Effects of the anesthetic agent propofol on neural populations

Abstract

The neuronal mechanisms of general anesthesia are still poorly understood. Besides several characteristic features of anesthesia observed in experiments, a prominent effect is the bi-phasic change of power in the observed electroencephalogram (EEG), i.e. the initial increase and subsequent decrease of the EEG-power in several frequency bands while increasing the concentration of the anaesthetic agent. The present work aims to derive analytical conditions for this bi-phasic spectral behavior by the study of a neural population model. This model describes mathematically the effective membrane potential and involves excitatory and inhibitory synapses, excitatory and inhibitory cells, nonlocal spatial interactions and a finite axonal conduction speed. The work derives conditions for synaptic time constants based on experimental results and gives conditions on the resting state stability. Further the power spectrum of Local Field Potentials and EEG generated by the neural activity is derived analytically and allow for the detailed study of bi-spectral power changes. We find bi-phasic power changes both in monostable and bistable system regime, affirming the omnipresence of bi-spectral power changes in anesthesia. Further the work gives conditions for the strong increase of power in the d-frequency band for large propofol concentrations as observed in experiments.

The population firing rate in the presence of GABAergic tonic inhibition in single neurons and application to general anaesthesia

“…To investigate the role of tonic inhibition in general anaesthesia, e.g. in the induction of the sedation and hypnosis, the subsequent paragraph considers a recent neural population model for general anaesthesia (Hutt and Longtin 2009) and studies the effect of tonic inhibition subjected to the concentration of propofol.…”

“…Introducing the control parameter p C 1, the decay time constant of the receptor response and the charge transfer are proportional to p in good approximation to experimental data, cf. (Hutt and Longtin 2009). Considering two populations of excitatory and inhibitory neurons and excitatory and inhibitory synapses, then the stationary state " U s of such a network of two populations obeys (Hutt and Longtin 2009) …”

“…(Hutt and Longtin 2009). Considering two populations of excitatory and inhibitory neurons and excitatory and inhibitory synapses, then the stationary state " U s of such a network of two populations obeys (Hutt and Longtin 2009) …”

“…Two of the most important features that should be taken into account are the synaptic activity on dendrites of single neurons and the threshold dynamics at the soma of the neurons. Most previous models (Bressloff and Coombes 1997;Hutt and Atay 2005;Hutt et al 2003;Hutt and Longtin 2009) have considered an effective synaptic response function of chemical synapse and a nonlinear transfer function resulting from distributed firing thresholds on the population level. In this context, previous studies considered the membrane potential and the neural firing threshold independently (Wilson and Cowan 1972;Hutt and Atay 2005;Freeman 1979;Amit 1989).…”

Human Brain Networks: Spiking Neuron Models, Multistability, Synchronization, Thermodynamics, Maximum Entropy Production, and Anesthetic Cascade Mechanisms

“…Since molecular studies suggest that one possible mechanism of action of anesthetics is the inhibition of synaptic transmission in cortical neurons [24,25], this suggests that general anesthesia is a phenomenon in which different equilibria can be attained with changing anesthetic agent concentrations. Hence, multistability theory can potentially provide a theoretical foundation for describing general anesthesia.…”