Introdução: Esquizofrenia é um distúrbio psicótico complexo e heterogêneo. Alucinações auditivas verbais ocorrem em 50% a 70% dos pacientes portadores de esquizofrenia, e estão associadas a prejuízo significativo, pior qualidade de vida e funcionamento social. Estudos prévios mostraram que a estimulação magnética transcraniana repetida (EMTr) parece ser capaz de modular a severidade das alucinações auditivas em pacientes com esquizofrenia. Este estudo investigou os efeitos da rTMS de 1Hz aplicada ao córtex temporoparietal esquerdo, comparada a estimulação sham, na psicopatologia geral, severidade das alucinações auditivas, qualidade de vida e funcionalidade. Métodos: Dezessete pacientes apresentando alucinações auditivas verbais pelo menos cinco vezes ao dia forma randomicamente distribuídos para receber EMTr ativa ou sham. Um total de 384 minutos de EMTr a 90% do limiar motor foram administrados ao longo de 20 dias usando um desenho paralelo, duplo-cego e controlado por placebo. Resultados: Houve um efeito positivo nos escores da BPRS no grupo ativo comparado ao grupo sham. Não houve diferenças significativas entre os grupos no final do tratamento nos escores da QLS, AHRS, CGI e FAST. Conclusões: Comparada a estimulação sham, a EMTr do cortex temporoparietal esquerdo mostrou um efeito positivo na psicopatologia geral. Novos estudos com tamanhos de amostra maiores são necessários para investigar efeitos na qualidade de vida e funcionalidade, uma vez que o poder deste estudo foi menor que 50%. Além disso, seu efeito em alucinações auditivas refratárias não é claro, uma vez que os escores de alucinações auditivas globais e individuais não foram diferentes. / Background: Schizophrenia is a complex and heterogeneous psychiatric disorder. Auditory verbal hallucinations occur in 50% to 70% of patients with schizophrenia, and are associated to significant distress, decreased quality of life and social functioning. Data from previous studies have shown that 1-hertz left temporo-parietal repetitive transcranial magnetic stimulation (rTMS) appears to be able to modulate the severity of auditory hallucinations in patients with schizophrenia. This study aimed to investigate the effects of 1 Hz rTMS of the left temporo-parietal cortex on general psychopathology, severity of auditory hallucinations, quality of life and functionality, compared to sham stimulation. Methods: Seventeen patients experiencing auditory verbal hallucinations at least 5 times per day were randomly allocated to receive either rTMS or sham stimulation. A total of 384 minutes of rTMS was administered over 20 days at 90% motor threshold using a double-masked, sham-controlled, parallel design. Results: There was a positive effect on BPRS scores on the active group compared to sham group. There was no significant difference between groups at the end of the treatment on QLS, AHRS, CGI and FAST scores. Conclusions: Compared to sham stimulation, rTMS of the left temporo-parietal cortex showed a positive effect on general psychopathology. Further studies with larger sample sizes are needed to investigate effects on quality of life and functionality, since the power of the study was lower than 50%. Also, its effect on refractory auditory hallucinations is not clear, since global and individual scores of auditory hallucinations were not different.

