Thesis (MA)--Stellenbosch University, 2002. / ENGLISH ABSTRACT: The focus of the present review is the quality of life (QOL) of parents caring for a child with epilepsy. The review is informed by published books and articles available on the Psychlit and Medline databases. The paper provides an overview of epilepsy and the problems patients, particularly children, are confronted with. The important roles that parents fulfil in their child's life is followed by a discussion of the stress and burden experienced by parents caring for a child with epilepsy. Descriptions and definitions of the construct QOL are followed by reported research findings on the QOL of patients with epilepsy. The importance of the QOL of parents caring for a child with epilepsy is emphasized and this leads to an examination of existing research on the QOL of these parents. Research on the QOL of parents of children with epilepsy is limited despite the important roles parents fulfil in the life of their child with epilepsy and the potentially negative consequences of these additional roles for the child, the parents and the remainder of the family. Identification and an understanding of the dimensions of QOL of parents that are impacted upon by a child's epilepsy may produce improved treatment outcomes and QOL for children diagnosed and living with epilepsy. Recommendations for future research are included in the present review. / AFRIKAANSE OPSOMMING: Die fokus van hierdie oorsig is die lewenskwaliteit van ouers wat 'n epileptiese kind versorg. Die oorsig is gebaseer op gepubliseerde boeke en artikels wat beskikbaar is op Psychlit en Medline databasisse. Die oorsig voorsien 'n omskrywing van epilepsie asook van die probleme wat pasiente, veral kinders, ondervind. Die belangrike rolle wat ouers in hul kinders se lewe speel word bespreek en dit word gevolg deur 'n bespreking van die stres en druk wat ouers wat epileptiese kinders versorg, ondervind. Beskrywings en definisies van die konstruk lewenskwaliteit word aangebied, gevolg deur 'n opgawe van navorsingsbevindinge oor die lewenskwaliteit van epiletiese pasiënte. Die belangrikheid van die lewenskwaliteit van ouers van 'n epileptiese kind word beklemtoon en dit lei tot 'n oorsig van huidige navorsing oor die lewenskwaliteit van hierdie ouers. Ten spyte van die belangrike rolle wat ouers in die lewe van hul epileptiese kind speel en die moontlike negatiewe gevolge van hierdie bykomende rolle vir die kind, die ouers en die ander familielede, is navorsing oor die lewenskwaliteit van ouers met epileptiese kinders beperk. Identifisering van en insig in die faktore wat 'n impak het op die lewenskwaliteit van ouers met 'n epileptiese kind, kan lei tot verbeterde behandelingresultate en hoër lewenskwaliteit vir kinders wat gediagnoseer word en wat met epilepsie saamleef. Aanbevelings vir toekomstige navorsing word ook in hierdie oorsig gemaak.

Accelerated long-term forgetting (ALF) is a recently described memory impairment associated with epilepsy. Patients with ALF appear to learn and initially retain new information normally, but forget it at an accelerated rate over subsequent days. ALF can have a profound impact on the lives of the people who suffer from it, but it is also of theoretical interest. In particular, the study of this disorder may provide insight into the mechanisms of memory consolidation. ALF is especially prevalent in transient epileptic amnesia (TEA), an epileptic syndrome in which the seizure focus is thought to be the medial temporal lobes (MTL). The MTL house the hippocampus and a number of other structures critical for declarative memory function. The aims of this doctoral thesis were to investigate which aspects of memory function are disrupted in patients with TEA-associated ALF, and to shed light on the neural basis of the memory impairment. Slow wave sleep (i.e. deep sleep) is known to exacerbate epileptic activity. It is also thought to play a key role in the consolidation of declarative memory. The most commonly posited explanation of ALF is the disruption of sleep- dependent memory consolidation. However, it remains possible that ALF is caused by a subtle problem with encoding that usually goes undetected until delayed memory tests. The results of this thesis demonstrate that sleep can actually benefit memory retention in TEA ALF patients just as much as it does in healthy people, and that it is not necessary for the retention interval to contain sleep in order for ALF to be seen. However, the relationship between slow wave sleep and memory was found to be abnormal in these patients. The amount of slow wave sleep, and the power in the slow oscillation frequency range, during the post-learning night correlated negatively with the benefit of that night of sleep for memory retention. Furthermore, resting-state brain activity patterns thought to reflect post-encoding memory reprocessing were found to correlate negatively with subsequent memory performance in these patients. Another chapter of this thesis provides evidence that TEA ALF patients encode memories abnormally; these patients showed reduced activity in the left hippocampus while viewing stimuli that they went on to forget. Furthermore, this encoding-related brain activity correlated with their long-term forgetting. The final experimental chapter reports a correlation in these patients between grey matter in the left hippocampus and long-term forgetting, which cannot entirely account for the encoding-related brain activity results. The hippocampus and its surrounding structures are thought to be critical to our ability to discriminate between similar stimuli and events. An intriguing hypothesis consistent with the pattern of results in this thesis is that ALF is caused by a functional impairment of the MTL that results in a diminished capacity to distinguish between similar experiences, ultimately causing memory problems; abnormally formed memories may interact with new material and memory consolidation processes in an aberrant manner, leading to retrieval deficits.

