La méthode de localisation de source qui permet d’identifier anatomiquement les générateurs de l’activité électrique cérébrale reste encore actuelle difficile à mettre en place et à utiliser en routine clinique. Une des étapes de cette méthode consiste à repérer spatialement les électrodes EEG positionnées sur le cuir chevelu. Ce travail de Doctorat a consisté à mettre au point de nouveaux capteurs EEG compatibles et repérables en IRM et à automatiser ce processus pour le rendre plus fiable et plus facile d’utilisation. Pour ce faire, nous avons développé et breveté de nouveaux capteurs de signaux électrophysiologiques et nous avons implémenté un algorithme informatique de détection et de labellisation automatique en IRM. Ces dispositifs ont été testés cliniquement chez des sujets sains et des patients épileptiques en comparaison avec la numérisation électromagnétique qui est la technique de référence. Nous avons montré dans un premier temps, l’efficacité de notre méthode du point de vue de la précision, de la reproductibilité et des performances. Nous avons montré ensuite que notre méthode n’engendrait pas d’erreurs de localisation anatomique des générateurs électroneurophysiologiques (PES, PEV, EPIC). Ces études cliniques ont été validées par des enregistrements d’IRM fonctionnelle et par une comparaison avec les données de la littérature. Enfin, nous avons développé un outil de projection de la position des capteurs de surface sur le cortex de façon à identifier les structures anatomiques et aires de Brodmann associées aux capteurs EEG du système international 10/10. Notre méthode de détection et de labellisation automatique des capteurs EEG grâce à l’IRM (ALLES) permet donc de limiter l’intervention humaine et de simplifier la méthode de localisation de source puisque seuls les examens d’EEG et d’IRM deviennent nécessaires. / Spatial localization of scalp EEG electrodes is a major step in dipole source localization and it must be accurate, reproducible and practical. Several methods have been proposed in the last fifteen years. The most widely used method is currently electromagnetic digitization. In this work, we introduce a new automatic method for localizing and labeling EEG sensors using MRI (ALLES). First, we designed a new scalp EEG sensor which is MR compatible and localizable. Secondly, we validated this new technique on a head phantom and then in a clinical environment with normal volunteers and epileptic patients. To do this, we compare the reproducibility, accuracy and performances of our method with electromagnetic digitization. We also demonstrate that our method provides better reproducibility with a significant difference (p < 0.01). Concerning accuracy, both methods are equally accurate with no statistical differences. We have tested our method both on normal volunteers (SEP and VEP studies) and epileptic patients (Spikes studies). Source localizations were not influenced by ALLES and we observe results consistent with the literature. Finally, we develop a method which projects the surface positions of the sensors (10-10 system) onto the cortex. This tool is helpful for visual inspection of high resolution EEG traces and for electroclinical diagnostic. To conclude, automation makes our method (ALLES) very reproducible and easy to handle in a routine clinical environment. It offers the possibility of using MRI volume for both source localization and spatial localization of EEG sensors.

Submitted by JÚLIO HEBER SILVA (julioheber@yahoo.com.br) on 2018-03-13T17:24:13Z No. of bitstreams: 2 Dissertação - Andrei Damian da Silva - 2018.pdf: 2168750 bytes, checksum: 4d47d811f294faae439470b427c48f3e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-03-14T10:57:00Z (GMT) No. of bitstreams: 2 Dissertação - Andrei Damian da Silva - 2018.pdf: 2168750 bytes, checksum: 4d47d811f294faae439470b427c48f3e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-03-14T10:57:00Z (GMT). No. of bitstreams: 2 Dissertação - Andrei Damian da Silva - 2018.pdf: 2168750 bytes, checksum: 4d47d811f294faae439470b427c48f3e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-02 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This paper presents a new approach for the processing and classification of visual evoked potentials of steady state (SSVEP). It introduces a ensemble tree model that combines canonical correlation analysis data with methods based on estimation of power spectral density. The stimuli were created using LEDs, from 7.04 Hz to 38.46 Hz. Data were collected using the Texas Instruments ADS1299EEG-Fe and three electrodes. The tests were performed for different distances and light intensities to evaluate the performance of the algorithm under different conditions. In all, 22 participants were recruited, and the average classification was 99.1 ± 2.27% with fixed decision time of 1 second. / Este trabalho apresenta uma nova abordagem para o processamento e classificação de potenciais evocados visuais de estado estacionário (SSVEP). Este trabalho introduz um modelo de em aprendizagem por agrupamento de árvores de decisão que combina dados de análise da correlação canônica com métodos baseados na estimativa da densidade espectral de potência. Os estímulos foram criados utilizando LEDs, com frequência de 7.04 Hz até 38.46 Hz. Os dados foram coletados utilizando a placa ADS1299EEG-Fe da Texas Instruments e três eletrodos. Os testes foram realizados para diferentes distâncias e intensidades luminosas com o objetivo de avaliar o desempenho do algoritmo em condições diversas. Ao todo, 22 participantes foram recrutados e a taxa de acertos média foi de 99.1±2.27% com tempo de decisão fixo em 1 segundo.

