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De tout temps, les humains ont cherché différents moyens pour améliorer leur quotidien. Avec les avancées technologiques actuelles, cette quête s’en trouve facilitée, notamment dans la volonté d’accroître leurs capacités cognitives et/ou motrices. La neuro imagerie permet dorénavant de renseigner les aires cérébrales activées lors de différentes tâches fonctionnelles. Il est aussi possible de moduler l’activité cérébrale en stimulant localement le cerveau avec de faibles courants électriques. Une des techniques les plus répandues à cet effet est appelée tDCS pour transcranial direct current stimulation. Il s’agit en fonction de la polarité du courant induit de moduler à la hausse (stimulation anodale) ou à la baisse (stimulation cathodale) l’excitabilité cortico-spinale en dépolarisant ou en hyperpolarisant la membrane des neurones, respectivement. Malgré une démocratisation grandissante de la neuromodulation via tDCS, les résultats rapportés par la communauté scientifique sont relativement hétérogènes. Les travaux initiés au début des années 2000 sont remis en cause par des résultats actuels faisant état d’une variabilité inter et intra individuelle assez importante. Cette pierre d’achoppement nécessite de développer de nouveaux protocoles d’application de la tDCS. Dans cette thèse, nous avons étudié plusieurs modalités d’application de la tDCS afin d’accroître la persistance des effets neuroplastiques induits et d’augmenter les performances comportementales. Deux études ont été menées afin de révéler dans un premier temps les apports induits par le couplage tâche motrice-tDCS pour ensuite mettre en avant les effets cumulatifs de la répétition de sessions de tâche motrice-tDCS avec pré conditionnement sur la performance motrice. La première étude à travers l’utilisation de la spectroscopie dans le proche infrarouge a permis de rapporter des changements hémodynamiques distincts subséquents au couplage tâche motrice-tDCS par rapport à des protocoles tDCS plus conventionnels. La primauté de l’utilisation concomitante de la tDCS à la tâche motrice a été révélée par la moindre activation du cortex sensorimoteur durant la stimulation ainsi que par une activation cérébrale retardée accrue qui pourrait représenter une réorganisation neuroplastique. La seconde étude s’est intéressée aux effets de la polarité du conditionnement lors de sessions répétées avec comme objectif d’améliorer l’apprentissage et la rétention du système sensorimoteur. Le conditionnement par tDCS était plus propice lors de sessions répétées à engendrer des performances motrices supérieures contrairement à la condition sham. La polarité cathodale engendrait une persistance prolongée. Les premiers résultats de ces travaux de thèse ont permis de défendre l’usage concomitant de la tDCS avec la tâche motrice. De futures recherches sont nécessaires afin d’étudier le transfert de ces résultats dans le monde de l’entraînement ainsi que celui de la réhabilitation. / Historically, humans have sought various ways to improve their daily lives. With the current technological advances, this quest is facilitated, especially in the desire to increase their cognitive and / or motor skills. Neuro imagery now makes it possible to inform the areas activated during different functional tasks. Today, it is now possible to modulate brain activity by stimulating the brain locally with weak electrical currents. One of the most common techniques for this purpose is called tDCS for transcranial direct current stimulation. The polarity of the induced current (anodal or cathodal stimulation) allows to modulate upward or downward cortico-spinal excitability by depolarizing or hyperpolarizing the membrane of the neurons, respectively. Despite a growing interest of neuromodulation techniques via tDCS, the results reported by the scientific community are relatively heterogeneous. The work initiated at the beginning of the 2000s is called into question by current results showing a rather large inter and intra variability. This stumbling block requires the development of new protocols for the application of anodal tDCS (atDCS). In this thesis, we were interested in optimizing atDCS protocols in order to increase the persistence of the induced-neuroplastic effects and to increase the behavioral performances. Two studies were carried out in order to first reveal the impact from the motor task/atDCS coupling and then to highlight the cumulative effects of multiple motor-tDCS task sessions with priming atDCS on motor performance. The first study through the use of near infrared spectroscopy allowed to report various hemodynamic changes subsequent to the motor task/atDCS coupling with respect to independent and controlled stimulation protocols. The primacy of the concomitant use of tDCS with the motor task was revealed by the slightest activation of the sensorimotor cortex during stimulation and by an increased delayed cerebral activation which could represent a neuroplastic reorganization. The second study examined the effects of repeated atDCS sessions with anoadal or cathodal tDCS priming in order to improve the learning and retention gains of the sensorimotor system. TDCS priming was more favorable for repeated atDCS sessions to generate higher motor performances contrary to sham. The cathodal polarity produced prolonged persistence. The major findings of this work allow to support the concomitant use of atDCS with the motor task. Future research is needed to study the transfer of these results into the fields of coaching and rehabilitation.

Background: Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types. Methods: We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. PROSPERO ID: CRD42016042055. Results: We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upperextremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events. Conclusion: Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.

