Epilepsy is a neurological disease causing seizures in its victims and affects approximately 50 million people worldwide. Successful treatment is dependent upon correct identification of the origin of the seizures within the brain. To achieve this, electroencephalograms (EEGs) are used to measure a patient’s brainwaves. This EEG data must be manually analyzed to identify interictal spikes that emanate from the afflicted region of the brain. This process can take a neurologist more than a week and a half per patient. This thesis presents a method to extract and process the interictal spikes in a patient, and use them to reduce the amount of data for a neurologist to manually analyze. The effectiveness of multiple neural network implementations is compared, and a data reduction of 3-4 orders of magnitude, or upwards of 99%, is achieved.

abstract: Interictal spikes, together with seizures, have been recognized as the two hallmarks of epilepsy, a brain disorder that 1% of the world's population suffers from. Even though the presence of spikes in brain's electromagnetic activity has diagnostic value, their dynamics are still elusive. It was an objective of this dissertation to formulate a mathematical framework within which the dynamics of interictal spikes could be thoroughly investigated. A new epileptic spike detection algorithm was developed by employing data adaptive morphological filters. The performance of the spike detection algorithm was favorably compared with others in the literature. A novel spike spatial synchronization measure was developed and tested on coupled spiking neuron models. Application of this measure to individual epileptic spikes in EEG from patients with temporal lobe epilepsy revealed long-term trends of increase in synchronization between pairs of brain sites before seizures and desynchronization after seizures, in the same patient as well as across patients, thus supporting the hypothesis that seizures may occur to break (reset) the abnormal spike synchronization in the brain network. Furthermore, based on these results, a separate spatial analysis of spike rates was conducted that shed light onto conflicting results in the literature about variability of spike rate before and after seizure. The ability to automatically classify seizures into clinical and subclinical was a result of the above findings. A novel method for epileptogenic focus localization from interictal periods based on spike occurrences was also devised, combining concepts from graph theory, like eigenvector centrality, and the developed spike synchronization measure, and tested very favorably against the utilized gold rule in clinical practice for focus localization from seizures onset. Finally, in another application of resetting of brain dynamics at seizures, it was shown that it is possible to differentiate with a high accuracy between patients with epileptic seizures (ES) and patients with psychogenic nonepileptic seizures (PNES). The above studies of spike dynamics have elucidated many unknown aspects of ictogenesis and it is expected to significantly contribute to further understanding of the basic mechanisms that lead to seizures, the diagnosis and treatment of epilepsy. / Dissertation/Thesis / Ph.D. Electrical Engineering 2012

Learning is central to infusing intelligence to any biologically inspired system. This study introduces a novel Cross-Correlated Delay Shift (CCDS) learning method for spiking neurons with the ability to learn and reproduce arbitrary spike patterns in a supervised fashion with applicability tospatiotemporalinformation encoded at the precise timing of spikes. By integrating the cross-correlated term,axonaland synapse delays, the CCDS rule is proven to be both biologically plausible and computationally efficient. The proposed learning algorithm is evaluated in terms of reliability, adaptive learning performance, generality to different neuron models, learning in the presence of noise, effects of its learning parameters and classification performance. The results indicate that the proposed CCDS learning rule greatly improves classification accuracy when compared to the standards reached with the Spike Pattern Association Neuron (SPAN) learning rule and the Tempotron learning rule. Network structureis the crucial partforany application domain of Artificial Spiking Neural Network (ASNN). Thus, temporal learning rules in multilayer spiking neural networks are investigated. As extensions of single-layer learning rules, the multilayer CCDS (MutCCDS) is also developed. Correlated neurons are connected through fine-tuned weights and delays. In contrast to the multilayer Remote Supervised Method (MutReSuMe) and multilayertempotronrule (MutTmptr), the newly developed MutCCDS shows better generalization ability and faster convergence. The proposed multilayer rules provide an efficient and biologically plausible mechanism, describing how delays and synapses in the multilayer networks are adjusted to facilitate learning. Interictalspikes (IS) aremorphologicallydefined brief events observed in electroencephalography (EEG) records from patients with epilepsy. The detection of IS remains an essential task for 3D source localization as well as in developing algorithms for seizure prediction and guided therapy. In this work, we present a new IS detection method using the Wavelet Encoding Device (WED) method together with CCDS learning rule and a specially designed Spiking Neural Network (SNN) structure. The results confirm the ability of such SNN to achieve good performance for automatically detecting such events from multichannel EEG records.

