Normal Brain Response to Propofol in Advance of Recovery from Unresponsive Wakefulness Syndrome

Abstract

Up to 40% of individuals with unresponsive wakefulness syndrome (UWS) actually might be conscious. Recent attempts to detect covert consciousness in behaviorally unresponsive patients via neurophysiological patterns are limited by the need to compare data from brain-injured patients to healthy controls. In this report, we pilot an alternative within-subject approach by using propofol to perturb the brain state of a patient diagnosed with UWS. An auditory stimulation series was presented to the patient before, during, and after exposure to propofol while high-density electroencephalograph (EEG) was recorded. Baseline analysis revealed residual markers in the continuous EEG and event-related potentials (ERPs) that have been associated with conscious processing. However, these markers were significantly distorted by the patient's pathology, challenging the interpretation of their functional significance. Upon exposure to propofol, changes in EEG characteristics were similar to what is seen in healthy individuals and ERPs associated with conscious processing disappeared. At the 1-month follow up, the patient had regained consciousness. We offer three alternative explanations for these results: (1) the patient was covertly consciousness, and was anesthetized by propofol administration; (2) the patient was unconscious, and the observed EEG changes were a propofol-specific phenomenon; and (3) the patient was unconscious, but his brain networks responded normally in a way that heralded the possibility of recovery. These alternatives will be tested in a larger study, and raise the intriguing possibility of using a general anesthetic as a probe of brain states in behaviorally unresponsive patients.

Keywords: anesthesia; consciousness; event-related potentials (ERPs); functional connectivity; propofol; unresponsive wakefulness syndrome/vegetative state (UWS/VS).

Figure 1

Patient computed tomography scan recorded 43 days post-trauma.

Figure 2

Event-related potential (ERP) analysis for baseline, propofol exposure and post-exposure periods. Waveforms (A) and subtraction waves (B–D) are presented for electrodes Fz (blue), Cz (purple) and C4 (red). Time periods where significant differences occurred are indicated by a color-matched bar above the waveform plot. Blue*, significant differences in Fz waveforms; Purple*, significant differences in Cz waveforms.

Figure 3

Analysis of continuous electroencephalograph (EEG) for (A) baseline, propofol-exposure and post-exposure periods using (B) spectrogram; (C) alpha topographic power map; (D) phase-amplitude coupling; (E) phase lag index; (F) directed phase lag index; and (G) network hub location.