Introdução: A osteoartrite de joelhos (KOA) apresenta alta prevalência, principalmente em mulheres. Com o envelhecimento da população esta prevalência irá aumentar. Os tratamentos conservadores apresentam limitada eficácia em expressivo número de pacientes no curso do tratamento . A cirurgia de protetização apresenta altos custos, possibilidade de complicações pós-operatórias graves e ainda que a correção anatômica seja perfeita, em torno de 20% dos pacientes persistem com dor crônica pós-operatória. Portanto, é preciso avançar no conhecimento dos mecanismos fisiopatológicos e estudar novas abordagens terapêuticas para agregar às existentes, visando melhor manejo da dor e para restabelecer a função de maneira mais efetiva. Estas questões motivaram três questões centrais que origiram os três estudos que compõem esta tese. Estudo I: No primeiro estudo avaliamos os mecanismos pelos quais há perpetuação da dor na KOA. Para responder a esta questão buscou respostas aos seguintes objetivos: I) Comparar se a função da via da dor inibitório descendente está associada com o estado de inibição no sistema corticospinal, indexado pelo potencial evocado motor (MEP) e o período de silêncio cortical (CSP) em pacientes com KOA e controles saudáveis. II) Determinar se há correlação entre as medidas de inibição intracortical (CSP, MEP) com alterações na escala de dor numérica (NPS 0-10) na KOA durante a tarefa de modulação condicionada de dor (CPM-task) considerando o efeito da capacidade funcional auto-relatada avaliada pelo Western Ontário and McMaster Universities Index (WOMAC) e uso de analgésicos. Métodos: Estudo transversal, foram incluídas 21 pacientes femininas com KOA e 10 controles saudáveis com idade entre 19 a 75 anos. Os parâmetros de excitabilidade do córtex motor (MEP e CSP) foram avaliados utilizando a estimulação magnética trasncraniana (EMT). Avaliação de dor e a incapacidade pelo WOMAC e a NPS (0-10) durante a CPM-task. Resultados: A média ajustada (DP) do CSP observada em pacientes com OA foi 23,43% menor do que em indivíduos saudáveis [54,54 (16,10) vs. 70,94 (22,87)], respectivamente (P = 0,01). A função do sistema modulador descendente de dor avaliado pela alteração do NPS (0-10) durante o CPM-task foi negativamente correlacionada com o parâmetro de excitabilidade cortical indexado pelo CSP (P = 0,001). O CSP foi negativamente correlacionado com a dor e incapacidade avaliada pelo índice WOMAC. Conclusão: Foi observado um sistema inibitório descendente de dor enfraquecido, corroborando com os achados em outras patologias de dor crônica. Estudo II O segundo estudo buscou determinar se na KOA, uma sessão de IMS (eletroestimulação intramuscular) ativa comparada com sham promove um efeito nos parâmetros de excitabilidade do córtex motor [MEP, inibição intracortical curta - SICI, facilitação intracortical (ICF) e CSP] e nas medidas de dor [limiar de dor a pressão (PPT); escala visual analógica de dor (VAS) e mudança na escala de dor numérica (NPS0-10) durante a CPM-task]. Esse estudo também se propôs a determinar se o fator neurotrófico derivado do cérebro (BDNF) sérico medeia o efeito desta estimulação no sistema cortico-espinhal, tal como avaliado pelo MEP e pelo PPT. Métodos: Foram incluídas 26 mulheres com KOA, com idade entre 50 a 75 anos. Elas foram divididas randomicamente para receber uma sessão de 30 minutos de IMS ativa (n = 13) ou IMS sham (n = 13) por meio de eletroestimulação com frequência de 2 Hz. As agulhas foram inseridas paravertebrais em nível da saída das raízes lombares de L1 a S2 e nos músculos cuja inervação corresponde a essas raízes e que sustentam a articulação do joelho (vasto medial, reto anterior, vasto lateral, tibial anterior e inserção da pata anserina). Os desfechos foram as medidas de dor (VAS, PPT, NPS durante CPM-task) e parâmetros de excitabilidade (MEP, CSP, SICI, ICF) realizados antes e imediatamente após a intervenção. Resultados: a IMS ativa comparado com sham diminuiu o MEP em 31,61% [intervalo de confiança (IC) 95%, 2,34-60,98]. Para os resultados secundários, IMS reduziu o ICF e aumentou o CSP. A IMS melhorou a dor relatada no VAS, o PPT e a pontuação do NPS (0-10) durante a CPM-task. O BDNF foi negativamente correlacionado com o PPT (r = 20,56). Conclusão: Obtivemos resultados demonstrando melhora da dor e reforço do sistema cortico-espinhal inibitório comparado ao tratamento sham com IMS. Estudo III O terceiro estudo buscou: 1) Avaliar se a utilização da ETCC (estimulação transcraniana de corrente contínua) combinada a IMS pode promover um resultado melhor de modulação da via cortico-espinhal de dor através da potenciação dos efeitos dos dois tratamentos; comparado a cada um deles isoladamente e ao tratamento sham. 2) Avaliar a capacidade da ETCC em reforçar o sistema inibitório descendente de dor e modular a excitabilidade neuronal através da VAS, PPT e NPS durante CPM-task. Além disso, avaliamos se o BDNF sérico poderia prever o efeito da terapia no final do tratamento. Métodos: 60 mulheres de 50 a 75 anos. Randomizadas em um de quatro grupos: ETCC+IMS, ETCC+IMS sham, ETCC sham+IMS, ETCC sham+IMS sham. Receberam 5 sessões de tratamento: ETCC anodal, lado contrário ao joelho acometido, 2mA, 30 min. IMS: estimulação com freqüência de 2Hz, 30 min; agulhas colocadas a 2cm de L1 á S2, nos músculos vasto medial, vasto lateral, reto anterior, tibial anterior e na inserção da pata anserina. Resultados: O a-tDCS + a-IMS mostrou os melhores resultados com diferença significativa na dor (VAS) [média (DP) relacionadas ao tratamento (pós e pré): 0.46 (0.04) vs. 6.32 (1.97); 95%CI -5.42 (-8.24 to -4.36), p=.003] e funcionalidade. Esse resultado iniciou na primeira sessão e manteve-se ao longo do estudo. A-tDCS+a-IMS foi o único capaz de modificar o sistema inibitório descendente de dor. Conclusão: Obtivemos melhora da dor e capacidade funcional com IMS, ETCC e ETCC+IMS. Mas somente o grupo de tratamento ETCC+IMS demonstrou