Changes in Intra- and Cross-hemispheric Directed Functional Connectivity in the Electroencephalographic Signals during Propofol-induced Loss of Consciousness

Background: Numerous, sometimes conflicting, changes in brain functional connectivity have been associated with the transition from wakefulness to unresponsiveness at induction of general anesthesia. However, relatively few studies have looked at the detailed time evolution of the transition, for different electroencephalogram (EEG) frequency bands, and in the clinical scenario of surgical patients undergoing general anesthesia. Methods: The authors investigated the changes in the frontal and frontoparietal directed and undirected functional connectivity to multichannel EEG data recorded from 29 adult male surgical patients undergoing propofol-induced loss of consciousness during induction of anesthesia. Directed functional connectivity was estimated using bivariate frequency domain Granger causality, and undirected connectivity was assessed using EEG coherence. Results: Around the point of loss of consciousness, local frontal, interhemispheric frontal, and frontoparietal feedback and feedforward Granger causality all decreased between 31% and 51.5% in the delta band (median [interquartile range] for local frontal, 0.14 [0.08, 0.27] to 0.08 [0.06, 0.12]; P = 0.02). After a lag of a few minutes, Granger causality markedly increased in the gamma and beta bands for local frontal (0.03 [0.02, 0.07] to 0.09 [0.07, 0.11]; P < 0.001) and long-distance cross-hemispheric frontoparietal feedback (0.02 [0.01, 0.04] to 0.07 [0.04, 0.09]; P < 0.001) and feedforward (0.02 [0.01, 0.04] to 0.03 [0.03, 0.04]; P = 0.01) coupling, but not for within-hemispheric frontoparietal feedback and feedforward. Frontal interhemispheric EEG coherence significantly decreased in the lower frequencies (f < 12 Hz) at loss of consciousness, while no significant increase for the beta and gamma bands was observed. Conclusions: Propofol-induced loss of consciousness in surgical patients is associated with a global breakdown in low-frequency directed functional connectivity, coupled with a high-frequency increase between closely located brain regions. At loss of consciousness, Granger causality shows more pronounced changes than coherence.