Cross modality matching is a magnitude matching procedure, developed to study the relationships between sensory modalities. Auditory and visual sensory integration can be examined through cross modality matching of brightness and loudness. Brightness and loudness are natural correlates of one another as they both represent the parameter of intensity for their respective sensory modalities. Past studies have demonstrated that typical individuals tend to match brighter lights with louder sounds and dimmer lights with softer sounds. The current study utilized a modified cross modality matching procedure, combined with electroencephalography (EEG) data, to examine the cortical response to sensory integration. It was hypothesized that the response latency and cortical distribution of the EEG data would show differences between matched and unmatched conditions of light and sound stimuli. Light and sound stimuli were presented to 10 participants (five males and five females between the ages of 18 and 28 years) in a forced choice paradigm. The behavioral responses, reaction times, and EEG data were recorded for each patient. Results demonstrated that there were significant differences in behavioral reaction time among the stimulus conditions. However, reaction times were only significantly faster for the loudest sound paired with the brightest light. No other pairs of matched stimuli resulted in faster reaction times. Event related potentials (ERPs) were identified for matched and unmatched stimulus conditions. No differences were identified in latency of the ERPs among conditions. Additionally, source localization revealed that dipole locations for each stimulus condition remained relatively constant in the prefrontal cortex. As the prefrontal cortex has been found to be associated with decision-making and sensory integration, it can be concluded that sensory integration did occur. However, the processing of sensory information did not change for matched or unmatched conditions of light and sound.

No description available.

Alzheimer’s disease (AD) is the leading cause of dementia and is alone responsible for 60-70% of all cases of dementia. Though sharing clinical symptoms with other types of dementia, the hallmarks of AD are the abundance of extracellular depositions of β-amyloid (Aβ) plaques, intracellular neurofibrillary tangles of hyper phosphorylated tau proteins and synaptic depletion. The onset of the physiological hallmarks may precede clinical symptoms with a decade or more, and once clinical symptoms occur it may be difficult to separate AD from other types of dementia based on clinical symptoms alone. Since the introduction of radiolabeled Aβ tracer substances for positron emission tomography (PET) imaging it is possible to image the Aβ depositions in-vivo, strengthening the confidence in the diagnosis. Because the accumulation of Aβ may occur years before the first clinical symptoms are shown and even reach a plateau, Aβ PET imaging may not be feasible for disease progress monitoring. However, a negative scan may be used to rule out AD as the underlying cause to the clinical symptoms. It may also be used as a predictor to evaluate the risk of developing AD in patients with mild cognitive impairment (MCI) as well as monitoring potential effects of anti-amyloid drugs.Though currently validated for dichotomous visual assessment only, there is evidence to suggest that quantification of Aβ PET images may reduce inter-reader variability and aid in the monitoring of treatment effects from anti-amyloid drugs.The aim of this thesis was to refine existing methods and develop new ones for processing, quantification and visualization of Aβ PET images to aid in the diagnosis and monitoring of potential treatment of AD in clinical routine. Specifically, the focus for this thesis has been to find a way to fully automatically quantify and visualize a patient’s Aβ PET image in such way that it is presented in a uniform way and show how it relates to what is considered normal. To achieve the aim of the thesis registration algorithms, providing the means to register a patient’s Aβ PET image to a common stereotactic space avoiding the bias of different uptake patterns for Aβ- and Aβ+ images, a suitable region atlas and a 3-dimensional stereotactic surface projections (3D SSP) method, capable of projecting cortical activity onto the surface of a 3D model of the brain without sampling white matter, were developed and evaluated.The material for development and testing comprised 724 individual amyloid PET brain images from six distinct cohorts, ranging from healthy volunteers to definite AD. The new methods could be implemented in a fully automated workflow and were found to be highly accurate, when tested by comparisons to Standards of Truth, such as defining regional uptake from PET images co-registered to magnetic resonance images, post-mortem histopathology and the visual consensus diagnosis of imaging experts.

