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In many fields of research nonlinear dynamical systems are investigated. When more than one process is measured, besides the distinct properties of the individual processes, their interactions are of interest. Often linear methods such as coherence are used for the analysis. The estimation of coherence can lead to false conclusions when applied without fulfilling several key assumptions. We introduce a data driven method to optimize the choice of the parameters for spectral estimation. Its applicability is demonstrated based on analytical calculations and exemplified in a simulation study. We complete our investigation with an application to nonlinear tremor signals in Parkinson's disease. In particular, we analyze electroencephalogram and electromyogram data.

From the very beginning the seizure prediction community faced problems concerning evaluation, standardization, and reproducibility of its studies. One of the main reasons for these shortcomings was the lack of access to high-quality long-term electroencephalography (EEG) data. In this article we present the EPILEPSIAE database, which was made publicly available in 2012. We illustrate its content and scope. The EPILEPSIAE database provides long-term EEG recordings of 275 patients as well as extensive metadata and standardized annotation of the data sets. It will adhere to the current standards in the field of prediction and facilitate reproducibility and comparison of those studies. Beyond seizure prediction, it may also be of considerable benefit for studies focusing on seizure detection, basic neurophysiology, and other fields., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Subclinical seizures (SCS) have rarely been considered in the diagnosis and therapy of epilepsy and have not been systematically analyzed in studies on seizure prediction. Here, we investigate whether predictions of subclinical seizures are feasible and how their occurrence may affect the performance of prediction algorithms. Using the European database of long-term recordings of surface and invasive electroencephalography data, we analyzed the data from 21 patients with SCS, including in total 413 clinically manifest seizures (CS) and 3341 SCS. Based on the mean phase coherence we investigated the predictive performance of CS and SCS. The two types of seizures had similar prediction sensitivities. Significant performance was found considerably more often for SCS than for CS, especially for patients with invasive recordings. When analyzing false alarms triggered by predicting CS, a significant number of these false predictions were followed by SCS for 9 of 21 patients. Although currently observed prediction performance may not be deemed sufficient for clinical applications for the majority of the patients, it can be concluded that the prediction of SCS is feasible on a similar level as for CS and allows a prediction of more of the seizures impairing patients, possibly also reducing the number of false alarms that were in fact correct predictions of CS. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction., (Copyright © 2011 Elsevier Inc. All rights reserved.)

An often addressed challenge in neuroscience research is the assignment of different tasks to specific brain regions. In many cases several brain regions are activated during a single task. Therefore, one is also interested in the temporal evolution of brain activity to infer causal relations between activated brain regions. These causal relations may be described by a directed, task specific network which consists of activated brain regions as vertices and directed edges. The edges describe the causal relations. Inference of the task specific brain network from measurements like electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) is challenging, due to the low spatial resolution of the former and the low temporal resolution of the latter. Here, we present a simulation study investigating a possible combined analysis of simultaneously measured EEG and fMRI data to address the challenge specified above. A nonlinear state space model is used to distinguish between the underlying brain states and the (simulated) EEG/fMRI measurements. We make use of a modified unscented Kalman filter and a corresponding unscented smoother for the estimation of the underlying neural activity. Model parameters are estimated using an expectation-maximization algorithm, which exploits the partial linearity of our model. Inference of the brain network structure is then achieved using directed partial correlation, a measure for Granger causality. The results indicate that the convolution effect of the fMRI forward model imposes a big challenge for the parameter estimation and reduces the influence of the fMRI in combined EEG-fMRI models. It remains to be investigated whether other models or similar combinations of other modalities such as, e.g., EEG and magnetoencephalography can increase the profit of the promising idea of combining various modalities.

Nowadays, data are recorded with increasing spatial and temporal resolution. Commonly these data are analyzed using univariate or bivariate approaches. Most of the analysis techniques assume stationarity of the underlying dynamical processes. Here, we present an approach that is capable of analyzing multivariate data, the so-called renormalized partial directed coherence. It utilizes the concept of Granger causality and is applicable to non-stationary data. We discuss its abilities and limitations, and demonstrate its usefulness in an application to murine electroencephalography (EEG) data during sleep transitions.

Seizure prediction performance is hampered by high numbers of false predictions. Here we present an approach to reduce the number of false predictions based on circadian concepts. Based on eight representative patients we demonstrate that this approach increases the performance considerably. The fraction of patients for whom we found a significant seizure prediction performance was increased from 25% to 38% by accounting for circadian dependencies.

