Abstracts

Rationale: Continuous early EEG contributes to outcome prediction in postanoxic encephalopathy. The observed EEG patterns change as a function of time and severity of hypoxic damage and often appear in fixed sequences. We aim to increase the understanding of this evolution by means of a computational model. Methods: The neural mean field model comprises excitatory and inhibitory neurons, their local synaptic connections, and thalamic afferents. The effect of anoxia is modeled as an aggravated activity-dependent synaptic depression, resulting from inhibition of ATP-dependent processes. For prolonged anoxia, the network becomes hyperexcitable as a result of long term potentiation of excitatory synapses. The effect of sedatives is modeled as an increased duration of inhibitory postsynaptic potentials. Results: In healthy conditions, the model generates an alpha rhythm. Anoxia initially leads to an isoelectric EEG. After brief anoxia, the alpha rhythm readily reappears. After prolonged anoxia, the EEG typically evolves from a long isoelectric interval, via burst-suppression to periodic discharges. The model shows that a return to physiological rhythms in this situation is very unlikely. Sedatives only lead to a transient suppression of periodic discharges. The simulation results agreed well with key EEG patterns and transitions observed in the patient data. Conclusions: The model simulations agree well with real-world EEG observations in postanoxic encephalopathy. Our findings indicate that these EEG abnormalities result from activity-dependent synaptic depression and long term potentiation of excitatory neurotransmission. Assuming the latter effect to be irreversible, the model also explains why periodic discharges in postanoxic encephalopathy are often refractory to treatment. Funding: Barry J. Ruijter was financially supported by the Dutch National Epilepsy Fund (Nationaal Epilepsie Fonds, grant reference NEF 14?"18).