capacidade de modificação do sistema inibitório descendente de dor. / Background: Knee osteoarthritis (KOA) has a high prevalence, especially in women. With the aging of the population this prevalence will increase. Conservative treatments have limited efficacy in expressive number of patients in the course of the treatment. The total knee replacement surgery presents high costs, possibility of serious postoperative complications and although the anatomical correction is perfect, around 20% persist with chronic postoperative pain. Therefore, it’s necessary to advance in the knowledge of pathophysiological mechanisms and to study new therapeutic approaches to add to the existing ones, aiming to better manage pain and to restore function more effectively. These questions motivated three central questions that originated the three studies that compose this thesis. Study I In the first study we evaluated the mechanisms by which there is perpetuation of pain in knee osteoarthritis and to answer this question sought to answer the following objectives: I) To compare if the function of the descending inhibitory pain pathway is associated with the state of inhibition in the corticospinal system, indexed by the motor evoked potential (MEP) and the cortical silent period (CSP) in patients with KOA and healthy controls. II) To determine if there is a correlation between the intracortical inhibition measures (CSP, MEP) with changes in the numerical pain scale (NPS 0-10) in the KOA during the task of conditioned pain modulation (CPM-task) considering the effect of the self-reported function evaluated by the Western Ontario and McMaster Universities Index (WOMAC) and the use of analgesics. Methods: A cross-sectional study included 21 female patients with KOA and 10 healthy controls aged 19-75 years old. Motor cortex excitability parameters (MEP and CSP) were assessed using transcranial magnetic stimulation (TMS). Pain assessment and disability by WOMAC and NPS (0-10) during the CPM-task. Results: The adjusted mean (SD) of CSP observed in patients with OA was 23.43% lower than in healthy subjects [54,54 (16,10) vs 70.94 (22.87)], respectively (P = 0.01). The function of the descending pain modulatory system evaluated by the NPS (0-10) change during the CPM-task was negatively correlated with the cortical excitability parameter indexed by CSP (P = 0.001). CSP was negatively correlated with pain and disability assessed by the WOMAC index. Conclusion: It was observed a descending pain inhibitory system weakened, corroborating the findings of other chronic pain conditions. Study II The second study sought to determine if one active IMS session compared to sham promoted an effect on motor cortex excitability (MEP, short intracortical inhibition - SICI, intracortical facilitation (ICF) and CSP and in the pain measures [pressure pain threshold (PPT); Visual analogue pain scale (VAS) and numerical pain scale change (NPS0-10) during the CPM-task]. This study also aimed to determine whether serum brain-derived neurotrophic factor (BDNF) mediates the effect of this stimulation on the cortico-spinal system, as assessed by MEP and PPT. Methods: Twenty-six women with KOA, aged 50-75 years old, were included. They were randomly divided to receive a 30-minute session of active IMS (n = 13) or IMS sham (n = 13) by electrostimulation with a frequency of 2 Hz. The needles were inserted paravertebral at the level of the lumbar roots exit from L1 to S2 and in the muscles whose innervation corresponds to these roots and which support the knee joint (vastus medialis, rectus anterior, vastus lateral, tibialis anterior and insertion of the anserine paw). The outcomes were pain measures (VAS, PPT, NPS during CPM-task) and excitability parameters (MEP, CSP, SICI, ICF) performed before and immediately after the intervention. Results: the active IMS compared with sham decreased the MEP by 31.61% [confidence interval (CI) 95%, 2.34-60.98]. For the secondary outcomes, IMS reduced ICF and increased CSP. IMS improved pain reported in VAS, PPT, and NPS score (0-10) during the CPM-task. BDNF was negatively correlated with PPT (r = 20.56). Conclusion: We obtained results demonstrating improvement of pain and enhancement of the inhibitory corticospinal system compared to sham treatment with IMS. Study III The third study aimed to: 1) Evaluate if the use of the combined tDCS (transcranial direct current stimulation) to IMS can promote a better result of modulation of the corticospinal pain pathway through the potentiation of the effects of the two treatments; compared to each of them alone, and with the sham treatment. 2) To evaluate the ability of the tDCS to strengthen the descending inhibitory pain system and to modulate neuronal excitability through VAS, PPT and NPS during CPM-task. In addition, we evaluated whether serum BDNF could predict the effect of therapy at the end of treatment. Methods: 60 women aged 50 to 75 years old. Randomized in one of four groups: tDCS + IMS, tDCS + IMS sham, tDCS sham + IMS, tDCS sham + IMS sham. They received 5 sessions of treatment: anodal tDCS, opposite side to affected knee, 2mA, 30 min. IMS: stimulation with frequency of 2Hz, 30 min; needles placed at 2 cm from L1 to S2, in the vastus medialis, vastus lateralis, rectus anterior, tibialis anterior and insertion of the anserine paw. Results: a-tDCS + a-IMS showed the best results with significant difference in pain (VAS) [mean (SD) related to treatment (post and pre): 0.46 (0.04) vs. 6.32 (1.97); 95% CI -5.42 (-8.24 to -4.36), p = .003] and functionality. This result started in the first session and was maintained throughout the study. A-tDCS + a-IMS was the only one able to modify the descending inhibitory pain system. Conclusion: We achieved improved pain and functional capacity with IMS, tDCS and tDCS + IMS. But only the tDCS + IMS treatment group demonstrated ability to modify the descending inhibitory pain system.

