Thesis (M.Eng.). / Written for the Dept. of Biomedical Engienering and Montreal Neurological Institute. Title from title page of PDF (viewed 2009/06/17). Includes bibliographical references.

Thesis (Ph.D.)--Indiana University, 2009. / Title from screen (viewed on November 4, 2009). School of Nursing, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Sharon Sims, Carrie Foote, Joan Austin, Melinda Swenson. Includes vita. Includes bibliographical references (leaves 104-110).

Thesis (M.S.)--University of Florida, 2002. / Title from title page of source document. Includes vita. Includes bibliographical references.

Thesis (Ph.D.)--Drexel University, 2010. / Includes abstract and vita. Includes bibliographical references (leaves 99-114).

Thesis (Ph.D.)--Drexel University, 2010. / Includes abstract and vita. Includes bibliographical references (leaves 95-104).

Thesis (Ph. D.)--Virginia Commonwealth University, 2006. / Prepared for: Dept. of Neurology. Bibliography: leaves 180-205. Also available online.

Thesis (doctoral)--Tampere University of Technology, 2009. / Includes bibliographical references. Also available on the World Wide Web.

Many cognitive and neurological disorders today, such as Autism Spectrum Disorders (ASD) and various forms of epilepsy such as infantile spasms (IS), manifest as changes in voltage activity recorded in scalp electroencephalograms (EEG). Diagnosis of brain disease often relies on the interpretation of complex EEG features through visual inspection by clinicians. Although clinically useful, such interpretation is subjective and suffers from poor inter-rater reliability, which affects clinical care through increased variability and uncertainty in diagnosis. In addition, such qualitative assessments are often binary, and do not parametrically measure characteristics of disease manifestations. Many cognitive disorders are grouped by similar behaviors, but may arise from distinct biological causes, possibly represented by subtle electrophysiological differences. To address this, quantitative analytical tools - such as functional network connectivity, frequency-domain, and time-domain features - are being developed and applied to clinically obtained EEG data to identify electrophysiological biomarkers. These biomarkers enhance a clinician’s ability to accurately diagnose, categorize, and select treatment for various neurological conditions. In the first study, we use spectral and functional network analysis of clinical EEG data recorded from a population of children to propose a cortical biomarker for autism. We first analyze a training set of age-matched (4–8 years) ASD and neurotypical children to develop hypotheses based on power spectral features and measures of functional network connectivity. From the training set of subjects, we derive the following hypotheses: 1) The ratio of the power of the posterior alpha rhythm (8–14 Hz) peak to the anterior alpha rhythm peak is significantly lower in ASD than control subjects. 2) The functional network density is lower in ASD subjects than control subjects. 3) A select group of edges provide a more sensitive and specific biomarker of ASD. We then test these hypotheses in a validation set of subjects and show that both the first and third hypotheses, but not the second, are validated. The validated features successfully classified the data with significant accuracy. These results provide a validated study for EEG biomarkers of ASD based on changes in brain rhythms and functional network characteristics. We next perform a follow-up study that utilizes the same group of ASD and neurotypical subjects, but focuses on differences between these two groups in the sleep state. Motivated by the results from the previous study, we utilize the previously validated biomarkers, including the alpha ratio and the subset of edges found to be a sensitive biomarker of ASD, and test their effectiveness in the sleep state. To complement these frequency domain features, we also investigate the efficacy of several time domain measures. This investigation did not lead to significant findings, which may have important implications for the differences between sleep and wake states in ASD, or perhaps generally for clinical assessment, as well as for the effect of noise on signal in clinically obtained data. Finally, we design a similar analysis framework to investigate a set of clinical EEG data recorded from a population of children with active infantile spasms (IS) (2-16 months), and age-matched neurotypical children, in both wake and sleep states. The goal of this analysis is to develop a quantitative biomarker from the EEG signal, which ultimately we will apply to predict the clinical outcome of children with IS. In addition to spectral and functional network analysis, we calculate time domain features previously found to correlate with seizures. We compare the two populations by each feature individually, test the effects of age on these features, use all features in a linear discriminant model to categorize IS versus neurotypical EEG, and test the findings using a leave-one-out validation test. We find almost every feature tested shows significant population differences between IS and control groups, and that taken together they serve as an effective classifier, with potential to be informative as to disease severity and long-term outcome. Furthermore, analysis of these features reveals two groups, indicating a possibility that these features reflect two distinct qualitative characteristics of IS and seizures.

