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Biomedical subjects

Ralph G Andrzejak

Publications and source records attributed to Ralph G Andrzejak.

15 recordsLinked to original sources

Seizure prediction: the long and winding road.

The sudden and apparently unpredictable nature of seizures is one of the most disabling aspects of the disease epilepsy. A method capable of predicting the occurrence of seizures from the electroencephalogram (EEG) of epilepsy patients would open new therapeutic possibilities. Since the 1970s investigations on the predictability of seizures have advanced from preliminary descriptions of seizure precursors to controlled studies applying prediction algorithms to continuous multi-day EEG recordings. While most of the studies published in the 1990s and around the turn of the millennium yielded rather promising results, more recent evaluations could not reproduce these optimistic findings, thus raising a debate about the validity and reliability of previous investigations. In this review, we will critically discuss the literature on seizure prediction and address some of the problems and pitfalls involved in the designing and testing of seizure-prediction algorithms. We will give an account of the current state of this research field, point towards possible future developments and propose methodological guidelines for future studies on seizure prediction.

Algorithms↗

Improved spatial characterization of the epileptic brain by focusing on nonlinearity.

An advanced characterization of the complicated dynamical system brain is one of science's biggest challenges. Nonlinear time series analysis allows characterizing nonlinear dynamical systems in which low-dimensional nonlinearity gives rise to complex and irregular behavior. While several studies indicate that nonlinear methods can extract valuable information from neuronal dynamics, others doubt their necessity and conjecture that the same information can be obtained using classical linear techniques. To address this issue, we compared these two concepts, but included furthermore a combination of nonlinear measures with surrogates, an approach that has been designed to specifically focus on nonlinearity. As a benchmark we used the discriminative power to detect the seizure-generating hemisphere in medically intractable mesial temporal lobe epilepsy. We analyzed intracranial electroencephalographic recordings from the seizure-free interval of 29 patients. While the performance of both linear and nonlinear measures was weak, if not insignificant, a very high performance was obtained by the use of surrogate-corrected measures. Focusing on nonlinearity by using a combination of nonlinear measures with surrogates appears as the key to a successful characterization of the spatial distribution of the epileptic process.

Electroencephalography↗

A distributed computing system for multivariate time series analyses of multichannel neurophysiological data.

We present a client-server application for the distributed multivariate analysis of time series using standard PCs. We here concentrate on analyses of multichannel EEG/MEG data, but our method can easily be adapted to other time series. Due to the rapid development of new analysis techniques, the focus in the design of our application was not only on computational performance, but also on high flexibility and expandability of both the client and the server programs. For this purpose, the communication between the server and the clients as well as the building of the computational tasks has been realized via the Extensible Markup Language (XML). Running our newly developed method in an asynchronous distributed environment with random availability of remote and heterogeneous resources, we tested the system's performance for a number of different univariate and bivariate analysis techniques. Results indicate that for most of the currently available analysis techniques, calculations can be performed in real time, which, in principle, allows on-line analyses at relatively low cost.

Algorithms↗

Detection of weak directional coupling: phase-dynamics approach versus state-space approach.

We compare two conceptually different approaches to the detection of weak directional couplings between two oscillatory systems from bivariate time series. The first approach is based on the analysis of the systems' phase dynamics, whereas the other one tests for interdependencies in the reconstructed state spaces of the systems. We analyze the sensitivity of both techniques to weak couplings in numerical experiments by considering couplings between almost identical as well as between significantly different nonlinear systems. We study different degrees of phase diffusion, test the robustness of the two techniques against observational noise, and investigate the influence of the time series length. Our results show that none of the two approaches is generally superior to the other, and we conclude that it is probably the combination of both techniques that would allow the most comprehensive and reliable characterization of coupled systems.

Journal Article↗

On the predictability of epileptic seizures.

