveux la plus fréquente du sujet jeune. Elle est définie comme une atteinte démyélinisante inflammatoire multifocale et chronique de la substance blanche du système nerveux central d’origine dysimmunitaire. Le handicap moteur est l’un des risques évolutifs principaux de cette maladie. Mieux caractériser les mécanismes du dysfonctionnement du système moteur (atteinte de la voie motrice centrale efférente, altération du réseau moteur cortical à l’origine du mouvement) de même que les mécanismes compensatoires qui le limitent est un enjeu important dans la compréhension et la prévention de l’apparition du handicap. L’étude de ces mécanismes au stade précoce de la maladie permet de mieux comprendre les liens entre l’atteinte tissulaire, les mécanismes de compensation et les conséquences fonctionnelles. Nos travaux ont permis au stade précoce de la SEP de mieux caractériser l’atteinte fonctionnelle de la voie motrice centrale, de montrer l’influence de l’atteinte encéphalique diffuse sur la réorganisation corticale du système moteur et enfin de démontrer l’existence d’une plasticité cérébrale fonctionnelle basale du réseau moteur non dominant corrélée avec les changements d’activation observés lors du mouvement au sein du même réseau. / Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system which is frequently responsible for motor disability. Better assessment of pathophysiological process implicated in motor system dysfunction (cortico-spinal tract or more diffuse tissue damage) as well as the compensatory mechanises are critical in the understanding and the prevention of disability. Their study in the early stage of the disease will allow to a better understanding of the links between tissue injury, compensatory mechanisms and functional consequences. We have better characterized functional dysfunction of the central motor pathway at the early stage of multiple sclerosis. We have also evidenced the influence of diffuse brain injury on functional motor cortical reorganization. Last, we have demonstrated the existence of a basal functional plasticity at rest of the nondominant motor network that is correlated with its functional plasticity during action.

Introdução e objetivos: Estudos recentes sugerem que a estimulação magnética transcraniana repetitiva (EMTr) aplicada sobre o córtex motor é eficaz no tratamento analgésico de doentes com dor crônica. O objetivo deste estudo foi avaliar os efeitos da aplicação da EMTr sobre o córtex motor, utilizada como co-intervenção terapêutica no tratamento de pacientes com síndrome complexa de dor regional (SCDR) refratária aos tratamentos convencionais. Métodos: Vinte e três doentes com SCDR na mão foram distribuídos aleatoriamente em dois grupos de tratamentos para receberem o tratamento padrão (analgésicos, medicações adjuvantes e terapia física) associado a dez sessões diárias e consecutivas de EMTr rápida ou estimulação magnética placebo (EMTp), aplicadas sobre a região correspondente ao córtex motor da mão acometida. Os grupos foram comparados em relação aos aspectos epidemiológicos, apresentação clínica da doença, intensidade da dor, alterações do humor, qualidade de vida e função do membro acometido até noventa dias após a conclusão do tratamento, utilizando-se de entrevistas estruturadas, da escala visual analógicas de dor (EVA), do questionário de dor de McGuill (QM), do questionário PIQ-6 (Pain Inpact Questionnaire), do questionário DASH (Disabilities of Arm, Shoulder and Hand), do questionário SF-36 e dos questionários Hamilton para ansiedade e depressão. Resultados: Ocorreu redução significativa dos escores da EVA no grupo tratado com EMTr durante o tratamento, que durou até o sétimo dia após o encerramento das aplicações (p<0.05). A redução média da EVA no grupo tratado com EMTr foi de 4.65 cm (redução de 50.9% dos escores de dor), estatisticamente superior ao grupo tratado com placebo, no qual a redução foi de 2.18 cm (redução de 24.7%). A diminuição dos escores de dor na EVA foi independente de outras variáveis em estudo, exceto pela melhora no domínio sete do questionário SF-36 (aspectos emocionais). Conclusões: A aplicação de EMTr rápida sobre a área motora da mão de doentes com SCDR, associada a um programa de tratamento padrão, resulta em diminuição maior da percepção espontânea da dor quando comparada ao efeito do tratamento padrão isolado, independentemente de outros possíveis efeitos da EMTr sobre o humor, função do membro acometido ou qualidade de vida / Background and aims: There are many evidences that repetitive transcranial magnetic stimulation (r-TMS) of the motor cortex is effective in relief of chronic pain. The aim of this study was to evaluate the analgesic effects of r-TMS in patients with refractory CRPS. Methods: Twenty-three patients presenting with complex regional pain syndrome (CRPS) of the hand were randomly selected and treated with conventional treatment (analgesics, adjuvant medications and physical therapy) plus sham-TMS or r-TMS to the motor cortex opposite the affected limb: 100% MT, 10 hz, 10 s trains, 25 trains daily, 10 daily sessions. The Visual Analogical Scale of Pain (VAS), McGill Questionnaire, Pain Impact Questionnaire (PIQ-6), Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH), Hamilton Depression and Anxiety Rating Scales and SF-36 Questionnaire were the instruments used for the evaluation. The groups were comparable with regards to socio-demographics, mood and pain intensity. Evaluations were performed before, during TMS treatment and up to three months the end of the treatment. Results: There was a significant reduction in VAS scores favoring the r-TMS group up to the seventh follow-up day (p <0.05). The mean reduction in the rTMS group was of 4.65 cm (fall of 50.9%) against 2.18 cm (fall of 24.7%) in sham group during treatment. Improvement in VAS scores was independent of other variables, except for improvement in emotional aspects in the SF-36. Conclusions: During r-TMS sessions there was significant and positive improvement in pain experience of CRPS patients regardless of mood, function or quality of life effects