INTRODUÇÃO: A esquizofrenia é um transtorno que se caracteriza pela desorganização de diversos processos mentais, dentre os quais a cognição. Pacientes com esquizofrenia apresentam alterações na amplitude e latência dos potenciais evocados P300 e MMN. A maioria das drogas antipsicóticas atuais têm pouco efeito sobre os sintomas negativos e prejuízos cognitivos dos pacientes, por isso, pesquisadores têm buscado alternativas farmacológicas que possam agir sobre os prejuízos cognitivos e sintomas negativos. Pesquisas recentes demonstraram que o nitroprussiato de sódio (NPS) é capaz de atenuar algumas das manifestações do transtorno que não respondem adequadamente aos tratamentos hoje disponíveis. OBJETIVO: Investigar os efeitos da infusão de NPS sobre a sintomatologia e os potenciais evocados auditivos MMN e P300 em pacientes com esquizofrenia em um ensaio duplo-cego controlado por placebo. MÉTODO: Foram avaliados 12 pacientes com idade entre 25 e 54 anos em tratamento antipsicótico acompanhados no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. Cada paciente participou de duas sessões experimentais, uma com infusão de NPS e outra com placebo. Escalas psiquiátricas (BPRS e PANSS) foram aplicadas imediatamente antes da infusão de NPS ou soro glicosado, a cada hora durante a infusão e imediatamente após a realização dos exames de P300 e MMN, realizados após o fim da infusão. RESULTADOS: A infusão de NPS foi associada a um aumento significativo da amplitude do potencial evocado MMN e a uma redução nos escores das escalas de sintomas psiquiátricos BPRS e PANSS em comparação com o placebo. CONCLUSÃO: A infusão de NPS foi associada à melhora dos sintomas de esquizofrenia conforme medidos pela BPRS e PANSS e a um aumento da amplitude do potencial evocado MMN. Não houve efeitos da administração do NPS sobre o potencial evocado P300. / INTRODUCTION: Schizophrenia is a mental disorder characterized by disorganization of several mental processes including cognition. Schizophrenia patients present alterations in the amplitude and latency of auditory evoked potentials P300 and MMN. Most current antipsychotics have little or no effect on the negative symptoms or cognitive impairment in schizophrenia, which led researchers to search for pharmacological alternatives that may counteract these manifestations. Recent evidence suggests that sodium nitroprusside (SNP) is able to ameliorate some of the manifestations associated with schizohrenia that do not respond adequately to currently available treatments. OBJECTIVE: To investigate the effects of SNP on schizophrenia symptoms and on the evoked potentials P300 and MMN in a double-blind, placebocontrolled trial. METHODS: The trial involved 12 patients aged 25-54 years in antipsychotic treatment followed up at the Ribeirã Preto Medical School University Hospital. Each patient attended two experimental sessions, one for the infusion of SNP and another for the infusion of placebo. The Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndromes Scale (PANSS) were completed immediately before the infusion, every consecutive hour, and immediately after the P300 and MMN tests, performed after the end of the infusion. RESULTS: The infusion of SNP was associated with a significant increase in the amplitude of MMN and with a reduction in the psychopathology scores of the BPRS and PANSS compared to placebo. CONCLUSION: The administration of SNP was associated with an improvement in schizophrenia symptoms as measured with the BPRS and PANSS and with an increase in the amplitude of the evoked potential MMN. There were no effects of SNP on the evoled potential P300.