Working memory training improves performance on trained and untrained working memory tasks, but there is little consistent evidence that these gains benefit everyday tasks that rely on working memory. Evidence has shown that transcranial electrical stimulation (tES) may be an effective tool for enhancing cognitive training and promoting transfer. In the first study, participants completed Cogmed working memory training with either active or sham transcranial random noise stimulation (tRNS). Training was associated with substantial gains on the training activities and on transfer measures of working memory with common processing and storage demands to the training tasks. tRNS did not enhance gains on trained or untrained activities. The second study systematically investigated the boundary conditions to training transfer by testing whether gains following backward digit recall (BDR) training transferred within- and across-paradigm to untrained backward recall and n-back tasks with varying degrees of overlap with the training activity. A further aim was to test whether transcranial direct current stimulation (tDCS) enhanced training and transfer. Participants were allocated to one of three conditions: (i) BDR training with active tDCS, (ii) BDR training with sham tDCS, or (iii) visual search control training with sham tDCS. The results indicated that training transfer is constrained by paradigm, but not by stimuli domain or stimuli materials. There was no evidence that tDCS enhanced performance on the training or transfer tasks. The results of Study 1 and Study 2 provide no evidence that tES enhances the benefits of working memory training. The absence of transfer between backward recall training and n-back in Study 2 suggested the tasks might tap into distinct aspects of working memory. Consequently, the final study used a latent variable approach to explore the degree of overlap between different forms of backward recall and n-back tasks containing digits, letters, or spatial locations as stimuli. The best-fitting factor model included two distinct but related (r = .68) constructs corresponding to backward recall and n-back. Both categories of task were linked to a separate fluid reasoning construct, providing evidence that both are valid measures of higher-order complex cognition. Overall, the experiments in this thesis suggest that working memory tasks tap into separate processes and that training may be targeting and improving these distinct processes, explaining the absence of cross-paradigm transfer.

Made available in DSpace on 2014-12-17T14:44:17Z (GMT). No. of bitstreams: 1 GertrudesNM_DISSERT.pdf: 3164686 bytes, checksum: e4de9859908d8c6840498816188878f8 (MD5) Previous issue date: 2013-02-28 / The fluctuacion force has been increasingly used in studies with elderly as a good predictor of performance and functionality of the motor. However, most analyzes the fluctuation of force in one session. Thus, identifying the minimum amount of sessions needed for familiarization with the fluctuation strength in isometric exercise become relevant. Furthermore, to investigate the effects of applying transcranial direct current stimulation (tDCS) associated with regular exercise on rates fluctuation task force is extremely important. In the first experiment, volunteers were subjected to a protocol marked by a familiarization session to establish the parameters of VCM and eight sessions with intensity of 30% MVC in office. It was observed that two familiarization sessions are required so there is a fluctuation stabilizing force. In experiment II, subjects performed an isometric contraction before and after applying tDCS (cathode, anode and sham) applied to M1. ETCC anodic effectively contributed to reducing the fluctuation of force during isometric exercise in the elderly, while the cathodic caused the increased levels of strength fluctuation. It was concluded that there is a need to implement a familiarization protocol with at least two sessions to avoid possible misunderstandings of measurements in tests of fluctuacion force. Besides that tDCS interfered with the behavior of the oscillations of force, with cathodic promoting increased fluctuation strength and anodic contributed to greater stability, demonstrating the potential of this technique neuromodulation associated with exercise as rehabilitation tools / A flutua??o de for?a tem sido cada vez mais utilizada em estudos com idosos como um bom preditor de desempenho e funcionalidade da motricidade. No entanto, a maioria analisa a flutua??o de for?a em sess?o ?nica. Assim, identificar a quantidade de sess?es m?nimas necess?rias para a familiariza??o ao teste de flutua??o de for?a em exerc?cio isom?trico tornar-se pertinente. Al?m disso, investigar os efeitos da aplica??o da Estimula??o Transcraniana por Corrente Cont?nua (ETCC) associada ? pr?tica regular de exerc?cio sobre os ?ndices de flutua??o de for?a ? tarefa de extrema relev?ncia. No experimento I, volunt?rias foram submetidas a um protocolo de familiariza??o marcado por uma sess?o para estabelecer os par?metros de CVM e oito sess?es com intensidade de 30%CVM em exerc?cio. Observou-se que duas sess?es de familiariza??o s?o necess?rias para que haja uma estabiliza??o da flutua??o de for?a. No experimento II, volunt?rias realizaram uma contra??o isom?trica antes e ap?s a aplica??o de ETCC (cat?dica, an?dica e sham) aplicada ao M1. ETCC an?dica contribuiu efetivamente para a redu??o da flutua??o de for?a em idosos durante exerc?cio isom?trico, enquanto que a cat?dica provocou o aumento dos ?ndices de flutua??o de for?a. Concluiu-se que h? a necessidade de aplica??o de um protocolo de familiariza??o com pelo menos duas sess?es para que sejam evitados equ?vocos de mensura??es em testes de avalia??o da flutua??o de for?a. Al?m de que a ETCC interferiu no comportamento das oscila??es de for?a, com cat?dica promovendo aumento da flutua??o de for?a e a an?dica contribuiu para uma maior estabilidade, demonstrando o potencial dessa t?cnica de neuromodula??o associada ao exerc?cio como ferramentas de reabilita??o