Orientador: Fernando Cendes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T20:41:16Z (GMT). No. of bitstreams: 1 Barbosa_PatriciaHorn_D.pdf: 4694168 bytes, checksum: 4b2bdfa4847274a2d3a88005c77669d2 (MD5) Previous issue date: 2015 / Resumo: Epilepsia de lobo temporal resulta com freqüência em refratariedade ao tratamento medicamentoso. Alguns fatores prognósticos da epilepsia focal e seu tratamento já foram descritos, mas outros ainda estão por ser melhor conhecidos. Nosso objetivo foi investigar associação entre alterações no EEG pré e pós-operatório e na ressonância de crânio pré-operatória com o resultado cirúrgico de pacientes com epilepsia de lobo temporal. Pacientes com epilepsia focal refratária submetidos a cirurgia após investigação não invasiva foram reavaliados. Calculamos o período livre de crises até a recorrência. Realizamos análise visual da RM crânio pré-operatória buscando sinais de atrofia hipocampal e alterações sutis no hipocampo contralateral. Revisamos exames de EEG pré e pós-operatórios buscando inicialmente a presença ou ausência de descargas epileptiformes. Posteriormente, quantificamos atividade epileptiforme interictal e buscamos associação com recorrência de crises. Utilizamos os testes estatísticos qui-quadrado e Fisher, quando adequados, e construímos curvas de sobrevivência de Kaplan-Meier, considerando recorrência de crises como desfecho, com comparação pelo método de Mantel. Na primeira parte do estudo foram incluídos 86 pacientes com atrofia hipocampal. EEG pré-operatório unilateral não se associou a resultado cirúrgico favorável; EEG pós-operatório com presença de atividade epileptiforme interictal não se associou a resultado cirúrgico desfavorável; RM cranio com hipocampo contralateral alterado se associou tanto a resultado cirúrgico desfavorável, quanto com bilateralidade nos EEGs pré-operatórios. Na segunda parte do estudo, com 129 pacientes incluídos, não encontramos associação significativa entre presença de atividade epileptiforme interictal no EEG pós-operatório e resultado cirúrgico. As curvas de sobrevivência dos grupos com descargas epileptiformes presentes versus ausentes não foram estatisticamente diferentes (p=0,09), porem observamos uma tendência, o que motivou a terceira parte. Desta forma, demonstramos, através da quantificação da atividade epileptiforme, associação entre descargas pouco frequentes no EEG pós-operatório com resultado cirúrgico favorável. Finalmente, na tentativa de estabelecer o EEG pós-operatório como preditor de recorrência de crises, não encontramos, com a amostra disponível, associação entre EEG pós-operatório com atividade epileptiforme pouco frequente e resultado cirúrgico favorável. Estes resultados demonstram que é importante valorizar alterações sutis no volume, conformação, eixo e sinal do hipocampo menos afetado na indicação de cirurgia de pacientes com epilepsia de lobo temporal e atrofia hipocampal. O resultado cirúrgico dos pacientes com hipocampo contralateral normal é mais favorável. Alteração eletrográfica bitemporal no EEG pré-operatório, em geral, está associada a alteração estrutural sutil no hipocampo contralateral, que muitas vezes não é valorizada. Tal achado corrobora evidências previamente descritas de que pacientes com EEG pré-operatório bitemporal tem prognóstico cirúrgico menos favorável. Os dados relacionados à análise quantitativa de descargas epileptiformes no EEG pós-operatório mostraram associação entre atividade epileptiforme e resultado cirúrgico. Tal achado sugere que o EEG pode ser uma ferramenta útil no seguimento clínico pós-operatório. Em conclusão, nossos resultados indicaram dois fatores importantes no prognóstico de controle de crises após cirurgia em ELT: presença de alteração hipocampal contralateral mesmo que sutil, e espículas em uma frequência maior que 4 por um período de 15 minutos / Abstract: Temporal lobe epilepsy is frequently linked to medical refractoriness. Many clinical prognostic data on focal epilepsy have repeatedly been described, while surgical outcome factors are yet to be fully known. We presently look into an association between interictal epileptiform discharges in pre and postoperative EEG, as well as preoperative brain magnetic resonance imaging, and surgical outcome of temporal lobe epilepsy. Patients with medically refractory focal epilepsy submitted to surgery following non invasive