O estudo dos sintomas neuropsiquiátricos em Doença de Alzheimer (DA) através do agrupamento destes em síndromes tem sido cada vez mais utilizado, uma vez que permitiria detectar diferenças em sua prevalência, em sua evolução, em relação a determinantes psicossociais e a correlatos neurobiológicos. O objetivo deste estudo foi identificar regiões de redução de substância cinzenta em áreas corticais associadas com sintomas e síndromes neuropsiquiátricos específicos, provenientes da Escala Inventário Neuropsiquiátricos (NPI), em pacientes com DA e comprometimento cognitivo sem demência (CIND). O método de morfometria baseada no voxel (VBM) com DARTEL (Diffeomorphic Anatomical Registration Using Exponentiated Lie Algebra) foi utilizado para verificar a correlação entre presença de sintomas e síndromes neuropsiquiátricos específicos e redução regional de volume de substância cinzenta em análise em todo cérebro e em regiões previstas a priori. As síndromes utilizadas foram SN1/Agitação (agitação, alterações de sono e apetite), SN2/Hiperatividade (desinibição, comportamento motor aberrante e irritabilidade), SN3/Afetiva (depressão e apatia) e SN4/Psicose (delírios e alucinações). A presença de delírios foi associada a volume de substância cinzenta reduzido em giro frontal inferior direito (BA45); depressão com xvii redução de substância cinzenta em giro temporal médio e inferior direito (BA 37/22) e giro frontal inferior (BA09-DLPFC) e giro parahipocampal esquerdos; ansiedade com redução em giro frontal médio esquerdo (BA10); e alterações de apetite com redução em córtex anterior cingulado esquerdo (BA32) em pacientes com DA. A presença de SN1/Agitação foi associada a volume de substância cinzenta reduzido em giro frontal médio direito (BA09-DLPFC); SN2/Hiperatividade com redução em giro temporal superior direito (BA22) e frontal inferior bilateral (BA47); e SN4/Psicose com redução em giro pré-central (BA44), temporal superior (BA22) e ínsula direitos em DA. No grupo CIND, somente SN1/Agitação evidenciou associação com redução de substância cinzenta regional. Atrofia de áreas corticais específicas parecem relacionadas aos sintomas e síndromes neuropsiquiátricos em DA. Síndromes neuropsiquiátricas em DA mostraram-se correlacionadas à atrofia de estruturas centrais de alguns circuitos neuronais envolvidos na fisiopatologia de transtornos psiquiátricos / The study of neuropsychiatric symptoms in patients with Alzheimer\'s disease (AD) by grouping these symptoms into syndromes has been increasingly used because it would detect differences in its prevalence and evolution, in relation to psychosocial determinants and neurobiological correlates. The aim of this study was to identify regions of reduced gray matter in cortical areas associated with specific neuropsychiatric symptoms and syndromes from the Neuropsychiatric Inventory (NPI) in patients with AD and cognitive impairment, no dementia (CIND). Voxel-based morphometry (VBM) plus Dartel (Diffeomorphic Anatomical Registration Exponentiated Using Lie Algebra) was used to verify the correlation between the presence of specific neuropsychiatric symptoms and syndromes and regional gray matter volume reduction throughout the brain and in regions predicted a priori. The syndromes were NS1/ Agitation (agitation, sleep and eating disorders), NS2/Hyperactivity (disinhibition, aberrant motor behavior and irritability), NS3/Affective (depression and apathy) and NS4/Psychosis (delusions and hallucinations). The presence of delusions was associated with gray matter volume reduction in right inferior frontal gyrus (BA45), depression with reduced gray matter in right inferior middle temporal gyrus (BA 37/22) and left inferior frontal gyrus (BA09-DLPFC) and left parahippocampal gyrus; anxiety with reduction in left middle frontal gyrus (BA10), and eating disorders with reduction in left anterior cingulate cortex (BA32) in patients with AD. The presence of NS1/Agitation was associated with gray matter volume reduction in the right middle frontal gyrus (BA09-DLPFC); NS2/ Hyperactivity with reduction in right superior temporal gyrus (BA22) and bilateral inferior frontal (BA47) and NS4/Psychosis with a reduction in right precentral gyrus (BA44), right superior temporal (BA22) and in right insula in AD. In the CIND group, only SN1/Agitation showed association with regional gray matter reduction. Atrophies of specific cortical areas were showed to be related to symptoms and neuropsychiatric syndromes in patients with AD