A depressão pós-parto (DPP), tal como o episódio depressivo maior, é uma manifestação psiquiátrica comum, caracterizada pela presença de alterações de humor, cognitivas, comportamentais, psicomotoras e vegetativas. Afeta a qualidade da interação mãe-bebê prejudicando a responsividade materna o que pode repercurtir negativamente na manutenção salutar do desenvolvimento da criança. Esta manifestação apresenta prevalência estimada entre 10 e 20%, considerando as mulheres que desenvolvem sintomas nas primeiras semanas depois do parto. As opções de tratamento incluem drogas antidepressivas e eletroconvulsoterapia (com anestesia). Porém, como ambas terapêuticas envolvem abordagens farmacológicas, há contra-indicação devido à toxidade que impediria a amamentação. Entretanto, existe uma preocupação sobre como garantir a eficácia do tratamento sem prejudicar o bebê. A Estimulação Magnética Transcraniana Repetitiva (EMTr), por ser uma técnica já consagrada quanto a eficácia antidepressiva, não toxicológica, indolor, não invasiva e bem tolerada para estimular o cérebro, parece ser uma boa alternativa de tratamento. Nos quadros depressivos em geral, são observados prejuízos substanciais a várias funções cognitivas cujas alterações cognitivas apresentadas são, em grande parte, semelhantes àquelas relacionadas a alterações do funcionamento do córtex pré-frontal. A função executiva é um dos principais domínios cognitivos afetados nos transtornos depressivos, geralmente avaliada por testes como Trail Making e o teste de Stroop. A presença de depressão em pacientes puerperais parece intensificar as alterações cognitivas, especialmente as funções associadas ao lobo frontal, além do que, também prejudicam o comportamento causando danos no funcionamento social global. No presente estudo, randomizado, controlado e duplo-cego, investigaram-se os possíveis efeitos da EMTr no funcionamento cognitivo e sua repercussão comportamental: Estimulação Magnética Transcraniana de repetição (EMTr) aplicada ao córtex prefrontal dorsolateral esquerdo (CPFDLE). Uma amostra inicial de dez pacientes com DPP foram distribuídos em dois grupos. Sete participantes de um dos grupos receberam EMTr ativa e três, do grupo controle, EMTr placebo. Os parâmetros utilizados na EMTr foram: freqüência de 5 Hz, intensidade de 120% do limiar motor, em intervalos de 10 segundos ligado e 20 segundos desligado, com 25 séries por dia (2500 pulsos), durante 20 dias (quatro semanas) com dois dias de pausa semanal. Os pacientes e os avaliadores eram cegos ao tipo de tratamento de cada grupo. A avaliação neuropsicológica se deu através de testes cognitivos relacionados às funções prejudicadas em quadros depressivos e com a área estimulada (CPFDLE). Foram também aplicadas as escalas de Adequação Social (EAS) de Weissmann e Bothwell para avaliar o comportamento funcional social global, de depressão de Hamilton, 17 itens, e de depressão pós-parto de Edinburgh. As avaliações foram realizadas em três momentos: antes do início do tratamento (T0), após 4 semanas (T2) e após 6 semanas (T3). Como principais resultados foram observadas: melhora significativa no quadro depressivo ao longo do tratamento e um melhor ajustamento comportamental no funcionamento social global geral, especialmente no contexto das relações familiares; ausência de efeitos negativos em todos os testes cognitivos após o tratamento com EMTr; desempenho superior do grupo EMTr ativa em comparação com o grupo EMTr placebo, principalmente no teste de Rey auditory Verbal Learning (RAVLT) evocação pós-interferência e tardia pós-trinta minutos, no teste Trail Making Parte A e no teste de Stroop Cores. Além disso, o melhor desempenho cognitivo observado no grupo EMTr ativa viii comparado ao grupo EMTr placebo, entre T0 e T4, foi mantido na semana 6 (T6) e por vezes até melhorou sutilmente, indicando que o efeito da estimulação mantém-se estável por, pelo menos 2 semanas após o término do tratamento. Discutem-se como possíveis fatores para esses resultados: ação local da EMTr, alteração dos níveis de alguns neurotransmissores como dopamina e serotonina, relação com a melhoria do quadro depressivo e possível efeito de aprendizado pela repetição em curto período de tempo entre as testagens. Concluí-se que, baseados em uma amostra de apenas 10 pacientes, a EMTr, no que diz respeito aos efeitos antidepressivos, no comportamento frente ao funcionamento social global e às funções cognitivas, não produziu efeitos negativos e sim, produziu alguns efeitos positivos. Esta melhora é de fundamental importância, para o bem estar da mãe e conseqüentemente para o desenvolvimento neuropsicomotor, afetivo e comportamental do bebê. Isto trará desdobramentos que poderão perdurar por toda uma vida para esta criança. Além disto, a segurança da EMT, já amplamente comprovada