Utility of Independent Component Analysis for Interpretation of Intracranial EEG

Electrode arrays are sometimes implanted in the brains of patients with intractable epilepsy to better localize seizure foci before epilepsy surgery. Analysis of intracranial EEG (iEEG) recordings is typically performed in the electrode channel domain without explicit separation of the sources that generate the signals. However, intracranial EEG signals, like scalp EEG signals, could be linear mixtures of local activity and volume-conducted activity arising in multiple source areas. Independent component analysis (ICA) has recently been applied to scalp EEG data, and shown to separate the signal mixtures into independently generated brain and non-brain source signals. Here, we applied ICA to unmix source signals from intracranial EEG recordings from four epilepsy patients during a visually cued finger movement task in the presence of background pathological brain activity. This ICA decomposition demonstrated that the iEEG recordings were not maximally independent, but rather are linear mixtures of activity from multiple sources. Many of the independent component (IC) projections to the iEEG recording grid were consistent with sources from single brain regions, including components exhibiting classic movement-related dynamics. Notably, the largest IC projection to each channel accounted for no more than 20–80% of the channel signal variance, implying that in general intracranial recordings cannot be accurately interpreted as recordings of independent brain sources. These results suggest that ICA can be used to identify and monitor major field sources of local and distributed functional networks generating iEEG data. ICA decomposition methods are useful for improving the fidelity of source signals of interest, likely including distinguishing the sources of pathological brain activity

Spatio-temporal modelling and analysis of epileptiform EEG

In this thesis we investigate the mechanisms underlying the generation of abnormal EEG rhythms in epilepsy, which is a crucial step towards better treatment of this disorder in the future. To this end, macroscopic scale mathematical models of the interactions between neuronal populations are examined. In particular, the role of interactions between neural masses that are spatially distributed in cortical networks are explored. In addition, two other important aspects of the modelling process are addressed, namely the conversion of macroscopic model variables into EEG output and the comparison of multivariate, spatio-temporal data. For the latter, we adopt a vectorisation of the correlation matrix of windowed data and subsequent comparison of data by vector distance measures. Our modelling studies indicate that excitatory connectivity between neural masses facilitates self-organised dynamics. In particular, we report for the first time the production of complex rhythmic transients and the generation of intermittent periods of 'abnormal' rhythmic activity in two different models of epileptogenic tissue. These models therefore provide novel accounts of the spontaneous, intermittent transition between normal and pathological rhythms in primarily generalised epilepsies and the evocation of complex, self-terminating, spatio-temporal dynamics by brief stimulation in focal epilepsies. Two key properties of these models are excitability at the macroscopic level and the presence of spatial heterogeneities. The identification of neural mass excitability as an important processes in spatially extended brain networks is a step towards uncovering the multi-scale nature of the pathological mechanisms of epilepsy. A direct consequence of this work is therefore that novel experimental investigations are proposed, which in itself is a validation of our modelling approach. In addition, new considerations regarding the nature of dynamical systems as applied to problems of transitions between rhythmic states are proposed and will prompt future investigations of complex transients in spatio-temporal excitable systems.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A multimodal imaging approach for quantitative assessment of epilepsy