Introdução: A osteoartrite de joelhos (KOA) apresenta alta prevalência, principalmente em mulheres. Com o envelhecimento da população esta prevalência irá aumentar. Os tratamentos conservadores apresentam limitada eficácia em expressivo número de pacientes no curso do tratamento . A cirurgia de protetização apresenta altos custos, possibilidade de complicações pós-operatórias graves e ainda que a correção anatômica seja perfeita, em torno de 20% dos pacientes persistem com dor crônica pós-operatória. Portanto, é preciso avançar no conhecimento dos mecanismos fisiopatológicos e estudar novas abordagens terapêuticas para agregar às existentes, visando melhor manejo da dor e para restabelecer a função de maneira mais efetiva. Estas questões motivaram três questões centrais que origiram os três estudos que compõem esta tese. Estudo I: No primeiro estudo avaliamos os mecanismos pelos quais há perpetuação da dor na KOA. Para responder a esta questão buscou respostas aos seguintes objetivos: I) Comparar se a função da via da dor inibitório descendente está associada com o estado de inibição no sistema corticospinal, indexado pelo potencial evocado motor (MEP) e o período de silêncio cortical (CSP) em pacientes com KOA e controles saudáveis. II) Determinar se há correlação entre as medidas de inibição intracortical (CSP, MEP) com alterações na escala de dor numérica (NPS 0-10) na KOA durante a tarefa de modulação condicionada de dor (CPM-task) considerando o efeito da capacidade funcional auto-relatada avaliada pelo Western Ontário and McMaster Universities Index (WOMAC) e uso de analgésicos. Métodos: Estudo transversal, foram incluídas 21 pacientes femininas com KOA e 10 controles saudáveis com idade entre 19 a 75 anos. Os parâmetros de excitabilidade do córtex motor (MEP e CSP) foram avaliados utilizando a estimulação magnética trasncraniana (EMT). Avaliação de dor e a incapacidade pelo WOMAC e a NPS (0-10) durante a CPM-task. Resultados: A média ajustada (DP) do CSP observada em pacientes com OA foi 23,43% menor do que em indivíduos saudáveis [54,54 (16,10) vs. 70,94 (22,87)], respectivamente (P = 0,01). A função do sistema modulador descendente de dor avaliado pela alteração do NPS (0-10) durante o CPM-task foi negativamente correlacionada com o parâmetro de excitabilidade cortical indexado pelo CSP (P = 0,001). O CSP foi negativamente correlacionado com a dor e incapacidade avaliada pelo índice WOMAC. Conclusão: Foi observado um sistema inibitório descendente de dor enfraquecido, corroborando com os achados em outras patologias de dor crônica. Estudo II O segundo estudo buscou determinar se na KOA, uma sessão de IMS (eletroestimulação intramuscular) ativa comparada com sham promove um efeito nos parâmetros de excitabilidade do córtex motor [MEP, inibição intracortical curta - SICI, facilitação intracortical (ICF) e CSP] e nas medidas de dor [limiar de dor a pressão (PPT); escala visual analógica de dor (VAS) e mudança na escala de dor numérica (NPS0-10) durante a CPM-task]. Esse estudo também se propôs a determinar se o fator neurotrófico derivado do cérebro (BDNF) sérico medeia o efeito desta estimulação no sistema cortico-espinhal, tal como avaliado pelo MEP e pelo PPT. Métodos: Foram incluídas 26 mulheres com KOA, com idade entre 50 a 75 anos. Elas foram divididas randomicamente para receber uma sessão de 30 minutos de IMS ativa (n = 13) ou IMS sham (n = 13) por meio de eletroestimulação com frequência de 2 Hz. As agulhas foram inseridas paravertebrais em nível da saída das raízes lombares de L1 a S2 e nos músculos cuja inervação corresponde a essas raízes e que sustentam a articulação do joelho (vasto medial, reto anterior, vasto lateral, tibial anterior e inserção da pata anserina). Os desfechos foram as medidas de dor (VAS, PPT, NPS durante CPM-task) e parâmetros de excitabilidade (MEP, CSP, SICI, ICF) realizados antes e imediatamente após a intervenção. Resultados: a IMS ativa comparado com sham diminuiu o MEP em 31,61% [intervalo de confiança (IC) 95%, 2,34-60,98]. Para os resultados secundários, IMS reduziu o ICF e aumentou o CSP. A IMS melhorou a dor relatada no VAS, o PPT e a pontuação do NPS (0-10) durante a CPM-task. O BDNF foi negativamente correlacionado com o PPT (r = 20,56). Conclusão: Obtivemos resultados demonstrando melhora da dor e reforço do sistema cortico-espinhal inibitório comparado ao tratamento sham com IMS. Estudo III O terceiro estudo buscou: 1) Avaliar se a utilização da ETCC (estimulação transcraniana de corrente contínua) combinada a IMS pode promover um resultado melhor de modulação da via cortico-espinhal de dor através da potenciação dos efeitos dos dois tratamentos; comparado a cada um deles isoladamente e ao tratamento sham. 2) Avaliar a capacidade da ETCC em reforçar o sistema inibitório descendente de dor e modular a excitabilidade neuronal através da VAS, PPT e NPS durante CPM-task. Além disso, avaliamos se o BDNF sérico poderia prever o efeito da terapia no final do tratamento. Métodos: 60 mulheres