Neural mass activity, bifurcations, and epilepsy.

International audienceIn this letter, we propose a general framework for studying neural mass models defined by ordinary differential equations. By studying the bifurcations of the solutions to these equations and their sensitivity to noise, we establish an important relation, similar to a dictionary, between their behaviors and normal and pathological, especially epileptic, cortical patterns of activity. We then apply this framework to the analysis of two models that feature most phenomena of interest, the Jansen and Rit model, and the slightly more complex model recently proposed by Wendling and Chauvel. This model-based approach allows us to test various neurophysiological hypotheses on the origin of pathological cortical behaviors and investigate the effect of medication. We also study the effects of the stochastic nature of the inputs, which gives us clues about the origins of such important phenomena as interictal spikes, interictal bursts, and fast onset activity that are of particular relevance in epilepsy

Global dynamics of neural mass models

Neural mass models are used to simulate cortical dynamics and to explain the electrical and magnetic fields measured using electro- and magnetoencephalography. Simulations evince a complex phase-space structure for these kinds of models; including stationary points and limit cycles and the possibility for bifurcations and transitions among different modes of activity. This complexity allows neural mass models to describe the itinerant features of brain dynamics. However, expressive, nonlinear neural mass models are often difficult to fit to empirical data without additional simplifying assumptions: e.g., that the system can be modelled as linear perturbations around a fixed point. In this study we offer a mathematical analysis of neural mass models, specifically the canonical microcircuit model, providing analytical solutions describing slow changes in the type of cortical activity, i.e. dynamical itinerancy. We derive a perturbation analysis up to second order of the phase flow, together with adiabatic approximations. This allows us to describe amplitude modulations in a relatively simple mathematical format providing analytic proof-of-principle for the existence of semi-stable states of cortical dynamics at the scale of a cortical column. This work allows for model inversion of neural mass models, not only around fixed points, but over regions of phase space that encompass transitions among semi or multi-stable states of oscillatory activity. Crucially, these theoretical results speak to model inversion in the context of multiple semi-stable brain states, such as the transition between interictal, pre-ictal and ictal activity in epilepsy

From oscillatory transcranial current stimulation to scalp EEG changes: a biophysical and physiological modeling study.

International audienceBoth biophysical and neurophysiological aspects need to be considered to assess the impact of electric fields induced by transcranial current stimulation (tCS) on the cerebral cortex and the subsequent effects occurring on scalp EEG. The objective of this work was to elaborate a global model allowing for the simulation of scalp EEG signals under tCS. In our integrated modeling approach, realistic meshes of the head tissues and of the stimulation electrodes were first built to map the generated electric field distribution on the cortical surface. Secondly, source activities at various cortical macro-regions were generated by means of a computational model of neuronal populations. The model parameters were adjusted so that populations generated an oscillating activity around 10 Hz resembling typical EEG alpha activity. In order to account for tCS effects and following current biophysical models, the calculated component of the electric field normal to the cortex was used to locally influence the activity of neuronal populations. Lastly, EEG under both spontaneous and tACS-stimulated (transcranial sinunoidal tCS from 4 to 16 Hz) brain activity was simulated at the level of scalp electrodes by solving the forward problem in the aforementioned realistic head model. Under the 10 Hz-tACS condition, a significant increase in alpha power occurred in simulated scalp EEG signals as compared to the no-stimulation condition. This increase involved most channels bilaterally, was more pronounced on posterior electrodes and was only significant for tACS frequencies from 8 to 12 Hz. The immediate effects of tACS in the model agreed with the post-tACS results previously reported in real subjects. Moreover, additional information was also brought by the model at other electrode positions or stimulation frequency. This suggests that our modeling approach can be used to compare, interpret and predict changes occurring on EEG with respect to parameters used in specific stimulation configurations

