Characterizing Regularization Techniques for Spatial Filter Optimization in Oscillatory EEG Regression Problems

International audienc

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

Magnetoencephalography

This is a practical book on MEG that covers a wide range of topics. The book begins with a series of reviews on the use of MEG for clinical applications, the study of cognitive functions in various diseases, and one chapter focusing specifically on studies of memory with MEG. There are sections with chapters that describe source localization issues, the use of beamformers and dipole source methods, as well as phase-based analyses, and a step-by-step guide to using dipoles for epilepsy spike analyses. The book ends with a section describing new innovations in MEG systems, namely an on-line real-time MEG data acquisition system, novel applications for MEG research, and a proposal for a helium re-circulation system. With such breadth of topics, there will be a chapter that is of interest to every MEG researcher or clinician

Statistical causality in the EEG for the study of cognitive functions in healthy and pathological brains

Understanding brain functions requires not only information about the spatial localization of neural activity, but also about the dynamic functional links between the involved groups of neurons, which do not work in an isolated way, but rather interact together through ingoing and outgoing connections. The work carried on during the three years of PhD course returns a methodological framework for the estimation of the causal brain connectivity and its validation on simulated and real datasets (EEG and pseudo-EEG) at scalp and source level. Important open issues like the selection of the best algorithms for the source reconstruction and for time-varying estimates were addressed. Moreover, after the application of such approaches on real datasets recorded from healthy subjects and post-stroke patients, we extracted neurophysiological indices describing in a stable and reliable way the properties of the brain circuits underlying different cognitive states in humans (attention, memory). More in detail: I defined and implemented a toolbox (SEED-G toolbox) able to provide a useful validation instrument addressed to researchers who conduct their activity in the field of brain connectivity estimation. It may have strong implication, especially in methodological advancements. It allows to test the ability of different estimators in increasingly less ideal conditions: low number of available samples and trials, high inter-trial variability (very realistic situations when patients are involved in protocols) or, again, time varying connectivity patterns to be estimate (where stationary hypothesis in wide sense failed). A first simulation study demonstrated the robustness and the accuracy of the PDC with respect to the inter-trials variability under a large range of conditions usually encountered in practice. The simulations carried on the time-varying algorithms allowed to highlight the performance of the existing methodologies in different conditions of signals amount and number of available trials. Moreover, the adaptation of the Kalman based algorithm (GLKF) I implemented, with the introduction of the preliminary estimation of the initial conditions for the algorithm, lead to significantly better performance. Another simulation study allowed to identify a tool combining source localization approaches and brain connectivity estimation able to provide accurate and reliable estimates as less as possible affected to the presence of spurious links due to the head volume conduction. The developed and tested methodologies were successfully applied on three real datasets. The first one was recorded from a group of healthy subjects performing an attention task that allowed to describe the brain circuit at scalp and source level related with three important attention functions: alerting, orienting and executive control. The second EEG dataset come from a group of healthy subjects performing a memory task. Also in this case, the approaches under investigation allowed to identify synthetic connectivity-based descriptors able to characterize the three main memory phases (encoding, storage and retrieval). For the last analysis I recorded EEG data from a group of stroke patients performing the same memory task before and after one month of cognitive rehabilitation. The promising results of this preliminary study showed the possibility to follow the changes observed at behavioural level by means of the introduced neurophysiological indices

Bayesian Modeling and Estimation Techniques for the Analysis of Neuroimaging Data

Brain function is hallmarked by its adaptivity and robustness, arising from underlying neural activity that admits well-structured representations in the temporal, spatial, or spectral domains. While neuroimaging techniques such as Electroencephalography (EEG) and magnetoencephalography (MEG) can record rapid neural dynamics at high temporal resolutions, they face several signal processing challenges that hinder their full utilization in capturing these characteristics of neural activity. The objective of this dissertation is to devise statistical modeling and estimation methodologies that account for the dynamic and structured representations of neural activity and to demonstrate their utility in application to experimentally-recorded data. The first part of this dissertation concerns spectral analysis of neural data. In order to capture the non-stationarities involved in neural oscillations, we integrate multitaper spectral analysis and state-space modeling in a Bayesian estimation setting. We also present a multitaper spectral analysis method tailored for spike trains that captures the non-linearities involved in neuronal spiking. We apply our proposed algorithms to both EEG and spike recordings, which reveal significant gains in spectral resolution and noise reduction. In the second part, we investigate cortical encoding of speech as manifested in MEG responses. These responses are often modeled via a linear filter, referred to as the temporal response function (TRF). While the TRFs estimated from the sensor-level MEG data have been widely studied, their cortical origins are not fully understood. We define the new notion of Neuro-Current Response Functions (NCRFs) for simultaneously determining the TRFs and their cortical distribution. We develop an efficient algorithm for NCRF estimation and apply it to MEG data, which provides new insights into the cortical dynamics underlying speech processing. Finally, in the third part, we consider the inference of Granger causal (GC) influences in high-dimensional time series models with sparse coupling. We consider a canonical sparse bivariate autoregressive model and define a new statistic for inferring GC influences, which we refer to as the LASSO-based Granger Causal (LGC) statistic. We establish non-asymptotic guarantees for robust identification of GC influences via the LGC statistic. Applications to simulated and real data demonstrate the utility of the LGC statistic in robust GC identification

Brain Computer Interfaces and Emotional Involvement: Theory, Research, and Applications