Le tecniche di coregistrazione elettroencefalogramma-risonanza magnetica funzionale (EEG-fMRI) ed EEG ad alta densità (hdEEG) consentono di mappare attivazioni cerebrali anomale evocate da processi epilettici. L’EEG-fMRI è una tecnica di imaging non invasivo che permette la localizzazione delle variazioni del livello di ossigenazione nel sangue presente nelle regioni irritative (segnale BOLD). Diversamente, l’analisi di sorgente stima, a partire da un potenziale elettrico misurato sullo scalpo (EEG), la densità di corrente della sorgente elettrica a livello corticale producendo una plausibile localizzazione del dipolo nelle regioni irritative. Lo scopo di questa tesi è quello di sviluppare un approccio multimodale attraverso l’uso di dati di coregistrazione EEG-fMRI e hdEEG al fine di localizzare l’attività epilettica e verificare l’affidabilità sia dell’attivazione BOLD che della localizzazione della sorgente. Nel Capitolo I si introduce il concetto di approccio multimodale. Il capitolo è suddiviso principalmente in due parti: la prima descrive la tecnica di coregistrazione EEG-fMRI e la seconda la tecnica di localizzazione della sorgente in epilessia. La prima parte consiste in una breve analisi delle basi fisiologiche del dato di coregistrazione EEG-fMRI, nella descrizione di tecniche di registrazione simultanea e nell’introduzione del metodo convenzionale di analisi dei dati. Sono inoltre descritti problemi tecnici, problemi di sicurezza, modalità di scansione e strategie di rimozione degli artefatti EEG. È quindi presentata una panoramica sullo stato dell’arte delle coregistrazioni EEG-fMRI con discussione dei problemi aperti riguardanti l’analisi convenzionale. La seconda parte introduce i principi di base della stima delle sorgenti da dati hdEEG ed i loro limiti. Il primo capitolo fornisce un quadro generale, mentre i due capitoli successivi sono dedicati ad introdurre approcci di tipo diverso. Nell’analisi convenzionale di dati EEG-fMRI, l’apparizione di eventi interictali (IED) guida l’analisi dei dati fMRI. Il neurologo identifica gli intervalli degli eventi IED, che sono rappresentati da un’onda quadra, e successivamente questo protocollo viene convoluto con una risposta emodinamica (HRF) canonica per la costruzione di un modello o regressore da impiegare nell’analisi con modelli lineari generalizzati (GLM). I problemi principali dell’analisi convenzionale consistono nel fatto che essa non è automatica, ossia soffre di soggettività nella classificazione degli IED, e che, se la scelta dell’HRF non è ottimale, l’attivazione può essere sovra o sotto stimata. Il nuovo metodo proposto integra nell’analisi GLM convenzionale due nuove funzioni: il regressore basato sul segnale EEG (Capitolo II), e l’individuazione di una risposta emodinamica individual-based (ibHRF) (Capitolo III). Nel Capitolo IV le prestazioni del nuovo metodo per l’analisi di dati EEG-fMRI sono validate su dati in silico. A questo scopo sono stati creati dati fMRI simulati per testare la scelta dell’HRF ottima tra cinque modelli: quattro standard ed un modello HRF individual-based. Le prestazioni del metodo sono state valutate utilizzando come selezione il criterio di Akaike. Le simulazioni dimostrano la superiorità del nuovo metodo rispetto a quelli convenzionali e mostrano come la variazione del modello HRF influisce sui risultati dell’analisi statistica. Il Capitolo V introduce un criterio automatico volto a separare le componenti del segnale fMRI relative a network interni dal rumore. Dopo il processo di decomposizione probabilistico delle componenti indipendenti (PICA), si seleziona il numero ottimale di componenti applicando un nuovo algoritmo che tiene conto, per ciascuna componente, dei valori medi delle mappe spaziali di attivazione seguito da passaggi di clustering, segmentazione ed analisi spettrale. Confrontando i risultati dell’identificazione visiva dei network neuronali con i risultati di quella automatica, l’algoritmo mostra elevata accuratezza e precisione. In questo modo, il metodo di selezione automatica permette di separare ed individuare i network in stato di riposo, riducendo la soggettività nella valutazione delle componenti indipendenti. Nel Capitolo VI sono descritti il design sperimentale e l’analisi dei dati reali. Il capitolo illustra i risultati di dodici pazienti epilettici, concentrandosi sull’attività BOLD, sulla localizzazione della sorgente e sulla concordanza con il quadro clinico del paziente. Lo scopo è quello di applicare un approccio multimodale che combini tecniche non invasive di acquisizione ed analisi. Sequenze di EEG standard e fMRI sono acquisite nel corso della stessa sessione di scansione. L’analisi dei dati EEG-fMRI è eseguita utilizzando l’approccio GLM tradizionale, il nuovo approccio e l’analisi PICA. La sorgente dell’attività epilettica è stimata a partire da tracciati EEG a 256-canali. L’attivazione BOLD è confrontata con la ricostruzione della sorgente EEG. Questi risultati sono infine confrontati con l’attività epilettica definita da EEG standard ed esiti clinici. La combinazione di tecniche multimodali ed i loro rispettivi metodi di analisi sono strumenti utili per creare un workup prechirurgico completo dell’epilessia, fornendo diversi metodi di localizzazione dello stesso focolaio epilettico. L’approccio non invasivo di integrazione multimodale di dati EEG-fMRI e hdEEG sembra essere uno strumento molto promettente per lo studio delle scariche epilettiche.Electroencephalography-functional magnetic resonance imaging (EEG-fMRI) coregistration and high density EEG (hdEEG) can be combined to noninvasively map abnormal brain activation elicited by epileptic processes. EEG-fMRI can provide information on the pathophysiological processes underlying interictal activity, since the hemodynamic changes are a consequence of the abnormal neural activity generating interictal epileptiform discharges (IEDs). The source analysis estimates the current density of the source that generates a measured electric potential and it yields a plausible dipole localization of irritative regions. The aim of this thesis is to develop a multimodal approach with hdEEG and EEG-fMRI coregistration in order to localize the epileptic activity and to verify the reliability of source localization and BOLD activation. In Chapter I the multimodal approach is introduced. The chapter is divided in two main parts: the first is based on EEG-fMRI coregistration and the second on the source localization in epilepsy. The first part consists of a brief review of the physiologic basis of EEG and fMRI and the technical basics of simultaneous recording, examining the conventional method for EEG-fMRI data. Technical challenges, safety issues, scanning modalities and EEG artifact removal strategies are also described. An overview of the state of EEG-fMRI is presented and the open problems of conventional analysis are discussed. The second part introduces the basic principles of the source estimation from EEG data in epilepsy and their limitations. The first chapter provides a general framework. The next two are devoted to introduce different approaches. Conventional analysis of EEG-fMRI data relies on spike-timing of epileptic activity: the neurologist identifies the intervals of the IEDs events, as represented by a square wave; this protocol is then convolved with a canonical hemodynamic response function (HRF) to construct a model for the general linear model (GLM) analysis. There are limitations to the technique, however. The conventional analysis is not automatic, suffers of subjectivity in IEDs classification, and using a suboptimal HRF to model the BOLD response the activation map may result over or under estimated. The novel method purposed integrates in the conventional GLM two new features: the regressor based on the EEG signal (Chapter II) and the individual-based hemodynamic response function (ibHRF) (Chapter III). In Chapter IV the performance of the novel method of EEG-fMRI data was tested on in silico data. Simulated fMRI datasets were created and used for the choice of the optimal HRF among five models: four standard and an individual-based HRF models. The performance of the method was evaluated using the Akaike information criterion as selection. Simulations would demonstrate the superiority of the novel method compared with the conventional ones and assess how the variations in HRF model affect the results of the statistical analysis. Chapter V introduces an automatic criterion aiming to separate in fMRI data the signal related to an internal network from the noise. After the decomposition process (probabilistic independent component analysis [PICA]), the optimal number of components was selected by applying a novel algorithm which takes into account, for each component, the mean values of the spatial activation maps followed by clustering, segmentation and spectral analysis steps. Comparing visual and automatic identification of the neuronal networks, the algorithm demonstrated high accuracy and precision. Thus, the automatic selection method allows to separate and detect the resting state networks reducing the subjectivity of the independent component assessment. In Chapter VI experimental design and analysis on real data are described. The chapter focuses on BOLD activity, source localization and agreement with the clinical history of twelve epileptic patients. The scope is to apply a multimodal approach combining noninvasive techniques of acquisition and analysis. Standard EEG and fMRI data were acquired during a single scanning session. The analysis of EEG-fMRI data was performed by using both the conventional GLM, the new GLM and the PICA. Source localization of IEDs was performed using 256-channels hdEEG. BOLD localizations were then compared to the EEG source reconstruction and to the expected epileptic activity defined by standard EEG and clinical outcome. The combination of multimodal techniques and their respectively methods of analysis are useful tools in the presurgical workup of epilepsy providing different methods of localization of the same epileptic foci. Furthermore, the combined use of EEG-fMRI and hdEEG offers a new and more complete approach to the study of epilepsy and may play an increasingly important role in the evaluation of patients with refractory focal epilepsy