A epilepsia é uma das mais comuns e sérias desordens neurológicas. Caracteriza-se pela ocorrência de crises convulsivas, as quais podem aumentar a geração de espécies reativas, desequilibrando o metabolismo redox dos pacientes epiléticos e aumentando a incidência de doenças associadas ao estresse oxidativo. Estudos têm mostrado que alguns polifenóis podem apresentar atividade anticonvulsivante em modelo animal de epilepsia. A erva-mate (Ilex paraguariensis) é uma planta rica em polifenóis, compostos com reconhecido potencial antioxidante. Atualmente, o cultivo da erva-mate pode ser feito a partir de dois métodos distintos, o orgânico, no qual o uso de fungicidas, inseticidas e/ou fertilizantes inorgânicos é proibido, e o convencional, onde a utilização destes insumos é permitida. Estudos têm mostrado que algumas plantas cultivadas sob manejo orgânico apresentam maiores teores polifenólicos do que àquelas produzidas pelo cultivo convencional. Em vista disso, o objetivo deste estudo foi avaliar o potencial anticonvulsivante, antioxidante e possíveis alterações comportamentais de infusões de erva-mate, orgânica e convencional em ratos Wistar. Avaliou-se ainda, o perfil polifenólico de ambas as amostras de erva-mate. Ratos machos foram divididos em três grupos e tratados, via gavagem, com água destilada, infusão de ervamate orgânica e infusão de erva-mate convencional, durante 15 dias. Ao término do tratamento, os animais foram avaliados comportamentalmente através do teste de campo aberto (Open Field). Subsequentemente, uma dose única da droga convulsivante pentilenotetrazol (PTZ) 60 mg/kg (i.p.), foi administrada e os animais foram observados durante 30 minutos em relação ao tempo de latência, tempo de crises tônico-clônicas, intensidade e freqüência de convulsões, duração total das crises e mortalidade induzida pelo PTZ. Após, os animais foram sacrificados e os tecidos do SNC (cerebelo, córtex cerebral e hipocampo), o fígado e o soro coletados para os ensaios de atividade antioxidante das infusões de erva-mate. Os resultados mostraram que ambas as infusões, tanto orgânica como convencional, não alteraram os parâmetros comportamentais (locomoção, exploração e ansiedade) dos animais. Observou-se que os tratamentos, tanto com a erva-mate orgânica quanto com a convencional, foram capazes de diminuir a freqüência das crises convulsivas em relação ao PTZ. Em adição, o tratamento com a erva-mate orgânica reduziu significativamente o tempo de crises tônico-clônicas quando comparado ao grupo controle. Ambas as infusões estudadas mostraram uma tendência de diminuição da intensidade das crises convulsivas (animais que atingiram o nível 5 na escala de Racine) induzida pelo PTZ. Além disso, as infusões de erva-mate orgânica e convencional reduziram os níveis de danos oxidativos a lipídios e proteínas, e a concentração de óxido nítrico induzidos pelo PTZ nos ratos. Ambas as infusões estudadas preveniram, ainda, a depleção das defesas antioxidantes enzimáticas (superóxido dismutase e catalase) e não-enzimáticas (conteúdo de proteína sulfidril) induzida pelo PTZ. Não foram observadas diferenças no conteúdo fenólico total entre as infusões de erva-mate orgânica e convencional. Os compostos fenólicos rutina, ácido clorogênico e acil derivados, e o alcalóide cafeína foram identificados em ambas as infusões de erva-mate estudadas. / Submitted by Marcelo Teixeira (mvteixeira@ucs.br) on 2014-06-12T13:21:43Z No. of bitstreams: 1 Dissertacao Catia dos