OBJECTIVE: An important issue in epileptology is the question whether information extracted from the EEG of epilepsy patients can be used for the prediction of seizures. Several studies have claimed evidence for the existence of a pre-seizure state that can be detected using different characterizing measures. In this paper, we evaluate the predictability of seizures by comparing the predictive performance of a variety of univariate and bivariate measures comprising both linear and non-linear approaches. METHODS: We compared 30 measures in terms of their ability to distinguish between the interictal period and the pre-seizure period. After completely analyzing continuous inctracranial multi-channel recordings from five patients lasting over days, we used ROC curves to distinguish between the amplitude distributions of interictal and preictal time profiles calculated for the respective measures. We compared different evaluation schemes including channelwise and seizurewise analysis plus constant and adaptive reference levels. Particular emphasis was placed on statistical validity and significance. RESULTS: Univariate measures showed statistically significant performance only in a channelwise, seizurewise analysis using an adaptive baseline. Preictal changes for these measures occurred 5-30 min before seizures. Bivariate measures exhibited high performance values reaching statistical significance for a channelwise analysis using a constant baseline. Preictal changes were found at least 240 min before seizures. Linear measures were found to perform similar or better than non-linear measures. CONCLUSIONS: Results provide statistically significant evidence for the existence of a preictal state. Based on our findings, the most promising approach for prospective seizure anticipation could be a combination of bivariate and univariate measures. SIGNIFICANCE: Many measures reported capable of seizure prediction in earlier studies are found to be insignificant in performance, which underlines the need for statistical validation in this field.

Algorithms↗

Measure profile surrogates: a method to validate the performance of epileptic seizure prediction algorithms.

In a growing number of publications it is claimed that epileptic seizures can be predicted by analyzing the electroencephalogram (EEG) with different characterizing measures. However, many of these studies suffer from a severe lack of statistical validation. Only rarely are results passed to a statistical test and verified against some null hypothesis H0 in order to quantify their significance. In this paper we propose a method to statistically validate the performance of measures used to predict epileptic seizures. From measure profiles rendered by applying a moving-window technique to the electroencephalogram we first generate an ensemble of surrogates by a constrained randomization using simulated annealing. Subsequently the seizure prediction algorithm is applied to the original measure profile and to the surrogates. If detectable changes before seizure onset exist, highest performance values should be obtained for the original measure profiles and the null hypothesis. "The measure is not suited for seizure prediction" can be rejected. We demonstrate our method by applying two measures of synchronization to a quasicontinuous EEG recording and by evaluating their predictive performance using a straightforward seizure prediction statistics. We would like to stress that the proposed method is rather universal and can be applied to many other prediction and detection problems.

Algorithms↗

Improved statistical test for nonstationarity using recurrence time statistics.

We have recently introduced a measure for nonstationarity using a recurrence time statistic to assess stationarity. In this paper we propose an extension of this method based on a detailed study of the statistics for the case of stationary systems. We derive a simple scheme that allows us to estimate the effective number of degrees of freedom relevant for this statistic. This substantially improves the statistical significance of the method and can be used to improve the significance of various other nonlinear statistics.

Journal Article↗

Bivariate surrogate techniques: necessity, strengths, and caveats.

The concept of surrogates allows testing results from time series analysis against specified null hypotheses. In application to bivariate model dynamics we here compare different types of surrogates, each designed to test against a different null hypothesis, e.g., an underlying bivariate linear stochastic process. Two measures that aim at a characterization of interdependence between nonlinear deterministic dynamics were used as discriminating statistics. We analyze eight different stochastic and deterministic models not only to demonstrate the power of the surrogates, but also to reveal some pitfalls and limitations.

Journal Article↗

Automated detection of a preseizure state based on a decrease in synchronization in intracranial electroencephalogram recordings from epilepsy patients.