New approaches for EEG signal processing: artifact EOG removal by ICA-RLS scheme and tracks extraction method

Localizing the bioelectric phenomena originating from the cerebral cortex and evoked by auditory and somatosensory stimuli are clear objectives to both understand how the brain works and to recognize different pathologies. Diseases such as Parkinson’s, Alzheimer’s, schizophrenia and epilepsy are intensively studied to find a cure or accurate diagnosis. Epilepsy is considered the disease with major prevalence within disorders with neurological origin. The recurrent and sudden incidence of seizures can lead to dangerous and possibly life-threatening situations. Since disturbance of consciousness and sudden loss of motor control often occur without any warning, the ability to predict epileptic seizures would reduce patients’ anxiety, thus considerably improving quality of life and safety. The common procedure for epilepsy seizure detection is based on brain activity monitorization via electroencephalogram (EEG) data. This process consumes a lot of time, especially in the case of long recordings, but the major problem is the subjective nature of the analysis among specialists when analyzing the same record. From this perspective, the identification of hidden dynamical patterns is necessary because they could provide insight into the underlying physiological mechanisms that occur in the brain. Time-frequency distributions (TFDs) and adaptive methods have demonstrated to be good alternatives in designing systems for detecting neurodegenerative diseases. TFDs are appropriate transformations because they offer the possibility of analyzing relatively long continuous segments of EEG data even when the dynamics of the signal are rapidly changing. On the other hand, most of the detection methods proposed in the literature assume a clean EEG signal free of artifacts or noise, leaving the preprocessing problem opened to any denoising algorithm. In this thesis we have developed two proposals for EEG signal processing: the first approach consists in electrooculogram (EOG) removal method based on a combination of ICA and RLS algorithms which automatically cancels the artifacts produced by eyes movement without the use of external “ad hoc” electrode. This method, called ICA-RLS has been compared with other techniques that are in the state of the art and has shown to be a good alternative for artifacts rejection. The second approach is a novel method in EEG features extraction called tracks extraction (LFE features). This method is based on the TFDs and partial tracking. Our results in pattern extractions related to epileptic seizures have shown that tracks extraction is appropriate in EEG detection and classification tasks, being practical, easily applicable in medical environment and has acceptable computational cost