Santos Branco.pdf: 2406491 bytes, checksum: 0caac22b54f7ca8da77062c8322a010b (MD5) / Made available in DSpace on 2014-06-12T13:21:43Z (GMT). No. of bitstreams: 1 Dissertacao Catia dos Santos Branco.pdf: 2406491 bytes, checksum: 0caac22b54f7ca8da77062c8322a010b (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Epilepsy is one of the most common and serious neurological disorders. It is characterized by the occurrence of seizures, which may increase the generation of reactive species, unbalancing the redox metabolism of epileptic patients and increasing the incidence of diseases associated with oxidative stress. Studies have shown that some polyphenols may have anticonvulsant activity in animal models of epilepsy. Yerba mate (Ilex paraguariensis) is a plant rich in polyphenols, compounds with known antioxidant potential. Currently, the cultivation of yerba mate can be made from two different methods, the organic, in which the use of fungicides, inseticides and/or inorganic fertilizers is prohibited, and conventional one, where the use of these inputs are allowed. Studies have shown that some plants grown under organic management have higher polyphenolic content than those produced by conventional cultivation. Thus, the objective of this study was to evaluate the potential anticonvulsant, antioxidant and possible behavioral changes of infusions of yerba mate, organic and conventional in Wistar rats. We also evaluated the polyphenolic profile of both yerba mate samples. Male rats were divided into three groups and treated by oral gavage with distilled water, infusion of organic yerba mate and infusion of conventional yerba mate for 15 days. At the end of treatment, the animals were behaviorally evaluated by the Open Field test. Subsequently, a single dose of the convulsant drug pentylenetetrazole (PTZ) 60 mg/kg (i.p.) was administered and animals were observed for 30 minutes in relation to the latency time, tonic-clonic seizures time, intensity and frequency of seizures, total duration of convulsions and mortality induced by PTZ. Then, the animals were sacrificed and the tissues of the CNS (cerebellum, cerebral cortex and hippocampus), the liver and serum were collected for the evaluation of antioxidant effects of yerba mate infusions. The results showed that both infusions, organic and conventional, did not alter the behavior (locomotor, exploration and anxiety) of the rats. It was observed that treatments with both organic and conventional yerba mate were able to decrease the frequency of seizures in relation to the PTZ group. In adittion, the treatment with organic yerba mate significaltly decreased the time of tonic-clonic seizures when compared to the control group. Both infusions studied showed a tendency of decreasing intensity of seizures (animals that have reached level 5 on the scale of Racine) induced by PTZ. Moreover, infusions of organic and conventional yerba mate reduced the levels of oxidative damage to lipids and proteins, and the levels of nitric oxide raised by PTZ in rats. Both infusions studied prevented, also, the depletion of enzymatic (superoxide dismutase and catalase) and non-enzymatic (protein sulfhydryl content) antioxidant defenses induced by PTZ. There were no differences in total phenolic content between infusions of organic and conventional yerba mate. The phenolic compounds rutin, chlorogenic acid and acyl derivatives, and the alkaloid caffeine were identified in both infusions of yerba mate.

