Convolutional Neural Networks for Epileptic Seizure Prediction

Epilepsy is the most common neurological disorder and an accurate forecast of seizures would help to overcome the patient's uncertainty and helplessness. In this contribution, we present and discuss a novel methodology for the classification of intracranial electroencephalography (iEEG) for seizure prediction. Contrary to previous approaches, we categorically refrain from an extraction of hand-crafted features and use a convolutional neural network (CNN) topology instead for both the determination of suitable signal characteristics and the binary classification of preictal and interictal segments. Three different models have been evaluated on public datasets with long-term recordings from four dogs and three patients. Overall, our findings demonstrate the general applicability. In this work we discuss the strengths and limitations of our methodology.Comment: accepted for MLESP 201

Towards improved design and evaluation of epileptic seizure predictors

Abstract—Objective: Key issues in the epilepsy seizure prediction research are (1) the reproducibility of results (2) the inability to compare multiple approaches directly. To overcome these problems, the Seizure Prediction Challenge was organized on Kaggle.com. It aimed at establishing benchmarks on a dataset with predefined train, validation and test sets. Our main objective is to analyse the competition format, and to propose improvements, which would facilitate a better comparison of algorithms. The second objective is to present a novel deep learning approach to seizure prediction and compare it to other commonly used methods using patient centered metrics. Methods: We used the competition’s datasets to illustrate the effects of data contamination. Having better data partitions, we compared three types of models in terms of different objectives. Results: We found that correct selection of test samples is crucial when evaluating the performance of seizure forecasting models. Moreover, we showed that models, which achieve state-of-the-art performance with respect to commonly used AUC, sensitivity and specificity metrics, may not yet be suitable for practical usage because of low precision scores. Conclusion: Correlation between validation and test datasets used in the competition limited its scientific value. Significance: Our findings provide guidelines which allow for a more objective evaluation of seizure prediction models

Towards Accurate Forecasting of Epileptic Seizures: Artificial Intelligence and Effective Connectivity Findings