em outros estudos, poderá, em um futuro próximo, torná-la terapêutica de primeira escolha para este grupo de pacientes. / The postpartum depression (PPD) as the major depressive episode is a common psychiatric manifestation, characterized by the presence of mood, cognitive, behavioral, psychomotor and vegetative changes. It affects the quality of mother-infant interaction jeopardizing the maternal responsiveness, which may adversely affect the maintenance of a healthy development of children. This event presents the estimated dominance between 10 and 20%, taking into account women who develop symptoms in the first weeks after delivery. Treatment options include antidepressant drugs and electroconvulsive therapy (with anesthetic). However, as both treatments involve pharmacological approaches, there is counter-indication because of toxicity that would preclude breastfeeding. Nevertheless, there is concern about the efficiency of the treatment without causing any harm to the baby. The repetitive Transcranial Magnetic Stimulation (rTMS), as it is a technique already established for antidepressant efficacy, non-toxic, painless, non-invasive and well-tolerated to stimulate the brain, it seems to be a good alternative for treatment. For general depressive conditions, substantial damages have been noticed to several cognitive functions, in which the presented cognitive changes are, in large part, similar to those related to changes in the functioning of the pre-frontal cortex (PFC). The executive function is one of the major cognitive domains affected in depressive disorders, usually assessed by tests such as Trail Making and Stroop test. The presence of depression in puerperal patients seems to strengthen cognitive changes; especially those associated to frontal lobe functions, in addition to that, it also affects the behavior causing harm to the overall social functioning. In this study, randomized, controlled and double-blind, possible effects of rTMS in the cognitive functioning and its behavioral effect were assessed: Repetitive Transcranial Magnetic Stimulation (rTMS) applied to left-dorsum-lateral-prefrontal-cortex (LDLPC). An initial sample of ten patients with PPD was divided into two groups. Firstly, seven participants in one of the groups received active rTMS and, three, of the control group, placebo rTMS. The parameters used in rTMS were: frequency of 5 Hz, intensity of 120% of the motor threshold, at intervals of 10 seconds on and 20 seconds off, with 25 sets per day (2500 pulses), during 20 days (four weeks) with two days of rest per week. Patients and evaluators were blinded to the type of treatment for each group. The neuropsychological assessment was carried out by means of cognitive tests related to impaired functions in depressive conditions and with the stimulated area (LDLPC). Social Adjustment Scal (SAS-SR) of Weissmann & Bothwell was also applied to assess the overall social functional behavior, of Hamilton depression, 17 items, and Edinburg postpartum depression. Evaluations were performed on three occasions: before starting the treatment (T0), after 4 weeks (T2) and after 6 weeks (T3). The main results were: significant improvement regarding the depression condition throughout the treatment and a better behavioral adjustment in the general overall social functioning, especially in the context of family relationships, lack of negative effects on all cognitive tests after treatment with rTMS; superior performance of the active rTMS group compared to the placebo rTMS group, especially in the Rey Auditory Verbal Learning Test (RAVLT) post-interference and late evocation after thirty minutes in the Trail Making Test - Part A and the Colors - Stroop Test. Further, the best cognitive performance was observed in the active rTMS group compared to placebo rTMS group, between T0 and T4, was maintained at week 6 (T6) and sometimes even improved slightly, indicating that the effect of the stimulation remains stable by at least 2 x weeks after the end of the treatment. It has been discussed as possible factors for these results: local rTMS action, change in the levels of some neurotransmitters such as dopamine and serotonin, relationship with the improvement of the depressive condition and possible learning effect by repetition within a short period of time between tests. Ergo, based on a sample of only 10 patients, the rTMS, regarding antidepressant effects, the behavior compared to the overall social functioning and cognitive functions, it did not yield negative effects, however it rendered some positive effects. This improvement is of primary importance for the welfare of the mother hence to the babys neuro-psychomotor, emotional and behavioral development. This will bring further outcomes that may last for the whole life for this child. In addition, the safety of TMS, which has been already proven in other researches, may, in the near future, make it a first-choice therapy for this group of patients

