Submitted by Fernanda Furlanetto Bellentani null (fernandafbelle@gmail.com) on 2017-03-07T01:02:32Z No. of bitstreams: 1 Tese Bellentani FF.pdf: 1557146 bytes, checksum: 788737393ee9b836ba8bd34728ed2c3d (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2017-03-10T16:53:16Z (GMT) No. of bitstreams: 1 bellentani_ff_dr_bot.pdf: 1557146 bytes, checksum: 788737393ee9b836ba8bd34728ed2c3d (MD5) / Made available in DSpace on 2017-03-10T16:53:16Z (GMT). No. of bitstreams: 1 bellentani_ff_dr_bot.pdf: 1557146 bytes, checksum: 788737393ee9b836ba8bd34728ed2c3d (MD5) Previous issue date: 2017-02-17 / A conectividade funcional é anormal na epilepsia do lobo temporal mesial (ELTm). O objetivo deste estudo foi investigar os efeitos de fármacos antiepilépticos (FAES) na conectividade funcional de pacientes com ELTm. Para isso, 31 pacientes com ELTm (16 à direita e 15 à esquerda) e 36 controles foram investigados. Sequências 3D volumétricas T1 e imagens funcionais a partir de sinal BOLD foram adquiridas em um equipamento 3T. Os dados da ressonância magnética funcional (RMf) em repouso foram processados e analisados utilizando o programa CONN. Para cada sujeito, duas formas de análise foram realizadas: uma de correlação entre as várias regiões de interesse e outra de região interesse para todos os voxels. A análise de grupos foi feita utilizando um modelo linear geral com nível de significância de p < 0,05 corrigido para múltiplas comparações. Foram realizadas comparações entre pacientes com ELTm (direita ou esquerda) e controles, seguidas de comparações de acordo com a carga de FAEs. A partir dessas análises, foi constatado uma redução de conectividade com volume total de 9092 mm3 (p<0,0001), em pacientes com ELTm esquerda e 5234 mm3 (p<0,0001), em pacientes com ELTm direita . Quando considerada a carga de medicação, pacientes com ELTm esquerda, recebendo doses altas, apresentaram redução de conectividade nas regiões temporais. Nos pacientes que recebiam doses baixas, essa redução atingiu uma área total mais extensa, no córtex frontal medial, na região posterior do cíngulo e pré-cúneo. Para o lado direito, em pacientes recebendo doses altas, a redução de conectividade foi observada apenas na área do cótex frontal medial. Nos que receberam doses baixas, 2 áreas com redução foram observadas (córtex frontal medial e região posterior do cíngulo) e com uma extensão maior. A análise de correlação envolvendo regiões de interesse mostrou, para ambos os lados, que o circuito amígdalo-hipocampal e a rede de modo padrão apresentaram maior conectividade quando utilizadas maiores doses de FAEs. Com base nesses resultados, foram confirmadas áreas de conectividade funcional anormal em pacientes com ELTm e que se apresentam mais difusas em pacientes com ELTm esquerda. Conclui-se também que as doses de medicamentos podem influenciar nestas observações, uma vez que o aumento de dose tende a normalizar a conectividade funcional cerebral. / The functional connectivity is abnormal in mesial temporal lobe epilepsy (MTLE). The objective of this study was to investigate the effects of antiepileptic drugs (AED) laterality and medication effect in the functional connectivity of MTLE. For this, 31 patients with MTLE (16 right and 15 left) and 36 controls were investigated. 3D volumetric sequences T1 and functional images from BOLD signal were acquired in a 3T equipment. Functional magnetic resonance imaging (fMRI) data were processed and analyzed using the CONN program. Two forms of analysis were performed for each patient: one of correlation between the various regions of interest and other of region of interest for all the voxels. The group analyzes was done following a general linear model with a level of significance of p < 0,05 corrected for the multiple comparisons. Comparisons were made between patients with MTLE (right or left) and controls, following of comparisons according to the AED. From these analysis, it was observed that in patients with left MTLE, there was a reduction in connectivity with total volume of 9092 mm³ (p<0,0001) and in patients with right MTLE, the areas of decreased connectivity totaled 5234 mm³ (p<0,0001). When considering the medication load, patients with left MTLE receiving high doses presented reduced connectivity in the temporal regions and in patients receiving low doses, this reduction reached a more extensive total area, in the medial frontal cortex, in the posterior region of the cingulate and pre-cuneous. To the right side, in patients receiving high doses, a reduced connectivity was observed only in the area of the medial frontal cortex, whereas in those receiving low doses, 2 areas with reduction were observed (medial frontal cortex and posterior cingulate region). The analysis of correlation involving regions of interest showed, to both sides that the amygdalo-hippocampal circuit and the network pattern mode presented greater connectivity when higher doses of AED. Based on these results were confirmed areas of abnormal functional connectivity in patients with MTLE and are more difuse in patients with left MTLE. It was also concluded that drug doses can influence these observations, once the doses increase tends to normalize functional brain connectivity.

