A neural mass model based on single cell dynamics to model pathophysiology.

Neural mass models are successful in modeling brain rhythms as observed in macroscopic measurements such as the electroencephalogram (EEG). While the synaptic current is explicitly modeled in current models, the single cell electrophysiology is not taken into account. To allow for investigations of the effects of channel pathologies, channel blockers and ion concentrations on macroscopic activity, we formulate neural mass equations explicitly incorporating the single cell dynamics by using a bottom-up approach. The mean and variance of the firing rate and synaptic input distributions are modeled. The firing rate curve (F(I)-curve) is used as link between the single cell and macroscopic dynamics. We show that this model accurately reproduces the behavior of two populations of synaptically connected Hodgkin-Huxley neurons, also in non-steady state.

Large-scale modeling of epileptic seizures: scaling properties of two parallel neuronal network simulation algorithms.

Our limited understanding of the relationship between the behavior of individual neurons and large neuronal networks is an important limitation in current epilepsy research and may be one of the main causes of our inadequate ability to treat it. Addressing this problem directly via experiments is impossibly complex; thus, we have been developing and studying medium-large-scale simulations of detailed neuronal networks to guide us. Flexibility in the connection schemas and a complete description of the cortical tissue seem necessary for this purpose. In this paper we examine some of the basic issues encountered in these multiscale simulations. We have determined the detailed behavior of two such simulators on parallel computer systems. The observed memory and computation-time scaling behavior for a distributed memory implementation were very good over the range studied, both in terms of network sizes (2,000 to 400,000 neurons) and processor pool sizes (1 to 256 processors). Our simulations required between a few megabytes and about 150 gigabytes of RAM and lasted between a few minutes and about a week, well within the capability of most multinode clusters. Therefore, simulations of epileptic seizures on networks with millions of cells should be feasible on current supercomputers.

Analysis of stability and bifurcations of fixed points and periodic solutions of a lumped model of neocortex with two delays.

A lumped model of neural activity in neocortex is studied to identify regions of multi-stability of both steady states and periodic solutions. Presence of both steady states and periodic solutions is considered to correspond with epileptogenesis. The model, which consists of two delay differential equations with two fixed time lags is mainly studied for its dependency on varying connection strength between populations. Equilibria are identified, and using linear stability analysis, all transitions are determined under which both trivial and non-trivial fixed points lose stability. Periodic solutions arising at some of these bifurcations are numerically studied with a two-parameter bifurcation analysis.

Comparing epileptiform behavior of mesoscale detailed models and population models of neocortex.

Two models of the neocortex are developed to study normal and pathologic neuronal activity. One model contains a detailed description of a neocortical microcolumn represented by 656 neurons, including superficial and deep pyramidal cells, four types of inhibitory neurons, and realistic synaptic contacts. Simulations show that neurons of a given type exhibit similar, synchronized behavior in this detailed model. This observation is captured by a population model that describes the activity of large neuronal populations with two differential equations with two delays. Both models appear to have similar sensitivity to variations of total network excitation. Analysis of the population model reveals the presence of multistability, which was also observed in various simulations of the detailed model.