Les oscillations jouent un rôle de premier plan dans la mise en place des réseaux cérébraux sains et pathologiques. En particulier, au niveau clinique, les activités oscillatoires sont d'une grande importance diagnostique en épilepsie. Par ailleurs, les méthodes non-invasives d'électrophysiologie sont particulièrement adaptées pour la compréhension des réseaux cérébraux à grande échelle. Cependant, la majorité des études en épilepsie a été dirigée vers les pointes intercritiques, qui sont des activités transitoires. Une question qui reste donc en suspens est le lien entre les pointes épileptiques et les activités oscillatoires épileptiques. Cette thèse a visé à résoudre deux problématiques complémentaires autour de cette question. La première problématique est la séparation adéquate entre les activités oscillatoires et transitoires. Il s'agit d'une tâche difficile surtout lors d'un grand chevauchement temporel, qui peut résulter en la contamination d'une activité par l'autre. Nous avons évaluée trois méthodes de filtrage : le filtre FIR (méthode classique), la transformé d'ondelette stationnaire et le filtrage parcimonieux par matching pursuit (MP, basé sur un dictionnaire). Sur des simulations, la SWT a donné de très bons résultats pour la reconstruction des transitoires et le MP pour les oscillations ; de plus, les deux méthodes ont donné un faible taux de faux positifs en détection automatique des oscillations. La SWT et le FIR ont donné les meilleurs résultats de filtrage sur les signaux réels, en particulier lors de la localisation de source. / The Oscillatory activities play a leading role in the development of healthy and pathological brain networks. In particular, at the clinical level, the oscillatory activities are of great importance in the diagnostic of epilepsy. In addition, the non-invasive electrophysiology methods are particularly suitable for understanding the large-scale brain networks. However, most studies in epilepsy have been directed to the interictal spikes, which are transitional activities. One issue that remains unresolved is the relationship between epileptic spikes and epileptic oscillatory activities. This thesis resolves two complementary problems. The first one is the suitable separation between the oscillatory and transitory activity, which is quite sensitive to the presence of the overlap in the time-frequency domain. This can lead to a contamination between the activities. We did evaluate three filtering methods: the FIR (classic methods), the stationary wavelet SWT and the parsimonious filter with the matching pursuit MP. The SWT gave good results in the reconstruction of transient activity and the MP in the reconstruction of oscillatory activity both for simulated data; also they provide a low false positive in automatic detection of oscillatory activity. The SWT and FIR gave the best results on real signals especially for source localization. In the simulated data, the MP is optimal since the atoms of the dictionary resembles to the simulated signals, which isn't guaranteed for real signals. The second problem is the comparison between network connectivity of transient and oscillatory activity, as measured in surface recordings (MEG) and invasive recordings SEEG.