Alta prevalência, farmacorresistência e bom prognóstico cirúrgico são algumas das características clínicas que tornam a epilepsia do lobo temporal mesial com esclerose hipocampal (ELTM-EH) uma das mais importantes formas de epilepsia. Ela é o modelo da epilepsia cirurgicamente curável. Infelizmente, cerca de 10% dos pacientes evoluem com resultado cirúrgico insatisfatório. A ELTM-EH está associada a alterações amplas do perfil de expressão dos microRNAs (miRNAs) do hipocampo. Recentemente, constatou-se a existência de miRNAs estáveis no sangue periférico e em outros fluidos corporais, comprovadamente aplicáveis como biomarcadores, cuja abrangência vai do diagnóstico à resposta terapêutica. Tendo isso em vista, a pesquisa partiu do seguinte questionamento: é possível a identificação, no sangue periférico, de assinaturas moleculares por miRNAs que predigam o resultado do tratamento cirúrgico da ELTM-EH? Por meio de técnicas de biologia molecular, avaliaram-se amostras de sangue e hipocampo de pacientes submetidos à lobectomia temporal anterior em consequência de ELTMEH farmacorresistente. As amostras eram representativas de indivíduos com resultado cirúrgico favorável (Engel IA) e desfavorável (Engel III e IV). Com a técnica de microarray obteve-se o perfil de expressão de miRNAs das amostras triadas e chegou-se a um conjunto de seis miRNAs candidatos a biomarcadores de prognóstico cirúrgico: miR-92b-3p; miR-1238-3p; miR-1181; miR-636; miR- 1229-3p e miR-486-5p. Em seguida, com a técnica de PCR em tempo real, quantificou-se a expressão destes seis miRNAs e, a partir da otimização de um ponto de corte na escala de expressão, cada miRNA circulante foi apreciado como preditor de resultado cirúrgico. Assim, constatou-se hiperexpressão sanguínea dos seis miRNAs, sem distinção estatística entre os grupos Engel IA e Engel III-IV, hiperexpressão hipocampal do miR-486-5p no grupo Engel IA e hipoexpressão hipocampal do miR-636 nos grupos Engel IA e Engel III-IV. Na análise dos miRNAs circulantes como preditores de sucesso cirúrgico, o miR- 1238-3p exibiu uma sensibilidade de 40,00%, especificidade de 92,86% e acurácia de 65,52%. O conjunto miR-1238/miR1181 mostrou sensibilidade de 46,67%, especificidade de 85,71% e acurácia de 65,52%. O único miRNA circulante sondado como preditor de insucesso cirúrgico, o miR-636, revelou sensibilidade de 21,43%, especificidade de 93,33% e acurácia de 58,62% / A high prevalence, drug resistance and good surgical prognosis are some of the clinical characteristics that cause mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) to be one of the most important forms of epilepsy. This condition is the model of surgically curable epilepsy, although unfortunately about 10% of the patients exhibit an unsatisfactory surgical outcome. MTLE-HS is associated with extensive changes in the expression profile of hippocampal microRNAs (miRNAs). It has been recently observed that stable miRNAs exist in peripheral blood and in other body fluids which have been proved to be applicable as biomarkers from diagnosis to therapeutic response. On this basis, the present investigation was based on the following question: is it possible to identify molecular signatures by peripheral blood miRNAS that predict the outcome of surgical treatment of MTLE-HS? Molecular biology techniques were used to evaluate blood and hippocampal samples of patients submitted to anterior temporal lobectomy as a consequence of drug-resistant MTLE-HS. The samples were representative of patients with a favorable (Engel IA) and unfavorable (Engel III and IV) surgical outcome. The microarray technique was used to obtain the expression profile of miRNAs in the samples, with a set of six miRNAs being reached as candidate biomarkers for surgical prognosis: miR-92b-3p, miR-1238- 3p, miR-1181, miR-636, miR-1229-3p, and miR-486-5p. Next, real-time PCR was used to quantitate the expression of these six miRNAs and, based on the optimization of a cut-off point on the expression scale, each circulating miRNA was evaluated as surgical outcome predictor. We observed blood hyperexpression of the six miRNAs with no significant difference between the Engel IA and Engel IIIIV groups, hippocampal hyperexpression of miR-486-5p in the Engel IA group, and hippocampal hypoexpression of miR-636 in the Engel IA and Engel III-IV groups. Analysis of circulating miRNAs as predictors of surgical success revealed that miR-1238-3p exhibited 40.00% sensitivity, 92.86% specificity and 65.52% accuracy. The miR-1238/miR1181 set showed 46.67% sensitivity, 85.71% specificity and 65.52% accuracy. The only circulating miRNA evaluated as a predictor of surgical failure, miR-636, showed 21.43% sensitiviy, 93.33% specificity, and 58.62% accuracy