investigation were reassessed. We calculated time until seizure recurrence. We visually analysed preoperative MRI searching for signs of hipoccampal atrophy, as well as subtle contralateral hipoccampal changes. We reviewed pre and postoperative EEGs concerning presence or absence of interictal epileptiform discharges. Later on, we quantified interictal discharges and tested association with seizure freedom. We used chi square or Fisher¿s exact test, when most adequate. We also built Kaplan-Meier¿s survival curves setting seizure recurrence as endpoint, and compared curves by Mantel method. We initially included 86 patients with hipoccampal atrophy. Preoperative unilateral EEG was not associated with favorable surgical outcome; presence of IED in postoperative EEG was not associated with unfavorable outcome; contralateral hipoccampal changes on preoperative MRI was strongly associated with unfavorable surgical outcome, as well as with bilateral preoperative EEGs. We then studied postoperative EEGs of 129 individuals. There was not a significant association between postoperative EEG and surgical outcome. Survival curves of group of patients with interictal discharges present and absent were not statistically different (p=0.09), but we observed a tendency in that direction. Therefore, we were able to demonstrate through manual quantification of epileptiform discharges that postoperative EEG direct association with surgical outcome. Our ultimate goal was to establish postoperative EEG as predictor of seizure recurrence. Unfortunately we were not able to demonstrate it with data available on our sample. These results highlight importance of assessing subtle changes in volume, form, axis and signal intensity on contralateral hipoccampus prior to indication of surgery in patients with temporal lobe epilepsy with hipoccampal atrophy. Surgical outcome is more favorable when contralateral hipoccampus is normal. Bilateral discharges over temporal electrodes in pre-operative EEG are associated with subtle structural changes on contralateral hipoccampus, which may be underestimated. Such findings is in agreement with previously described evidence of bitemporal preoperative EEG associated with less favorable surgical outcome. Quantification data on postoperative EEG sets forth direct association with epileptiform discharges and surgical outcome. Such finding suggests EEG may be a useful tool in postoperative followup. In conclusion, our results indicate two important prognostic factors for seizure control in surgically treated temporal lobe epilepsy patients: presence of contralateral signs of hipoccampal sclerosis, even if subtle, and interictal epileptiform discharges occuring in a frequency higher than 4 at 15 minutes period / Doutorado / Neurociencias / Fisiopatologia Médica

L'hétérotopie en bande sous-corticale (SBH) est une malformation caractérisée par la présence d'une bande de neurones ectopiques en regard du cortex normal ou normotopique. La plupart des patients ont une mutation d'un gène encodant une protéine indispensable à la migration des neurones. Les patients présentent une épilepsie pharmacorésistante. La chirurgie ne donne pas de résultats satisfaisants, le foyer épileptogène n'étant jamais clairement délimité. Un modèle de rat reproduisant les caractéristiques observées chez les patients à pu être généré. Même s'il est clair que le cortex normotopique et l'hétérotopie participent aux évènements épileptiformes, leur zone de genèse reste néanmoins inconnue. Le but de cette thèse a été de localiser l'origine de l'activité épileptiforme in vitro sur tranches de cerveau à l'aide d'une technique d'enregistrement multisite.Des activités épileptiformes (ILEs) ont été enregistrées à l'aide d'une technique d'enregistrement extracellulaire multisite à 60 canaux. Un outil d'analyse développé sous Matlab a ensuite permis de caractériser les ILEs et notamment leur origine et étendues spatiales. Après avoir identifié l'importance du cortex normotopique dans la genèse des ILEs, nous en avons supprimé l'excitabilité in vivo. Nous montrons que la surexpression de ces canaux dans les neurones ectopiques n'altère pas la susceptibilité aux crises des animaux concernés alors que la surexpression de ces canaux dans l'hétérotopie et dans le cortex normotopique améliore le phénotype épileptique. Nos résultats suggèrent ainsi un rôle majeur du cortex