Model of intracellular ATP production reproduces common electrophysiological signatures of anesthesia

Accumulating evidence suggest that general anesthetics with diverse chemical structure reduce cerebral metabolism with consequent reduction of intracellular adenosine triphosphate (ATP) levels. How cerebral hypometabolism is associated with the typical electroencephalographic (EEG) changes under general anesthesia remains largely unknown.. We hypothesized that the deficit in ATP production would reduce high-frequency activity, increase low-frequency activity, and cause burst suppression, which are common dose-dependent anesthetic effects on the EEG. To test the hypothesis, we developed a novel neural network model consisting of leaky integrate-and-fire neurons with additional dependency on ATP dynamics. The effect of varying rate of ATP production on neuronal and population activity patterns was simulated under various excitatory/inhibitory balance conditions. A decrease of ATP production suppressed neuronal spiking and enhanced synchronization of neurons over a range of excitatory/inhibitory synaptic strength ratios. As anticipated, the initially asynchronous fast activity was replaced by globally desynchronized slow oscillation and, on further decrease of ATP production, changed into burst suppression with enhanced global synchronization. This study substantiates a novel biophysical mechanism for anesthetic-induced EEG changes through a relationship between energy production and synchronization of neural network.