L’épilepsie est une des maladies neurologiques les plus fréquentes, touchant près d’un pourcent de la population mondiale. De nos jours, bien qu’environ deux tiers des patients épileptiques répondent adéquatement aux traitements pharmacologiques, il reste qu’un tiers des patients doivent vivre avec des crises invalidantes et imprévisibles. Quoique la chirurgie d’épilepsie puisse être une autre option thérapeutique envisageable, le recours à la chirurgie de résection demeure très faible en partie pour des raisons diverses (taux de réussite modeste, peur des complications, perceptions négatives). D’autres avenues de traitement sont donc souhaitables. Une piste actuellement explorée par des groupes de chercheurs est de tenter de prédire les crises à partir d’enregistrements de l’activité cérébrale des patients. La capacité de prédire la survenue de crises permettrait notamment aux patients, aidants naturels ou personnels médical de prendre des mesures de précaution pour éviter les désagréments reliés aux crises voire même instaurer un traitement pour les faire avorter. Au cours des dernières années, d’importants efforts ont été déployés pour développer des algorithmes de prédiction de crises et d’en améliorer les performances. Toutefois, le manque d’enregistrements électroencéphalographiques intracrâniens (iEEG) de longue durée de qualité, la quantité limitée de crises, ainsi que la courte durée des périodes interictales constituaient des obstacles majeurs à une évaluation adéquate de la performance des algorithmes de prédiction de crises. Récemment, la disponibilité en ligne d’enregistrements iEEG continus avec échantillonnage bilatéral (des deux hémisphères) acquis chez des chiens atteints d’épilepsie focale à l’aide du dispositif de surveillance ambulatoire implantable NeuroVista a partiellement facilité cette tâche. Cependant, une des limitations associées à l’utilisation de ces données durant la conception d’un algorithme de prédiction de crises était l’absence d’information concernant la zone exacte de début des crises (information non fournie par les gestionnaires de cette base de données en ligne). Le premier objectif de cette thèse était la mise en oeuvre d’un algorithme précis de prédiction de crises basé sur des enregistrements iEEG canins de longue durée. Les principales contributions à cet égard incluent une localisation quantitative de la zone d’apparition des crises (basée sur la fonction de transfert dirigé –DTF), l’utilisation d’une nouvelle fonction de coût via l’algorithme génétique proposé, ainsi qu’une évaluation quasi-prospective des performances de prédiction (données de test d’un total de 893 jours). Les résultats ont montré une amélioration des performances de prédiction par rapport aux études antérieures, atteignant une sensibilité moyenne de 84.82 % et un temps en avertissement de 10 %. La DTF, utilisée précédemment comme mesure de connectivité pour déterminer le réseau épileptique (objectif 1), a été préalablement validée pour quantifier les relations causales entre les canaux lorsque les exigences de quasi-stationnarité sont satisfaites. Ceci est possible dans le cas des enregistrements canins en raison du nombre relativement faible de canaux. Pour faire face aux exigences de non-stationnarité, la fonction de transfert adaptatif pondérée par le spectre (Spectrum weighted adaptive directed transfer function - swADTF) a été introduit en tant qu’une version variant dans le temps de la DTF. Le second objectif de cette thèse était de valider la possibilité d’identifier les endroits émetteurs (ou sources) et récepteurs d’activité épileptiques en appliquant la swADTF sur des enregistrements iEEG de haute densité provenant de patients admis pour évaluation pré-chirurgicale au CHUM. Les générateurs d’activité épileptique étaient dans le volume réséqué pour les patients ayant des bons résultats post-chirurgicaux alors que différents foyers ont été identifiés chez les patients ayant eu de mauvais résultats postchirurgicaux. Ces résultats démontrent la possibilité d’une identification précise des sources et récepteurs d’activités épileptiques au moyen de la swADTF ouvrant la porte à la possibilité d’une meilleure sélection d’électrodes de manière quantitative dans un contexte de développement d’algorithme de prédiction de crises chez l’humain. Dans le but d’explorer de nouvelles avenues pour la prédiction de crises épileptiques, un nouveau précurseur a aussi été étudié combinant l’analyse des spectres d’ordre supérieur et les réseaux de neurones artificiels (objectif 3). Les résultats ont montré des différences statistiquement significatives (p<0.05) entre l’état préictal et l’état interictal en utilisant chacune des caractéristiques extraites du bi-spectre. Utilisées comme entrées à un perceptron multicouche, l’entropie bispectrale normalisée, l’entropie carré normalisée, et la moyenne ont atteint des précisions respectives de 78.11 %, 72.64% et 73.26%. Les résultats de cette thèse confirment la faisabilité de prédiction de crises à partir d’enregistrements d’électroencéphalographie intracrâniens. Cependant, des efforts supplémentaires en termes de sélection d’électrodes, d’extraction de caractéristiques, d’utilisation des techniques d’apprentissage profond et d’implémentation Hardware, sont nécessaires avant l’intégration de ces approches dans les dispositifs implantables commerciaux.----------ABSTRACT Epilepsy is a chronic condition characterized by recurrent “unpredictable” seizures. While the first line of treatment consists of long-term drug therapy about one-third of patients are said to be pharmacoresistant. In addition, recourse to epilepsy surgery remains low in part due to persisting negative attitudes towards resective surgery, fear of complications and only moderate success rates. An important direction of research is to investigate the possibility of predicting seizures which, if achieved, can lead to novel interventional avenues. The paucity of intracranial electroencephalography (iEEG) recordings, the limited number of ictal events, and the short duration of interictal periods have been important obstacles for an adequate assessment of seizure forecasting. More recently, long-term continuous bilateral iEEG recordings acquired from dogs with naturally occurring focal epilepsy, using the implantable NeuroVista ambulatory monitoring device have been made available on line for the benefit of researchers. Still, an important limitation of these recordings for seizure-prediction studies was that the seizure onset zone was not disclosed/available. The first objective of this thesis was to develop an accurate seizure forecasting algorithm based on these canine ambulatory iEEG recordings. Main contributions include a quantitative, directed transfer function (DTF)-based, localization of the seizure onset zone (electrode selection), a new fitness function for the proposed genetic algorithm (feature selection), and a quasi-prospective assessment of seizure forecasting on long-term continuous iEEG recordings (total of 893 testing days). Results showed performance improvement compared to previous studies, achieving an average sensitivity of 84.82% and a time in warning of 10 %. The DTF has been previously validated for quantifying causal relations when quasistationarity requirements are met. Although such requirements can be fulfilled in the case of canine recordings due to the relatively low number of channels (objective 1), the identification of stationary segments would be more challenging in the case of high density iEEG recordings. To cope with non-stationarity issues, the spectrum weighted adaptive directed transfer function (swADTF) was recently introduced as a time-varying version of the DTF. The second objective of this thesis was to validate the feasibility of identifying sources and sinks of seizure activity based on the swADTF using high-density iEEG recordings of patients admitted for pre-surgical monitoring at the CHUM. Generators of seizure activity were within the resected volume for patients with good post-surgical outcomes, whereas different or additional seizure foci were identified in patients with poor post-surgical outcomes. Results confirmed the possibility of accurate identification of seizure origin and propagation by means of swADTF paving the way for its use in seizure prediction algorithms by allowing a more tailored electrode selection. Finally, in an attempt to explore new avenues for seizure forecasting, we proposed a new precursor of seizure activity by combining higher order spectral analysis and artificial neural networks (objective 3). Results showed statistically significant differences (p<0.05) between preictal and interictal states using all the bispectrum-extracted features. Normalized bispectral entropy, normalized squared entropy and mean of magnitude, when employed as inputs to a multi-layer perceptron classifier, achieved held-out test accuracies of 78.11%, 72.64%, and 73.26%, respectively. Results of this thesis confirm the feasibility of seizure forecasting based on iEEG recordings; the transition into the ictal state is not random and consists of a “build-up”, leading to seizures. However, additional efforts in terms of electrode selection, feature extraction, hardware and deep learning implementation, are required before the translation of current approaches into commercial devices

