Synaptic damage underlies EEG abnormalities in postanoxic encephalopathy: A computational study

Clin Neurophysiol. 2017 Sep;128(9):1682-1695. doi: 10.1016/j.clinph.2017.06.245. Epub 2017 Jul 8.


Objective: In postanoxic coma, EEG patterns indicate the severity of encephalopathy and typically evolve in time. We aim to improve the understanding of pathophysiological mechanisms underlying these EEG abnormalities.

Methods: We used a mean field model comprising excitatory and inhibitory neurons, local synaptic connections, and input from thalamic afferents. Anoxic damage is modeled as aggravated short-term synaptic depression, with gradual recovery over many hours. Additionally, excitatory neurotransmission is potentiated, scaling with the severity of anoxic encephalopathy. Simulations were compared with continuous EEG recordings of 155 comatose patients after cardiac arrest.

Results: The simulations agree well with six common categories of EEG rhythms in postanoxic encephalopathy, including typical transitions in time. Plausible results were only obtained if excitatory synapses were more severely affected by short-term synaptic depression than inhibitory synapses.

Conclusions: In postanoxic encephalopathy, the evolution of EEG patterns presumably results from gradual improvement of complete synaptic failure, where excitatory synapses are more severely affected than inhibitory synapses. The range of EEG patterns depends on the excitation-inhibition imbalance, probably resulting from long-term potentiation of excitatory neurotransmission.

Significance: Our study is the first to relate microscopic synaptic dynamics in anoxic brain injury to both typical EEG observations and their evolution in time.

Keywords: Electroencephalography; Long-term potentiation; Mean field model; Postanoxic encephalopathy; Short-term synaptic depression; Synaptic failure.

MeSH terms

  • Aged
  • Coma / diagnosis
  • Coma / epidemiology
  • Coma / physiopathology*
  • Electroencephalography / trends*
  • Female
  • Heart Arrest / diagnosis
  • Heart Arrest / epidemiology
  • Heart Arrest / physiopathology*
  • Humans
  • Hypoxia, Brain / diagnosis
  • Hypoxia, Brain / epidemiology
  • Hypoxia, Brain / physiopathology*
  • Long-Term Potentiation / physiology
  • Male
  • Membrane Potentials / physiology
  • Middle Aged
  • Netherlands / epidemiology
  • Neural Networks, Computer*
  • Synapses / physiology*
  • Synaptic Transmission / physiology