Introdução e objetivos: A estimulação magnética transcraniana (EMT) é um método exclusivo para estimulação cerebral não-invasiva. A diferença fundamental entre EMT e as outras técnicas disponíveis de mapeamento por imagem do cérebro é que se estabelece haver uma relação de causa e efeito entre a resposta fisiológica evocada e o estímulo magnético. A relação entre estrutura e função como a principal característica, constitui uma modalidade de mapeamento cerebral ainda não estabelecido. Os recentes avanços no processamento de imagem permitiram refinar EMT através de sua combinação com a ressonância magnética utilizando-se do sistema de neuronavegação para orientar o posicionamento da bobina em relação ao córtex. Assim a posição da bobina sobre o couro cabeludo pode ser mantida constante conforme verificado pela orientação de navegação em tempo real com registro visual. O objetivo deste estudo foi avaliar a utilidade da EMT no mapeamento cortical motor em comparação com o mapeamento cirúrgico com estimulação cortical direta. Métodos: O estudo foi conduzido com 30 mapeamentos consecutivos em pacientes com programação de cirurgia para tumores adjacentes ao córtex motor. O mapeamento pré-operatório foi realizado com o sistema de estimulação magnética transcraniana navegada. Esta estimulação gera um pulso magnético através de uma bobina. Este método permite estimulação diretamente no córtex cerebral. Eletródios de superfície foram anexados ao abdutor curto do polegar. Em seguida, o limiar motor em repouso (LM) foi determinado através da aplicação de estimulação para região cortical da mão presumida. Mapeamento peritumoral foi realizado na intensidade de 120% do LM. O mapeamento foi realizando com definição de coordenadas vetoriais. Estas coordenadas foram ponderadas previamente por potencial evocado motor. O mapeamento intra-operatório foi realizado pelo cirurgião antes da ressecção do tumor também com neuronavegação. Os locais de estimulação intraoperatória foram selecionados de forma independente dos resultados da EMT. Resultados: Os pontos obtidos na ECD foram comparados ao mapa da EMT segundo coordenadas vetoriais dos centros geométricos da nuvem de pontos obtidos. Verificamos que a distância dos pontos vetoriais médios (centro geométrico) dos pontos obtidos nos dois métodos de mapeamentos diferiu em 4,85 +/- 1,89 mm. A análise de correlação intraclasse revelou uma correlação de 0,901 com p<0,001. As distâncias dos pontos obtidos para o tumor, identificamos uma alta correlação entre estas variáveis com r=0,87, p=0,001. O Limiar motor na EMT é maior no córtex motor do adjacente ao tumor, comparado ao córtex normal. Não há correlação entre os limiares motores de repouso na EMT e na estimulação elétrica. A exatidão do mapeamento com EMT é mantida em pacientes com déficits motores. A condição clínica dos pacientes melhorou significativamente em 3 meses após a cirurgia. Conclusões: A estimulação magnética transcraniana navegada é uma ferramenta confiável e precisa com congruência de pontos obtidos comparados com o mapeamento intraoperatório. EMT navegada é um método promissor para o mapeamento funcional pré-operatória em cirurgia de tumor adjacente ao motor córtex / Introduction and aims: Transcranial magnetic stimulation (TMS) is a unique method for non-invasive brain stimulation. The fundamental difference between TMS and other available non-invasive brain imaging techniques is that when a physiological response is evoked by stimulation of a cortical area, that specific cortical area is causally related to the response. The relationship between structure and function as the major feature constituting a brain mapping modality can therefore not be established. Recent advances in image processing allowed us to refine TMS by combining magnetic resonance imaging modalities with TMS using a neuronavigation system to measure the position of the stimulating coil and map this position onto a MRI data set. This technique has several advantages over recent TMS mapping strategies. The position of the coil on the scalp can be held constant as verified by real time visual guidance. The aim of this study was to evaluate the usefulness of navigayed TMS for cortical mapping compared with surgical mapping with direct cirtical stimulation. Methods: The study was performed with 30 neurosurgeries for tumors in or near precentral gyrus. Preoperative mapping was performed with the navigated transcranial brain stimulation system. The TMS system calculates the strength, location, and direction of the stimulating electric field in cortical tissue. It allows online targeting of stimulation directly to peritumoral