de 50 a 75 anos. Randomizadas em um de quatro grupos: ETCC+IMS, ETCC+IMS sham, ETCC sham+IMS, ETCC sham+IMS sham. Receberam 5 sessões de tratamento: ETCC anodal, lado contrário ao joelho acometido, 2mA, 30 min. IMS: estimulação com freqüência de 2Hz, 30 min; agulhas colocadas a 2cm de L1 á S2, nos músculos vasto medial, vasto lateral, reto anterior, tibial anterior e na inserção da pata anserina. Resultados: O a-tDCS + a-IMS mostrou os melhores resultados com diferença significativa na dor (VAS) [média (DP) relacionadas ao tratamento (pós e pré): 0.46 (0.04) vs. 6.32 (1.97); 95%CI -5.42 (-8.24 to -4.36), p=.003] e funcionalidade. Esse resultado iniciou na primeira sessão e manteve-se ao longo do estudo. A-tDCS+a-IMS foi o único capaz de modificar o sistema inibitório descendente de dor. Conclusão: Obtivemos melhora da dor e capacidade funcional com IMS, ETCC e ETCC+IMS. Mas somente o grupo de tratamento ETCC+IMS demonstrou capacidade de modificação do sistema inibitório descendente de dor. / Background: Knee osteoarthritis (KOA) has a high prevalence, especially in women. With the aging of the population this prevalence will increase. Conservative treatments have limited efficacy in expressive number of patients in the course of the treatment. The total knee replacement surgery presents high costs, possibility of serious postoperative complications and although the anatomical correction is perfect, around 20% persist with chronic postoperative pain. Therefore, it’s necessary to advance in the knowledge of pathophysiological mechanisms and to study new therapeutic approaches to add to the existing ones, aiming to better manage pain and to restore function more effectively. These questions motivated three central questions that originated the three studies that compose this thesis. Study I In the first study we evaluated the mechanisms by which there is perpetuation of pain in knee osteoarthritis and to answer this question sought to answer the following objectives: I) To compare if the function of the descending inhibitory pain pathway is associated with the state of inhibition in the corticospinal system, indexed by the motor evoked potential (MEP) and the cortical silent period (CSP) in patients with KOA and healthy controls. II) To determine if there is a correlation between the intracortical inhibition measures (CSP, MEP) with changes in the numerical pain scale (NPS 0-10) in the KOA during the task of conditioned pain modulation (CPM-task) considering the effect of the self-reported function evaluated by the Western Ontario and McMaster Universities Index (WOMAC) and the use of analgesics. Methods: A cross-sectional study included 21 female patients with KOA and 10 healthy controls aged 19-75 years old. Motor cortex excitability parameters (MEP and CSP) were assessed using transcranial magnetic stimulation (TMS). Pain assessment and disability by WOMAC and NPS (0-10) during the CPM-task. Results: The adjusted mean (SD) of CSP observed in patients with OA was 23.43% lower than in healthy subjects [54,54 (16,10) vs 70.94 (22.87)], respectively (P = 0.01). The function of the descending pain modulatory system evaluated by the NPS (0-10) change during the CPM-task was negatively correlated with the cortical excitability parameter indexed by CSP (P = 0.001). CSP was negatively correlated with pain and disability assessed by the WOMAC index. Conclusion: It was observed a descending pain inhibitory system weakened, corroborating the findings of other chronic pain conditions. Study II The second study sought to determine if one active IMS session compared to sham promoted an effect on motor cortex excitability (MEP, short intracortical inhibition - SICI, intracortical facilitation (ICF) and CSP and in the pain measures [pressure pain threshold (PPT); Visual analogue pain scale (VAS) and numerical pain scale change (NPS0-10) during the CPM-task]. This study also aimed to determine whether serum brain-derived neurotrophic factor (BDNF) mediates the effect of this stimulation on the cortico-spinal system, as assessed by MEP and PPT. Methods: Twenty-six women with KOA, aged 50-75 years old, were included. They were randomly divided to receive a 30-minute session of active IMS (n = 13) or IMS sham (n = 13) by electrostimulation with a frequency of 2 Hz. The needles were inserted paravertebral at the level of the lumbar roots exit from L1 to S2 and in the muscles whose innervation corresponds to these roots and which support the knee joint (vastus medialis, rectus anterior, vastus lateral, tibialis anterior and insertion of the anserine paw). The outcomes were pain measures (VAS, PPT, NPS during CPM-task) and excitability parameters (MEP, CSP, SICI, ICF) performed before and immediately after the intervention. Results: the active IMS compared with sham decreased the MEP by 31.61% [confidence interval (CI) 95%, 2.34-60.98]. For the secondary outcomes, IMS reduced ICF and increased CSP. IMS improved pain reported in VAS, PPT, and NPS score (0-10) during the CPM-task. BDNF was negatively correlated with PPT (r = 20.56). Conclusion: We obtained results demonstrating improvement of pain and enhancement of the inhibitory corticospinal system compared to sham treatment with IMS. Study III The third study aimed to: 1) Evaluate if the use of the combined tDCS (transcranial direct current stimulation) to IMS can promote a better result of modulation of the corticospinal pain pathway through the potentiation of the effects of the two treatments; compared to each of them alone, and with the sham treatment. 