Methods for noninvasive localization of focal epileptic activity with magnetoencephalography

Magnetoencephalography (MEG) is a noninvasive brain signal acquisition technique that provides excellent temporal resolution and a whole-head coverage allowing the spatial mapping of sources. These characteristics make MEG an appropriate technique to localize the epileptogenic zone (EZ) in the preoperative evaluation of refractory epilepsy. Presurgical evaluation with MEG can guide the placement of intracranial EEG (iEEG), the current gold standard in the clinical practice, and even supply sufficient information for a surgical intervention without invasive recordings, reducing invasiveness, discomfort, and cost of the presurgical epilepsy diagnosis. However, MEG signals have low signal-to-noise ratio compared with iEEG and can sometimes be affected by noise that masks or distorts the brain activity. This may prevent the detection of interictal epileptiform discharges (IEDs) and high-frequency oscillations (HFOs), two important biomarkers used in the preoperative evaluation of epilepsy. In this thesis, the reduction of two kinds of interference is aimed to improve the signal-to-noise ratio of MEG signals: metallic artifacts mask the activity of IEDs; and the high-frequency noise, that masks HFO activity. Considering the large number of MEG channels and the long duration of the recordings, reducing noise and marking events manually is a time-consuming task. The algorithms presented in this thesis provide automatic solutions aimed at the reduction of interferences and the detection of HFOs. Firstly, a novel automatic BSS-based algorithm to reduce metallic interference is presented and validated using simulated and real MEG signals. Three methods are tested: AMUSE, a second-order BSS technique; and INFOMAX and FastICA, based on high-order statistics. The automatic detection algorithm exploits the known characteristics of metallic-related interferences. Results indicate that AMUSE performes better when recovering brain activity and allows an effective removal of artifactual components.Secondly, the influence of metallic artifact filtering using the developed algorithm is evaluated in the source localization of IEDs in patients with refractory focal epilepsy. A comparison between the resulting positions of equivalent current dipoles (ECDs) produced by IEDs is performed: without removing metallic interference, rejecting only channels with large metallic artifacts, and after BSS-based reduction. The results show that a significant reduction on dispersion is achieved using the BSS-based reduction procedure, yielding feasible locations of ECDs in contrast to the other approaches. Finally, an algorithm for the automatic detection of epileptic ripples in MEG using beamformer-based virtual sensors is developed. The automatic detection of ripples is performed using a two-stage approach. In the first step, beamforming is applied to the whole head to determine a region of interest. In the second step, the automatic detection of ripples is performed using the time-frequency characteristics of these oscillations. The performance of the algorithm is evaluated using simultaneous intracranial EEG recordings as gold standard.The novel approaches developed in this thesis allow an improved noninvasive detection and localization of interictal epileptic biomarkers, which can help in the delimitation of the epileptogenic zone and guide the placement of intracranial electrodes, or even to determine these areas without additional invasive recordings. As a consequence of this improved detection, and given that interictal biomarkers are much more frequent and easy to record than ictal episodes, the presurgical evaluation process can be more comfortable for the patient and in a more economic way.La magnetoencefalografía (MEG) es una técnica no invasiva de adquisición de señales cerebrales que proporciona una excelente resolución temporal y una cobertura total de la cabeza, permitiendo el mapeo espacial de las fuentes cerebrales. Estas características hacen del MEG una técnica apropiada para localizar la zona epileptogénica (EZ) en la evaluación preoperatoria de la epilepsia refractaria. La evaluación prequirúrgica con MEG puede orientar la colocación del EEG intracraneal (iEEG), el actual modelo de referencia en la práctica clínica, e incluso suministrar información suficiente para una intervención quirúrgica sin registros invasivos; reduciendo la invasividad, la incomodidad y el costo del diagnóstico de la epilepsia prequirúrgica. Sin embargo, las señales MEG tienen baja relación señal ruido en comparación con el iEEG pudiendo imposibilitar la detección de descargas epileptiformes interictales (IEDs) y oscilaciones de alta frecuencia (HFOs), dos importantes biomarcadores utilizados en la evaluación preoperatoria de la epilepsia.En esta tesis, la reducción de dos tipos de interferencia está dirigida a mejorar la relación señal-ruido de la señal MEG: los artefactos metálicos que enmascaran la actividad de las IEDs; y el ruido de alta frecuencia, que enmascara la actividad de las HFOs. Debido al gran número de canales MEG y la larga duración de los registros, tanto reducir el ruido como seleccionar los biomarcadores manualmente es una tarea que consume mucho tiempo. Los algoritmos presentados en esta tesis aportan soluciones automáticas dirigidas a la reducción de interferencias y la detección de HFOs. En primer lugar, se presenta y valida un nuevo algoritmo automático basado en BSS para reducir interferencias metálicas mediante señales simuladas y reales. Se prueban tres métodos: AMUSE, una técnica BSS de segundo orden; y INFOMAX y FastICA, basados en estadísticos de orden superior. El algoritmo de detección automático utiliza las características conocidas de la señal producida por la interferencia metálica. Los resultados indican que AMUSE recupera mejor la actividad cerebral y permite una eliminación efectiva de componentes artefactuales.Posteriormente, se evalúa la influencia del filtrado de artefactos metálicos en la localización de IEDs en pacientes con epilepsia focal refractaria. Se realiza una comparación entre las posiciones resultantes de dipolos de corriente equivalentes (ECDs) producidos por IEDs: sin eliminar interferencias metálicas, rechazando solamente canales con elevados artefactos metálicos y, por último, después de una reducción utilizando el algoritmo BSS desarrollado. Los resultados muestran que se logra una reducción significativa en la dispersión utilizando el procedimiento de reducción basado en BSS, lo que produce ubicaciones factibles de los dipolos en contraste con los otros enfoques.En segundo lugar, se desarrolla un algoritmo para la detección automática ripples epilépticos en MEG utilizando sensores virtuales basados en la técnica de beamformer. La detección de ripples se realiza mediante un enfoque en dos etapas. Primero, se determina el área de interés usando beamformer. Posteriormente, se realiza la detección automática de ripples utilizando las características en tiempo-frecuencia. El rendimiento del algoritmo se evalúa utilizando registros iEEG simultáneos.Los nuevos enfoques desarrollados en esta tesis permiten una detección no invasiva mejor de los biomarcadores interictales, que pueden ayudar a delimitar la zona epileptogénica y guiar la colocación de electrodos intracraneales, o incluso determinar estas áreas sin este tipo de registros. Como consecuencia de esta mejora en la detección, y dado que los biomarcadores interictales son mucho más frecuentes y fáciles de registrar que los episodios ictales, la evaluación prequirúrgica puede ser más cómoda y menos costosa para el paciente.Postprint (published version