Anomalies de structure du génome et Déficience Intellectuelle : Recherche des gènes candidats de Déficience intellectuelle en utilisant l'analyse chromosomique sur microréseau d'ADN pangénomique 180K et l'analyse chromosomique sur microréseau d'ADN de haute résolution 1M ciblée des gènes candidats de Déficience intellectuelle. L'analyse chromosomique sur microréseau d'ADN (ACM) de haute résolution est une innovation technologique puissante afin de détecter les aberrations chromosomiques concernant les variations du nombre de copies. En utilisant l'ACM 180K, l'ACM 1M et la PCR quantitative, nous avons identifié les 5 variations du nombre de copies (CNV) intragéniques pathogènes de novo impliquant les gènes : RUNX1T1, KIAA1468, FABP7, ZEB2 (syndrome de Mowat-Wilson) et ANKRD11 (syndrome de KBG). Les 5 patients ayant une DI et une dysmorphie faciale. L'ACM 180K a révélé une délétion d'une taille de 92 kb emportant le gène KIAA1468 candidat pour le syndrome de West chez un enfant de 3 ans présentant une DI sévère et une encéphalopathie épileptique infantile précoce. Le criblage des mutations du gène KIAA1468 a été réalisé chez 35 patients atteints de syndrome de West. Un variant intronique c.2761-7 T>C et un variant faux-sens hérité de la mère c.3547 G>A avec signification clinque inconnue ont été identifiés. En utilisant des approches par l'ACM 1M de haute résolution chez 45 patients atteints de DI idiopathique modérée à sévère, un seul CNV causal a été identifié, une délétion intragénique d'une taille de 28.37 kb du gène ZEB2. Notre étude confirme une fréquence très faible des délétions/duplications intragéniques avec la détection d'une seule aberration chromosomique (1/45). En conclusion, si la fréquence des mutations ponctuelles est élevée, nous avons également souligné l'application de la technique de séquençage à haut débit avec un rendement diagnostique jusqu'à 45%-55% des cas de DI sévère idiopathique chez lesquels aucun CNV n'a été détecté sur ACM / Chromosomal structural abnormalities and Intellectual Disability : In search of intellectual disability candidate genes by using pangenomic comparative genomic hybridization 180 K and high resolution comparative genomic hybridization 1M targeting intellectual disability candidate gene.High resolution microarray-based comparative genomic hybridization (a-CGH) has been a powerful technical innovation in order to detect submicroscopic chromosomal aberrations related to copy number variations. By using a-CGH 180K, 1M high resolution a-CGH and quantitative PCR, we have identified 5 pathogenic intragenic copy number variations (CNVs) de novo : RUNX1T1, KIAA1468, FABP7, ZEB2 (Mowat-Wilson syndrome) and ANKRD11 (KBG syndrome). All five patients had intellectual disability (ID) and facial dysmorphism. Interestingly, a-CGH 180K has revealed a 92 kb deletion of a candidate gene KIAA1468 for West syndrome in a 3 year-old boy with severe ID and early infantile epileptic encephalopathy. Mutational screening for candidate gene KIAA1468 was performed in 35 patients with West syndrome. An intronic variant c.2761-7 T>C and a non synonymous maternally inherited variant c.3547 G>A with unknown clinical significance were identified. By using 1M high-resolution a-CGH approach in 45 patients presenting moderate to severe idiopathic ID, only one causal CNV was identified, a 28.37 kb intragenic ZEB2 deletion. Our study has confirmed the low frequency of intragenic deletion/duplication with the detection of only one chromosomal aberration (1/45). In conclusion, providing that the high frequency of intragenic point mutation, we also stressed the application of next-generation sequencing technology with 45-55% diagnostic yield in patients with idiopathic severe ID in case of no apparent CNV(s) on high-resolution a-CGH

L’EEG de surface permet l'étude spatio-temporelle de l’activité cérébrale avec une résolution temporelle élevée, cependant elle souffre de la forte atténuation du champ électrique propagée par l'os du crâne et de la présence de sources de bruits externes. De ce fait, nous souhaitons exploiter les mesures issues de la Stéréo-EEG (SEEG). Cette modalité consiste en l'introduction d'électrodes d'enregistrement au plus près des générateurs, bénéficiant ainsi d'un rapport signal à bruit bien supérieur à celui observé en EEG. Nous proposons ainsi dans cette thèse une étude de faisabilité de l'imagerie de sources à partir de ces mesures, basée sur une méthode d'inversion de type dipôle équivalent associée à un modèle de propagation à une sphère, capable d'amener à une précision de localisation de l'ordre de quelques millimètres. A partir d'une implantation clinique usuelle de la SEEG, nous évaluons les performances de localisation lorsque différents sous-ensembles de capteurs sont considérés. En présence de bruit réaliste, nous constatons que l'ajout de capteurs lointains peut amener à une dégradation de la précision de localisation. Ces conclusions nous