O efeito país de origem é um dos assuntos mais abordados na literatura internacional de negó-cios, marketing e comportamento do consumidor. Diante da importância deste tema, esta pesquisa realizou, utilizando a ferramenta eletroencefalografia, um experimento geral que foi subdividido em três experimentos. No primeiro experimento, buscou-se verificar a influência que a origem de fabricação dos vinhos exercia sobre as atividades cerebrais dos consumidores brasileiros em geral em relação a vinho com a informação de ser do Brasil, da França e sem informação. No segundo experimento, 3(País de origem: Brasil, França e sem informação ) x 2(Gênro: Masculino e Feminino) buscou-se verificar a influência da origem de fabricação sobre as respostas cerebrais dos homens e das mulheres. No terceiro experimento, 3(País de origem: Brasil, França e sem informação ) x 2(Envolvimento: Alto e Baixo) buscou-se verificar esta influência para os consumidores de alto e baixo envolvimento. O vinho utilizado era o mesmo e de origem brasileira. A amostra foi constituída por estudantes da universidade de São Paulo. Como resultados, foram verificados, por meio da análise espectral de potência, que a informação do país de origem não gerou influências significativas para os consumidores em geral e nem para as mulheres nem nenhum dos grupos (experimental e de controle). Mas gerou influência significativas para os homens no grupo experimental. Também foram verificados resultados diferentes para os consumidores de alto e baixo envolvimento. Os consumidores de alto envolvimento prestaram mais atenção a informação do país de origem, contudo esta informação não impactou emocionalmente os consumidores. Já para os consumidores de baixo envolvimento verificou-se diferenças significativas entre o grupo experimental Brasil e França e o grupo de controle França e sem informação. Em termos teóricos, esta pesquisa apresenta uma grande contribuição para a literatura ao conciliar de forma inédita o efeito país de origem com a ferramenta da neurociência EEG. Em termos práticos sugere uma diferenciação das ações de marketing (propaganda, anúncios, campanhas, disponibilização no ponto de venda) sobre os grupos de consumidores / The country-of-origin effect is one of the most addressed issues in the international business literature, marketing and consumer behavior. Considering the importance of this theme, this research carried out, using the electroencephalography tool, a general experiment that was subdivided into three experiments. In the first experiment, it was sought to verify the influence that the origin of wine manufacturing exerted on the brain activities of Brazilian consumers in general in relation to wine with the information of being from Brazil, France and without information. In the second experiment, 3 (Country of origin: Brazil, France and without information) x 2 (Gênro: Male and Female) sought to verify the influence of manufacturing origin on the brain responses of men and women. In the third experiment, 3 (Country of origin: Brazil, France and without information) x 2 (Involvement: High and Low) sought to verify this influence for the consumers of high and low involvement. The wine used was the same and of Brazilian origin. The sample consisted of students from the University of São Paulo. As results, power spectral analysis verified that the information from the country of origin did not generate significant influences for consumers in general, neither for women nor for any of the groups (experimental and control). But it generated significant influence for men in the experimental group. Different results have also been found for high and low involvement consumers. High-involvement consumers paid more attention to home country information, but this information did not impact consumers emotionally. For the low-involvement consumers, there were significant differences between the experimental group Brazil and France and the control group France and without information. In theoretical terms, this research presents a great contribution to the literature in unprecedented reconciliation of the country of origin effect with the EEG neuroscience tool. In practical terms, it suggests a differentiation of marketing actions (advertising, ads, campaigns, availability at the point of sale) on consumer groups

