Registered report: Common signatures of loss of responsiveness in human and macaque electrocorticogram

Propofol anesthesia induces loss of responsiveness in both humans and macaque monkeys, and common brain-activity features in frontal recordings distinguish awake from unresponsive states across species. Analysis of over 7000 time-series features from electrocorticography data identified univariate metrics that generalize across sessions and species, particularly in frontal regions. However, distinguishing loss of responsiveness from loss of consciousness proved challenging: frontal, temporal, and parietal recordings all contained features sensitive to conscious experience when comparing sedated yet conscious states to unresponsive states. The findings support cross-species commonality in neural signatures of propofol-induced unresponsiveness but highlight the difficulty of isolating features that track consciousness itself rather than mere responsiveness.

Study at a glance

Abstract

Despite the widespread application of general anesthesia since the 19th century, a fundamental understanding of its operating principle and a reliable metric of consciousness remains elusive. We here analyze Loss of Responsiveness (LoR) induced by propofol anesthesia in humans and macaque monkeys. Through application of “highly comparable time series analysis” (hctsa) over 7000 features, we aim to identify LoR metrics common to both humans and macaque monkeys. In Stage 1 analysis, we trained a nearest median classifier using 200 ms data epochs using one macaque individual, and evaluated its classification accuracy on human intracranial data, recorded from one participant. This analysis suggested the existence of univariate features capable of discriminating between awake and propofol-induced unresponsive states in both species. Stage 2 extended the analysis to additional macaque and human recordings to evaluate cross-session and cross-species generalization. We identified many hctsa features that commonly distinguished awake from unresponsive states across sessions and species, in the frontal, but not in parietal and temporal, recordings. In exploratory analyses, we aimed to distinguish loss of responsiveness from consciousness, by additionally analyzing human data under sedated yet conscious state in a within-subject manner. This analysis revealed that frontal, temporal and parietal recordings contain similarly sensitive features and channels as signatures of consciousness. These results support the existence of ECoG time-series features associated with propofol-induced loss of responsiveness across humans and macaques, while also highlighting the challenge to determine whether such features specifically track conscious experience rather than responsiveness.