2) To evaluate the ability of the tDCS to strengthen the descending inhibitory pain system and to modulate neuronal excitability through VAS, PPT and NPS during CPM-task. In addition, we evaluated whether serum BDNF could predict the effect of therapy at the end of treatment. Methods: 60 women aged 50 to 75 years old. Randomized in one of four groups: tDCS + IMS, tDCS + IMS sham, tDCS sham + IMS, tDCS sham + IMS sham. They received 5 sessions of treatment: anodal tDCS, opposite side to affected knee, 2mA, 30 min. IMS: stimulation with frequency of 2Hz, 30 min; needles placed at 2 cm from L1 to S2, in the vastus medialis, vastus lateralis, rectus anterior, tibialis anterior and insertion of the anserine paw. Results: a-tDCS + a-IMS showed the best results with significant difference in pain (VAS) [mean (SD) related to treatment (post and pre): 0.46 (0.04) vs. 6.32 (1.97); 95% CI -5.42 (-8.24 to -4.36), p = .003] and functionality. This result started in the first session and was maintained throughout the study. A-tDCS + a-IMS was the only one able to modify the descending inhibitory pain system. Conclusion: We achieved improved pain and functional capacity with IMS, tDCS and tDCS + IMS. But only the tDCS + IMS treatment group demonstrated ability to modify the descending inhibitory pain system.

A depressão pós Acidente Vascular Cerebral (AVC) é uma condição desabilitante que ocorre em um terço dos casos. Há uma dificuldade no tratamento farmacológico devido a efeitos adversos e eficácia limitada. Recentemente, a estimulação trasncraniana por corrente contínua (ETCC) tem demonstrado eficácia no tratamento da depressão unipolar, apesar dos seus efeitos em depressões secundárias serem desconhecidos. O objetivo do estudo foi avaliar a eficácia e segurança da ETCC, uma intervenção não farmacológica, para depressão pós AVC (DPA), através de um ensaio clínico, randomizado, duplo-cego, sham-controlado. Foram incluídos quarenta e oito pacientes sem uso de antidepressivos com DPA foram igualmente divididos em 2 grupos que não diferiram em gênero, idade, gravidade do AVC ou da depressão e nem em outras variáveis clínicas. Foram realiadas 12 sessões de 30 minutos de ETCC com 2mA de corrente com ânodo à esquerda e cátodo à direita em córtex pré-frontal dorsolateral. Para a ETCC sham foi feita um minuto de estimulação somente, seguida por desligamento da máquina até um total de 30 minutos. Foi feita uma análise por intenção de tratamento, na qual o desfecho primário foi mudança na Hamilton Depression Rating Scale na sexta-semana (final). Resposta clínica e remissão foram desfechos secundários. Segurança foi avaliada usando um questionário de efeitos adversos, avaliação da cognição e a escala de mania de Young. A ETCC ativa foi significantemente superior a sham no desfecho final (diferença de médias de 4.7 pontos, IC95% de 2.1 a 7.3, P < 0.001). Taxas de resposta e remissão também foram estatisticamente maior no grupo ativo (37.5% e 20.8%, respectivamente) em relação ao grupo sham (4.1% e 0). O número necessário para tratar para resposta e remissão foi, respectivamente, 3 e 5. A região ou lado do AVC não predisse resposta. Nenhum efeito adverso grave foi relatado e a frequência dos efeitos adversos foi semelhante em ambos grupos. Pacientes e avaliadores foram cegados de forma efetiva. Este é o primeiro estudo controlado que mostra a eficácia da ETCC na DPA. Dessa forma, a ETCC pode ser uma opção terapêutica para esses pacientes / Depression after a stroke is a disabling condition that occurs in up to one-third of cases. Pharmacological treatment is challenging due to adverse effects and presents limited efficacy. Recently, transcranial direct current stimulation (tDCS) has shown efficacy in the treatment of unipolar depression, although its antidepressant effects in secondary depressions are unknown. The objective of the study was to assess the efficacy and safety of tDCS, a nonpharmacological intervention, for post-stroke depression (PSD) in a prospective, randomized, double blind, sham-controlled trial. Forty-eight antidepressant-free patients with PSD were equally divided in two groups that did not differ in gender, age, stroke and depression severity and other clinical variables. Twelve 30-minute sessions of 2-mA anodal left/cathodal right dorsolateral prefrontal tDCS applied over 6 weeks. For sham tDCS we performed 1-min of stimulation only, followed by no stimulation during the remaining period. Intention-to-treat analysis, in which the primary outcome measure was the change in Hamilton Depression Rating scale score at 6 weeks (endpoint). Clinical response and remission were secondary outcomes. Safety was assessed using an adverse effects questionnaire, cognitive assessment and the Young mania rating scale. Active tDCS was significantly superior to sham at endpoint (mean difference, 4.7 points; 95% CI, 2.1 to 7.3; P <.001). Response and remission rates were also statistically higher in active (37.5% and 20.8%, respectively) vs. sham (4.1% and 0) groups. The number needed to treat for response and remission was, respectively, 3 and 5. Stroke region or side did not predict response. No serious adverse effects were reported and the frequency of common adverse effects was similar in both groups. Patients and raters were effectively blinded. This is the first controlled study that demonstrates the safety and clinically meaningful efficacy of tDCS in patients with PSD. Therefore, tDCS could be an option for the treatment of these patients