L'objectif de cette thèse était de mieux comprendre les mécanismes mnésiques liés à une stimulation nociceptive. Un premier axe de notre travail a été d'étudier l'influence de la douleur sur la mémorisation de mots grâce à une étude comportementale. Contrairement à d'autres émotions, nous avons montré qu'une douleur n'influençait pas la mémorisation du contenu d'un texte, qu'il soit lié à la douleur ou pas. Le deuxième axe, correspondant à la thématique majeure de la thèse, a été abordé à travers trois études : une étude comportementale permettant de tester la robustesse de la mémorisation nociceptive et ses spécificités; des enregistrements électro-encéphalographiques (EEG) intra-cérébraux afin d'identifier les régions cérébrales impliquées dans la mémorisation nociceptive et leurs interactions et enfin une exploration EEG de scalp chez des sujets sains permettant une vision plus globale des mécanismes mnésiques de ces stimulations. Ces études ont montré des phénomènes liés à la mémorisation non spécifiques à la stimulation nociceptive, telle que l'augmentation de la puissance alpha pendant la phase de rétention. Elles ont également mis en relief des spécificités liées à la mémorisation nociceptive en révélant l'existence d'un biais mnésique suite à une stimulation nociceptive de forte intensité, faussant l'évaluation d'une autre stimulation survenant ultérieurement. Les enregistrements EEG ont montré une augmentation de la connectivité beta entre des régions corticales de la matrice douleur et du cortex préfrontal lors de la phase de rétention. Cette connectivité pourrait refléter une trace de la mise en mémoire des informations nociceptives / The aim of this thesis was to better understand memory mechanisms of a nociceptive stimulation.A first axis of our work was to study pain influence on memorisation of words by a behavioural study. Contrary to other emotions, we demonstrated that pain didn’t influence the memory content of a text, related or not to pain.Our second axis, corresponding to the major thematic of this thesis, was addressed through three studies: a behavioural one allowing us to test robustness of nociceptive memorisation and it specificities; intracerebral electroencephalographic recordings (EEG) to identify brain regions involved in nociceptive memorisation and their interactions, and finally scalp EEG exploration in healthy subjects allowing a broader view of memorisation mechanisms of these stimulations.These studies demonstrated phenomena related to memorisation that was nonspecific to nociceptive stimulation, like alpha power enhancement during retention phase. They also highlight specificities related to nociceptive memorisation revealing memory bias existence following nociceptive stimulation of high intensity, distorting next stimulation evaluation. EEG recordings demonstrated beta connectivity enhancement between cortical regions of the pain matrix and prefrontal cortex during retention phase. This connectivity could reflect memory trace of nociceptive information

O efeito país de origem é um dos assuntos mais abordados na literatura internacional de negó-cios, marketing e comportamento do consumidor. Diante da importância deste tema, esta pesquisa realizou, utilizando a ferramenta eletroencefalografia, um experimento geral que foi subdividido em três experimentos. No primeiro experimento, buscou-se verificar a influência que a origem de fabricação dos vinhos exercia sobre as atividades cerebrais dos consumidores brasileiros em geral em relação a vinho com a informação de ser do Brasil, da França e sem informação. No segundo experimento, 3(País de origem: Brasil, França e sem informação ) x 2(Gênro: Masculino e Feminino) buscou-se verificar a influência da origem de fabricação sobre as respostas cerebrais dos homens e das mulheres. No terceiro experimento, 3(País de origem: Brasil, França e sem informação ) x 2(Envolvimento: Alto e Baixo) buscou-se verificar esta influência para os consumidores de alto e baixo envolvimento. O vinho utilizado era o mesmo e de origem brasileira. A amostra foi constituída por estudantes da universidade de São Paulo. Como resultados, foram verificados, por meio da análise espectral de potência, que a informação do país de origem não gerou influências significativas para os consumidores em geral e nem para as mulheres nem nenhum dos grupos (experimental e de controle). Mas gerou influência significativas para os homens no grupo experimental. Também foram verificados resultados diferentes para os consumidores de alto e baixo envolvimento. Os consumidores de alto envolvimento prestaram mais atenção a informação do país de origem, contudo esta informação não impactou emocionalmente os consumidores. Já para os consumidores de baixo envolvimento verificou-se diferenças significativas entre o grupo experimental Brasil e França e o grupo de controle França e sem informação. Em termos teóricos, esta pesquisa apresenta uma grande contribuição para a literatura ao conciliar de forma inédita o efeito país de origem com a ferramenta da neurociência EEG. Em termos práticos sugere uma diferenciação das ações de marketing (propaganda, anúncios, campanhas, disponibilização no ponto de venda) sobre os grupos de consumidores / The country-of-origin effect is one of the most addressed issues in the international business literature, marketing and consumer behavior. Considering the importance of this theme, this