Granger Causality of the Electroencephalogram Reveals Abrupt Global Loss of Cortical Information Flow during Propofol-induced Loss of Responsiveness

• Published in: Anesthesiology (Philadelphia) 2020-10, Vol.133 (4), p.774-786
• Main Authors: Pullon, Rebecca M., Yan, Lucy, Sleigh, Jamie W., Warnaby, Catherine E.
• Format: Article
• Language: English
• Subjects: Adult; Anesthetics, Intravenous - administration & dosage; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Electroencephalography - drug effects; Electroencephalography - methods; Female; Humans; Hypnotics and Sedatives - administration & dosage; Male; Nerve Net - drug effects; Nerve Net - physiology; Perioperative Medicine: Clinical Science; Propofol - administration & dosage; Psychomotor Performance - drug effects; Psychomotor Performance - physiology; Unconsciousness - chemically induced; Unconsciousness - psychology
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0000000000003398

BACKGROUND:It is a commonly held view that information flow between widely separated regions of the cerebral cortex is a necessary component in the generation of wakefulness (also termed “connected” consciousness). This study therefore hypothesized that loss of wakefulness caused by propofol anesthesia should be associated with loss of information flow, as estimated by the effective connectivity in the scalp electroencephalogram (EEG) signal. METHODS:Effective connectivity during anesthesia was quantified by applying bivariate Granger to multichannel EEG data recorded from 16 adult subjects undergoing a slow induction of, and emergence from, anesthesia with intravenous propofol. During wakefulness they were conducting various auditory and motor tasks. Functional connectivity using EEG coherence was also estimated. RESULTS:There was an abrupt, substantial, and global decrease in effective connectivity around the point of loss of responsiveness. Recovery of behavioral responsiveness was associated with a comparable recovery in information flow pattern (expressed as normalized values). The median (interquartile range) change was greatest in the delta frequency banddecreasing from 0.15 (0.21) 2 min before loss of behavioral response, to 0.06 (0.04) 2 min after loss of behavioral response (P < 0.001). Regional decreases in information flow were maximal in a posteromedial direction from lateral frontal and prefrontal regions (0.82 [0.24] 2 min before loss of responsiveness, decreasing to 0.17 [0.05] 2 min after), and least for information flow from posterior channels. The widespread decrease in bivariate Granger causality reflects loss of cortical coordination. The relationship between functional connectivity (coherence) and effective connectivity (Granger causality) was inconsistent. CONCLUSIONS:Propofol-induced unresponsiveness is marked by a global decrease in information flow, greatest from the lateral frontal and prefrontal brain regions in a posterior and medial direction. Loss of information flow may be a useful measure of connected consciousness.