Temporally correlated fluctuations drive epileptiform dynamics

Published onlineJournal ArticleMacroscopic models of brain networks typically incorporate assumptions regarding the characteristics of afferent noise, which is used to represent input from distal brain regions or ongoing fluctuations in non-modelled parts of the brain. Such inputs are often modelled by Gaussian white noise which has a flat power spectrum. In contrast, macroscopic fluctuations in the brain typically follow a 1/f(b) spectrum. It is therefore important to understand the effect on brain dynamics of deviations from the assumption of white noise. In particular, we wish to understand the role that noise might play in eliciting aberrant rhythms in the epileptic brain. To address this question we study the response of a neural mass model to driving by stochastic, temporally correlated input. We characterise the model in terms of whether it generates "healthy" or "epileptiform" dynamics and observe which of these dynamics predominate under different choices of temporal correlation and amplitude of an Ornstein-Uhlenbeck process. We find that certain temporal correlations are prone to eliciting epileptiform dynamics, and that these correlations produce noise with maximal power in the δ and θ bands. Crucially, these are rhythms that are found to be enhanced prior to seizures in humans and animal models of epilepsy. In order to understand why these rhythms can generate epileptiform dynamics, we analyse the response of the model to sinusoidal driving and explain how the bifurcation structure of the model gives rise to these findings. Our results provide insight into how ongoing fluctuations in brain dynamics can facilitate the onset and propagation of epileptiform rhythms in brain networks. Furthermore, we highlight the need to combine large-scale models with noise of a variety of different types in order to understand brain (dys-)function.This work was supported by the European Commission through the FP7 Marie Curie Initial Training Network 289146 (NETT: Neural Engineering Transformative Technologies), by the Spanish Ministry of Economy and Competitiveness and FEDER (project FIS2012-37655-C02-01). J.G.O. also acknowledges support from the ICREA Academia programme, the Generalitat de Catalunya (project 2014SGR0947), and the “María de Maeztu” Programme for Units of Excellence in R&D (Spanish Ministry of Economy and Competitiveness, MDM-2014-0370) M.G. gratefully acknowledges the financial support of the EPSRC via grant EP/N014391/1. The contribution of M.G. was generously supported by a Wellcome Trust Institutional Strategic Support Award (WT105618MA)

Treatment effects in epilepsy:a mathematical framework for understanding response over time

Epilepsy is a neurological disorder characterized by recurrent seizures, affecting over 65 million people worldwide. Treatment typically commences with the use of anti-seizure medications, including both mono- and poly-therapy. Should these fail, more invasive therapies such as surgery, electrical stimulation and focal drug delivery are often considered in an attempt to render the person seizure free. Although a significant portion ultimately benefit from these treatment options, treatment responses often fluctuate over time. The physiological mechanisms underlying these temporal variations are poorly understood, making prognosis a significant challenge when treating epilepsy. Here we use a dynamic network model of seizure transition to understand how seizure propensity may vary over time as a consequence of changes in excitability. Through computer simulations, we explore the relationship between the impact of treatment on dynamic network properties and their vulnerability over time that permit a return to states of high seizure propensity. For small networks we show vulnerability can be fully characterised by the size of the first transitive component (FTC). For larger networks, we find measures of network efficiency, incoherence and heterogeneity (degree variance) correlate with robustness of networks to increasing excitability. These results provide a set of potential prognostic markers for therapeutic interventions in epilepsy. Such markers could be used to support the development of personalized treatment strategies, ultimately contributing to understanding of long-term seizure freedom

A Thalamocortical Neural Mass Model of the EEG during NREM Sleep and Its Response to Auditory Stimulation

Few models exist that accurately reproduce the complex rhythms of the thalamocortical system that are apparent in measured scalp EEG and at the same time, are suitable for large-scale simulations of brain activity. Here, we present a neural mass model of the thalamocortical system during natural non-REM sleep, which is able to generate fast sleep spindles (12–15 Hz), slow oscillations (<1 Hz) and K-complexes, as well as their distinct temporal relations, and response to auditory stimuli. We show that with the inclusion of detailed calcium currents, the thalamic neural mass model is able to generate different firing modes, and validate the model with EEG-data from a recent sleep study in humans, where closed-loop auditory stimulation was applied. The model output relates directly to the EEG, which makes it a useful basis to develop new stimulation protocols