Made available in DSpace on 2016-03-15T19:39:55Z (GMT). No. of bitstreams: 1 Olivia Morgan Lapenta.pdf: 1151745 bytes, checksum: 91e51a2bad20664489c6aae6c59924b6 (MD5) Previous issue date: 2012-08-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The Mental Simulation theory suggests activation of the motor network during imagery and execution of movements, similarly to the activation during observation and execution of actions, which is mediated by the Mirror Neuron System. This activation can be measured using eletroencefalography register of Mu rhythm suppression. It is propose that motor network activation and therefore increase of cortical excitability at primary motor cortex and Mu dessynchronization are due to premotor Miror-Neuron System inputs. Transcranial direct current stimulation is a neuromodulation technique that induce facilitation and inhibition of neural firing leading to enhance or decrease in cortical excitability, respectively. Thus, we propose to evaluate the polarity dependent effects of this technique in the Mu rhythm during biological and non-biological movements observation and imagery tasks. Therefore we applied anodal, cathodal and sham stimulation in 21 male subjects (mean age 23.8+3,06), over left primary motor cortex (2mA for 20min) and immediately after we registered the electroencephalography considering the electrodes C3, C4 and surrounding C3 and C4 and Cz. Analyses of C3 and C4 showed significant effects according to Movement (p=0.005), and also for the interactions between type of stimulation and hemisphere (p=0.04) and type of stimulation, movement and hemisphere (p=0.02). Surrounding electrodes analyses revealed significant effect for the interaction between stimulation type, task condition and movement type (p=0.03). Thus, the main findings of this study were i. Mu suppression for biological movement (in both imagery and observation) of the hand region in the contralateral hemisphere after sham stimulation, ii. reverse effect for the surrounding electrodes during imagery condition and iii. polarity-dependent neuromodulation of the Mu rhythm. The results are discussed considering focal ERD/ surrounding ERS according to the type of task. We concluded that there are contralateral focal Mu dessynchronization during observation and imagery of biological movements together with syncronizarion of the motor areas not involved in the task only for the imagery condition and that transcranial direct current stimulation has a significant effect under the entire electrode and according to the applied polarity. The use of transcranial direct current stimulation followed by observation and imagery tasks might be an interesting intervention strategy for disturbances involving motor ability impairment as well as deficits related to imitation and comprehension of other s actions. / A teoria de simulação mental sugere ativação da rede neural motora durante mentalização e execução de movimentos, de maneira análoga à ativação em observação e execução de ações, o que é mediado pelo Sistema de Neurônios-Espelho. Esta ativação pode ser mensurada por supressão do ritmo Mu registrado por eletroencefalografia. É proposto que a ativação de áreas motoras e, portanto, o aumento de excitabilidade cortical em cortex motor primário e a dessincronização do ritmo Mu ocorram em consequência de insumo proveniente do Sistema Neurônios-Espelho pré-motor. A estimulação transcraniana por corrente contínua consiste numa técnica de neuromodulação por facilitação e inibição de disparo neuronal levando a aumento e redução de excitabilidade cortical, respectivamente. Assim, foi proposto avaliar os efeitos polaridade dependentes desta técnica sobre ritmo Mu durante tarefas de observação e mentalização de movimentos biológicos e não biológicos. Para tal, aplicamos estimulação anódica, catódica e placebo em 21 homens destros (idade média de 23.8+3,06), sobre córtex motor primário esquerdo (2mA por 20min) e, em seguida foi feito o registro eletroencefalográfico considerando os eletrodos C3, C4 e entorno de C3 e C4 e Cz. A análise de C3 e C4 apresentou efeitos significativos quanto ao tipo de Movimento (p=0.005) e ainda quanto as interações entre tipo de estimulação e hemisfério (p=0.04) e tipo de estimulação, de movimento e hemisfério (p=0.02). A análise dos eletrodos do entorno revelou efeito significativo para a interação entre tipo de estimulação, condição da tarefa e tipo de movimento (p=0.03). Assim, os principais achados do estudo foram i. supressão de Mu para movimento biológico (em mentalização e observação) da região da mão em hemisfério contralateral após estimulação placebo, ii. efeitos inversos para eletrodos de entorno em condição de mentalização e iii. neuromodulação polaridade dependente de ritmo Mu. Os resultados de oscilação de Mu são discutidos considerando ERD focal/ ERS entorno de acordo com o tipo de tarefa. Concluímos que há dessincronização contralateral focal de Mu durante observação e mentalização de movimentos biológicos, acompanhada por sincronização de áreas motoras não envolvidas na tarefa apenas na condição de mentalização e que a estimulação transcraniana por corrente contínua tem efeito sob toda a superfície do eletrodo e difere de acordo com a polaridade aplicada. O uso da estimulação transcraniana por corrente contínua combinada com tarefas de observação e mentalização pode conferir uma estratégia interessante de intervenção em distúrbios envolvendo comprometimento das habilidades motoras bem como comprometimento de habilidades de imitação e compreensão das ações do outro.