Assessing criticality in pre-seizure single-neuron activity of human epileptic cortex

Epileptic seizures are characterized by abnormal and excessive neural activity, where cortical network dynamics seem to become unstable. However, most of the time, during seizure-free periods, cortex of epilepsy patients shows perfectly stable dynamics. This raises the question of how recurring instability can arise in the light of this stable default state. In this work, we examine two potential scenarios of seizure generation: (i) epileptic cortical areas might generally operate closer to instability, which would make epilepsy patients generally more susceptible to seizures, or (ii) epileptic cortical areas might drift systematically towards instability before seizure onset. We analyzed single-unit spike recordings from both the epileptogenic (focal) and the nonfocal cortical hemispheres of 20 epilepsy patients. We quantified the distance to instability in the framework of criticality, using a novel estimator, which enables an unbiased inference from a small set of recorded neurons. Surprisingly, we found no evidence for either scenario: Neither did focal areas generally operate closer to instability, nor were seizures preceded by a drift towards instability. In fact, our results from both pre-seizure and seizure-free intervals suggest that despite epilepsy, human cortex operates in the stable, slightly subcritical regime, just like cortex of other healthy mammalians.Comment: 19 pages, 8 Figure

Whole Brain Network Dynamics of Epileptic Seizures at Single Cell Resolution

Epileptic seizures are characterised by abnormal brain dynamics at multiple scales, engaging single neurons, neuronal ensembles and coarse brain regions. Key to understanding the cause of such emergent population dynamics, is capturing the collective behaviour of neuronal activity at multiple brain scales. In this thesis I make use of the larval zebrafish to capture single cell neuronal activity across the whole brain during epileptic seizures. Firstly, I make use of statistical physics methods to quantify the collective behaviour of single neuron dynamics during epileptic seizures. Here, I demonstrate a population mechanism through which single neuron dynamics organise into seizures: brain dynamics deviate from a phase transition. Secondly, I make use of single neuron network models to identify the synaptic mechanisms that actually cause this shift to occur. Here, I show that the density of neuronal connections in the network is key for driving generalised seizure dynamics. Interestingly, such changes also disrupt network response properties and flexible dynamics in brain networks, thus linking microscale neuronal changes with emergent brain dysfunction during seizures. Thirdly, I make use of non-linear causal inference methods to study the nature of the underlying neuronal interactions that enable seizures to occur. Here I show that seizures are driven by high synchrony but also by highly non-linear interactions between neurons. Interestingly, these non-linear signatures are filtered out at the macroscale, and therefore may represent a neuronal signature that could be used for microscale interventional strategies. This thesis demonstrates the utility of studying multi-scale dynamics in the larval zebrafish, to link neuronal activity at the microscale with emergent properties during seizures

Delay Differential Analysis of Seizures in Multichannel Electrocorticography Data

High-density electrocorticogram (ECoG) electrodes are capable of recording neurophysiological data with high temporal resolution with wide spatial coverage. These recordings are a window to understanding how the human brain processes information and subsequently behaves in healthy and pathologic states. Here, we describe and implement delay differential analysis (DDA) for the characterization of ECoG data obtained from human patients with intractable epilepsy. DDA is a time-domain analysis framework based on embedding theory in nonlinear dynamics that reveals the nonlinear invariant properties of an unknown dynamical system. The DDA embedding serves as a low-dimensional nonlinear dynamical basis onto which the data are mapped. This greatly reduces the risk of overfitting and improves the method's ability to fit classes of data. Since the basis is built on the dynamical structure of the data, preprocessing of the data (e.g., filtering) is not necessary. We performed a large-scale search for a DDA model that best fit ECoG recordings using a genetic algorithm to qualitatively discriminate between different cortical states and epileptic events for a set of 13 patients. A single DDA model with only three polynomial terms was identified. Singular value decomposition across the feature space of the model revealed both global and local dynamics that could differentiate electrographic and electroclinical seizures and provided insights into highly localized seizure onsets and diffuse seizure terminations. Other common ECoG features such as interictal periods, artifacts, and exogenous stimuli were also analyzed with DDA. This novel framework for signal processing of seizure information demonstrates an ability to reveal unique characteristics of the underlying dynamics of the seizure and may be useful in better understanding, detecting, and maybe even predicting seizures

Path Signatures for Seizure Forecasting

Forecasting the state of a system from an observed time series is the subject of research in many domains, such as computational neuroscience. Here, the prediction of epileptic seizures from brain measurements is an unresolved problem. There are neither complete models describing underlying brain dynamics, nor do individual patients exhibit a single seizure onset pattern, which complicates the development of a `one-size-fits-all' solution. Based on a longitudinal patient data set, we address the automated discovery and quantification of statistical features (biomarkers) that can be used to forecast seizures in a patient-specific way. We use existing and novel feature extraction algorithms, in particular the path signature, a recent development in time series analysis. Of particular interest is how this set of complex, nonlinear features performs compared to simpler, linear features on this task. Our inference is based on statistical classification algorithms with in-built subset selection to discern time series with and without an impending seizure while selecting only a small number of relevant features. This study may be seen as a step towards a generalisable pattern recognition pipeline for time series in a broader context

Early warning signals for critical transitions in complex systems

In this review, we present the different measures of early warning signals that can indicate the occurrence of critical transitions in complex systems. We start with the mechanisms that trigger critical transitions, how they relate to warning signals and the methods used to detect early warning signals (EWS) for sudden transitions or tipping. We discuss briefly a few applications in real systems in this context, like transitions in ecology, climate and environment, medicine, epidemics, finance and engineering. Towards the end, we mention the issues in detecting EWS in specific applications and our perspective on future trends in this area, especially related to sudden transitions in the dynamics of connected systems on complex networks.Comment: 35 pages, 11 figure

Noise-induced Regime Shifts: A Quantitative Characterization

Diverse complex dynamical systems are known to exhibit abrupt regime shifts at bifurcation points of the saddle-node type. The dynamics of most of these systems, however, have a stochastic component resulting in noise driven regime shifts even if the system is away from the bifurcation points. In this paper, we propose a new quantitative measure, namely, the propensity transition point as an indicator of stochastic regime shifts. The concepts and the methodology are illustrated for the one-variable May model, a well-known model in ecology and the genetic toggle, a two-variable model of a simple genetic circuit. The general applicability and usefulness of the method for the analysis of regime shifts is further demonstrated in the case of the mycobacterial switch to persistence for which experimental data are available.Comment: 10 Pages, 9 figures, revtex4-1, published versio

Investigating structural and functional aspects of the brain’s criticality in stroke

This paper addresses the question of the brain’s critical dynamics after an injury such as a stroke. It is hypothesized that the healthy brain operates near a phase transition (critical point), which provides optimal conditions for information transmission and responses to inputs. If structural damage could cause the critical point to disappear and thus make self-organized criticality unachievable, it would offer the theoretical explanation for the post-stroke impairment of brain function. In our contribution, however, we demonstrate using network models of the brain, that the dynamics remain critical even after a stroke. In cases where the average size of the second-largest cluster of active nodes, which is one of the commonly used indicators of criticality, shows an anomalous behavior, it results from the loss of integrity of the network, quantifiable within graph theory, and not from genuine non-critical dynamics. We propose a new simple model of an artificial stroke that explains this anomaly. The proposed interpretation of the results is confirmed by an analysis of real connectomes acquired from post-stroke patients and a control group. The results presented refer to neurobiological data; however, the conclusions reached apply to a broad class of complex systems that admit a critical state