INTRODUÇÃO: As bases neurofisiológicas do declínio cognitivo associado ao envelhecimento normal ainda não são adequadamente conhecidas. Estudos sobre conectividade funcional cerebral estimada através de imagens por ressonância magnética funcional durante o repouso têm identificado diminuições de conectividade dentro da rede de modo padrão (default mode network) em idosos e correlações entre desempenho cognitivo e conectividade funcional. Há evidências de que idosos apresentam maior dificuldade em recuperar informações episódicas de eventos autobiográficos mas não existem investigações sobre a relação entre tal função cognitiva e conectividade de repouso. Além disso, estudos desta área geralmente não têm utilizado entrevista psiquiátrica para seleção da amostra, apesar de transtornos psiquiátricos apresentarem alta prevalência, serem subdiagnosticados e afetarem o funcionamento cerebral. OBJETIVOS: caracterizar as mudanças de conectividade funcional de repouso associadas a idade e a desempenho cognitivo, em especial à função de memória autobiográfica, em uma amostra de adultos de diferentes idades e livres de deficiências cognitivas e de transtornos psiquiátricos. MÉTODOS: adultos jovens, de meia idade e idosos sem transtornos cognitivos ou psiquiátricos foram selecionados através de avaliação neuropsicológica e entrevista psiquiátrica estruturada. Quantificamos o desempenho em recuperar informações episódicas de eventos autobiográficos. Conectividade funcional cerebral foi estimada a partir de imagens de ressonância magnética funcional adquiridas durante o repouso vigil, utilizando um atlas de 278 regiões englobando todo o cérebro. As relações entre conectividade e idade e conectividade e desempenho cognitivo foram avaliadas através do método dos quadrados parciais mínimos. RESULTADOS: em uma amostra de 59 adultos (19 jovens, 20 de meia idade e 20 idosos), idade apresentou correlação negativa com desempenho cognitivo geral, mas sua relação com memória autobiográfica não foi significativa. Caracterizamos um padrão de conectividade associado ao envelhecimento caracterizado por aumento difuso de magnitude de correlações positivas entre diferentes circuitarias, diminuições de magnitude de anticorrelação envolvendo principalmente as conexões entre a rede de modo padrão e as redes atencionais e uma perda de correlações positivas intra-circuitarias, especialmente dentro do sistema visual e da rede de modo padrão. Não identificamos um padrão de conectividade associado a desempenho cognitivo geral ou autobiográfico. DISCUSSÃO: idade mostrou-se negativamente correlacionada com desempenho cognitivo geral. Os resultados sugerem que o efeito do envelhecimento sobre memória autobiográfica seja de menor tamanho e/ou sujeito a maiores variações entre estudos. O padrão de mudanças de conectividade associado ao envelhecimento que encontramos inclui os achados mais comumente descritos na literatura (diminuições de conectividade intra-circuitaria) mas também abrange mudanças funcionais mais amplas (aumentos difusos de correlação positiva e ! ! xii perdas de anticorrelação). Estes achados estão em linha com a hipótese de que o cérebro sofre um processo de desdiferenciação durante o envelhecimento no qual há perda de diversidade funcional. CONCLUSÃO: Na presente amostra não identificamos relação entre desempenho em memória autobiográfica e idade. Envelhecimento normal, inclusive em voluntários sem transtornos mentais, está associado a um aumento difuso de correlações positivas entre diferentes circuitarias, a perdas focais de anticorrelação, especialmente entre a rede de modo padrão e as redes atencionais e a uma redução de conectividade dentro da rede de modo padrão e da rede visual / INTRODUCTION: The neurophysiological basis of the cognitive decline associated with aging is not yet known. Brain functional connectivity studies using functional magnetic resonance images acquired during rest have shown that aging is associated with decreases in connectivity within the default mode network. Moreover, cognitive performance has been associated with resting functional connectivity. There is evidence that older adults present worse performance during retrieval of episodic information from autobiographical events but there is no investigation regarding the relationship between functional connectivity at rest and this cognitive function. Moreover, studies in this field have not applied a structured psychiatric interview to select the sample, although it is known that psychiatric disorders present high prevalence, are underdiagnosed and are associated with functional abnormalities. OBJECTIVES: to characterize changes in resting-state functional connectivity associated with age and cognitive performance, especially with autobiographical memory, in adults from different ages, free of cognitive deficits and psychiatric disorders. METHODS: using a neuropsychological evaluation and a structured psychiatric interview we selected a sample of young, middle aged and elderly adults free of cognitive and psychiatric disorders. We measured the performance to recover episodic information from autobiographical events. Brain functional connectivity was estimated from resting-state functional magnetic resonance images acquired during rest, using a whole-brain 278-region atlas. We used partial least squares to characterize the relationships between connectivity and age and connectivity and cognitive performance. RESULTS: in