normotopique dans la genèse des activités épileptiques dans le syndrome du double cortex. / Subcortical Band Heterotopia (SBH) is a cortical malformation formed when neocortical neurons prematurely stop their migration in the white matter, forming a heterotopic band below the normotopic cortex, and is generally associated with intractable epilepsy. Although it is clear that the band heterotopia and the overlying cortex both contribute to creating an abnormal circuit prone to generate epileptic discharges, it is less understood which part of this circuitry is the most critical. Here, we sought to identify the origin of epileptiform activity in a targeted genetic model of SBH in rats.Rats with SBH were generated by knocking‐down the Dcx gene into neocortical progenitors of rat embryos. Origin, spatial extent and laminar profile of bicuculline‐induced interictal‐like activity on neocortical slices were analyzed by using extracellular recordings from 60‐channels microelectrode arrays. Susceptibility to pentylenetetrazole‐induced seizures was assessed by electrocorticography in head‐restrained nonanaesthetized rats. We show that the band heterotopia does not constitute a primary origin for interictal‐like epileptiform activity in vitro and is dispensable for generating induced seizures in vivo. Further, we report that most interictal‐like discharges originating in the overlying cortex secondarily propagates to the band heterotopia. Importantly, we found that in vivo suppression of neuronal excitability in SBH does not alter the higher propensity of Dcx‐KD rats to display seizures. These results suggest a major role of the normotopic cortex over the band heterotopia in generating interictal epileptiform activity and seizures in brains with SBH.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-12-11T14:10:12Z No. of bitstreams: 1 KARINA NIQUE FRANZ SILBERMANN.pdf: 24305952 bytes, checksum: 2707c9d644d7f53ccbd72659a1adda31 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-12-13T18:40:06Z (GMT) No. of bitstreams: 1 KARINA NIQUE FRANZ SILBERMANN.pdf: 24305952 bytes, checksum: 2707c9d644d7f53ccbd72659a1adda31 (MD5) / Made available in DSpace on 2018-12-13T19:18:32Z (GMT). No. of bitstreams: 1 KARINA NIQUE FRANZ SILBERMANN.pdf: 24305952 bytes, checksum: 2707c9d644d7f53ccbd72659a1adda31 (MD5) Previous issue date: 2018-08-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The equipment and processes used in nuclear medicine must be included in a quality control program that includes a series of tests and calibrations following the frequency established by current standards, which are based on international institutions protocols. The capability of anthropomorphic simulators mimic realistic situations are widely appointed to gauge essential data that guarantee the quality in medical generating processes. The purpose of this study was developing a cerebral anthropomorphic phantom for image simulation of ictal activity in nuclear medicine with 18F, PET-CT. It was made in an industrial printer with SLS (Selective Laser Sintering) technology, 4mm thick, using nylon 12. The model was segmented from a magnetic resonance study of a 40-year-old female adult. Two 40 nm thickness metal (Ag) electrodes were inserted in the right frontal lobe region to simulate ictal activity. For the images acquisition, the phantom was filled with distillated water and the 18F radioisotope. The images were acquired in PET-CT equipment with specific protocol for tomographic and dynamic cerebral studies. Images from the simulator without the insertion of the electrodes were acquired as pattern (basal), also were acquired images from the simulator with the electrodes and without electric field application, and the simulator with electric field application. The images were compared through SUV maximum values and uptake index. The non-parametric Wilcoxon-Mann-Whitney test was used as statistic approach, considering the three image conditions as independent groups. There was significant difference amongst the groups, being p < 0,001 when compared the average SUV maximum values by slices in the situations: basal x with electric field, and basal x without electric field, p = 0,129 when compared situations with electric field x without electric field, suggesting that this difference is not significant. All the groups presented significant differences for the uptake indexes