Coherence analysis: Methods, solutions and problems

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.A coherence function is a measure of the correlation of two signals and may be used as a measure for functional relationship between brain areas. In studying functional relationships, referenced EEG (REEG) coherence analysis yields important new aspects of brain activities, which complement the data obtained by power spectral analysis. However, REEG-based coherence tends to show a false high value due to volume conduction from un correlated sources (VCUS). Existing signal processing methods address this issue using a Fourier coherence function of scalp Laplacian. Although this method has been proved useful to reveal correlation between EEG signals with minimum VCUS effects, it only provides frequency-domain analysis. Since EEG signals are highly non-stationary, it is more appropriate to use time-frequency methods for coherence analysis of scalp Laplacian. Thus this research applies the wavelet transform on coherence analysis of scalp Laplacian. To verify our technique, already recorded EEG data of event related potentials were obtained from a study of two large groups of alcoholic and abstinent alcoholic subjects, performing visual picture-recognition tasks. The proposed coherence method successfully detected time-frequency correlation between EEG signals with minimum VCUS effects. It showed significant spatial specificity and revealed detailed coherence patterns. Some new important results regarding time-frequency characteristics of VCUS effects on wavelet and short-time Fourier transform (STFT) coherence analysis of REEG signals were deduced. The proposed coherence method was also compared to a conventional wavelet coherence method of REEG signals in the study of coherence difference between coherences of alcoholic and abstinent alcoholic EEG signals. Results of this study provided substantial evidence that VCUS effects are not additive and therefore can not be ignored in comparison of different brain states between groups of subjects