a sample of 59 adults (19 young, 20 middle aged and 20 elderly), age was negatively correlated with general cognitive performance but its relationship with autobiographical memory was not statistically significant. The pattern of connectivity changes associated with aging was characterized by a diffuse increase in the magnitude of positive correlations between different networks, decreases in magnitude of anticorrelations (especially between the default mode network and the attentional networks) and a loss of within-network positive correlations (mainly within the visual system and the default mode network). We did not find a pattern of connectivity associated with general cognitive performance or with autobiographical memory. DISCUSSION: age was negatively correlated with general cognitive performance. The results suggest that the effect of age on autobiographical memory is smaller and/or present greater between-study variability. The age-related pattern of changes in connectivity found in this study includes the most commonly reported findings in the literature (decreases in withinnetwork connectivity) but it also contains broader functional changes (diffuse increases in positive correlations and losses of anticorrelations). These findings are in accordance with the hypothesis that the brain undergoes dedifferentiation processes during aging with loss of functional diversity. CONCLUSION: in our sample, we could not identify a significant relationship between age and autobiographical memory. Normal aging, even in individuals with no mental disorder, is associated with an increase in positive correlations between different brain networks, focal losses of anticorrelations (especially between the default mode network and the attentional networks) and reductions in connectivity within the default mode network and the visual system

Touchant plus de 50 millions de personnes dans le monde, l’épilepsie est un problème majeur de santé publique. Un tiers des patients souffrent d’épilepsie pharmaco-résistante. Une chirurgie visant à enlever la région cérébrale à l’origine des crises – la zone épileptogène – est considérée comme l’option de référence pour rendre libre de crises ces patients. Le taux d’échec chirurgical non négligeable a poussé la recherche d’autres marqueurs. Un marqueur potentiel est les oscillations à haute fréquence (HFOs). Une HFO est une brève oscillation entre 80-500 Hz qui dure au moins 4 périodes enregistrée en EEG intracérébrale. Par leur caractère très bref, le marquage visuel de ces petites oscillations est fastidieux et chronophage.. Il semble impératif de trouver un moyen de détecter automatiquement ces oscillations pour étudier les HFOs sur des cohortes de patients. Aucun détecteur automatique existant ne fait cependant l’unanimité. Durant cette thèse, nous avons développé un nouveau moyen de visualiser les HFOs grâce à une normalisation originale de la transformée en ondelettes pour ensuite mieux les détecter automatiquement. Puis, nous avons mise en place une stratégie pour caractériser et valider des détecteurs. Enfin, nous avons appliqué le nouveau détecteur à une cohorte de patients pour déterminer la fiabilité des HFOs et des pointes épileptiques - le marqueur standard - dans la prédiction de la zone épileptogène. La conclusion de cette thèse est que les HFOs ne sont pas meilleurs que les pointes épileptiques pour prédire la zone épileptogène mais que combiner ces deux marqueurs permettait d’obtenir un marqueur plus robuste. / Epilepsy is a major health problem as it affects 50 million people worldwide. One third of the patients are resistant to medication. Surgical removal of the brain areas generating the seizure – the epileptogenic zone – is considered as the standard option for these patients to be seizure free. The non-negligible rate of surgical failure has led to seek other electrophysiological criteria. One putative marker is the high-frequency oscillations (HFOs).An HFO is a brief oscillation between 80-500 Hz lasting at least 4 periods recorded in intracerebral EEG. Due to their short-lasting nature, visually marking of these small oscillations is tedious and time-consuming. Automatically detecting these oscillations seems an imperative stage to study HFOs on cohorts of patients. There is however no general agreement on existing detectors.In this thesis, we developed a new way of representing HFOs thanks to a novel normalisation of the wavelet transform and to use this representation as a base for detecting HFOs automatically. We secondly designed a strategy to properly characterise and validate automated detectors. Finally, we characterised, in a cohort of patients, the reliability of HFOs and epileptic spikes - the standard marker - as predictors of the epileptogenic zone using the validated detector. The conclusion of this thesis is that HFOs are not better than epileptic spikes in predicting the epileptogenic zone but combining the two leads to a more robust biomarker.