obtained, being p < 0,001 in the situations basal x with electric field and basal x without electric field. The TAC (time-activity-curve) curves were obtained in A PET-CT dynamic protocol to demonstrate the 18F uptake in time, in the conditions with electric field and without electric field. The images were subtracted through SISCOM, using the basal condition as reference. The values found for p (SUV and uptake index) are compatible. The SISCOM histograms demonstrate differences for the three image comparisons. Although there are gradual raise of 18F uptake in time obtained in TAC evaluation for both with and without electric field conditions, the highest uptake visualized was when the electric field is applied. The anthropomorphic phantom developed is capable of simulating compatible zones with ictal activity, however the material used as resin in the electrodes must be modified so that the product may be commercialized in the future. / Os equipamentos e processos utilizados em medicina nuclear devem estar inclu?dos em um programa de controle de qualidade, o que inclui uma s?rie de testes e calibra??es com periodicidade estabelecida pelas normas vigentes, baseadas nos protocolos de institui??es internacionais. Os simuladores antropom?rficos, pela sua capacidade de mimetizar situa??es real?sticas, s?o amplamente empregados para aferir dados essenciais que garantam a qualidade nos processos geradores de imagens m?dicas. O objetivo deste trabalho foi desenvolver um phantom antropom?rfico cerebral para simula??o de imagens de atividade ictal em medicina nuclear, utilizando metodologia PET com Fl?or-18 (18F). O phantom foi confeccionado em impressora industrial com tecnologia SLS (Selective Laser Sintering), de espessura de 4 mm, utilizando como mat?ria prima nylon 12. O modelo foi segmentado a partir de um estudo de resson?ncia magn?tica de um adulto normal, do sexo feminino, com 40 anos. Para a simula??o de atividade ictal foram inseridos, na regi?o correspondente ao lobo frontal direito, dois eletrodos met?licos constitu?dos de filme fino de 40 nm de prata (Ag). Para a aquisi??o das imagens, o modelo foi preenchido com ?gua destilada e com o radiois?topo 18F. As imagens foram adquiridas em equipamento de PET-CT com protocolo espec?fico para estudos cerebrais tomogr?fico e din?mico. Foram adquiridas imagens: (1) simulador sem a inser??o dos eletrodos (padr?o/basal), (2) simulador com eletrodos sem aplica??o de campo el?trico e (3) simulador com os eletrodos e aplica??o de campo el?trico. As imagens foram comparadas entre si atrav?s dos valores de SUV m?ximo e do ?ndice de capta??o. A abordagem estat?stica utilizada considerou as tr?s condi??es de imagens como grupos independentes e o teste n?o param?trico de Wilcoxon-Mann-Whitney foi aplicado. Houve diferen?a significativa entre os grupos, sendo o valor de p < 0,001 quando comparados os valores de m?dia de SUV m?ximo por corte nas situa??es basal x sem campo el?trico e basal x com campo el?trico. Na compara??o sem campo el?trico x com campo el?trico, o valor de p = 0,129 indica que a diferen?a entre os grupos n?o ? significativa. Quando avaliado o ?ndice de capta??o entre os grupos, todas as condi??es apresentaram diferen?a significativa, sendo p < 0,001 para os grupos basal x sem campo el?trico e basal x com campo el?trico, e p = 0,0123 na compara??o sem campo el?trico x com campo el?trico. As curvas TAC (time-activity-curve) foram adquiridas para demonstrar a capta??o de 18F no tempo, nas condi??es com campo el?trico e sem campo el?trico, em estudo din?mico de PET-CT. As imagens foram subtra?das atrav?s da metodologia SISCOM, utilizando a condi??o basal como refer?ncia. Os valores encontrados para p, tanto para SUV como para ?ndice de capta??o, s?o compat?veis com os achados visualizados nas imagens obtidas. Os histogramas gerados com a metodologia SISCOM demonstram que h? diferen?as entre as tr?s condi??es de imagem. As curvas TAC tra?adas correspondem ao aumento gradativo da concentra??o 18F no tempo, embora exista este aumento nas condi??es sem campo e com campo, obtivemos a maior concentra??o quando o sistema est? sob efeito do campo el?trico. O phantom antropom?rfico desenvolvido ? capaz de simular zonas an?logas ?s de imagens de atividade ictal, por?m o material utilizado como resina nos eletrodos deve ser modificado para que o produto possa ser comercializado futuramente.

