Propofol anesthesia and sleep: a high-density EEG study

Abstract

Study objectives: The electrophysiological correlates of anesthetic sedation remain poorly understood. We used high-density electroencephalography (hd-EEG) and source modeling to investigate the cortical processes underlying propofol anesthesia and compare them to sleep.

Design: 256-channel EEG recordings in humans during propofol anesthesia.

Setting: Hospital operating room.

Patients or participants: 8 healthy subjects (4 males).

Interventions: N/A.

Measurements and results: Initially, propofol induced increases in EEG power from 12-25 Hz. Loss of consciousness (LOC) was accompanied by the appearance of EEG slow waves that resembled the slow waves of NREM sleep. We compared slow waves in propofol to slow waves recorded during natural sleep and found that both populations of waves share similar cortical origins and preferentially propagate along the mesial components of the default network. However, propofol slow waves were spatially blurred compared to sleep slow waves and failed to effectively entrain spindle activity. Propofol also caused an increase in gamma (25-40 Hz) power that persisted throughout LOC. Source modeling analysis showed that this increase in gamma power originated from the anterior and posterior cingulate cortices. During LOC, we found increased gamma functional connectivity between these regions compared to the wakefulness.

Conclusions: Propofol anesthesia is a sleep-like state and slow waves are associated with diminished consciousness even in the presence of high gamma activity.

Keywords: EEG; Slow oscillation; anesthesia; consciousness; gamma.

Figures

Figure 1

The descent into loss of consciousness (LOC) with propofol is accompanied by changes in the EEG signal. (A) The top row shows representative EEG traces from channel Fz during wakefulness, sedation, and LOC. The second row shows corresponding changes in the EMG. (B) A logarithmic plot of power spectra from channel Fz in waking (black), sedation (blue) and LOC (red). (C) Frequency band specific changes in EEG topography occur during the transition from waking to sedation to sleep. W, Waking; S, Sedation; L, LOC. The EEG following recovery from anesthesia is similar to the EEG preceding anesthesia. (D) Statistically significant clusters of electrodes (green, SnPM suprathreshold cluster test, P < 0.05) where power was different in sedation compared to waking (upper row), LOC compared to waking (middle row), and sedation compared to LOC (bottom row).

Figure 2

EEG slow waves occur during LOC with propofol anesthesia. (A) 15 seconds of data from channel Fz recorded during propofol sedation (upper) and spontaneous sleep (lower). The green dots indicate slow waves in the spontaneous sleep data and slow wave-like events in the propofol data. (B) Butterfly plots of mastoid-referenced hd-EEG traces for the average of 295 events detected during anesthesia (right panel) and 643 amplitude-matched slow waves (left panel). (C) The top row shows the average slow wave recorded from channel Fz (filtered at 0.5–6.0 Hz, see Methods) for spontaneous sleep and LOC with propofol. The bottom row shows the average RMS for spindle activity (12–15 Hz) with standard error bars across subjects during the slow waves. In spontaneous sleep but not propofol anesthesia, spindle RMS increased during the positive-going slope of the slow waves compared to the negative peak of the slow wave and after the slow wave (P < 0.05, Student's t-test). (D) The mean voltage topography during the propofol events and the spontaneous events. (E) The mean negative-going slopes calculated for each channel for the propofol events and the spontaneous events. The white dot indicates a channel that has a significantly larger negative slope in propofol compared to spontaneous sleep (P < 0.05, SnPM). (F) The mean positive-going slopes calculated for each channel for propofol and spontaneous events.

Figure 3

Slow waves induced by propofol anesthesia are unique events that spread across the cortex. (A, B) Butterfly plots of mastoid-referenced hd-EEG traces for 2 propofol slow waves. (C) Cortical flat maps showing relative current density at the time points indicated by the red lines in A. (D) Cortical flat maps showing relative current density at the time points indicated by red lines in B. INS, insula; AC, anterior cingulate cortex; PCC, posterior cingulate cortex; CIN, cingulate cortex; PreC, precuneus.

Figure 4

Slow waves during propofol anesthesia share similar patterns of origin, propagation, and involvement with spontaneous sleep slow waves but are more spatially blurred in the cortex. (A) Inflated cortical maps showing the average percentage of slow waves to originate in each voxel for propofol and spontaneous sleep. The areas outlined in white show significantly higher percentages of slow wave origins in propofol slow waves than in spontaneous sleep slow waves (SnPM suprathreshold cluster test, P < 0.05). (B) Inflated cortical maps showing the average percent of waves across subjects that propagate through each voxel. (C) Comparison of the mean involvement per voxel between propofol and spontaneous sleep slow waves.

Figure 5

Long-range cortical functional connectivity varies across vigilance state. (A) Two ROIs showing increased gamma power in LOC compared to wakefulness (P < 0.05, SnPM). The frontal ROI is a portion of the anterior cingulate and the posterior ROI is a portion of the posterior cingulate. (B) Phase synchrony as measured by the SAPD metric between the ROIs at various frequencies. *P < 0.05, SnPM.