research carried out, using the electroencephalography tool, a general experiment that was subdivided into three experiments. In the first experiment, it was sought to verify the influence that the origin of wine manufacturing exerted on the brain activities of Brazilian consumers in general in relation to wine with the information of being from Brazil, France and without information. In the second experiment, 3 (Country of origin: Brazil, France and without information) x 2 (Gênro: Male and Female) sought to verify the influence of manufacturing origin on the brain responses of men and women. In the third experiment, 3 (Country of origin: Brazil, France and without information) x 2 (Involvement: High and Low) sought to verify this influence for the consumers of high and low involvement. The wine used was the same and of Brazilian origin. The sample consisted of students from the University of São Paulo. As results, power spectral analysis verified that the information from the country of origin did not generate significant influences for consumers in general, neither for women nor for any of the groups (experimental and control). But it generated significant influence for men in the experimental group. Different results have also been found for high and low involvement consumers. High-involvement consumers paid more attention to home country information, but this information did not impact consumers emotionally. For the low-involvement consumers, there were significant differences between the experimental group Brazil and France and the control group France and without information. In theoretical terms, this research presents a great contribution to the literature in unprecedented reconciliation of the country of origin effect with the EEG neuroscience tool. In practical terms, it suggests a differentiation of marketing actions (advertising, ads, campaigns, availability at the point of sale) on consumer groups

Ce travail de thèse vise à étudier les mécanismes de contrôle cognitif mobilisés durant les modulations séquentielles de l’exécution stratégique. Nous avons également étudié l’évolution au cours du vieillissement de ces mécanismes. Les données recueillies montrent que, contrairement aux postulats des modèles des stratégies, l’exécution stratégique sur un problème est modulée par la stratégie utilisée sur le problème précédent. De plus, les données de la neuro-imagerie (i.e., électroencéphalographie et magnétoencéphalographie) ont montré l’activation des régions cingulaires antérieures et frontales inférieures, précédemment observées dans les tâches de conflit. Chez les participants âgés, on observe globalement un déclin de la capacité à moduler d’un essai à l’autre l’exécution stratégique. Toutefois, nous avons étudié un sous-groupe d’adultes âgés présentant un maintien des modulations séquentielles. Au niveau neurophysiologique, ces participants présentaient un décours temporel plus précoce et l’activation d’un réseau neuronal plus étendu. Ces modifications ont été interprétées comme reflétant l’activation de processus compensatoires afin de maintenir des performances similaires à celles des adultes jeunes. Les résultats nous permettent de préciser l’implication des mécanismes de contrôle cognitif dans les performances stratégiques, et de comprendre la contribution de ces mécanismes dans les variations stratégiques observées avec l’âge. / Recent studies suggest that cognitive control mechanisms, allowing regulations of behavior to support goal-directed behaviors, are involved during strategy execution, together with aging effects therein. However, the processes involved and how they change with age need further investigations. The present work aims to study cognitive control processes involved in sequential modulations of strategy execution. It also examines how these mechanisms evolve during aging. Altogether, these findings reveal that, in contrast with theoretical models of strategies that assume strategy independence, strategy execution on a given trial is modulated as a function of strategy execution on previous trial. Moreover, neuroimaging data (i.e., electroencephalography and magnetoencephalography) showed a specific neural network activated during such sequential modulations, involving anterior cingulate and inferior frontal regions. These regions are known to be activated in conflict tasks. In older adults, a decline in sequential modulations of strategy execution was observed. However, some older adults showed preserved behavioral performance, associated with changes in time course and brain regions engaged. Such changes were interpreted as reflecting compensatory mechanisms involved to maintain behavioral performance similar to young adults. All in all, results specify the implication of cognitive control mechanisms in strategic processing, and in strategic variations during aging.

