Evaluating individual sensitivity to propofol through EEG complexity and information integration: from neural dynamics to precision anesthesia

<i>Objective.</i>Understanding the neural mechanisms underlying consciousness during anesthesia is critical for advancing anesthesiology and neuroscience. However, given the high variability in individual sensitivity to anesthetic agents, accurately elucidating the relationship between individual characteristics and drug responses is also crucial for ensuring clinical anesthesia safety.<i>Approach.</i>This study utilized high-density EEG data from 20 participants under various propofol-induced sedation states. We stratified participants into low- and high-sensitivity cohorts based on their behavioral responsiveness to standardized auditory stimuli during sedation. Then the metrics such as permutation entropy (PE), phase-lag entropy (PLE), and permutation cross mutual information (PCMI) were analyzed to evaluate neural complexity, the diversity of connectivity, and information integration. Machine learning models, including support vector machines (SVM), were applied to classify individual sensitivity to propofol, with SHapley Additive exPlanations (SHAP) analysis providing feature interpretability.<i>Main results.</i>Subjects were divided into high-performance (low-sensitivity) group and low-performance (high-sensitivity) group based on the accuracy of their responses to auditory stimuli. In the moderate sedation, the high-performance group exhibited elevated PE, increased PLE in alpha band and the decreased PLE in beta band, and decreased PCMI in alpha band. In the resting-state, we extracted 18 metrics that were significantly different between the two groups. Using these resting-state metrics as features, the SVM model achieved an accuracy of 87.5% ± 0.06% in classifying individuals into high- or low-sensitivity groups. SHAP analysis results indicated that the features, including the PLE value of temporal in alpha band (<i>α</i>-PLET) and the PCMI value of frontal-parietal in beta band (<i>β</i>-PCMIFP), were identified as robust predictors of propofol sensitivity, with high weights across various models.<i>Significance.</i>This study highlights the differential neural dynamics induced by propofol across performance groups. This study highlights that resting-state metrics can predict individual sensitivity to propofol. Our findings provide preliminary insights into the potential utility of pre-anesthesia brain state assessments in predicting individual propofol sensitivity, which may contribute to the development of more precise personalized anesthesia plans.