Xenon anaesthesia is associated with a reduction in frontal electroencephalogram peak alpha frequency

Background: Administration of conventional anaesthetic agents is associated with changes in electroencephalogram (EEG) oscillatory dynamics, including a reduction in the peak alpha frequency. Computational models of neurones can reproduce such phenomena and are valuable tools for investigating their underlying mechanisms. We hypothesised that EEG data acquired during xenon anaesthesia in humans would show similar changes in peak alpha frequency and that computational neuronal models of recognised cellular actions of xenon would be consistent with the observed changes.

Methods: EEG recordings were obtained for 11 participants from a randomised controlled trial of xenon anaesthesia and for 21 participants from a volunteer study of xenon administration. The frontal peak alpha frequency was calculated for both cohorts at awake baseline and during xenon administration. In silico simulations with two computational models of neurones were performed to investigate how xenon antagonism of hyperpolarisation-activated cyclic nucleotide-gated channel 2 (HCN2) and glutamatergic excitatory neurotransmission would influence peak alpha frequency.

Results: Compared with awake baseline, frontal peak alpha frequency was significantly lower during xenon administration in the randomised controlled trial cohort, median (inter-quartile range) frequency 7.73 Hz (7.27-8.08 Hz) vs 8.81 Hz (8.35-9.03 Hz), P=0.012, and the volunteer cohort, 8.69 Hz (8.34-8.98 Hz) vs 9.41 Hz (9.11-9.92 Hz), P=0.001. In silico simulations with both computational models suggest that antagonism of HCN2 and glutamatergic excitatory neurotransmission are associated with a reduction in peak alpha frequency.

Conclusions: Xenon administration is associated with a reduction of peak alpha frequency in the frontal EEG. In silico simulations utilising two computational models of neurones suggest that these changes are consistent with antagonism of HCN2 and glutamatergic excitatory neurotransmission.

Clinical trial registration: The Australian New Zealand Clinical Trials Registry: ANZCTR number 12618000916246.