The question whether information extracted from the electroencephalogram (EEG) of epilepsy patients can be used for the prediction of seizures has recently attracted much attention. Several studies have reported evidence for the existence of a preseizure state that can be detected using different measures derived from the theory of dynamical systems. Most of these studies, however, have neglected to sufficiently investigate the specificity of the observed effects or suffer from other methodological shortcomings. In this paper we present an automated technique for the detection of a preseizure state from EEG recordings using two different measures for synchronization between recording sites, namely, the mean phase coherence as a measure for phase synchronization and the maximum linear cross correlation as a measure for lag synchronization. Based on the observation of characteristic drops in synchronization prior to seizure onset, we used this phenomenon for the characterization of a preseizure state and its distinction from the remaining seizure-free interval. After optimizing our technique on a group of 10 patients with temporal lobe epilepsy we obtained a successful detection of a preseizure state prior to 12 out of 14 analyzed seizures for both measures at a very high specificity as tested on recordings from the seizure-free interval. After checking for in-sample overtraining via cross validation, we applied a surrogate test to validate the observed predictability. Based on our results, we discuss the differences of the two synchronization measures in terms of the dynamics underlying seizure generation in focal epilepsies.

Journal Article↗

Testing the null hypothesis of the nonexistence of a preseizure state.

A rapidly growing number of studies deals with the prediction of epileptic seizures. For this purpose, various techniques derived from linear and nonlinear time series analysis have been applied to the electroencephalogram of epilepsy patients. In none of these works, however, the performance of the seizure prediction statistics is tested against a null hypothesis, an otherwise ubiquitous concept in science. In consequence, the evaluation of the reported performance values is problematic. Here, we propose the technique of seizure time surrogates based on a Monte Carlo simulation to remedy this deficit.

Biophysical Phenomena↗

Epileptic seizures are preceded by a decrease in synchronization.

The exact mechanisms leading to the occurrence of epileptic seizures in humans are still poorly understood. It is widely accepted, however, that the process of seizure generation is closely associated with an abnormal synchronization of neurons. In order to investigate this process, we here measure phase synchronization between different regions of the brain using intracranial EEG recordings. Based on our preliminary finding of a preictal drop in synchronization, we investigate whether this phenomenon can be used as a sensitive and specific criterion to characterize a preseizure state and to distinguish this state from the interictal interval. Applying an automated technique for detecting decreased synchronization to EEG recordings from a group of 18 patients with focal epilepsy comprising a total of 117 h, we observe a characteristic decrease in synchronization prior to 26 out of 32 analyzed seizures at a very high specificity as tested on interictal recordings. The duration of this preictal state is found to range from several minutes up to a few hours. Investigation of the spatial distribution of preictal desynchronization indicates that the process of seizure generation in focal epilepsy is not necessarily confined to the focus itself but may instead involve more distant, even contralateral areas of the brain. Finally, we demonstrate an intrahemispheric asymmetry in the spatial dynamics of preictal desynchronization that is found in the majority of seizures and appears to be an immanent part of the mechanisms underlying the initiation of seizures in humans.

Adult↗

Discerning nonstationarity from nonlinearity in seizure-free and preseizure EEG recordings from epilepsy patients.

A number of recent studies indicate that nonlinear electroencephalogram (EEG) analyses allow to define a state predictive of an impending epileptic seizure. In this paper, we combine a method for detecting nonlinear determinism with a novel test for stationarity to characterize EEG recordings from both the seizure-free interval and the preseizure phase. We discuss differences between these periods, particularly an increased occurrence of stationary, nonlinear segments prior to seizures. These differences seem most prominent for recording sites within the seizure-generating area and for EEG segments less than one minute's length.

Electroencephalography↗

Measuring nonstationarity by analyzing the loss of recurrence in dynamical systems.

We propose a measure for nonstationarity which is based on the analysis of distributions of temporal distances of neighboring vectors in state space. As an extension of previous techniques our method does not require a partitioning of the time series. Moreover, the deviation of mean recurrence times from frequency distributions that would be expected under stationary conditions allows us to estimate the statistical significance of the method.

Journal Article↗