A presença de déficits cognitivos nos indivíduos com epilepsia de lobo temporal é amplamente reconhecida, sendo os mesmos caracterizados por prejuízos da capacidade de nomeação, memória e função executiva. Embora as disfunções mnésticas sejam bastante estudadas na epilepsia de lobo temporal, a presença de disfunção executiva permanece controversa. A epilepsia gera, ainda, restrições na vida diária e prejuízo na qualidade de vida, levando a alterações na vida do indivíduo, tanto no aspecto físico quanto no psicossocial. Diversos estudos verificaram o impacto negativo da epilepsia sobre o ajustamento psicossocial através de questionários de qualidade de vida ou observações clínicas. No entanto, as medidas de qualidade de vida correspondem à percepção pessoal e subjetiva do paciente, mas geram informações inespecíficas frente à sua atual condição de vida. A despeito da evidência crescente de pior ajustamento psicossocial, não há até o momento, estudos que realizem avaliação formal da adequação social nos pacientes com epilepsia de lobo temporal e diferenciem o desempenho nos questionários de qualidade de vida e adequação social. Os objetivos deste estudo foram: avaliar o desempenho neuropsicológico, a qualidade de vida e a adequação social nos pacientes com epilepsia de lobo temporal através de instrumentos específicos e padronizados para estes fins. Além disso, buscou-se investigar a presença de associação entre estes fatores. Para tal, foram avaliados 35 pacientes com epilepsia de lobo temporal associada à atrofia hipocampal e 38 voluntários sadios, através de: a) bateria compreensiva de testes neuropsicológicos; b) questionários específicos de qualidade de vida e; c) escala padronizada de adequação social. Os pacientes com epilepsia de lobo temporal apresentaram pior desempenho que os voluntários sadios em testes de memória, tanto verbal quanto visual. Além disso, observou-se que os pacientes apresentaram qualidade de vida diminuída nos domínios relacionados a medo de crises, cognição e efeitos colaterais da medicação. Quanto à adequação social, os pacientes com epilepsia de lobo temporal apresentaram pior adequação global e, mais especificamente, pior adequação nos fatores trabalho e lazer quando comparados aos voluntários sadios. Não houve correlação estatisticamente significante entre desempenho cognitivo e qualidade de vida. No entanto, disfunções atencionais e mnésticas se correlacionaram positivamente com a pior adequação social. Além disso, observou-se correlação significativa entre a pior adequação social e a pior qualidade de vida. Os achados confirmam o impacto negativo da epilepsia sobre a cognição, qualidade de vida e adequação social de pacientes com epilepsia de lobo temporal. A ausência de correlação entre achados neuropsicológicos e qualidade de vida indica a imprecisão de queixas cognitivas mensuradas através de escalas de auto-preenchimento. A correlação entre adequação social e o desempenho atencional e mnéstico verbal demonstra a necessidade de programas de reabilitação neuropsicológica para estas funções a fim de melhorar a adequação social desta população / The presence of cognitive deficits in patients with temporal lobe epilepsy is widely recognized, being characterized by impairment of naming, memory and executive functioning. Although, mnestic dysfunction is well-studied in temporal lobe epilepsy, the presence of executive dysfunction remains controversial. Epilepsy is associated with restrictions on daily life and impairment in quality of life leading changes in peoples live, on physical and psychosocial aspects. Several studies described the negative impact of epilepsy on psychosocial adjustment by quality of life questionnaires or clinical observations. However, measures of quality of life match personal and subjective perception of the patient, but generate non-specific information