Characterising the dynamics of EEG waveforms as the path through parameter space of a neural mass model: application to epilepsy seizure evolution.

In this paper we propose that the dynamic evolution of EEG activity during epileptic seizures may be characterised as a path through parameter space of a neural mass model, reflecting gradual changes in underlying physiological mechanisms. Previous theoretical studies have shown how boundaries in parameter space of the model (so-called bifurcations) correspond to transitions in EEG waveforms between apparently normal, spike and wave and subsequently poly-spike and wave activity. In the present manuscript, we develop a multi-objective genetic algorithm that can estimate parameters of an underlying model from clinical data recordings. A standard approach to this problem is to transform both clinical data and model output into the frequency domain and then choose parameters that minimise the difference in their respective power spectra. Instead in the present manuscript, we estimate parameters in the time domain, their choice being determined according to the best fit obtained between the model output and specific features of the observed EEG waveform. This results in an approximate path through the bifurcation plane of the model obtained from clinical data. We present comparisons of such paths through parameter space from separate seizures from an individual subject, as well as between different subjects. Differences in the path reflect subtleties of variation in the dynamics of EEG, which at present appear indistinguishable using standard clinical techniques.

Mappings between a macroscopic neural-mass model and a reduced conductance-based model.

We present two alternative mappings between macroscopic neuronal models and a reduction of a conductance-based model. These provide possible explanations of the relationship between parameters of these two different approaches to modelling neuronal activity. Obtaining a physical interpretation of neural-mass models is of fundamental importance as they could provide direct and accessible tools for use in diagnosing neurological conditions. Detailed consideration of the assumptions required for the validity of each mapping elucidates strengths and weaknesses of each macroscopic model and suggests improvements for future development.

A method for detecting false bifurcations in dynamical systems: application to neural-field models.

In this article, we present a method for tracking changes in curvature of limit cycle solutions that arise due to inflection points. In keeping with previous literature, we term these changes false bifurcations, as they appear to be bifurcations when considering a Poincaré section that is tangent to the solution, but in actual fact the deformation of the solution occurs smoothly as a parameter is varied. These types of solutions arise commonly in electroencephalogram models of absence seizures and correspond to the formation of spikes in these models. Tracking these transitions in parameter space allows regions to be defined corresponding to different types of spike and wave dynamics, that may be of use in clinical neuroscience as a means to classify different subtypes of the more general syndrome.

Derivation and analysis of an ordinary differential equation mean-field model for studying clinically recorded epilepsy dynamics.

In this paper we describe how an ordinary differential equation model of corticothalamic interactions may be obtained from a more general system of delay differential equations. We demonstrate that transitions to epileptic dynamics via changes in system parameters are qualitatively the same as in the original model with delay, as well as demonstrating that the onset of epileptic activity may arise due to regions of bistability. Hence, the model presents in one unique framework, two competing theories for the genesis of epileptiform activity. Similarities between model transitions and clinical data are presented and we argue that statistics obtained from, and a parameter estimation of this model may be a potential means of classifying and predicting the onset and offset of seizure activity.

Bacterial secretion and the role of diffusive and subdiffusive first passage processes.

By funneling protein effectors through needle complexes located on the cellular membrane, bacteria are able to infect host cells during type III secretion events. The spatio-temporal mechanisms through which these events occur are however not fully understood, due in part to the inherent challenges in tracking single molecules moving within an intracellular medium. As a result, theoretical predictions of secretion times are still lacking. Here we provide a model that quantifies, depending on the transport characteristics within bacterial cytoplasm, the amount of time for a protein effector to reach either of the available needle complexes. Using parameters from Shigella flexneri we are able to test the role that translocators might have to activate the needle complexes and offer semi-quantitative explanations of recent experimental observations.

Onset of polyspike complexes in a mean-field model of human electroencephalography and its application to absence epilepsy.

In this paper, we introduce a modification of a mean-field model used to describe the brain's electrical activity as recorded via electroencephalography (EEG). The focus of the present study is to understand the mechanisms giving rise to the dynamics observed during absence epilepsy, one of the classical generalized syndromes. A systematic study of the data from a number of different subjects with absence epilepsy demonstrates a wide variety of dynamical phenomena in the recorded EEG. In addition to the classical spike and wave activity, there may be polyspike and wave, wave spike or even no discernible spike-wave onset during seizure events. The model we introduce is able to capture all of these different phenomena and we describe the bifurcations giving rise to these different types of seizure activity. We argue that such a model may provide a useful clinical tool for classifying different subclasses of absence epilepsy.