Objective: Retrospective evaluation and comparison of performances of a multivariate method for seizure detection and prediction on simultaneous long-term EEG recordings from scalp and intracranial electrodes., Methods: Two multivariate techniques based on simulated leaky integrate-and-fire neurons were investigated in order to detect and predict seizures. Both methods were applied and assessed on 423h of EEG and 26 seizures in total, recorded simultaneously from the scalp and intracranially continuously over several days from six patients with pharmacorefractory epilepsy., Results: Features generated from simultaneous scalp and intracranial EEG data showed a similar dynamical behavior. Significant performances with sensitivities of up to 73%/62% for scalp/invasive EEG recordings given an upper limit of 0.15 false detections per hour were obtained. Up to 59%/50% of all seizures could be predicted from scalp/invasive EEG, given a maximum number of 0.15 false predictions per hour. A tendency to better performances for scalp EEG was obtained for the detection algorithm., Conclusions: The investigated methods originally developed for non-invasive EEG were successfully applied to intracranial EEG. Especially, concerning seizure detection the method shows a promising performance which is appropriate for practical applications in EEG monitoring. Concerning seizure prediction a significant prediction performance is indicated and a modification of the method is suggested., Significance: This study evaluates simultaneously recorded non-invasive and intracranial continuous long-term EEG data with respect to seizure detection and seizure prediction for the first time.

Several procedures have been proposed to be capable of predicting the occurrence of epileptic seizures. Up to now, all proposed algorithms are far from being sufficient for a clinical application. This is, however, often not obvious when results of seizure prediction performance are reported. Here, we discuss impacts of long prediction horizons with respect to clinical needs and the strain on patients by analyzing long-term continuous intracranial electroencephalography data.

Purpose: Available seizure-prediction algorithms are accompanied by high numbers of false predictions to achieve high sensitivity. Little is known about the extent to which changes in EEG dynamics contribute to false predictions. This study addresses potential causes and the circadian distribution of false predictions as well as their relation to the sleep-wake cycle., Methods: In 21 patients, each with 24 h of interictal invasive EEG recordings, two methods, the dynamic similarity index and the mean phase coherence, were assessed with respect to time points of false predictions. Visual inspection of the invasive EEG data and additional scalp electroencephalogram data was performed at times of false predictions to identify possible correlates of changes in the EEG dynamics., Results: A dependency of false predictions on the time of day is shown. Renormalized to the duration of the period patients are asleep and awake, 86% of all false predictions occurred during sleep for the dynamic similarity index and 68% for the mean phase coherence, respectively. Combining two reference intervals, one during sleep and one in an awake state, the dynamic similarity index increases its performance by reducing the number of false predictions by almost 50% without major changes in sensitivity. No obvious dependence of false predictions was noted on visible epileptic activity, such as spikes, sharp waves, or subclinical ictal patterns., Conclusions: Changes in the EEG dynamics related to the sleep-wake cycle contribute to limits of specificity of both seizure-prediction methods investigated. This may provide a clue for improving prediction methods in general. The combination of reference states yields promising results and may offer opportunities to increase further the performance of prediction methods.

Objective: Abnormal synchronization of neurons plays a central role for the generation of epileptic seizures. Therefore, multivariate time series analysis techniques investigating relationships between the dynamics of different neural populations may offer advantages in predicting epileptic seizures., Methods: We applied a phase and a lag synchronization measure to a selected subset of multicontact intracranial EEG recordings and assessed changes in synchronization with respect to seizure prediction., Results: Patient individual results, group results, spatial aspects using focal and extra-focal electrode contacts as well as two evaluation schemes analyzing decreases and increases in synchronization were examined. Averaged sensitivity values of 60% are observed for a false prediction rate of 0.15 false predictions per hour, a seizure occurrence period of half an hour, and a prediction horizon of 10 min. For approximately half of all 21 patients, a statistically significant prediction performance is observed for at least one synchronization measure and evaluation scheme., Conclusions: The results indicate that synchronization changes in the EEG dynamics preceding seizures can be used for seizure prediction. Nevertheless, the underlying pathogenic mechanisms differ and both decreases and increases in synchronization may precede epileptic seizures depending on the structures investigated., Significance: The prediction method, optimized values of intervention times, as well as preferred brain structures for the EEG recordings have to be determined for each patient individually offering the chance of a better patient-individual prediction performance.

Nonlinear time series analysis techniques have been proposed to detect changes in the electroencephalography dynamics prior to epileptic seizures. Their applicability in practice to predict seizure onsets is hampered by the present lack of generally accepted standards to assess their performance. We propose an analytic approach to judge the prediction performance of multivariate seizure prediction methods. Statistical tests are introduced to assess patient individual results, taking into account that prediction methods are applied to multiple time series and several seizures. Their performance is illustrated utilizing a bivariate seizure prediction method based on synchronization theory.