córtex. The coordinates of TMS mapping were weighted by motor evoked potential. Surface electromyography electrodes were attached to abductor pollicis brevis. Next, the resting motor threshold was determined. The motor threshold was then defined traditionally as the lowest stimulation intensity capable of eliciting motor evoked potentials in at least 5 of 10 trials. The motor threshold was reported both as the percentage of the maximum stimulator intensity. Peritumoral mapping was performed at 120% motor threshold. The intraoperative mapping was performed by the surgeon performing the tumor resection. The Intraoperative direct cortical stimulation locations were chosen independently of the TMS results. The direct electric cortical stimulation points were compared with TMS responses according to original distances of vectorial modules. Results: There is a similarity of the points performed in two mapping methods. We found the distances between geometric centers of TMS and DCS 4,85 +/- 1,89. We identified a strong correlation between these vectorial points (r = 0.901 and p < 0.001). The motor threshold in TMS is the largest in the motor cortex near to the tumor compared to normal cortex (p<0,001). Patients with deficits presented excellent accuracy in two methods. The clinical performance of the patient improved significantly 3 months after surgery. Conclusion: TMS allowed for reliable, precise application in brain mapping and the peritumoral somatotopy corresponded well between the 2 modalities. Navigated TMS is a promising method for preoperative functional mapping in motor cortex tumor surgery

Submitted by Daniely Januário (daniely.januario@gmail.com) on 2018-03-02T12:16:08Z No. of bitstreams: 1 anaelliaparecidanogueiracampos.pdf: 15440844 bytes, checksum: a786f15fa4f523f31128b53fda8765c2 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-03-02T12:24:59Z (GMT) No. of bitstreams: 1 anaelliaparecidanogueiracampos.pdf: 15440844 bytes, checksum: a786f15fa4f523f31128b53fda8765c2 (MD5) / Made available in DSpace on 2018-03-02T12:24:59Z (GMT). No. of bitstreams: 1 anaelliaparecidanogueiracampos.pdf: 15440844 bytes, checksum: a786f15fa4f523f31128b53fda8765c2 (MD5) Previous issue date: 2012-12-21 / PROQUALI (UFJF) / O objetivo desse estudo foi investigar por meio da estimulação magnética transcraniana (EMT), se a excitabilidade córtico-espinhal durante a preparação motora é afetada pela valência emocional de um estímulo com o qual se irá interagir. Além disso, avaliamos se o efeito da modulação emocional sobre a excitabilidade córtico-espinhal era específica para o músculo diretamente envolvido na tarefa. Dez participantes foram orientados a realizar uma tarefa que incluía duas condições: mover (condição AÇÃO) ou observar (condição NÃO-AÇÃO) objetos com diferentes valências (agradável, neutro e desagradável). A ordem de apresentação das condições e das valências foi aleatória, compreendendo quatro blocos, sendo dois de cada condição. O peso de todos os objetos foi contrabalançado e apresentado dentro de copos transparentes a fim de uniformizar o tipo de preensão manual que os participantes teriam que utilizar para segurá-los. O início de cada tentativa foi marcado pela apresentação do estímulo. Dado a apresentação de cada estímulo, 3s depois um sinal resposta acendia, indicando que o participante deveria mover ou apenas observar, dependendo da condição experimental. O pulso de EMT foi aplicado sobre o córtex motor primário em 500 ou 250 ms antes do sinal resposta, de forma aleatória. O potencial evocado motor (PEM) foi medido através do registro do sinal eletromiográfico dos músculos: primeiro interósseo dorsal (PID) e abdutor do dedo mínimo (ADM). Uma ANOVA para medidas repetidas de três fatores foi utilizada para avaliar o efeito da emoção em cada um dos músculos. Na condição AÇÃO, a ANOVA revelou uma interação condição x valência (p = 0,003) para o músculo PID. A amplitude do PEM foi maior para a categoria desagradável, quando comparado com a neutra e agradável. Além disso, a amplitude do PEM para a categoria agradável foi menor do que a neutra. Não houve efeito significativo da valência na condição NÃO-AÇÃO. Um efeito de valência entre as condições também foi encontrado. A amplitude do PEM para a categoria desagradável foi maior na condição AÇÃO do que na NÃO-AÇÃO. O contrário ocorreu para a categoria agradável, onde a amplitude do PEM foi menor na condição AÇÃO, quando comparado com a NÃOAÇÃO. Para o ADM, não houve efeito significativo entre as categorias emocionais nem entre as condições (p = 0,76). Concluímos que a atividade preparatória que antecede a preensão de um estímulo, medida pela excitabilidade córtico-espinhal, é afetada por seu valor emocional. A modulação emocional sobre a excitabilidade é músculo-específica. / The aim of this