A method of monitoring depth of anesthesia comprises generating differential EEG signals from EEG signals acquired by electrode pairs during an anesthesia protocol, processing the differential EEG signals to determine at least one signal feature and monitoring changes in the at least one signal feature to determine depth of anesthesia. The at least one signal feature comprises at least one of normalized power of the differential EEG signals acquired from at least one of the electrode pairs, and wavelet bicoherence between the differential EEG signals acquired from at least two of the electrode pairs.