Epileptic syndromes with continuous spikes and waves during slow sleep (CSWS) are age-related epileptic encephalopathy characterized by the development of various psychomotor regressions in close temporal concordance with the appearance of the electroencephalogram (EEG) pattern of CSWS (Tassinari et al., 2000). This EEG pattern consists in sleep-related activation and diffusion of spike-wave discharges during usually more than 85% of non-rapid eye movement (non-REM) sleep (Tassinari et al., 2000). A minority of the CSWS cases has been associated to cortical or thalamic lesions (symptomatic cases), while in the other cases, the aetiology is unknown. We reported two families combining benign childhood epilepsy with centro-temporal spikes (BCECS), which is the most common form of idiopathic epilepsy in childhood, and cryptogenic epilepsy with CSWS in first-degree relatives. As idiopathic epilepsies are by definition epilepsies related to a genetic predisposition, these data suggests the existence of a continuum ranging from asymptomatic carriers of centro-temporal spikes to cryptogenic epilepsies with CSWS. This hypothesis is further supported by common clinical characteristics between BCECS and epilepsies with CSWS (Fejerman et al., 2000). Epileptic syndromes with CSWS are characterized by an acute phase defined by the emergence of psychomotor deficits, various types of seizures and CSWS activity at around three to eight years of age (Holmes and Lenck-Santini, 2006; Veggiotti et al., 2001). This acute phase is followed by a recovery phase in which patients’ clinical condition improves together with the remission of CSWS pattern, which spontaneously occur at around 15 years of age but may be prompted by using antiepileptic drugs (AED) including corticosteroids (Holmes and Lenck-Santini, 2006; Veggiotti et al., 2001). This biphasic evolution suggests that CSWS activity largely contributes to the psychomotor deficits observed in these patients (Holmes and Lenck-Santini, 2006; Van Bogaert et al., 2006). However, some authors still consider CSWS activity as an epiphenomenon reflecting the underlying brain pathology, rather than the direct cause of the psychomotor regression (Aldenkamp and Arends, 2004). The pathophysiological mechanisms of how CSWS activity could actually lead to psychomotor regression are still poorly understood. Functional cerebral imaging techniques such as positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), represent unique ways to non-invasively study the impact of epileptic activity on normal brain function. The PET technique using [18F]-fluorodeoxyglucose (FDG) gives information about the regional neuronal glucose consumption via the neurometabolic coupling while the fMRI technique studies the regional perfusional changes directly related to specific events of interest via the neurovascular coupling. We applied both FDG-PET and EEG combined with fMRI (EEG-fMRI) techniques to epileptic children with CSWS to better approach the functional repercussions of CSWS activity on neurophysiological functions and to determine the potential pathophysiological link between CSWS activity and psychomotor regression. In a first FDG-PET study, we determined the regional cerebral glucose metabolic patterns at the acute phase of CSWS in 18 children. We found three types of metabolic patterns: the association of focal hypermetabolism with distinct hypometabolism in 10 patients, focal hypometabolism without any associated area of increased metabolism in five children, and the absence of any significant metabolic abnormality in three patients. The hypermetabolic brain areas were anatomically related to an EEG focus. This anatomical relationship was clearly less consistent for hypometabolic regions. The metabolic abnormalities involved mainly the associative cortices. The metabolic heterogeneity found in these children could be due to the use of corticosteroids before PET as it was significantly associated with the absence of focal hypermetabolism. At the group level, patients with at least one hypermetabolic brain areas showed significant increased metabolism in the right parietal region that was associated to significant hypometabolism in the prefrontal cortex. This finding was interpreted as a phenomenon of remote inhibition of the frontal lobes by highly epileptogenic and hypermetabolic posterior cortex. This hypothesis was supported by effective connectivity analyses which demonstrated the existence of significant changes in the metabolic relationship between these brain areas in this group of children compared to the control group or to the group of children without any significant hypermetabolic brain area. This remote inhibition hypothesis would be reinforced by the demonstration, at the recovery phase of CSWS, of a common resolution of hypermetabolism at the site of epileptic foci and hypometabolism in distant