A epilepsia é uma das mais comuns e sérias desordens neurológicas. Caracteriza-se pela ocorrência de crises convulsivas, as quais podem aumentar a geração de espécies reativas, desequilibrando o metabolismo redox dos pacientes epiléticos e aumentando a incidência de doenças associadas ao estresse oxidativo. Estudos têm mostrado que alguns polifenóis podem apresentar atividade anticonvulsivante em modelo animal de epilepsia. A erva-mate (Ilex paraguariensis) é uma planta rica em polifenóis, compostos com reconhecido potencial antioxidante. Atualmente, o cultivo da erva-mate pode ser feito a partir de dois métodos distintos, o orgânico, no qual o uso de fungicidas, inseticidas e/ou fertilizantes inorgânicos é proibido, e o convencional, onde a utilização destes insumos é permitida. Estudos têm mostrado que algumas plantas cultivadas sob manejo orgânico apresentam maiores teores polifenólicos do que àquelas produzidas pelo cultivo convencional. Em vista disso, o objetivo deste estudo foi avaliar o potencial anticonvulsivante, antioxidante e possíveis alterações comportamentais de infusões de erva-mate, orgânica e convencional em ratos Wistar. Avaliou-se ainda, o perfil polifenólico de ambas as amostras de erva-mate. Ratos machos foram divididos em três grupos e tratados, via gavagem, com água destilada, infusão de ervamate orgânica e infusão de erva-mate convencional, durante 15 dias. Ao término do tratamento, os animais foram avaliados comportamentalmente através do teste de campo aberto (Open Field). Subsequentemente, uma dose única da droga convulsivante pentilenotetrazol (PTZ) 60 mg/kg (i.p.), foi administrada e os animais foram observados durante 30 minutos em relação ao tempo de latência, tempo de crises tônico-clônicas, intensidade e freqüência de convulsões, duração total das crises e mortalidade induzida pelo PTZ. Após, os animais foram sacrificados e os tecidos do SNC (cerebelo, córtex cerebral e hipocampo), o fígado e o soro coletados para os ensaios de atividade antioxidante das infusões de erva-mate. Os resultados mostraram que ambas as infusões, tanto orgânica como convencional, não alteraram os parâmetros comportamentais (locomoção, exploração e ansiedade) dos animais. Observou-se que os tratamentos, tanto com a erva-mate orgânica quanto com a convencional, foram capazes de diminuir a freqüência das crises convulsivas em relação ao PTZ. Em adição, o tratamento com a erva-mate orgânica reduziu significativamente o tempo de crises tônico-clônicas quando comparado ao grupo controle. Ambas as infusões estudadas mostraram uma tendência de diminuição da intensidade das crises convulsivas (animais que atingiram o nível 5 na escala de Racine) induzida pelo PTZ. Além disso, as infusões de erva-mate orgânica e convencional reduziram os níveis de danos oxidativos a lipídios e proteínas, e a concentração de óxido nítrico induzidos pelo PTZ nos ratos. Ambas as infusões estudadas preveniram, ainda, a depleção das defesas antioxidantes enzimáticas (superóxido dismutase e catalase) e não-enzimáticas (conteúdo de proteína sulfidril) induzida pelo PTZ. Não foram observadas diferenças no conteúdo fenólico total entre as infusões de erva-mate orgânica e convencional. Os compostos fenólicos rutina, ácido clorogênico e acil derivados, e o alcalóide cafeína foram identificados em ambas as infusões de erva-mate estudadas. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Epilepsy is one of the most common and serious neurological disorders. It is characterized by the occurrence of seizures, which may increase the generation of reactive species, unbalancing the redox metabolism of epileptic patients and increasing the incidence of diseases associated with oxidative stress. Studies have shown that some polyphenols may have anticonvulsant activity in animal models of epilepsy. Yerba mate (Ilex paraguariensis) is a plant rich in polyphenols, compounds with known antioxidant potential. Currently, the cultivation of yerba mate can be made from two different methods, the organic, in which the use of fungicides, inseticides and/or inorganic fertilizers is prohibited, and conventional one, where the use of these inputs are allowed. Studies have shown that some plants grown under organic management have higher polyphenolic content than those produced by conventional cultivation. Thus, the objective of this study was to evaluate the potential anticonvulsant, antioxidant and possible behavioral changes of infusions of yerba mate, organic and conventional in Wistar rats. We also evaluated the polyphenolic profile of both yerba mate samples. Male rats were divided into three groups and treated by oral gavage with distilled water, infusion of organic yerba mate and infusion of conventional yerba mate for 15 days. At the end of treatment, the animals were behaviorally evaluated by the Open Field test. Subsequently, a single dose of the convulsant drug pentylenetetrazole (PTZ) 60 mg/kg (i.p.) was administered and animals were observed for 30 minutes in relation to the latency time, tonic-clonic seizures time, intensity and frequency of seizures, total duration of convulsions and mortality induced by PTZ. Then, the animals were sacrificed and the tissues of the CNS (cerebellum, cerebral cortex and hippocampus), the liver and serum were collected for the evaluation of antioxidant effects of yerba mate infusions. The results showed that both infusions, organic and conventional, did not alter the behavior (locomotor, exploration and anxiety) of the rats. It was observed that treatments with both organic and conventional yerba mate were able to decrease the frequency of seizures in relation to the PTZ group. In adittion, the treatment with organic yerba mate significaltly decreased the time of tonic-clonic seizures when compared to the control group. Both infusions studied showed a tendency of decreasing intensity of seizures (animals that have reached level 5 on the scale of Racine) induced by PTZ. Moreover, infusions of organic and conventional yerba mate reduced the levels of oxidative damage to lipids and proteins, and the levels of nitric oxide raised by PTZ in rats. Both infusions studied prevented, also, the depletion of enzymatic (superoxide dismutase and catalase) and non-enzymatic (protein sulfhydryl content) antioxidant defenses induced by PTZ. There were no differences in total phenolic content between infusions of organic and conventional yerba mate. The phenolic compounds rutin, chlorogenic acid and acyl derivatives, and the alkaloid caffeine were identified in both infusions of yerba mate.