amènent à proposer une approche de sélection des capteurs locaux dans le but d'optimiser la fiabilité des résultats. Les atouts et faiblesses de cette approche sont analysés dans un cadre de simulation réaliste afin d'explorer de façon pertinente les différents paramètres pouvant influer sur la qualité de résolution du problème inverse. Les approches sont appliquées sur des enregistrements SEEG récoltés au CHRU de Nancy afin de confronter les méthodes de localisation proposées à des mesures réelles / The surface EEG makes it possible to study the brain activity with a high temporal resolution, however it suffers from the severe attenuation of the electrical propagation through the skull bone as well as the addition of external artifacts. As an alternative, we would like to exploit the Stereo-EEG (SEEG) recordings, consisting in shaft electrodes implanted in the brain volume in the direct vicinity of the brain generators. These data benefit from a high signal to noise ratio compared to this observed in surface EEG. We propose in this thesis a feasibility study of source imaging from the SEEG, based on an equivalent current dipole inversion method associated with an analytical One-Sphere propagation model, able to bring localization precision of the order of a few millimeters. Using a typical clinical electrode implantation, we evaluate the localization performance when different subsets of sensors are considered. In the presence of realistic noise, we observe that the addition of distant sensors with respect to the source can lead to a degradation of the localization accuracy. These conclusions lead us to propose a local sensor selection approach in order to optimize the reliability of the results. The strengths and weaknesses of this approach are analyzed on a realistic simulation framework, for a relevant exploration of the different parameters impacting on the quality of the SEEG source imaging. The approaches are applied on SEEG recordings collected at the CHRU of Nancy to evaluate their performance when facing real measurements

The thesis titled Educational Specifics of Children with Epilepsy aims to find out what are the specifics of education of children with epilepsy. The theoretical part of the thesis defines the characteristics of epilepsy, contains information about epilepsy and epileptic seizure, it deals with etiology of epilepsy, classification of epileptic and non epileptic seizures. It deals with the provocative factors of epileptic seizure and informs about the possibilities of treating this disease. The diploma thesis further outlines the current topic of today, and this is the education of children with epilepsy in the family and especially at school. In the thesis one can read about the issues of family education and healthy siblings of a child with disabilities, as well as some prejudices that an individual with epilepsy can encounter today. The work highlights the educational specifics of the education of children with epilepsy and does not forget to mention the legislative framework and the possibilities of education. It explains the support measures and the concept of inclusion. In the practical part, it contains the questions and the objectives that have been answered by qualitative research. Four case studies of epilepsy children aged between 5 and 16 years, a semi-structured interview with the family...

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The study of cultured neuronal networks has opened up avenues for understanding the ion channels, receptor molecules, and synaptic plasticity that may form the basis of learning and memory. The hippocampal neurons prepared from Wistar rats and put in culture, show, after a few days, spontaneous activity with typical electrophysiological pattern ranging from stochastic spiking to synchronized bursting. Using a multi-electrode array (MEA) having 64 electrodes, the electrophysiological signals are acquired, and connectivity maps are constructed using correlation matrix to understand how the neurons in a network communicate during the burst. The response of the neuronal system to epilepsy caused by induced glutamate injury and subsequent exposure of the system to phenobarbital to form different connectivity networks is analyzed in this study. The correlation matrix of the neuronal network before and after administering glutamate as well as after administering phenobarbital is used to understand the neuronal and network level changes that take place in the system. In order to interface a neuronal network to a physical world, the major computations to be performed are noise removal, pattern recovery, pattern matching and clustering. These computations are to be performed in real time. The system should be able to identify a pattern and relate a physical task to the pattern in about 200-400 ms. Algorithms have been developed for the implementation of a real-time neuronal system on a multi-node digital processor system.