connected brain areas. We thus performed a second FDG-PET study to determine the evolution of cerebral metabolism in nine children recovering from CSWS. At the acute phase of CSWS, all children had a metabolic pattern characterized by the association of focal hypermetabolism with distinct focal hypometabolic areas. The evolution to CSWS recovery was characterized by a complete or almost complete regression of both hypermetabolic and hypometabolic abnormalities. At the group level, the altered effective connectivity found at the acute phase between focal hypermetabolism (centro-parietal regions and right fusiform gyrus) and widespread hypometabolism (prefrontal and orbito-frontal cortices, temporal lobes, left parietal cortex, precuneus and cerebellum) markedly regressed at recovery. These results were of particular interest because they strongly suggested that the metabolic abnormalities observed during the acute phase of CSWS were mainly related to the neurophysiological effects of CSWS activity and not to the underlying cause of the epileptic disease. Moreover, this study confirmed that phenomena of remote inhibition do occur in epileptic syndromes with CSWS. EEG-fMRI is a functional cerebral imaging technique that allows non-invasive mapping of haemodynamic changes directly associated to epileptic activity. In a first EEG-fMRI study, we determined the clinical relevance of the perfusional changes linked to interictal epileptic discharges in a group of seven children with pharmacoresistant focal epilepsy. This study showed that the EEG-fMRI technique is a promising tool to non-invasively localize the epileptic focus and its repercussion on normal brain function in children with epilepsy. Then, to further demonstrate the involvement of CSWS activity in the neurophysiological changes detected by FDG-PET, we used the EEG-fMRI technique to study the perfusional changes directly related to the epileptic activity in an epileptic girl with CSWS. This patient developed a cognitive and behavioural regression in association with a major increase in frequency and diffusion of the spike-wave discharges during the awake state (spike index: 50-75%) and non-REM sleep (spike index: 85-90%). The patient’s neuropsychological profile was dominated by executive dysfunction and memory impairment. During runs of secondarily generalized spike-wave discharges, EEG-fMRI demonstrated deactivations in the lateral and medial fronto-parietal cortices, posterior cingulate gyrus and cerebellum together with focal relative activations in the right frontal, parietal and temporal cortices. These results suggested that the neuropsychological impairment in this case could be related to specific cortical dysfunction secondary to the spread of the epileptic activity from focal hypermetabolic foci. Taken together, both FDG-PET and EEG-fMRI investigations performed in epileptic children with CSWS have shown increases in metabolism/perfusion at the site of the epileptic focus that were associated to decreases in metabolism/perfusion in distinct connected brain areas. These data highly suggest that the neurophysiological effects of CSWS activity are not restricted to the epileptic focus but spread to connected brain areas via a possible mechanism of surrounding and/or remote inhibition. This mechanism is characterised by an epilepsy-induced inhibition of neurons that surround or are remote from the epileptic focus and connected with it via cortico-cortical or polysynaptic pathways (Witte and Bruehl, 1999). The existence of surrounding and remote inhibition phenomena have been well documented in different types of animal models of focal epilepsy using various functional cerebral imaging methods such as autoradiography or optical imaging (Bruehl et al., 1998; Bruehl and Witte, 1995; Witte et al., 1994). Their occurrence in human epilepsy have also been suspected in temporal or extra-temporal lobe epilepsies using FDG-PET, EEG-fMRI or single photon emission computed tomography (SPECT) (Blumenfeld et al., 2004; Schwartz and Bonhoeffer, 2001; Van Paesschen et al., 2003; Van Paesschen et al., 2007). Moreover, the demonstration of the regression of distant hypometabolic areas after surgical resection or disconnection of the epileptic focus further suggest that such inhibition mechanism do occur in epilepsy (Bruehl et al., 1998; Jokeit et al., 1997). On a clinical point of view, the demonstration of the existence of such inhibition mechanisms in epilepsies with CSWS brings new important insights for the understanding of the pathophysiological mechanisms involved in the psychomotor regression observed in these conditions. Indeed, these data highly suggest that the psychomotor regression is not only related to the neurophysiological impairment at the site of the epileptic foci but also to epilepsy-induced neurophysiological changes in distant connected brain areas.