INTRODUÇÃO: Sabe-se que a doença periodontal é a doença infecciosa crônica mais prevalente na população adulta, acometendo 1/5 da população em fase ativa de trabalho e causadora de dor. As citocinas e demais substâncias moduladoras da inflamação que promovem e perpetuam a doença periodontal interagem e agravam outras doenças como o diabetes mellitus, aterosclerose e doenças autoimunes. O periodonto, com suas aferências proprioceptivas especializadas, desempenha importante papel de regulação dos movimentos da mastigação. Apesar da região orofacial ter uma ampla área de representação no córtex cerebral não se sabem os efeitos de uma inflamação crônica periodontal nesta representação. Ansiedade e estresse são conhecidos fatores correlacionados à doença periodontal e moduladores de condições dolorosas. Assim, são objetivos deste estudo a avaliação da sensibilidade mecânica em vibrissas, avaliação da ansiedade e o mapeamento do córtex motor de ratos com doença periodontal de 14 e 28 dias de evolução. MÉTODOS: Foram utilizados ratos Wistar machos pesando inicialmente entre 140 e 180 gramas, divididos em 3 grupos principais: grupo controle, grupo sham e grupo de estudo, em que a doença periodontal foi induzida por amarria no primeiro molar inferior direito. Os animais foram avaliados com 14 e 28 dias de doença, sendo a sensibilidade mecânica aferida por filamentos de Von Frey e a ansiedade avaliada por meio do labirinto em cruz elevado. O mapeamento do córtex motor foi realizado por estimulação elétrica epidural de um a dez volts. RESULTADOS: Ambos os períodos de evolução da doença causaram alterações condizentes com doença periodontal. Não houve diferenças no ganho de peso dos animais independente do grupo ao longo do estudo. Nos animais com 28 dias de doença houve maior nocicepção no lado doente com diferença estatística (p=0,042). Os animais do grupo de estudo 14 dias demonstraram mais comportamentos sugestivos de ansiedade nos parâmetros de congelamento (p=0,031), entradas nas extremidades dos braços abertos (p=0,048) e esticamento nos braços abertos (p=0,047) do labirinto em cruz elevado do que os grupos sham e controle. Os animais do grupo de estudo de 28 dias apresentaram maior comportamento de dor e medo observado através da presença do congelamento (p=0,016). O mapeamento do córtex motor evidenciou áreas representativas da mandíbula sobrepostas à área das vibrissas. Foi observada uma expansão da área da mandíbula no grupo da doença periodontal de 14 dias (p=0,038). CONCLUSÃO: A doença periodontal com 14 dias de evolução causou um aumento da resposta motora ipsilateral da mandíbula-mais-vibrissas e alterações de comportamento sugestivas de ansiedade / BACKGROUND: Periodontal disease is the most prevalent chronical infectious disease in adults, affecting 1/5 of people in active phase of labor and causing pain. Cytokines and substances that modulate inflammation promotes and perpetuate de periodontal disease, interacting and worsening other conditions such as diabetes mellitus, aterosclerosis and autoimmune diseases. The periodontium has specialized proprioceptive afferents and plays a role in the regulation of masticatory movements. Despite the wide brain cortical representation area of the orofacial structures, the periodontium has not been described in the literature and the effects of a chronical inflammation in its representation has not been clarified. Anxiety and stress are factors correlated to periodontal disease and modulators of pain. The aim of this study was evaluate vibrissae nociception through mechanical response, anxiety and the motor cortex mapping in rats with periodontal disease after 14 or 28 days of evolution. METHODS: Male Wistar rats (initial weight 140-180 grams) divided into 3 main groups: controls, sham and periodontal disease induced by placement of a cotton ligature in the mandibular right first molar tooth. The evaluations took place after 14 or 28 days of disease. Mechanical response was evaluated by von Frey filaments and anxiety was evaluated through the elevated plus maze. Epidural electrical stimulation (1 to 10 volts) was the method used for the cortical motor mapping. RESULTS: Both evolution periods caused clinical outcomes consistent to periodontal disease. There was no difference in the weight gain of the animals, whatever the group during the study. The animals with 28 days appeared to have a higher nociception in the side affected, with statistical difference (p=0.042). Animals with the disease evolution through 14 days showed more anxious behavior seen by freezing (p=0.031), entries in the extremities of open arms (p=0.048) and stretching in open arms (p=0.047) than the sham and control groups, in the elevated plus maze test. The 28 day disease evolution group showed more pain and fear behavior, seen by freezing (p=0.016). The cortical motor mapping showed an overlapping of jaw and vibrissae areas. There was an expansion of the mandibular area in the 14-day disease group (p=0.038). CONCLUSION: at 14-days, PD led to an expansion of the mandibular-plus-vibrissae motor cortical representation ipsilateral to the disease and behaviors suggestive of anxiety

