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

Neonatal Seizure Detection using Convolutional Neural Networks

This study presents a novel end-to-end architecture that learns hierarchical representations from raw EEG data using fully convolutional deep neural networks for the task of neonatal seizure detection. The deep neural network acts as both feature extractor and classifier, allowing for end-to-end optimization of the seizure detector. The designed system is evaluated on a large dataset of continuous unedited multi-channel neonatal EEG totaling 835 hours and comprising of 1389 seizures. The proposed deep architecture, with sample-level filters, achieves an accuracy that is comparable to the state-of-the-art SVM-based neonatal seizure detector, which operates on a set of carefully designed hand-crafted features. The fully convolutional architecture allows for the localization of EEG waveforms and patterns that result in high seizure probabilities for further clinical examination.Comment: IEEE International Workshop on Machine Learning for Signal Processin

Deep Neural Networks for Automatic Classification of Anesthetic-Induced Unconsciousness

Despite the common use of anesthetics to modulate consciousness in the clinic, brain-based monitoring of consciousness is uncommon. We com-bined electroencephalographic measurement of brain activity with deep neural networks to automatically discriminate anesthetic states induced by propofol. Our results with leave-one-participant-out-cross-validation show that convolutional neural networks significantly outperform multilayer perceptrons in discrimination accuracy when working with raw time series. Perceptrons achieved comparable accuracy when provided with power spec-tral densities. These findings highlight the potential of deep convolutional networks for completely automatic extraction of useful spatio-temporo-spectral features from human EEG

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

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

Intelligent monitoring and interpretation of preterm physiological signals using machine learning

Every year, more than one in ten babies are born prematurely. In Ireland of the 70000 babies delivered every year, 4500 are born too early. Premature babies are at a higher risk of complications, which may lead to both short-term and long-term adverse health outcomes. The neonatal population is especially vulnerable and a delay in the identification of medical conditions, as well as delays in the initiating the correct treatment, may be fatal. After birth, preterms are admitted to the neonatal intensive care unit (NICU), where a continuous flow of information in the form of physiological signals is available. Physiological signals can assist clinicians in decision making related to the diagnosis and treatment of various diseases. This information, however, can be highly complex, and usually requires expert analysis which may not be available at all times. The work conducted in this thesis develops a decision support systems for the intelligent monitoring of preterms in the NICU. This will allow for an accurate estimation of the current health status of the preterm neonate as well as the prediction of possible long-term complications. This thesis is comprised of three main work packages (WP), each addressing health complication of preterm on three different stages of life. At the first 12 hours of life the health status is quantified using the clinical risk index for babies (CRIB). This is followed by the assessment of the preterm’s well-being at discharge from the NICU using the clinical course score (CCS). Finally, the long-term neurodevelopmental follow-up is assessed using the Bayley III scales of development at two years. This is schematically represented in Figure 1 along with the main findings and contributions. Low blood pressure (BP) or hypotension is a recognised problem in preterm infants particularly during the first 72 hours of life. Hypotension may cause decreased cerebral perfusion, resulting in deprived oxygen delivery to the brain. Deciding when and whether to treat hypotension relies on our understanding of the relation between BP, oxygenation and brain activity. The electroencephalogram (EEG) is the most commonly used technology to assess the ‘brain health’ of a newborn. The first WP investigates the relationship between short-term dynamics in BP and EEG energy in the preterm on a large dataset of continuous multi-channel unedited EEG recordings in the context of the health status measured by the CRIB score. The obtained results indicate that a higher risk of mortality for the preterm is associated with a lower level of nonlinear interaction between EEG and BP. The level of coupling between these two systems can potentially serve as an additional source of information when deciding whether or not to intervene in the preterm. The electrocardiogram (ECG) is also routinely recorded in preterm infants. Analysis of heart rate variability (HRV) provides a non-invasive assessment of both the sympathetic and parasympathetic control of the heart rate. A novel automated objective decision support tool for the prediction of the short-term outcome (CCS) in preterm neonates who may have low BP is proposed in the second WP. Combining multiple HRV features extracted during hypotensive episodes, the classifier achieved an AUC of 0.97 for the task of short-term outcome prediction, using a leave-one-patient-out performance assessment. The developed system is based on the boosted decision tree classifier and allows for the continuous monitoring of the preterm. The proposed system is validated on a large clinically collected dataset of multimodal recordings from preterm neonates. If the correct treatment is initiated promptly after diagnosis, it can potentially improve the neurodevelopmental outcome of the preterm infant. The third WP presents a pilot study investigating the predictive capability of the early EEG recorded at discharge from the NICU with respect to the 2-year neurodevelopmental outcome using machine learning techniques. Two methods are used: 1) classical feature-based classifier, and 2) end-to-end deep learning. This is a fundamental study in this area, especially in the context of applying end-to-end learning to the preterm EEG for the problem of long-term outcome prediction. It is shown that for the available labelled dataset of 37 preterm neonates, the classical feature-based approach outperformed the end-to-end deep learning technique. A discussion of the obtained result as well as a section highlighting the possible limitations and areas that need to be investigated in the future are provided