Epilepsy is characterized by the hyperexcitability of individual neurons and hyper synchronization of groups of neurons (networks). The acquired changes that take place at molecular, cellular and network levels are important for the induction and maintenance of epileptic activity in the brain. Epileptic activity is known to alter the intrinsic properties and signaling of neurons. Understanding acquired changes that cause epilepsy may lead to innovative strategies to prevent or cure this neurological disorder. Advances in in vitro electrophysiological techniques together with experimental models of epilepsy are indispensible tools to understand molecular, cellular and network mechanisms that underlie epileptiform activity. The aim of the study was to investigate the epileptiform activity induced alterations in Ca2+ dynamics in apical dendrites of hippocampal subicular pyramidal neurons in slices and changes in network properties of cultured hippocampal neurons. We have also made attempts to develop an in vitro model of epilepsy using organotypic hippocampal slice cultures. In the first part of the present study, investigations on the basic properties of dendritic Ca2+ signaling in subicular pyramidal neurons during epileptiform activity are described. Subiculum, a part of the hippocampal formation is present, adjacent to the CA1 subfield. It acts as a transition zone between the hippocampus and entorhinal cortex. It receives inputs directly from the CA1 region, the entorhinal cortex, subcortical and other cortical areas. Several forms of evidences support the role of subiculum in temporal lobe epilepsy. Pronounced neuronal loss has been reported in various regions of the hippocampal formation (CA1 and CA3) leaving the subiculum generally intact in human epileptic tissue. It has been observed that epileptic activity is generated in subiculum in cases where the CA3 and CA1 regions are damaged or even absent. However, it is not clear how subicular neurons protect themselves from epileptic activity induced neuronal death. It is widely accepted that epileptiform activity induced neuronal damage is a result of an abnormally large influx of Ca2+ into neuronal compartments. In the present study, combined hippocampus / entorhinal cortical brain slices were exposed to zero Mg2+ + 4-amino pyridine artificial cerebrospinal fluid (ACSF) to generate spontaneous epileptiform discharges. Whole cell current-clamp recordings combined with Ca2+ imaging experiments (by incorporating Oregon green BAPTA-1 in the recording pipette) were performed on subicular pyramidal neurons to understand the changes in [Ca2+]i transients elicited in apical dendrites, in response to spontaneous epileptic discharges. To understand the changes occurring with respect to control, experiments were performed (in both control and in vitro epileptic conditions) where [Ca2+]i transients in dendrites were elicited by back propagating action potentials following somatic current injections. The results show clear distance-dependent changes in decay kinetics of [Ca2+]i transients (τdecay), without change in the amplitude of the [Ca2+]i transients, in distal parts (95–110 µm) compared to proximal segments (30–45 µm) of apical dendrites of subicular pyramidal neurons under in vitro epileptic condition, but not in control conditions. Pharmacological agents that block Ca2+ transporters viz. Na+/Ca2+ exchangers (Benzamil), plasma membrane Ca2+-ATPase pumps (Calmidazolium) and smooth endoplasmic reticulum Ca2+-ATPase pumps (Thapsigargin) were applied locally to the proximal and distal part of the apical dendrites in both experimental conditions to understand the molecular aspects of the Ca2+ extrusion mechanisms. The relative contribution of Na+/Ca2+ exchangers in Ca2+ extrusion was higher in the distal apical dendrite in in vitro epileptic condition. Using computer simulations with NEURON, biophysically realistic models were built to understand how faster decay of [Ca2+]i transients in the distal part of apical dendrite associated with [Ca2+]i extrusion mechanisms affect excitability of the neurons. With a linear increase in the density of Na+/Ca2+ exchangers along the apical dendrite, the decrease in τ decay values of [Ca2+]i transients in distal regions seen in experimental epileptic condition was reproduced in simulation. This linear increase in Na+/Ca2+ exchangers lowered the threshold for firing in response to consecutive synaptic inputs to the distal apical dendrite. Our results thus, show the existence of a novel neuroprotective mechanism in distal parts of the apical dendrite of subicular pyramidal neurons under in vitro epileptic condition with the Na+/Ca2+ exchangers being the major contributors to this mechanism. Although the enhanced contribution of Na+/Ca2+ exchangers helps the neuron in removing excess [Ca2+]i loads, it paradoxically makes the neuron hyperexcitable to synaptic