A transition in brain state during propofol-induced unconsciousness

Abstract

Rhythmic oscillations shape cortical dynamics during active behavior, sleep, and general anesthesia. Cross-frequency phase-amplitude coupling is a prominent feature of cortical oscillations, but its role in organizing conscious and unconscious brain states is poorly understood. Using high-density EEG and intracranial electrocorticography during gradual induction of propofol general anesthesia in humans, we discovered a rapid drug-induced transition between distinct states with opposite phase-amplitude coupling and different cortical source distributions. One state occurs during unconsciousness and may be similar to sleep slow oscillations. A second state occurs at the loss or recovery of consciousness and resembles an enhanced slow cortical potential. These results provide objective electrophysiological landmarks of distinct unconscious brain states, and could be used to help improve EEG-based monitoring for general anesthesia.

Keywords: Slow oscillation; anesthesia; cross-frequency coupling; propofol; unconsciousness; α rhythm.

Figures

Figure 1.

Phase-amplitude coupling reveals a transition during general anesthesia. a, Propofol effect-site concentration. b, Probability of response to sounds (red line indicates median; gray represents 5–95% confidence interval). c, Power spectrum of frontal EEG shows increased LFA and α band power during unconsciousness. d, Modulation of α power by LFA phase (gray bars represent p < 0.005, permutation test). e, f, Raw (e) and bandpass-filtered (f) EEG traces during trough-max (left) and peak-max (right) coupling.

Figure 2.

Stereotyped phase-amplitude coupling in unconsciousness. a, Frontal phase-amplitude coupling aligned to tLOC and tROC (gray bars: p < 0.005, uncorrected). b, Mean coupling pattern across subjects at each drug concentration. c, Mean propofol concentration at LOC, ROC, and during trough-max and peak-max epochs (circles represent individual subjects). d, e, Median MI (d) and modulation phase (e) across subjects as a function of the center of the frequency bands used for phase and amplitude. Yellow contour indicates that ≥6 of 10 subjects showed significant modulation (p < 0.05; n.s., not significant).

Figure 3.

Peak-max coupling is not identical with burst suppression. a, Examples of frontal EEG records during epochs showing peak-max coupling with (ii) or without (i) burst suppression. b, Time course of propofol concentration. c, Phase-amplitude modulogram (average of 6 frontal electrodes) shows consistent peak-max coupling in both burst suppression and nonburst suppression periods.

Figure 4.

Spatial distribution of phase-amplitude coupling. a, b, Scalp distribution of MI (a) and phase (b) (median across 10 subjects). *Location of frontal electrodes used in Figs. 1, 2, and 3. a, Yellow contour indicates locations where at least 6 of 10 subjects had significant modulation (p < 0.05; n.s., not significant). c, Average MI at cortical patches estimated by source localization analysis of the EEG. Only patches with significant modulation are included (1% false discovery rate). d, Locations of intracranial cortical surface electrodes (n = 605 sites, 8 patients), mapped to an average cortical surface. Colored points indicate modulation phase of electrodes with significant phase-amplitude coupling.