O mapeamento das respostas BOLD (Blood Oxygenation Level Dependent) constitui etapa importante nos experimentos de imagem funcional por ressonância magnética (Functional Magnetic Resonance Imaging fMRI) e de EEG-fMRI simultâneo. Em sua grande maioria, a análise de dados de fMRI e de EEG-fMRI está baseada no modelo linear geral (General Linear Model GLM), que procura localizar as respostas BOLD por meio de modelos definidos a priori. Porém, em muitos casos, como em pacientes, variações na forma e/ou atraso podem reduzir a confiabilidade dos resultados. Desse modo, o primeiro objetivo deste trabalho foi explorar métodos clássicos e propor novos métodos para análise de dados de fMRI e de EEG-fMRI simultâneo. Neste trabalho, um método modificado baseado na distância de Kullback-Leibler generalizada (dKLg) foi desenvolvido. Diferentemente do GLM, essa abordagem não requer um modelo para a resposta. Dados simulados foram utilizados para otimizá-lo e compará-lo ao GLM sob diferentes condições de resposta como a relação sinal ruído e a latência. Em seguida, o dKLg foi testado em dados reais, adquiridos em 14 voluntários assintomáticos, submetidos a tarefas motoras e auditivas padrões. Os resultados mostram a equivalência entre o dKLg e o GLM. Em seguida, essa estratégia foi testada em 02 pacientes com com estenose carotídea unilateral. Neste caso, o dKLg foi capaz de detectar regiões significativas ipsilaterais à estenose, não detectadas pelo GLM, em virtude do atraso do sinal BOLD. Em seguida, esses métodos foram aplicados sobre exames de EEG-fMRI realizados em 45 pacientes com epilepsia. Para esse conjunto de dados, mais uma abordagem foi elaborada, que utiliza a Análise de Componentes Independentes (Independent Component Analysis ICA). Denominado ICA-GLM, ele permite extrair de modo semi-automático a amplitude, duração e topografia das descargas epileptiformes interictais (Interictal Epileptiform Discharges IED), favorecendo a inclusão de sinais do EEG de menor destaque. Além dessa vantagem, ele ainda permite incluir modelos do sinal BOLD com diferentes latências, aumentando a abrangência da variabilidade das respostas encontradas em pacientes com epilepsia. A eficiência do ICA-GLM também foi comparado à do GLM e dKLg nos exames de EEG-fMRI. Embora os resultados tenham demonstrado a robustez do GLM, em alguns pacientes o dKLg foi mais eficiente para localizar regiões concordantes que não foram detectadas pelo GLM. Ainda, em boa parte dos casos o ICA-GLM detectou regiões mais extensas e com maior valor estatístico, quando comparado ao GLM. De forma geral, nota-se que o dKLg e ICA-GLM podem ser ferramentas complementares importantes ao GLM, aumentando a sensibilidade dos exames de EEG-fMRI como um todo. Outra etapa importante nas avaliações de EEG-fMRI em pacientes com epilepsia tem sido a utilização de imagens de fontes elétricas (Electrical Source Imaging ESI). Neste trabalho, os mapas de ESI foram obtidos por dois métodos de solução inversa distribuída nunca usados no cenários da EEG-fMRI: Bayesian Model Averaging (BMA) e constrained Low Resolution Electromagnetic Tomography (cLORETA). Além da construção dos mapas de ESI, avaliamos a utilidade de combinar as técnicas de ESI e de EEG-fMRI para promover a diferenciação entre fontes primárias e de propagação temporal. Essa análise permitiu avaliar a concordância entre as regiões detectadas pelo ESI e EEG-fMRI e diferenciar as respostas BOLD relacionadas aos componentes iniciais e posteriores da IED. Embora os resultados ainda sejam preliminares para eleger qual método seria mais eficiente (cLORETA ou BMA), a distância encontrada entre o máximo ESI e o cluster de EEG-fMRI mais próximo foi consistentemente similar, em ambos, com os dados recentes da literatura. / Functional magnetic resonance imaging (fMRI) and combined EEG-fMRI usually rely on the successful detection of Blood Oxygenation Level Dependent (BOLD) signal. Typically, the analysis of both fMRI and EEG-fMRI are based on the General Linear Model (GLM) that aims at localizing the BOLD responses associated to an a priori model. However, the responses are not always canonical, as is the case of those from patients, which may reduce