compared to their current living conditions. Despite the growing evidence of poor psychosocial adjustment, to the moment, there is no formal assessment of social adjustment in patients with temporal lobe epilepsy and differentiate the performance on quality of life and social adjustment questionnaires. The objectives of this study were to evaluate the neuropsychological performance, quality of life and social adjustment in patients with temporal lobe epilepsy by means of specific and standardized instruments for these purposes. In addition, we verified the presence of association between these factors. We evaluated 35 patients with temporal lobe epilepsy caused by hippocampal atrophy and 38 healthy volunteers, through: a) comprehensive battery of neuropsychological tests; b) specific quality of life questionnaires and; c) standard scale of social adjustment. Patients with temporal lobe epilepsy had a worse performance than the healthy volunteers on tests of memory, both verbal and visual. In addition, we observed that patients had reduced quality of life in areas related to fear of seizures, cognition, and side effects of medication. As to social adjustment, patients had worse overall adequacy and, more specifically, on subfactors related to work and leisure compared to healthy volunteers. There was no statistical significant correlation between cognitive performance and quality of life. However, attentional and verbal mnestic dysfunctions were positively correlated with the worse social adjustment. Moreover, there was significant correlation between worse social adjustment and reduced QOL. These findings confirm the negative impact of epilepsy on cognition, social adjustment and quality of life in patients with temporal lobe epilepsy. The lack of correlation between neuropsychological findings and quality of life indicates the imprecision of cognitive complaints measured by self-report scales. The correlation between social adjustment with attentional and memory performance show the importance of neuropsychological rehabilitation for these functions in order to obtain a better social adjustment

INTRODUÇÃO: O processamento temporal pode ser definido como a percepção das características temporais do som, ou a percepção na mudança da duração dessas características, dentro de um intervalo de tempo restrito. Para que essas sutis mudanças possam ser percebidas, o sistema nervoso auditivo central necessita de um processamento preciso da estrutura de tempo do sinal acústico recebido. Nesse estudo, os objetivos foram: avaliar a resolução temporal, por meio de dois diferentes testes, o GIN (gap-in-noise), um teste comportamental, e o Potencial evocado auditivo de estado estável, um teste eletrofisiológico, em indivíduos normais, com lesão neurológica, e com transtorno de processamento auditivo (central); e verificar a sensibilidade e a especificidade, de ambos os testes. MÉTODOS: Foram avaliados 70 indivíduos voluntários, de ambos os gêneros, com idade entre 16 e 50 anos, divididos em três grupos: G1(grupo normal), G2 (grupo com lesão de lobo temporal, causada por Esclerose mesial temporal), e G3 ( indivíduos com transtorno do processamento auditivo (central)). Todos os indivíduos realizaram ambos os testes. No teste GIN foram utilizadas as listas um e dois. Os limiares de detecção de gap e a porcentagem de acertos foram calculados para todos os indivíduos. O potencial evocado auditivo de estado estável foi realizado com modulação de freqüência de 46 Hz, nas intensidades de 500 e 2000 Hz, em ambas as orelhas. Foram calculados os limiares eletrofisiológicos, os limiares estimados, e a diferença entre o limiar tonal comportamental e o eletrofisiológico, para todos os indivíduos. RESULTADOS: Os resultados do teste GIN mostraram que os indivíduos do G2 apresentam limiares de detecção de gap significantemente piores que os indivíduos do G1 e do G3. O mesmo ocorreu para a porcentagem de acertos, o G2 apresentou uma porcentagem de acertos pior que os grupos G1 e G3. Os indivíduos do G3 apresentaram limiares de detecção de gap aumentados em relação ao G1, porém, sem diferença estatisticamente significante. O teste GIN apresentou uma boa especificidade em todos os grupos, e uma sensibilidade melhor para lesão neurológica do que para transtorno do processamento