For children with intractable seizures, surgical removal of epileptic foci, if identifiable and feasible, can be an effective way to reduce or eliminate seizures. The success of this type of surgery strongly hinges upon the ability to identify and demarcate those epileptic foci. The ultimate goal of this research project is to develop an effective technology for detection of unique in vivo pathophysiological characteristics of epileptic cortex and, subsequently, to use this technology to guide epilepsy surgery intraoperatively. In this PhD dissertation the feasibility of using optical spectroscopy to identify unique in vivo pathophysiological characteristics of epileptic cortex was evaluated and proven using the data collected from children undergoing epilepsy surgery. In this first in vivo human study, static diffuse reflectance and fluorescence spectra were measured from the epileptic cortex, defined by intraoperative ECoG, and its surrounding tissue from pediatric patients undergoing epilepsy surgery. When feasible, biopsy samples were taken from the investigated sites for the subsequent histological analysis. Using the histological data as the gold standard, spectral data was analyzed with statistical tools. The results of the analysis show that static diffuse reflectance spectroscopy and its combination with static fluorescence spectroscopy can be used to effectively differentiate between epileptic cortex with histopathological abnormalities and normal cortex in vivo with a high degree of accuracy. To maximize the efficiency of optical spectroscopy in detecting and localizing epileptic cortex intraoperatively, the static system was upgraded to investigate histopathological abnormalities deep within the epileptic cortex, as well as to detect unique temporal pathophysiological characteristics of epileptic cortex. Detection of deep abnormalities within the epileptic cortex prompted a redesign of the fiberoptic probe. A mechanical probe holder was also designed and constructed to maintain the probe contact pressure and contact point during the time dependent measurements. The dynamic diffuse reflectance spectroscopy system was used to characterize in vivo pediatric epileptic cortex. The results of the study show that some unique wavelength dependent temporal characteristics (e.g., multiple horizontal bands in the correlation coefficient map g(λref = 800 nm, λcomp,t)) can be found in the time dependent recordings of diffuse reflectance spectra from epileptic cortex defined by ECoG.

Plusieurs études de simulation in vitro et in vivo ont été réalisées au cours des dernières décennies afin de clarifier les interrelations des sources corticales avec leurs corrélats électrophysiologiques enregistrés sur l’EEG invasif et l’EEG de scalp. L’amplitude des potentiels corticaux, l’étendue de l’aire corticale impliquée par la décharge, de même que la localisation et la géométrie de la source corticale sont des facteurs indépendants qui modulent l’observabilité et la contribution de ces sources sur l’EEG de surface. L’enregistrement simultané et multi-échelle de l’EEG de scalp et intra-crânien (avec des électrodes sous-durales ou profondes) durant l’exploration pré-chirurgicale des patients épileptiques offre une opportunité unique d’explorer cette question fondamentale. Alors que les études précédentes ont considéré essentiellement des sources néocorticales dans le contexte de l’épilepsie du lobe temporal, notre travail s’est intéressé à l’observabilité et la contribution de sources profondes temporales et frontales. Nous avons pu montrer : (1) que les sources épileptiques profondes enregistrées dans les régions temporales médianes et fronto-basales ne sont pas visibles par l’analyse visuelle de routine mais sont détectables après élimination du bruit de fond physiologique généré par les sources corticales de surface sus-jacentes ; (3) que l’amplitude des pointes enregistrées en surface est corrélée avec la surface d’activation corticale de la convexité et avec des ratios élevés d’amplitude pointes/activité de fond / Several in vitro, in vivo, and simulation studies have been performed in the past decades aiming to clarify the interrelations of cortical sources with their scalp and invasive EEG correlates. The amplitude ratio of cortical potentials to their scalp EEG correlates, the extent of the cortical area involved in the discharge, as well as the localization of the cortical source and its geometry, have been each independently linked to the recording of the cortical discharge with scalp electrodes. Simultaneous multiscale EEG recordings with scalp, subdural and depth electrodes, applied in presurgical epilepsy workup, offer an excellent opportunity to address this fundamental issue. Whereas past studies have considered predominantly neocortical sources in the context of temporal lobe epilepsy, the present work addresses deep sources, in mesial temporal and extra-temporal epilepsies. We showed that deep sources, such as those in mesial temporal or fronto-basal regions, are not visible, but are detectable in scalp EEG. Scalp EEG spikes correlate with extensive activation of the cortical convexity and high spike-to-background amplitude ratios

