Cross-frequency coupling during isoflurane anaesthesia as revealed by electroencephalographic harmonic wavelet bicoherence

Fourier bicoherence has previously been applied to investigate phase coupling in the EEG in anaesthesia. However, there are significant theoretical limitations regarding its sensitivity in detecting transient episodes of inter-frequency coupling. Therefore, we used a recently developed wavelet bicoherence method to investigate the cross-frequency coupling in the EEG of patients under isoflurane anaesthesia; examining the relationship between the patterns of wavelet bicoherence and the isoflurane concentrations. We analysed a set of previously published EEG data, obtained from 29 patients who underwent elective abdominal surgery under isoflurane anaesthesia. Artifact-free, 1 min EEG segments at different isoflurane concentrations were extracted from each subject and the wavelet bicoherence calculated for all pairs of frequencies from 0.5 to 20 Hz. Isoflurane caused two peaks in the (613 Hz) and slow (1 Hz) regions of the bicoherence matrix diagonal. Higher concentrations of isoflurane shifted the peak to lower frequencies [11.3 (0.9) Hz at 0.3 to 7.1 (1.2) Hz at 1.5], as has been previously observed in the power spectra. Outside the diagonal, we also found a significant peak that was phase-coupled to the slow waves; higher concentrations of isoflurane shifted this peak to lower frequencies [10.8 (1.2) to 7.7 (0.7) Hz]. Isoflurane caused cross-frequency coupling between and slow waves. Increasing isoflurane concentration slowed the frequencies where the coupling had occurred. This phenomenon of coupling suggests that slow cortical oscillations organize the higher band activity, which is consistent with other studies in natural sleep.