auditivo (central). Os resultados do potencial evocado auditivo de estado estável mostraram que o G2 apresentou limiares eletrofisiológicos e estimados significantemente piores que os encontrados no G1 e G3. A diferença entre o limiar eletrofisiológico e o comportamental no G2 foi maior que a obtida no G1 e no G3. Os resultados da especificidade e da sensibilidade foram semelhantes aos encontrados no GIN. Além disso, foi encontrada uma boa especificidade, e sensibilidade melhor para lesão neurológica que para transtorno do processamento auditivo. CONCLUSÕES: Os indivíduos com lesão de sistema nervoso auditivo central mostraram um maior comprometimento da habilidade de resolução temporal, avaliada no teste GIN e no potencial evocado auditivo de estado estável, que os indivíduos com disfunção do sistema nervoso auditivo central, e os indivíduos normais. Os valores de especificidade foram melhores que os valores de sensibilidade em ambos os testes, nos três grupos avaliados. A sensibilidade para lesão neurológica foi melhor que a sensibilidade para transtorno do processamento auditivo (central) em ambos os testes / INTRODUCTION: Temporal processing can be defined as a perception of temporal characteristics of the sound, or as a perception of the change in the duration of these characteristics, in a restrict period of time. For these subtle changes to be noticed, the central nervous system needs an accurate processing of the structure of the acoustic stimulus received. The aims of this study were: to assess the temporal resolution using two different tests - the gaps-in-noise test (a behavioral test) and the Auditory steady-state response (an electrophysiological test) in three groups of subjects: normal group; neurological group and (central) auditory processing disorder group. It also aimed to verify the sensitivity and specificity of the two tests. METHODS: Seventy volunteers of both genders were evaluated. Subjects ranged in age from 16 to 50 years, and were divided in three groups: G1 (normal group); G2 (subjects with temporal lobe insult caused by temporal mesial sclerosis) and G3 (subjects with (central) auditory processing disorder). Both tests were conducted on all subjects. The lists 1 and 2 of the gap-in-noise test were applied in all subjects. Gap detection threshold and the percentage of correct responses were calculated for all participants. Auditory steady-state response with 46 Hz of frequency modulation was applied for the frequencies of 500 Hz and 2000 Hz in both ears. Electrophysiological and estimated thresholds were calculated, and the difference between estimated and behavioral tonal thresholds was also obtained for the subjects. RESULTS: results of the gaps-in-noise test showed that the G2 gap detection thresholds were significantly worse than the G1 and G3 thresholds. The same result was observed for the percentage of correct responses, G2 showed a worse percentage of correct responses than those verified for the G1 and the G3 groups. Individuals of the G3 showed increased gap detection threshold compared with the G1, although this difference was not statistically significant. Gaps-in-noise test showed a good specificity for all groups, and a better sensitivity for the neurological lesions group than for the central auditory processing disorder group. Auditory steady-state response results suggested that G2 had electrophysiological and estimated thresholds significantly worse than G1 and G3. The difference between electrophysiological and behavioral threshold for G2 was bigger than the difference obtained in G1 and G3. Specificity and sensitivity results were similar to what was observed for the gaps-in-noise test results. Moreover, a good specificity was detected and the sensitivity showed better results for neurological lesions than for (central) auditory processing disorder. CONCLUSIONS: Individuals with central auditory nervous system lesions showed larger commitment of temporal resolution ability, evaluated through the gaps-innoise test and through the auditory steady state test, than normal individuals. Specificity values for all groups in both tests were better than sensitivity values. The sensitivity for the neurological lesion group was better than for the central auditory processing disorder group, for the two tests.