Assessing complex brain activity as a function of the type of epilepsy and in the context of the 3D source of seizure onset remains a critical and challenging endeavor. In this dissertation, we tried to extract the attributes of the epileptic brain by looking at the modular interactions from scalp electroencephalography (EEG). A classification algorithm is proposed for the connectivity-based separation of interictal epileptic EEG from normal. Connectivity patterns of interictal epileptic discharges were investigated in different types of epilepsy, and the relation between patterns and the epileptogenic zone are also explored in focal epilepsy. A nonlinear recurrence-based method is applied to scalp EEG recordings to obtain connectivity maps using phase synchronization attributes. The pairwise connectivity measure is obtained from time domain data without any conversion to the frequency domain. The phase coupling value, which indicates the broadband interdependence of input data, is utilized for the graph theory interpretation of local and global assessment of connectivity activities. The method is applied to the population of pediatric individuals to delineate the epileptic cases from normal controls. A probabilistic approach proved a significant difference between the two groups by successfully separating the individuals with an accuracy of 92.8%. The investigation of connectivity patterns of the interictal epileptic discharges (IED), which were originated from focal and generalized seizures, was resulted in a significant difference ( ) in connectivity matrices. It was observed that the functional connectivity maps of focal IED showed local activities while generalized cases showed global activated areas. The investigation of connectivity maps that resulted from temporal lobe epilepsy individuals has shown the temporal and frontal areas as the most affected regions. In general, functional connectivity measures are considered higher order attributes that helped the delineation of epileptic individuals in the classification process. The functional connectivity patterns of interictal activities can hence serve as indicators of the seizure type and also specify the irritated regions in focal epilepsy. These findings can indeed enhance the diagnosis process in context to the type of epilepsy and effects of relative location of the 3D source of seizure onset on other brain areas.

Made available in DSpace on 2014-12-17T15:28:53Z (GMT). No. of bitstreams: 1 AndersonBS_DISSERT.pdf: 4240084 bytes, checksum: 0331343a1aab5e54d0d9cb6baeccb72d (MD5) Previous issue date: 2013-12-13 / Epilepsies are neurological disorders characterized by recurrent and spontaneous seizures due to an abnormal electric activity in a brain network. The mesial temporal lobe epilepsy (MTLE) is the most prevalent type of epilepsy in adulthood, and it occurs frequently in association with hippocampal sclerosis. Unfortunately, not all patients benefit from pharmacological treatment (drug-resistant patients), and therefore become candidates for surgery, a procedure of high complexity and cost. Nowadays, the most common surgery is the anterior temporal lobectomy with selective amygdalohippocampectomy, a procedure standardized by anatomical markers. However, part of patients still present seizure after the procedure. Then, to increase the efficiency of this kind of procedure, it is fundamental to know the epileptic human brain in order to create new tools for auxiliary an individualized surgery procedure. The aim of this work was to identify and quantify the occurrence of epilepticform activity -such as interictal spikes (IS) and high frequency oscillations (HFO) - in electrocorticographic (ECoG) signals acutely recorded during the surgery procedure in drug-resistant patients with MTLE. The ECoG recording (32 channels at sample rate of 1 kHz) was performed in the surface of temporal lobe in three moments: without any cortical resection, after anterior temporal lobectomy and after amygdalohippocampectomy (mean duration of each record: 10 min; N = 17 patients; ethic approval #1038/03 in Research Ethic Committee of Federal University of S?o Paulo). The occurrence of IS and HFO was quantified automatically by MATLAB routines and