A Performance Comparison of Neural Network and SVM Classifiers Using EEG Spectral Features to Predict Epileptic Seizures

Epilepsy is one of the most common neurological disorders, and afflicts approximately 70 million people globally. 30-40% of patients have refractory epilepsy, where seizures cannot be controlled by anti-epileptic medication, and surgery is neither appropriate, nor available. The unpredictable nature of epileptic seizures is the primary cause of mortality among patients, and leads to significant psychosocial disability. If seizures could be predicted in advance, automatic seizure warning systems could transform the lives of millions of people. This study presents a performance comparison of artificial neural network and sup port vector machine classifiers, using EEG spectral features to predict the onset of epileptic seizures. In addition, the study also examines the influence of EEG window size, feature selection, and data sampling on classification performance. A total of 216 generalised models were trained and tested on a public seizure database, which contained over 1300 hours of EEG data from 7 subjects. The results showed that ANN outperform SVM, when using spectral features (p = 0.035). The beta and gamma frequency bands were shown to be the best predictors of seizure onset. No significant differences in performance were determined for the dif ferent window sizes, or for the feature selection methods. The data sampling method significantly influenced the performance (p \u3c 0.001), and highlighted the importance of treating class imbalance in EEG datasets

Bispectrum and recurrent neural networks: Improved classification of interictal and preictal states

This work proposes a novel approach for the classification of interictal and preictal brain states based on bispectrum analysis and recurrent Long Short-Term Memory (LSTM) neural networks. Two features were first extracted from bilateral intracranial electroencephalography (iEEG) recordings of dogs with naturally occurring focal epilepsy. Single-layer LSTM networks were trained to classify 5-min long feature vectors as preictal or interictal. Classification performances were compared to previous work involving multilayer perceptron networks and higher-order spectral (HOS) features on the same dataset. The proposed LSTM network proved superior to the multilayer perceptron network and achieved an average classification accuracy of 86.29% on held-out data. Results imply the possibility of forecasting epileptic seizures using recurrent neural networks, with minimal feature extraction

Machine learning from wristband sensor data for wearable, noninvasive seizure forecasting

Objective: Seizure forecasting may provide patients with timely warnings to adapt their daily activities and help clinicians deliver more objective, personalized treatments. Although recent work has convincingly demonstrated that seizure risk assessment is in principle possible, these early approaches relied largely on complex, often invasive setups including intracranial electrocorticography, implanted devices, and multichannel electroencephalography, and required patient-specific adaptation or learning to perform optimally, all of which limit translation to broad clinical application. To facilitate broader adaptation of seizure forecasting in clinical practice, noninvasive, easily applicable techniques that reliably assess seizure risk without much prior tuning are crucial. Wristbands that continuously record physiological parameters, including electrodermal activity, body temperature, blood volume pulse, and actigraphy, may afford monitoring of autonomous nervous system function and movement relevant for such a task, hence minimizing potential complications associated with invasive monitoring and avoiding stigma associated with bulky external monitoring devices on the head. Methods: Here, we applied deep learning on multimodal wristband sensor data from 69 patients with epilepsy (total duration > 2311 hours, 452 seizures) to assess its capability to forecast seizures in a statistically significant way. Results: Using a leave-one-subject-out cross-validation approach, we identified better-than-chance predictability in 43% of the patients. Time-matched seizure surrogate data analyses indicated forecasting not to be driven simply by time of day or vigilance state. Prediction performance peaked when all sensor modalities were used, and did not differ between generalized and focal seizure types, but generally increased with the size of the training dataset, indicating potential further improvement with larger datasets in the future. Significance: Collectively, these results show that statistically significant seizure risk assessments are feasible from easy-to-use, noninvasive wearable devices without the need of patient-specific training or parameter optimization

Prediction of canine epilepsy

Seizure prediction is a problem in biomedical science which now is possible to solve with machine learning methods. A seizure prediction system has the power to assist those affected by epilepsy in better managing their medication, daily activities and improving the quality of life. Usage of machine learning algorithms and the availability of long term Intracranial Electroencephalographic (iEEG) recordings have tremendously reduced the complications involved in the challenging seizure prediction problem. Data, in the form of iEEG was collected from canines with naturally occurring epilepsy for the analysis and a seizure prediction system consisting of a machine learning based pipeline was implemented to generate seizure warnings when potential preictal activity is observed in the iEEG recording. A comparison between the different extracted features, dimensionality reduction techniques, and machine learning techniques was performed to investigate the relative effectiveness of the different techniques in the application of seizure prediction. The machine learning protocol performed significantly better than a chance prediction algorithm in all the analyzed subjects. Moreover, the analysis revealed subject-specific neurophysiological changes in the extracted features prior to lead seizures suggesting the existence of a distinct, identifiable preictal state