A presença de déficits cognitivos nos indivíduos com epilepsia de lobo temporal é amplamente reconhecida, sendo os mesmos caracterizados por prejuízos da capacidade de nomeação, memória e função executiva. Embora as disfunções mnésticas sejam bastante estudadas na epilepsia de lobo temporal, a presença de disfunção executiva permanece controversa. A epilepsia gera, ainda, restrições na vida diária e prejuízo na qualidade de vida, levando a alterações na vida do indivíduo, tanto no aspecto físico quanto no psicossocial. Diversos estudos verificaram o impacto negativo da epilepsia sobre o ajustamento psicossocial através de questionários de qualidade de vida ou observações clínicas. No entanto, as medidas de qualidade de vida correspondem à percepção pessoal e subjetiva do paciente, mas geram informações inespecíficas frente à sua atual condição de vida. A despeito da evidência crescente de pior ajustamento psicossocial, não há até o momento, estudos que realizem avaliação formal da adequação social nos pacientes com epilepsia de lobo temporal e diferenciem o desempenho nos questionários de qualidade de vida e adequação social. Os objetivos deste estudo foram: avaliar o desempenho neuropsicológico, a qualidade de vida e a adequação social nos pacientes com epilepsia de lobo temporal através de instrumentos específicos e padronizados para estes fins. Além disso, buscou-se investigar a presença de associação entre estes fatores. Para tal, foram avaliados 35 pacientes com epilepsia de lobo temporal associada à atrofia hipocampal e 38 voluntários sadios, através de: a) bateria compreensiva de testes neuropsicológicos; b) questionários específicos de qualidade de vida e; c) escala padronizada de adequação social. Os pacientes com epilepsia de lobo temporal apresentaram pior desempenho que os voluntários sadios em testes de memória, tanto verbal quanto visual. Além disso, observou-se que os pacientes apresentaram qualidade de vida diminuída nos domínios relacionados a medo de crises, cognição e efeitos colaterais da medicação. Quanto à adequação social, os pacientes com epilepsia de lobo temporal apresentaram pior adequação global e, mais especificamente, pior adequação nos fatores trabalho e lazer quando comparados aos voluntários sadios. Não houve correlação estatisticamente significante entre desempenho cognitivo e qualidade de vida. No entanto, disfunções atencionais e mnésticas se correlacionaram positivamente com a pior adequação social. Além disso, observou-se correlação significativa entre a pior adequação social e a pior qualidade de vida. Os achados confirmam o impacto negativo da epilepsia sobre a cognição, qualidade de vida e adequação social de pacientes com epilepsia de lobo temporal. A ausência de correlação entre achados neuropsicológicos e qualidade de vida indica a imprecisão de queixas cognitivas mensuradas através de escalas de auto-preenchimento. A correlação entre adequação social e o desempenho atencional e mnéstico verbal demonstra a necessidade de programas de reabilitação neuropsicológica para estas funções a fim de melhorar a adequação social desta população / The presence of cognitive deficits in patients with temporal lobe epilepsy is widely recognized, being characterized by impairment of naming, memory and executive functioning. Although, mnestic dysfunction is well-studied in temporal lobe epilepsy, the presence of executive dysfunction remains controversial. Epilepsy is associated with restrictions on daily life and impairment in quality of life leading changes in peoples live, on physical and psychosocial aspects. Several studies described the negative impact of epilepsy on psychosocial adjustment by quality of life questionnaires or clinical observations. However, measures of quality of life match personal and subjective perception of the patient, but generate non-specific information compared to their current living conditions. Despite the growing evidence of poor psychosocial adjustment, to the moment, there is no formal assessment of social adjustment in patients with temporal