Purpose: In recent years, a variety of methods developed in the field of linear and nonlinear time series analysis have been used to obtain reliable predictions of epileptic seizures. Because individual methods for seizure prediction so far have shown statistical significance but insufficient performance for clinical applications, we investigated possible improvements by combining algorithms capturing different aspects of electroencephalogram (EEG) dynamics. Methods: We applied the mean phase coherence and the dynamic similarity index to long-term continuous intracranial EEG data. The predictive performance of both methods was assessed and statistically evaluated separately, as well as by using logical “AND” and “OR” combinations. Results: Used independently, either method resulted in a statistically significant prediction performance in only a few patients. Particularly the “AND” combination led to improved prediction performances, leading to an increase in sensitivity and/or specificity. For a maximum false prediction rate of 0.15/h, the mean sensitivity improved from about 25% for the individual methods to 43.2% for the “AND” and to 35.2% for the “OR” combination. Discussion: This study shows that combinations of prediction methods are promising new approaches to enhance seizure prediction performance considerably. It allows merging the individual benefits of prediction methods in a complementary manner. Because either sensitivity or specificity of seizure prediction methods can be improved depending on the needs of the desired clinical application, the combination opens a new window for future use in a clinical setting. [ABSTRACT FROM AUTHOR]

Objective: The present study was aimed at investigating the effect of attention and precision level of exerted force on beta range EEG-EMG synchronization.Methods: We simultaneously recorded cortical electrical activity (EEG) in a bipolar manner from the contralateral sensorimotor areas and surface electromyographic (EMG) activity from the flexor digitorum superficialis muscle in 10 healthy subjects during a maintained motor contraction task at 8% of the maximal voluntary contraction (MVC) force level. The coherence between oscillatory processes in the EEG and EMG was calculated. Three different conditions were investigated: (i) performing the task with high precision (HP); (ii) performing the task with high precision and simultaneously performing a mental arithmetic task (HPAT), i.e. attention was divided between the motor task and the mental arithmetic task; and (iii) performing the task with low precision (LP).Results: We have found that the amount of beta range EEG-EMG synchronization decreases below the 95% confidence level when attention is divided between the motor task and the mental arithmetic task. The results also show that the frequency of beta range synchronization is higher with a higher level of precision but still lies within the beta frequency range (15–30 Hz).Conclusions: The data indicate that beta range synchronization represents a state of the cortico-muscular network when attention is directed towards the motor task. The frequency of synchronization of this network is associated with, and possibly encodes, precision in force production. [ABSTRACT FROM AUTHOR]

Background Measurements in the neurosciences are afflicted with observational noise. Granger-causality inference typically does not take this effect into account. We demonstrate that this leads to false positives conclusions and spurious causalities. New method State space modelling provides a convenient framework to obtain reliable estimates for Granger-causality. Despite its previous application in several studies, the analytical derivation of the statistics for parameter estimation in the state space model was missing. This prevented a rigorous evaluation of the results. Results In this manuscript we derive the statistics for parameter estimation in the state space model. We demonstrate in an extensive simulation study that our novel approach outperforms standard approaches and avoids false positive conclusions about Granger-causality. Comparison with existing methods In comparison with the naive application of Granger-causality inference, we demonstrate the superiority of our novel approach. The wide-spread applicability of our procedure provides a statistical framework for future studies. The application to mice electroencephalogram data demonstrates the immediate applicability of our approach. Conclusions The analytical derivation of the statistics presented in this manuscript enables a rigorous evaluation of the results of Granger causal network inference. It is noteworthy that the statistics can be readily applied to various measures for Granger causality and other approaches that are based on vector autoregressive models. [ABSTRACT FROM AUTHOR]

Abstract: With a worldwide prevalence of about 1%, epilepsy is one of the most common serious brain diseases with profound physical, psychological and, social consequences. Characteristic symptoms are seizures caused by abnormally synchronized neuronal activity that can lead to temporary impairments of motor functions, perception, speech, memory or, consciousness. The possibility to predict the occurrence of epileptic seizures by monitoring the electroencephalographic activity (EEG) is considered one of the most promising options to establish new therapeutic strategies for the considerable fraction of patients with currently insufficiently controlled seizures. Here, a database is presented which is part of an EU-funded project “EPILEPSIAE” aiming at the development of seizure prediction algorithms which can monitor the EEG for seizure precursors. High-quality, long-term continuous EEG data, enriched with clinical metadata, which so far have not been available, are managed in this database as a joint effort of epilepsy centers in Portugal (Coimbra), France (Paris) and Germany (Freiburg). The architecture and the underlying schema are here reported for this database. It was designed for an efficient organization, access and search of the data of 300 epilepsy patients, including high quality long-term EEG recordings, obtained with scalp and intracranial electrodes, as well as derived features and supplementary clinical and imaging data. The organization of this European database will allow for accessibility by a wide spectrum of research groups and may serve as a model for similar databases planned for the future. [Copyright &y& Elsevier]

Abstract: One major challenge in neuroscience is the identification of interrelations between signals reflecting neural activity. When applying multivariate time series analysis techniques to neural signals, detection of directed relationships, which can be described in terms of Granger-causality, is of particular interest. Partial directed coherence has been introduced for a frequency domain analysis of linear Granger-causality based on modeling the underlying dynamics by vector autoregressive processes. We discuss the statistical properties of estimates for partial directed coherence and propose a significance level for testing for nonzero partial directed coherence at a given frequency. The performance of this test is illustrated by means of linear and non-linear model systems and in an application to electroencephalography and electromyography data recorded from a patient suffering from essential tremor. [Copyright &y& Elsevier]