the reliability of the results. Therefore, the first objective of the present study was to explore the usage of classical methods, such as the GLM, and to propose alternative strategies to the analysis of fMRI and combined EEG-fMRI. A first method developed was based on the computation of the generalized Kullback-Leibler distance (gKLd), which does not require the use of an a priori model. Simulated data was used to allow quantitative comparison between the gKLd and GLM under different response conditions such as the signal to noise ratio and delay. The gKLd was then tested on real data, first from 14 asymptomatic subjects, submitted to classical motor and auditory fMRI protocols. The results demonstrate that under these conditions the GLM and gKLd are equivalent. The same strategy was applied to 02 patients with unilateral carotid stenosis. Now the dKLg was capable of detecting the expected bilateral BOLD responses that were not detected by the GLM, as a consequence of the response delay imposed by the stenosis. Those comparisons were now extended to the evaluation of EEG-fMRI exams from 45 patients with epilepsy. For this data set, an additional method was used, based on the use of Independent Component Analysis (ICA), which was called ICA-GLM. It allows extracting semi-automatically the amplitude, duration and topography of EEG interictal Epileptiform Discharges (IED), favoring the use of less prominent signals. Moreover, it also allows the use of BOLD response models with different delays, expanding the variability of the responses to be detected in patients with epilepsy. ICA-GLM was also compared to GLM and dKLg in these EEG-fMRI evaluations. Although in general the results have demonstrated the robustness of the GLM, dKLg was more efficient in detecting the responses from some pacients, while the ICA-GLM mostly detected broader regions with more significant results when compared to GLM. In general, dKLg and ICA-GLM seem to offer an important complementary aspect to the GLM, increasing its sensibility in EEG-fMRI as a whole. Another important aspect of EEG-fMRI applied to patients with epilepsy has been the inspection of Electrical Source Imaging (ESI) to evaluate some dynamical aspects of the IED. Herein, ESI maps were obtained from two inverse distributed solutions that were not applied so far to EEG-fMRI: Bayesian Model Averaging (BMA) and constrained Low Resolution Electromagnetic Tomography (cLORETA). Besides, we also evaluated the combined information from ESI and EEG-fMRI in order to differentiate from primary sources to temporal propagation of the signal. Such analysis allowed us to inspect for the correspondence between regions detected by ESI e EEG-fMRI and to separate BOLD signals whose sources are related to the initial and later components of the IED. Although the results are preliminary to determine which ESI method (cLORETA or BMA) is more efficient, the distance between the maximum ESI and the closest EEG-fMRI cluster was consistently similar with those reported in the literature.

This research presents engineering tools that address an important area impacting many persons worldwide: epilepsy. Over 60 million people are affected by epilepsy, a neurological disorder characterized by recurrent seizures that occur suddenly. Surgery and anti-epileptic drugs (AED s) are common therapies for epilepsy patients. However, only persons with seizures that originate in an unambiguous, focal portion of the brain are candidates for surgery, while AED s can lead to very adverse side-effects. Although medical devices based upon focal cooling, drug infusion or electrical stimulation are viable alternatives for therapy, a reliable method to automatically pinpoint dysfunctional brain and direct these devices is needed. This research introduces a method to effectively localize epileptic networks, or connectivity between dysfunctional brain, to guide where to insert electrodes in the brain for therapeutic devices, surgery, or further investigation. The method uses an evolutionary algorithm (EA) and frequent itemset mining (FIM) to detect and cluster frequent concentrations of epileptic neuronal action potentials within human intracranial electroencephalogram (EEG) recordings. In an experiment applying the method to seven patients with neocortical epilepsy (a total of 35 seizures), the approach reliably identifies the seizure onset zone, in six of the subjects (a total of 31 seizures). Hopefully, this research will lead to a better control of seizures and an improved quality of life for the millions of persons affected by epilepsy.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2009. / Härtill 5 uppsatser.