inputs in the distal parts of the apical dendrites. Thus, the Na+/Ca2+ exchangers may actually protect subicular pyramidal neurons and at the same time contribute to the maintenance of epileptiform activity. In the second part of the study, neuronal network topologies and connectivity patterns were explored in control and glutamate injury induced epileptogenic hippocampal neuronal networks, cultured on planar multielectrode array (8×8) probes. Hyper synchronization of neuronal networks is the hallmark of epilepsy. To understand hyper synchronization and connectivity patterns of neuronal networks, electrical activity from multiple neurons were monitored simultaneously. The electrical activity recorded from a single electrode mainly consisted of randomly fired single spikes and bursts of spikes. Simultaneous measurement of electrical activity from all the 64 electrodes revealed network bursts. A network burst represents the period (lasting for 0.1–0.2 s) of synchronized activity in the network and, during this transient period, maximum numbers of neurons interact with each other. The network bursts were observed in both control and in vitro epileptic networks, but the frequency of network bursts was more in the latter, compared to former condition. Time stamps of individual spikes (from all 64 electrodes) during such time-aligned network burst were collected and stored in a matrix and used to construct the network topology. Connectivity maps were obtained by analyzing the spike trains using cross-covariance analysis and graph theory methods. Analysis of degree distribution, which is a measure of direct connections between electrodes in a neuronal network, showed exponential and Gaussian distributions in control and in vitro epileptic networks, respectively. Quantification of number of direct connections per electrode revealed that the in vitro epileptic networks showed much higher number of direct connections per electrode compared to control networks. Our results suggest that functional two-dimensional neuronal networks in vitro are not scale-free (not a power law degree distribution). After brief exposure to glutamate, normal hippocampal neuronal networks became hyperexcitable and fired a larger number of network bursts with altered network topology. Quantification of clustering coefficient and path length in these two types of networks revealed that the small-world network property was lost once the networks become epileptic and this was accompanied by a change from an exponential to a Gaussian network. In the last part of the study, we have explored if an excitotoxic glutamate injury (20 µM for 10 min) that produces spontaneous, recurrent, epileptiform discharges in cultured hippocampal neurons can induce epileptogenesis in hippocampal neurons of organotypic brain slice cultures. In vitro models of epilepsy are necessary to understand the mechanisms underlying seizures, the changes in brain structure and function that underlie epilepsy and are the best methods for developing new antiseizure and antiepileptogenic strategies. Glutamate receptor over-activation has been strongly associated with epileptogenesis. Recent studies have shown that brief exposure of dissociated hippocampal neurons in culture to glutamate (20 µM for 10 min) induces epileptogenesis in surviving neurons. Our aim was to extend the in vitro model of glutamate injury induced epilepsy to the slice preparations with intact brain circuits. Patch clamp technique in current-clamp mode was employed to monitor the expression of spontaneous epileptiform discharges from CA1 and CA3 neurons using several combinations of glutamate injury protocols. The results presented here represent preliminary efforts to standardize the glutamate injury protocol for inducing epileptogenesis in organotypic slice preparations. Our results indicate that glutamate injury protocols that induced epileptogenesis in dissociated hippocampal neurons in culture failed to turn CA1 and CA3 neurons of organotypic brain slice cultures epileptic. We also found that the CA1 and CA3 neurons of organotypic brain slice cultures are resilient to induction of epileptogenesis by glutamate injury protocols with 10 times higher concentrations of glutamate (200µM) than that used for neuronal cultures and long exposure periods (upto 30 min). These results clearly show that the factors involved in induction of epileptiform activity after glutamate injury in neuronal cultures and those involved in making the neurons in organotypic slices resilient to such insults are different, and understanding them could give vital clues about epileptogenesis and its control. The resilience of CA1 and CA3 neurons seen could be due to differences in homeostatic plasticity that operate in both these experimental systems. However, further studies are required to corroborate this hypothesis.

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