validated manually. The events rate (number of events/channels) in each recording time was correlated with seizure control outcome. In 8 hours and 40 minutes of record, we identified 36,858 IS and 1.756 HFO. We observed that seizure-free outcome patients had more HFO rate before the resection than non-seizure free, however do not differentiate in relation of frequency, morphology and distribution of IS. The HFO rate in the first record was better than IS rate on prediction of seizure-free patients (IS: AUC = 57%, Sens = 70%, Spec = 71% vs HFO: AUC = 77%, Sens = 100%, Spec = 70%). We observed the same for the difference of the rate of pre and post-resection (IS: AUC = 54%, Sens = 60%, Spec = 71%; vs HFO: AUC = 84%, Sens = 100%, Spec = 80%). In this case, the algorithm identifies all seizure-free patients (N = 7) with two false positives. To conclude, we observed that the IS and HFO can be found in intra-operative ECoG record, despite the anesthesia and the short time of record. The possibility to classify the patients before any cortical resection suggest that ECoG can be important to decide the use of adjuvant pharmacological treatment or to change for tailored resection procedure. The mechanism responsible for this effect is still unknown, thus more studies are necessary to clarify the processes related to it / As epilepsias s?o dist?rbios neurol?gicos caracterizados por crises espont?neas e recorrentes, resultantes de uma atividade el?trica anormal de uma rede neural. Dentre os diferentes tipos de epilepsia, a epilepsia mesial do lobo temporal (EMLT) ? a mais observada em adultos, sendo frequentemente associada ? esclerose hipocampal. Infelizmente, nem todos os pacientes s?o beneficiados pelo tratamento farmacol?gico (pacientes f?rmaco-resistentes). Para estes sujeitos, uma alternativa ? a realiza??o de cirurgia, um procedimento de alta complexidade e elevado custo. Atualmente, o procedimento mais realizado ? a lobectomia temporal anterior com amigdalo-hipocampectomia seletiva, uma cirurgia padronizada por marcos anat?micos. Entretanto, uma parcela dos pacientes continua a apresentar crises incapacitantes ap?s o tratamento cir?rgico. Desta forma, para aumentar a efici?ncia deste tipo de tratamento, ? fundamental a compreens?o do enc?falo humano epil?ptico com vistas a se criar ferramentas que auxiliem na realiza??o de procedimentos individualizados. O objetivo do presente trabalho foi identificar e quantificar a ocorr?ncia de atividade epileptiforme - esp?culas interictais (EI) e oscila??es de alta frequ?ncia (OAF) - em registros eletrocorticogr?ficos (ECoG) realizados durante procedimento cir?rgico em pacientes com EMLT refrat?ria ao tratamento farmacol?gico. Registros ECoG (32 canais a uma taxa de amostragem de 1 kHz) foram realizados na superf?cie do lobo temporal em 3 momentos cir?rgicos: no c?rtex intacto, ap?s lobectomia temporal anterior e ap?s amigdalo-hipocampectomia (dura??o m?dia de cada um desses registros: 10 min; N=17 pacientes). A ocorr?ncia de EI e OAF foi quantificada automatica-mente, por meio de rotinas em MATLAB, e validadas manualmente. A taxa de ocorr?ncia em cada um dos tempos cir?rgicos foi correlacionada com o resultado cir?rgico quanto ao controle das crises, num seguimento de 2 anos. De um total de 8 h e 40 min de registro, identificamos 36.858 EI e 1.756 OAF. Observamos que os pacientes que ficaram livres de crises no p?s-operat?rio apresentaram maior quanti-dade de OAF antes da cirurgia do que aqueles que continuaram a ter crises; por?m, n?o diferiram quanto a frequ?ncia, morfologia e distribui??o de EI. A ocorr?ncia de OAF no registro basal apresentou melhor desempenho que as EI na previs?o do controle total das crises no p?s-operat?rio (EI: AUC = 57%, S = 71% , E = 70% vs OAF: AUC = 77%, S = 100%, E=70%). O mesmo foi observado com a varia??o da ocorr?ncia entre os momentos pr?- e p?s-ressec??o (EI: AUC = 54%, S = 71%, E = 60% vs OAF: AUC = 84%, S = 100%, E = 80%). Nesse caso, o classificador foi capaz de identificar todos os pacientes livres de crises (N = 7) , apresentando apenas dois falsos positivos. Desta forma, podemos concluir que as OAF, juntamente com as EI, podem ser encontradas no registro ECoG intra-operat?rio, mesmo na presen?a de anest?sicos e em uma curta sess?o de registro. Al?m disso, a observa??o de que a ocorr?ncia desses eventos no in?cio da cirurgia permite classificar o paciente quanto ao progn?stico cir?rgico abre caminho para aplicar o ECoG intra-operat?rio, por exemplo, na decis?o sobre o uso de tratamento farmacol?gico adjuvante ou da convers?o para ressec??es individualizadas. No entanto, o mecanismo respons?vel por esse efeito ainda ? desconhecido, logo novos estudos s?o necess?rios para melhor esclarec?-lo