lobe epilepsy and differentiate the performance on quality of life and social adjustment questionnaires. The objectives of this study were to evaluate the neuropsychological performance, quality of life and social adjustment in patients with temporal lobe epilepsy by means of specific and standardized instruments for these purposes. In addition, we verified the presence of association between these factors. We evaluated 35 patients with temporal lobe epilepsy caused by hippocampal atrophy and 38 healthy volunteers, through: a) comprehensive battery of neuropsychological tests; b) specific quality of life questionnaires and; c) standard scale of social adjustment. Patients with temporal lobe epilepsy had a worse performance than the healthy volunteers on tests of memory, both verbal and visual. In addition, we observed that patients had reduced quality of life in areas related to fear of seizures, cognition, and side effects of medication. As to social adjustment, patients had worse overall adequacy and, more specifically, on subfactors related to work and leisure compared to healthy volunteers. There was no statistical significant correlation between cognitive performance and quality of life. However, attentional and verbal mnestic dysfunctions were positively correlated with the worse social adjustment. Moreover, there was significant correlation between worse social adjustment and reduced QOL. These findings confirm the negative impact of epilepsy on cognition, social adjustment and quality of life in patients with temporal lobe epilepsy. The lack of correlation between neuropsychological findings and quality of life indicates the imprecision of cognitive complaints measured by self-report scales. The correlation between social adjustment with attentional and memory performance show the importance of neuropsychological rehabilitation for these functions in order to obtain a better social adjustment

Amygdala kindling is commonly used to study the mechanisms involved in epileptogenesis, with long-term amygdala kindling providing a useful model of the behavioural disturbances such as heightened anxiety that can occur between epileptic seizures. The purpose of this thesis was to determine whether increased fear behaviours exhibited by long-term amygdala kindled rats are reflective of previously observed kindling-mediated alterations in the hippocampus. As the hippocampus plays an integral role in contextual learning, the ability of the animals to habituate to a novel environment was evaluated, in order to determine if the rats displayed impairments in this hippocampal-dependent function. In Experiment 1, long-term kindled rats demonstrated consistently elevated exploration and fear over repeated exposure to an initially novel open field, indicating impaired habituation. In Experiment 2, all kindled rats showed elevated exploration and an inability to form a home base in relation to static visual cues, again demonstrating an inability to habituate over repeated exposures to the initially novel environment. Rats that had received 30 or 60 stimulations demonstrated hyperexploratory behaviour and elevated fear, although this behaviour did dissipate to a certain degree by the final day of testing. Long-term kindled rats, having received 99 stimulations, demonstrated extremely heightened fear behaviours that interfered with normal exploration, home base formation and habituation. These fear behaviours included high levels of freezing, disorganized running, and purposive jumping from the open field. Taken together, these results indicate that long-term amygdala kindling does produce deficits in habituation to an initially novel environment. As habituation necessarily involves the hippocampal-dependent roles of contextual learning and memory, the current research suggests that long-term kindling does impair hippocampal function and that this may contribute to kindling-induced fear behaviours. This research may help to understand the mechanisms involved in emotional disturbances experienced by human epileptics.