La faiblesse des muscles périphériques, définie par une diminution de la force maximale volontaire en dehors de tout état de fatigue neuromusculaire, est une complication fréquente de la broncho-pneumopathie chronique obstructive (BPCO). La force maximale volontaire dépend à la fois des propriétés musculaires périphériques (i.e. volume et architecture musculaire, qualités contractiles) et de la capacité du système nerveux à activer le muscle maximalement. Dans la BPCO, plusieurs travaux ont souligné l'existence paradoxale d'une perte de force maximale volontaire sans altérations musculaires périphériques et sans qu'un déficit d'activation volontaire n'ait clairement été identifié. Pourtant, les patients atteints de BPCO présentent de nombreuses altérations du système nerveux, compatibles avec une capacité d'activation volontaire altérée.L'objectif de ce travail de thèse était donc de tester l'implication du système nerveux dans la faiblesse musculaire de la BPCO et d'en déterminer les mécanismes sous-jacents. Au cours de nos travaux, nous avons mis en évidence une activité corticale diminuée dans la BPCO lors de contractions maximales et sous-maximales volontaires. Nous avons par ailleurs rapporté une perte d'excitabilité du cortex moteur et un déficit d'activation volontaire spécifique aux patients atteints de faiblesse musculaire. Ces résultats sont en accord avec une implication des altérations cérébrales dans la faiblesse musculaire périphérique de la BPCO. Nous sommes ensuite parvenus à identifier une origine potentielle des altérations cérébrales : les désaturations en O2 au cours du sommeil avec mouvements non-rapides des yeux (NREM). Cette hypothèse a été corroborée par l'observation d'un niveau d'activation volontaire réduit chez les patients désatureurs en sommeil NREM. En revanche, aucune répercussion significative n'a pu être observée sur la force maximale volontaire de ces patients, suggérant l'existence d'un mécanisme compensatoire. In fine, nos résultats constituent une avancée importante dans la compréhension du phénomène de faiblesse musculaire, classiquement attribué à la seule perte de masse musculaire. L'implication du système nerveux central dans la faiblesse musculaire ouvre notamment la voie à de nouvelles modalités de prise en charge par des approches spécifiques, dans l'optique de lutter contre la faiblesse musculaire et ses multiples répercussions négatives dans la vie du patient atteint de BPCO. / Peripheral muscle weakness, as defined by a reduced voluntary strength outside any state of neuromuscular fatigue, is a common complication of chronic obstructive pulmonary disease (COPD). Maximal voluntary strength is determined by both peripheral muscle properties (i.e. muscle volume and architecture, contractile quality) and the nervous system's ability to activate the muscle maximally. In COPD, many studies highlighted the paradoxical existence of maximal voluntary strength loss without any peripheral muscle impairment, and without a clearly identified voluntary activation deficit. However, patients with COPD exhibited several nervous system alterations compatible with a reduced maximal voluntary activation capacity. The aim of this thesis was to test the nervous system implication in COPD muscle weakness and to determine the involved mechanisms. As major results, we found a reduced cortical activity in COPD during maximal and sub-maximal voluntary contractions. Furthermore, we reported reduced motor cortex excitability and voluntary activation deficit, specifically in patients with muscle weakness. These results are in accordance with an involvement of cortical alterations in COPD muscle weakness. Then, we indentified a potential origin for cortical alterations: O2 desaturation during non-rapid eye movement (NREM) sleep. This hypothesis has been corroborated by the observation of a reduced voluntary activation in patients with NREM sleep desaturation. However, no significant repercussion could have been observed on maximal voluntary strength in these patients, suggesting a compensatory mechanism.Our results are an important step forward in understanding the COPD muscle weakness that was classically attributed to loss of muscle mass only. The involvement of the central nervous system in COPD muscle weakness also brings about new patient care opportunities via tailored approaches, in order to fight against muscle weakness and its deleterious consequences on a patient's life.

No description available.