Das Forschungsthema Synchronisation bildet einen Schnittpunkt von Nichtlinearer Dynamik und Neurowissenschaft. So hat zum einen neurobiologische Forschung gezeigt, daß die Synchronisation neuronaler Aktivität einen wesentlichen Aspekt der Funktionsweise des Gehirns darstellt. Zum anderen haben Fortschritte in der physikalischen Theorie zur Entdeckung des Phänomens der Phasensynchronisation geführt. Eine dadurch motivierte Datenanalysemethode, die Phasensynchronisations-Analyse, ist bereits mit Erfolg auf empirische Daten angewandt worden.<br> Die vorliegende Dissertation knüpft an diese konvergierenden Forschungslinien an. Ihren Gegenstand bilden methodische Beiträge zur Fortentwicklung der Phasensynchronisations-Analyse, sowie deren Anwendung auf ereigniskorrelierte Potentiale, eine besonders in den Kognitionswissenschaften wichtige Form von EEG-Daten.<br> Die methodischen Beiträge dieser Arbeit bestehen zum ersten in einer Reihe spezialisierter statistischer Tests auf einen Unterschied der Synchronisationsstärke in zwei verschiedenen Zuständen eines Systems zweier Oszillatoren. Zweitens wird im Hinblick auf den viel-kanaligen Charakter von EEG-Daten ein Ansatz zur multivariaten Phasensynchronisations-Analyse vorgestellt.<br> Zur empirischen Untersuchung neuronaler Synchronisation wurde ein klassisches Experiment zur Sprachverarbeitung repliziert, in dem der Effekt einer semantischen Verletzung im Satzkontext mit demjenigen der Manipulation physischer Reizeigenschaften (Schriftfarbe) verglichen wird. Hier zeigt die Phasensynchronisations-Analyse eine Verringerung der globalen Synchronisationsstärke für die semantische Verletzung sowie eine Verstärkung für die physische Manipulation. Im zweiten Fall läßt sich der global beobachtete Synchronisationseffekt mittels der multivariaten Analyse auf die Interaktion zweier symmetrisch gelegener Gehirnareale zurückführen. Die vorgelegten Befunde zeigen, daß die physikalisch motivierte Methode der Phasensynchronisations-Analyse einen wesentlichen Beitrag zur Untersuchung ereigniskorrelierter Potentiale in den Kognitionswissenschaften zu leisten vermag. / The topic of synchronization forms a link between nonlinear dynamics and neuroscience. On the one hand, neurobiological research has shown that the synchronization of neuronal activity is an essential aspect of the working principle of the brain. On the other hand, recent advances in the physical theory have led to the discovery of the phenomenon of phase synchronization. A method of data analysis that is motivated by this finding - phase synchronization analysis - has already been successfully applied to empirical data.<br> The present doctoral thesis ties up to these converging lines of research. Its subject are methodical contributions to the further development of phase synchronization analysis, as well as its application to event-related potentials, a form of EEG data that is especially important in the cognitive sciences.<br> The methodical contributions of this work consist firstly in a number of specialized statistical tests for a difference in the synchronization strength in two different states of a system of two oscillators. Secondly, in regard of the many-channel character of EEG data an approach to multivariate phase synchronization analysis is presented.<br> For the empirical investigation of neuronal synchronization a classic experiment on language processing was replicated, comparing the effect of a semantic violation in a sentence context with that of the manipulation of physical stimulus properties (font color). Here phase synchronization analysis detects a decrease of global synchronization for the semantic violation as well as an increase for the physical manipulation. In the latter case, by means of the multivariate analysis the global synchronization effect can be traced back to an interaction of symmetrically located brain areas.<BR> The findings presented show that the method of phase synchronization analysis motivated by physics is able to provide a relevant contribution to the investigation of event-related potentials in the cognitive sciences.

Frontal EEG alpha asymmetry and its relation to depression / Die frontale EEG Alphaasymmetrie und Beziehungen zu Depression/Depressivität