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An Introduction To The Event Related Potential Technique

Large-Scale Simultaneous Hypothesis Testing: The Choice of a Null Hypothesis

In reality, the road to a marketed drug is often far from the frequently depicted linear path. Extracting practical insights and lessons from such experiences by discussing drug discovery 'Case histories' is the aim of an inaugural forum this month.

The long and winding road.

Abstract. This paper introduces a new frequency-domain approach to describe the relationships (direction of information flow) between multivariate time series based on the decomposition of multivariate partial coherences computed from multivariate autoregressive models. We discuss its application and compare its performance to other approaches to the problem of determining neural structure relations from the simultaneous measurement of neural electrophysiological signals. The new concept is shown to reflect a frequency-domain representation of the concept of Granger causality.

Partial directed coherence: a new concept in neural structure determination

We review work on extreme events, their causes and consequences, by a group of European and American researchers involved in a three-year project on these topics. The review covers theoretical aspects of time series analysis and of extreme value theory, as well as of the deterministic modeling of extreme events, via continuous and discrete dynamic models. The applications include climatic, seismic and socio-economic events, along with their prediction. Two important results refer to (i) the complementarity of spectral analysis of a time series in terms of the continuous and the discrete part of its power spectrum; and (ii) the need for coupled modeling of natural and socio-economic systems. Both these results have implications for the study and prediction of natural hazards and their human impacts.

Extreme Events: Dynamics, Statistics and Prediction

There is an ongoing debate whether generic early warning signals for critical transitions exist that can be applied across diverse systems. The human epileptic brain is often considered as a prototypical system, given the devastating and, at times, even life-threatening nature of the extreme event epileptic seizure. More than three decades of international effort has successfully identified predictors of imminent seizures. However, the suitability of typically applied early warning indicators for critical slowing down, namely, variance and lag-1 autocorrelation, for indexing seizure susceptibility is still controversially discussed. Here, we investigated long-term, multichannel recordings of brain dynamics from 28 subjects with epilepsy. Using a surrogate-based evaluation procedure of sensitivity and specificity of time-resolved estimates of early warning indicators, we found no evidence for critical slowing down prior to 105 epileptic seizures.

No evidence for critical slowing down prior to human epileptic seizures.

The human brain is a complex network of interacting nonstationary subsystems, whose complicated spatial–temporal dynamics is still poorly understood. Deeper insights can be gained from recent improvements of time-series-analysis techniques to assess strength and direction of interactions together with methodologies for deriving and characterizing evolving networks from empirical time series. We here review these developments, and by taking the example of evolving epileptic brain networks, we discuss the progress that has been made in capturing and understanding brain dynamics that varies on time scales ranging from seconds to years.

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Capturing time-varying brain dynamics

Extreme events occur in a variety of natural, technical, and societal systems and often have catastrophic consequences. Their low-probability, high-impact nature has recently triggered research into improving our understanding of generating mechanisms, providing early warnings as well as developing control strategies. For the latter to be effective, knowledge about dynamical resistance of a system prior to an extreme event is of utmost importance. Here we introduce a novel time-series-based and non-perturbative approach to efficiently monitor dynamical resistance and apply it to high-resolution observations of brain activities from 43 subjects with uncontrollable epileptic seizures. We gain surprising insights into pre-seizure dynamical resistance of brains that also provide important clues for success or failure of measures for seizure prevention. The novel resistance monitoring perspective advances our understanding of precursor dynamics in complex spatio-temporal systems with potential applications in refining control strategies.

/pdf/traceability-and-dynamical-resistance-of-precursor-of-4tdavh0i84.pdf

Traceability and dynamical resistance of precursor of extreme events

Knowing when, where, and how seizures are initiated in large-scale epileptic brain networks remains a widely unsolved problem. Seizure precursors – changes in brain dynamics predictive of an impending seizure – can now be identified well ahead of clinical manifestations, but either the seizure onset zone or remote brain areas are reported as network nodes from which seizure precursors emerge. We aimed to shed more light on the role of constituents of evolving epileptic networks that recurrently transit into and out of seizures. We constructed such networks from more than 3200 hours of continuous intracranial electroencephalograms recorded in 38 patients with medication refractory epilepsy. We succeeded in singling out predictive edges and predictive nodes. Their particular characteristics, namely edge weight respectively node centrality (a fundamental concept of network theory), from the pre-ictal periods of 78 out of 97 seizures differed significantly from the characteristics seen during inter-ictal periods. The vast majority of predictive nodes were connected by most of the predictive edges, but these nodes never played a central role in the evolving epileptic networks. Interestingly, predictive nodes were entirely associated with brain regions deemed unaffected by the focal epileptic process. We propose a network mechanism for a transition into the pre-seizure state, which puts into perspective the role of the seizure onset zone in this transition and highlights the necessity to reassess current concepts for seizure generation and seizure prevention.

/pdf/precursors-of-seizures-due-to-specific-spatial-temporal-1enm6l95b2.pdf

Precursors of seizures due to specific spatial-temporal modifications of evolving large-scale epileptic brain networks

We investigate the relative merit of phase-based methods for inferring directional couplings in complex networks of weakly interacting dynamical systems from multivariate time-series data. We compare the evolution map approach and its partialized extension to each other with respect to their ability to correctly infer the network topology in the presence of indirect directional couplings for various simulated experimental situations using coupled model systems. In addition, we investigate whether the partialized approach allows for additional or complementary indications of directional interactions in evolving epileptic brain networks using intracranial electroencephalographic recordings from an epilepsy patient. For such networks, both direct and indirect directional couplings can be expected, given the brain's connection structure and effects that may arise from limitations inherent to the recording technique. Our findings indicate that particularly in larger networks (number of nodes ≫10), the partialized approach does not provide information about directional couplings extending the information gained with the evolution map approach.

Thorsten Rings

Papers

No evidence for critical slowing down prior to human epileptic seizures.

Capturing time-varying brain dynamics

Traceability and dynamical resistance of precursor of extreme events

Precursors of seizures due to specific spatial-temporal modifications of evolving large-scale epileptic brain networks

Distinguishing between direct and indirect directional couplings in large oscillator networks: Partial or non-partial phase analyses?