study was to examine by means of Transcranial Magnetic Stimulation (TMS) if the corticospinal excitability (CSE) is affected by the emotional valence of the stimulus which with one is about to grab. We also examined if effect of emotional modulation upon CSE is specific to the muscle directly enrolled in the task. Ten participants were instructed to perform a task with two experimental conditions: to grasp (ACTION condition) or just to look (NO-ACTION condition) at objects with different valences (pleasant, neutral and unpleasant). Conditions and valence order were randomly presented within four blocks. Objects were balanced in weight and placed inside transparent cups to prompt a similar grip among trials. Trials began with the stimulus presentation. After stimulus presentation, a go signal was turned on 3 s later indicating that the participant should move or just observe, depending on the experimental condition. TMS was applied over the participant primary motor cortex at 500 or 250 ms before the go signal, randomly. Motor evoked potentials (MEP) were measured by recording the electromyographic signal from first dorsalis interosseous - FDI and abductor digiti minimi - ADM muscles. Tree-way ANOVA was conducted to evaluate the emotional effect for each muscle. In ACTION condition, the ANOVA revealed a condition x valence interaction (p = 0.003) for FDI. The MEP was larger for unpleasant compared to neutral and pleasant category. Also, MEP amplitude for pleasant was lower than neutral category. There was no significant effect for FDI in NO-ACTION condition. Furthermore, a significant valence effect across conditions (ACTION and NO-ACTION) was also found: higher MEP amplitudes were found for the unpleasant category in ACTION condition as compared to NON-ACTION condition. The reverse was true for the pleasant category: lower MEP amplitudes were found in the ACTION as compared to NON-ACTION condition. For the ADM, there was neither a significant effect among emotional categories nor across conditions (p = 0.76). In conclusion, we showed here that the preparatory activity preceding the grasping of a stimulus, as measured by corticospinal excitability, is affected by its emotional value. In other words, our findings show a muscle specific modulation of corticospinal excitability during motor preparation depending on the valence of the stimuli to be grasped.

Les champs électromagnétiques sont couramment utilisés pour stimuler de manière non-invasive le cerveau humain soit à des fins thérapeutiques ou dans un contexte de recherche. Les effets de la stimulation magnétique varient en fonction de la fréquence et de l'intensité du champ magnétique. Les mécanismes mis en jeu restent inconnus, d'autant plus lors de stimulations à faible intensité. Dans cette thèse, nous avons évalué les effets de stimulations magnétiques répétées à différentes fréquences appliqués à faible intensité (10-13 mT ; Low Intensity Repetitive Magnetic Stimulation : LI-rMS) in vitro, sur des cultures corticales primaires et sur des modèles de réparation neuronale. De plus, nous décrivons une méthodologie pour la construction d'un dispositif instrumental fait sur mesure pour stimuler des cultures cellulaires.Les résultats montrent des effets dépendant de la fréquence sur la libération du calcium des stocks intracellulaires, sur la mort cellulaire, sur la croissance des neurites, sur la réparation neuronale, sur l'activation des neurones et sur l'expression de gènes impliqués. En conclusion, nous avons montré pour la première fois un nouveau mécanisme d'activation cellulaire par les champs magnétiques à faible intensité. Cette activation se fait en l'absence d'induction de potentiels d'action. Les résultats soulignent l'importance biologique de la LI-rMS par elle-même mais aussi en association avec les effets de la rTMS à haute intensité. Une meilleure compréhension des effets fondamentaux de la LI-rMS sur les tissus biologiques est nécessaire afin de mettre au point des applications thérapeutiques efficaces pour le traitement des conditions neurologiques. / Electromagnetic fields are widely used to non-invasively stimulate the human brain in clinical treatment and research. This thesis investigates the effects of different low intensity (mT) repetitive magnetic stimulation (LI-rMS) parameters on single neurons and neural networks and describes key aspects of custom tailored LI-rMS delivery in vitro. Our results show stimulation specific effects of LI-rMS on cell survival, neuronal morphology, neural circuit repair and gene expression. We show novel mechanisms underlying cellular responses to stimulation below neuronal firing threshold, extending our understanding of the fundamental effects of LI-rMS on biological tissue which is essential to better tailor therapeutic applications.

