Age-dependent cross frequency coupling features from children to adults during general anesthesia

Background: The frequency coupling characteristics in electroencephalogram (EEG) induced by anesthetics have been well studied in adults, but the investigation of the age-dependent cross frequency coupling features from children to adults is still lacking. Methods: We analyzed EEG signals recorded from pediatric to adult patients ( n = 131), separated into six age groups: < 1 year ( n = 15), 1-3 years ( n = 23), 3-6 years ( n = 19), 6-12 years ( n = 18), 12-18 years ( n = 16), and 18-45 years ( n = 40). Age related EEG power and cross frequency coupling analysis (phase amplitude coupling (PAC) and quadratic phase coupling) of data from maintenance of a surgical state of anesthesia (MOSSA) was conducted. Also, for patients of ages less than 6 years, we analyzed the performance of cross frequency coupling derived indices in distinguishing the states of wakefulness, MOSSA, and recovery of consciousness (ROC). Results: (1) During MOSSA, EEG power substantially increased with age from infancy to 3-6 years then decreased with age in the theta-gamma frequency bands. The infant group ( < 1 year) had the highest slow oscillation (SO) power among all age groups. (2) The distinct PAC pattern is absent in patients less than 1 year of age both in SO alpha and delta-alpha frequency band coupling during propofol induced unconsciousness. The modulation index between delta and alpha oscillations in MOSSA increased with age. (3) Wavelet bicoherence derived indices reach their peaks in the 3-6 years group and then decrease with age growth. (4) The Diag_En index (normalized entropy of the diagonal bicoherence entries of the bicoherence matrix) performed the best at distinguishing different states for ages less than 6 years ( p < 0.05). Conclusions: The combination of propofol induction and sevoflurane maintenance exhibited age-dependent EEG power spectra, PAC, and bicoherence, likely related to brain development. These observations suggest new rules for infant and child brain state monitoring during general anesthesia are needed.