This reprint is dedicated to the study of brain activity related to emotional and attentional involvement as measured by Brain–computer interface (BCI) systems designed for different purposes. A BCI system can translate brain signals (e.g., electric or hemodynamic brain activity indicators) into a command to execute an action in the BCI application (e.g., a wheelchair, the cursor on the screen, a spelling device or a game). These tools have the advantage of having real-time access to the ongoing brain activity of the individual, which can provide insight into the user’s emotional and attentional states by training a classification algorithm to recognize mental states. The success of BCI systems in contemporary neuroscientific research relies on the fact that they allow one to “think outside the lab”. The integration of technological solutions, artificial intelligence and cognitive science allowed and will allow researchers to envision more and more applications for the future. The clinical and everyday uses are described with the aim to invite readers to open their minds to imagine potential further developments

Applications of multi-way analysis for characterizing paediatric electroencephalogram (EEG) recordings

This doctoral thesis outlines advances in multi-way analysis for characterizing electroencephalogram (EEG) recordings from a paediatric population, with the aim to describe new links between EEG data and changes in the brain. This entails establishing the validity of multi-way analysis as a framework for identifying developmental information at the individual and collective level. Multi-way analysis broadens matrix analysis to a multi-linear algebraic architecture to identify latent structural relationships in naturally occurring higher order (n-way) data, like EEG. We use the canonical polyadic decomposition (CPD) as a multi-way model to efficiently express the complex structures present in paediatric EEG recordings as unique combinations of low-rank matrices, offering new insights into child development. This multi-way CPD framework is explored for both typically developing (TD) children and children with potential developmental delays (DD), e.g. children who suffer from epilepsy or paediatric stroke. Resting-state EEG (rEEG) data serves as an intuitive starting point in analyzing paediatric EEG via multi-way analysis. Here, the CPD model probes the underlying relationships between the spatial, spectral and subject modes of several rEEG datasets. We demonstrate the CPD can reveal distinct population-level features in rEEG that reflect unique developmental traits in varying child populations. These development-affiliated profiles are evaluated with respect to capturing structures well-established in childhood EEG. The identified features are also interrogated for their predictive abilities in anticipating new subjects’ ages. Assessing simulations and real rEEG datasets of TD and DD children establishes the multi-way analysis framework as well suited for identifying developmental profiles from paediatric rEEG. We extend the multi-way analysis scheme to more complex EEG scenarios common in EEG rehabilitation technology, like brain-computer interfaces. We explore the feasibility of multi-way modelling for interventions where developmental changes often pose as barriers. The multi-way CPD model is expanded to include four modes- task, spatial, spectral and subject data, with non-negativity and orthogonality constraints imposed. We analyze a visual attention task that elucidates a steady-state visual evoked potential and present the advantages gained from the extended CPD model. Through direct multi-linear projection, we demonstrate that linear profiles of the CPD can be capitalized upon for rapid task classification sans individual subject classifier calibration. Incorporating concepts from the multi-way analysis scheme with child development measured by psychometric tests, we propose the Joint EEG Development Inference (JEDI) model for inferring development from paediatric EEG. We utilize a common EEG task (button-press) to establish a 4-way CPD model of paediatric EEG data. Structured data fusion of the CPD model and cognitive scores from psychometric evaluations then permits joint decomposition of the two datasets to identify common features associated with each representation of development. Use of grid search optimization and a fully cross-validated design supports the JEDI model as another technique for rapidly discerning the developmental status of a child via EEG. We then briefly turn our attention to associating child development as measured by psychometric tests to markers in the EEG using graph network properties. Using graph networks, we show how the functional connectivity can inform on potential developmental delays in very young epileptic children using routine, clinical rEEG measures. This establishes a potential tool complementary to the JEDI model for identifying and inferring links between the established psychometric evaluation of developing children and functional analysis of the EEG. Multi-way analysis of paediatric EEG data offers a new approach for handling the developmental status and profiles of children. The CPD model offers flexibility in terms of identifying development-related features, and can be integrated into EEG tasks common in rehabilitation paradigms. We aim for the multi-way framework and associated techniques pursued in this thesis to be integrated and adopted as a useful tool clinicians can use for characterizing paediatric development

Interpretable Convolutional Neural Networks for Decoding and Analyzing Neural Time Series Data

Machine learning is widely adopted to decode multi-variate neural time series, including electroencephalographic (EEG) and single-cell recordings. Recent solutions based on deep learning (DL) outperformed traditional decoders by automatically extracting relevant discriminative features from raw or minimally pre-processed signals. Convolutional Neural Networks (CNNs) have been successfully applied to EEG and are the most common DL-based EEG decoders in the state-of-the-art (SOA). However, the current research is affected by some limitations. SOA CNNs for EEG decoding usually exploit deep and heavy structures with the risk of overfitting small datasets, and architectures are often defined empirically. Furthermore, CNNs are mainly validated by designing within-subject decoders. Crucially, the automatically learned features mainly remain unexplored; conversely, interpreting these features may be of great value to use decoders also as analysis tools, highlighting neural signatures underlying the different decoded brain or behavioral states in a data-driven way. Lastly, SOA DL-based algorithms used to decode single-cell recordings rely on more complex, slower to train and less interpretable networks than CNNs, and the use of CNNs with these signals has not been investigated. This PhD research addresses the previous limitations, with reference to P300 and motor decoding from EEG, and motor decoding from single-neuron activity. CNNs were designed light, compact, and interpretable. Moreover, multiple training strategies were adopted, including transfer learning, which could reduce training times promoting the application of CNNs in practice. Furthermore, CNN-based EEG analyses were proposed to study neural features in the spatial, temporal and frequency domains, and proved to better highlight and enhance relevant neural features related to P300 and motor states than canonical EEG analyses. Remarkably, these analyses could be used, in perspective, to design novel EEG biomarkers for neurological or neurodevelopmental disorders. Lastly, CNNs were developed to decode single-neuron activity, providing a better compromise between performance and model complexity