Amygdala kindling is commonly used to study the mechanisms involved in epileptogenesis, with long-term amygdala kindling providing a useful model of the behavioural disturbances such as heightened anxiety that can occur between epileptic seizures. The purpose of this thesis was to determine whether increased fear behaviours exhibited by long-term amygdala kindled rats are reflective of previously observed kindling-mediated alterations in the hippocampus. As the hippocampus plays an integral role in contextual learning, the ability of the animals to habituate to a novel environment was evaluated, in order to determine if the rats displayed impairments in this hippocampal-dependent function. In Experiment 1, long-term kindled rats demonstrated consistently elevated exploration and fear over repeated exposure to an initially novel open field, indicating impaired habituation. In Experiment 2, all kindled rats showed elevated exploration and an inability to form a home base in relation to static visual cues, again demonstrating an inability to habituate over repeated exposures to the initially novel environment. Rats that had received 30 or 60 stimulations demonstrated hyperexploratory behaviour and elevated fear, although this behaviour did dissipate to a certain degree by the final day of testing. Long-term kindled rats, having received 99 stimulations, demonstrated extremely heightened fear behaviours that interfered with normal exploration, home base formation and habituation. These fear behaviours included high levels of freezing, disorganized running, and purposive jumping from the open field. Taken together, these results indicate that long-term amygdala kindling does produce deficits in habituation to an initially novel environment. As habituation necessarily involves the hippocampal-dependent roles of contextual learning and memory, the current research suggests that long-term kindling does impair hippocampal function and that this may contribute to kindling-induced fear behaviours. This research may help to understand the mechanisms involved in emotional disturbances experienced by human epileptics.

Multielectrode arrays may have several advantages compared to the traditional single macroelectrode brain electrical stimulation technique including less tissue damage due to implantation and the ability to deliver several spatio-temporal patterns of stimulation. Prior work on cell cultures has shown that multielectrode arrays are capable of completely stopping seizure-like spontaneous bursting events through a distributed asynchronous multi-site approach. In my studies, I used a similar approach for controlling seizures in a rat model of temporal lobe epilepsy. First, I developed a new method of electroplating in vivo microelectrode arrays for durably improving their impedance. I showed that microelectrode arrays electroplated through the new technique called sonicoplating, required the least amount of voltage in current controlled stimulation studies and also produced the least amplitude and duration of stimulation artifact compared to unplated, DC electroplated or pulse-plated microelectrodes. Second, using c-fos immunohistochemistry, I showed that 16-electrode sonicoplated microelectrode arrays can activate 5.9 times more neurons in the dorsal hippocampus compared to a single macroelectrodes while causing < 77% the tissue damage. Next, through open-loop multisite asynchronous microstimulation, I reduced seizure frequency by ~50% in the rodent model of temporal lobe epilepsy. Preliminary studies aimed at using the same stimulation protocol in closed-loop responsive and predictive seizure control did not stop seizures. Finally, through an internship at Medtronic Neuromodulation, I worked on developing and implementing a rapid algorithm prototyping research tool for closed-loop human deep brain stimulation applications.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 204-214).

Η παρούσα διπλωματική εργασία ασχολείται με τον προεγχειρητικό έλεγχο ασθενών με κροταφική επιληψία που είναι υποψήφιοι να χειρουργηθούν. Συγκεκριμένα εστιάζει στην αξιολόγηση της χρήσης του εξωκρανιακού ΗΕΓ (ηλεκτροεγκεφαλογραφήματος) ως προεγχειρητικού συνεπικουρικού εργαλείου για την εντόπιση και χαρτογράφηση της βλάβης του κροταφικού λοβου για ένα άριστο μετεγχειρητικό αποτέλεσμα. / This study focuses on the preoperative evaluation of extracranial EEG of patients with temporal lobe epilepsy who are candidates for surgery. More precisely, it focuses on the efficiency of the extracranial EEG to map the intracranial lesion that causes the epileptic syndrome.