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 EEG frequency bands; and in the clinical scenario of surgical patients undergoing general anesthesia. Methods: We investigated the changes in the frontal and fronto-parietal 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<12Hz) 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.