Nous ne pouvons tout voir. L'attention, notre capacité à filtrer et moduler les informations, nous permet d'interagir de façon efficace avec le monde. Nous avons utilisé une technique non-invasive de modulation de l'activité cérébrale, la Stimulation Magnétique Transcrânienne (SMT) pour manipuler l'activité d'une région clé du réseau de l'attention spatiale, le champ oculomoteur frontal (FEF) droit. L'accent est mis sur les connexions anatomiques observées en IRM de diffusion sous-tendant la modulation de la perception visuelle. Après avoir présenté nos connaissances tirées de données comportementales, physiologiques et anatomiques ainsi que les techniques utilisées, nous présentons nos études qui montrent une amélioration des performances visuelles après des impulsions simples ou des trains d'impulsions de SMT à une fréquence spécifique (30Hz) appliqués sur le FEF droit juste avant l'apparition d'une cible visuelle. Nous examinons ensuite si des différences interindividuelles de connectivité anatomique influencent la modulation perceptive induite par SMT. Nous décrivons un faisceau fronto-tectal qui connecte le FEF avec le colliculus supérieurs et montrons que la probabilité de connexion entre ces deux régions dans l'hémisphère droit influence la contribution du FEF sur la détection visuelle. Nous décrivons aussi les trois branches du faisceau longitudinal supérieur et démontrons l'influence de la 1ère branche dans l'hémisphère droit sur la modulation visuelle induite par des trains de SMT à 30 Hz. Ces résultats suggèrent un rôle important de la connectivité anatomique dans la possibilité de synchroniser les aires d'un réseau à une fréquence spécifique. / We are unable to see everything. Attention, our ability to filter, select and modulate information, allows us to interact efficiently with the world. We employed a non-invasive brain stimulation technique, the Transcranial Magnetic Stimulation (TMS), to manipulate in humans the activity of a key area of the attentional network, the right Frontal Eye Field (FEF). Our work focuses on the characterization with diffusion MRI of anatomical connections and their role underlying the modulation of visual perception. We first introduce previous behavioral, physiological and anatomical findings and the techniques used in our work. We then present evidence showing an improvement of visual performances tied to activity patterns consisting in either single pulses or frequency-specific rhythmic TMS bursts (30Hz) applied over the right FEF, prior to the onset of a visual target. We also examine whether inter-individual differences in white matter connectivity could influence the modulatory role that the FEF exerts on visual perception. We describe a fronto-tectal pathway connecting the FEF with the superior colliculus and show that the probability of connection between these two sites in the right hemisphere influences the FEF contributions to visual detection. We also characterize the three branches of the superior longitudinal fasciculus connecting frontal and parietal lobes and demonstrate an influence of its first branch in the right hemisphere on visual modulation induced by frequency-specific TMS bursts. Our results suggest a crucial role in the modulation of visual perception of the anatomical connectivity to synchronize areas of a network at a specific frequency.

This thesis describes a series of experiments in human observers using neurophysiological and behavioural approaches to investigate the effects of varying haptic stimuli, attentional demand and age on motor control and perception during haptic sensing (i.e., using the hand to seek sensory information by touch). In Experiments I-IV, transcranial magnetic stimulation (TMS) was used to explore changes in corticomotor excitability when participants were actively engaged in haptic sensing tasks. These studies showed that corticospinal excitability, as reflected in motor evoked potential (MEP) amplitude, was greatly enhanced when participants were engaged in different forms of haptic sensing. Interestingly, this extra corticomotor facilitation was absent when participants performed finger movements without haptic sensing or when attention was diverted away from haptic input by a concurrent cognitive task (Exp I). This provided strong evidence that the observed corticomotor facilitation was likely central in origin and related to haptic attention. Neuroimaging has shown activation of the parieto-frontal network likely subserves this aspect of haptic perception. Further, this haptic-specific corticomotor facilitation was finely modulated depending on whether participants focused attention on identifying material (texture) as opposed to geometric properties of scanned surfaces (Exp II). With regards to aging effects, haptic-related corticomotor facilitation was associated with higher recognition accuracy in seniors (Exp III). In line with this, seniors exhibited similar levels of haptic-related corticomotor