Background: Growth pattern in the electroencephalographic bicoherence spectrum has recently been found to relate to anesthetic depth, and bicoherence analysis can reflect behavior of the thalamocortical reverberating network. Because the thalamocortical network is known to represent a key factor in sleep by anesthesia, systematic and qualitative bicoherence studies of different anesthetic depths is necessary throughout all pairs of frequencies.Methods: Sixteen patients were anesthetized using sevoflurane (1, 2, or 3%) combined with remifentanil (0.4 g ⅐ kg ؊1 ⅐
min ؊1). Raw electroencephalographic signals were collected, and bicoherence was estimated in all pairs of frequencies, between 0.5 and 40 Hz at 0.5-Hz intervals.Results: Sevoflurane (1%) caused two main peaks, spindle frequencies (11.0 ؎ 1.2 Hz, 44.7 ؎ 12.3% [bicoherence growth]) and ␦-frequencies (5.4 ؎ 0.5 Hz, 33.0 ؎ 8.4%), in the diagonal line of biphasic bicoherence plots. High concentrations of sevoflurane (2% and 3%) shifted these peaks to 9.8 ؎ 1.1 Hz, 46.2 ؎ 12.7%; 8.7 ؎ 1.3 Hz, 37.2 ؎ 13.7% and 4.9 ؎ 0.5 Hz, 44.6 ؎ 7.0%; 4.3 ؎ 0.8 Hz, 45.2 ؎ 10.6%, respectively. Sevoflurane caused a third bicoherence peak to appear in another heterogeneous pair frequency (pair of ␣ basal frequency and its double frequency), outside the diagonal line, which also inherited the behavior of ␣ bicoherence peaks at different anesthetic depths.Conclusions: Sevoflurane anesthesia caused bicoherence peaks in ␣ and ␦-areas and also formed secondary third peaks. Deeper sevoflurane anesthesia shifted all bicoherence peaks to lower frequencies and caused increased bicoherence growth in the ␦-area. The obtained features are consistent with characteristics of the thalamocortical reverberating network and suggest the importance of bicoherence analysis for the thalamic system. BICOHERENCE analysis, a power-independent bispectral analysis, has been developed to detect cross-frequency phase coupling, as a method to examine nonlinear regulation of brain electrical activities. Although a theoretical link between neural network physiology and phase coupling had not been fully established, 1 a certain reverberating system can contribute to high bicoherence values. Bicoherence is a signal-processing technique capable of tracking changes in any reentry system, investigating phase relations between two input signals (f 1 , f 2 ) by introducing an output signal (f 1 ϩ f 2 ), and by quantifying the quadratic phase coupling between these signals. 2 In nonlinear modulation such as seen in a certain reverberating system, the output signal from the reverberating circuit is expected to reenter into the system as the input signal and cause self-modulated characteristics, namely the components of intermodulation products (a signal component produced by multiplication of input signal components). Because this results in quadratic phase coupling between input signal components, bicoherence is expected to grow in these frequency components. A reverberating source such as seen in the thalamocortical ...