facilitation to young adults when task demands were adjusted for age (Exp IV). Interestingly, both young and senior adults also showed substantial corticomotor facilitation in the ‘resting’ hand when the ipsilateral hand was engaged in haptic sensing (Exp IV). Simply touching the stimulus without being required to identify its properties (no attentional task demands) produced no extra corticomotor facilitation in either hand or age group, attesting again to the specificity of the effects with regards to haptic attention. In Experiments V-VI, the ability to recognise 2-D letters by touch was investigated using kinematic and psychophysical measures. In Experiment V, we characterized how age affected contact forces deployed at the fingertip. This investigation showed that older adults exhibited lower normal force and increased letter-to-letter variability in normal force when compared to young adults. This difference in contact force likely contributed to longer contact times and lower recognition accuracy in older adults, suggesting a central contribution to age-related declines in haptic perception. Consistent with this interpretation, Experiment VI showed that haptic letter recognition in older adults was characterized not only by lower recognition accuracy but also by substantial increases in response times and specific patterns of confusion between letters. All in all, these investigations highlight the critical interaction of central factors such as attentional demand with aging effects on motor and perceptual aspects of haptic sensing. Of particular significance is the clear demonstration that corticomotor excitability is greatly enhanced when a haptic sensing component (i.e., attending to specific haptic features) is added to simple finger movements performed at minimal voluntary effort levels (typically <15 % of the maximal effort). These observations underline the therapeutic potential of active sensory training strategies based on haptic sensing tasks for the re-education of motor and perceptual deficits in hand function (e.g., subsequent to a stroke). The importance of adjusting attentional demands and stimuli is highlighted, particularly with regards to special considerations in the aging population.

Transcranial magnetic stimulation (TMS) is a 37-year-old non-invasive tool and can be used for diagnostic, therapeutics, and research purposes. In research, TMS is mostly used to stimulate the motor cortex, resulting in a neuroelectric excitatory response called a motor evoked potential (MEP). The resulting nerve signal leads to muscle movement, which can be measured by electromyography (EMG). Majority of previous research has targeted muscles of the upper limbs, due to the relative inaccessibility of the cortical leg area. Thus, the aim of this study is to investigate whether asymmetry occurs during lower limb stimulation and if there is a difference in stimulated muscles between dominant and non-dominant leg. Nine healthy adults conducted cortical stimulation over the motor cortex using double cone coil. EMG was recorded from the rectus femoris, tibialis anterior and abductor hallucis on both left and right leg. Depending on the subject's tolerance, data was collected by delivering 30 or 35 pulses. For each intensity, five MEPs were recorded, starting at 30% of the intensity and increasing in steps of 10%. Results showed no significant difference (p&gt;0,05) between the dominant and non-dominant leg in all three muscles. In conclusion, the study no stimulus response asymmetry between the dominant and non-dominant leg in the respective muscle.

Prediction of the therapeutic response in the treatment of affective disorders using repetitive transcranial magnetic stimulation MUDr. Jakub Albrecht Summary Background: Transcranial magnetic stimulation (TMS) is an effective and safe neuromodulatory treatment of several neuropsychiatric conditions. Treatment resistant depression (TRD) is becoming the leading cause of morbidity and mortality. The design was narutallistic and observational. Methods: The cohort (2016-2018) contains 39 depressed patients (STAR*D grade ≥3). The parameters of TMS were: 10 days of 10 Hz stimulation with an energy of 100 % of motor evoked potential (MEP), 1500 pulses in 15 trains over the left dorsolateral prefrontal cortex. Self-reporting scales were administered prior to and after the final stimulation: Zung's Self-Rating Depression Scale (SDS), Perceived Stress Scale (PSS), Beck's Anxiety Inventory (BAI) and Quick Inventory of Depressive Symptomatology (QIDS-SR). Co-medication was not altered. Results: The subjective effect was significant and widespread with a median decrease: in SDS of 10 points (from 75 ±8.16 to 65 ±9.56), 59 % of patients improved ≥10 % from the baseline; in PSS of 4 points (29 ±5.34 to 25 ±5.90), 62 % improved ≥10 %; in BAI of 4 points (46 ±13.72 to 42 ±11.51), 54 % improved ≥10 %; in QIDS-SR 6 points (17...

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