Background Propofol exposure can produce heterogenous neural responses, from the expected suppression to transient paradoxical excitation. EEG measures of signal complexity and entropy have emerged as reliable markers of consciousness, but different types of complexity and entropy measures are often conflated. We used Type I and II complexity measures on the Complexity–Entropy Causal Plane (CECP) to characterize divergent neural trajectories during propofol-induced loss of consciousness. We hypothesized that paradoxical excitation is reflected in both Type I and Type II complexity; that divergent trajectories on the CECP separate paradoxical excitation from suppression; and that baseline EEG complexity is associated with susceptibility to propofol.

Methods We analyzed EEG data from two independent cohorts of healthy adults receiving propofol: the Chennu dataset (n = 20), which included resting-state baseline, mild, and moderate sedation, followed by a recovery period; and the RecCognition dataset (n = 8), which used escalating infusions from baseline to deep sedation. For each participant and sedation level, we extracted Lempel–Ziv Complexity (LZC; Type I) and Statistical Complexity (SC; Type II) and projected them onto the CECP. Pearson correlations related baseline SC to changes in SC during moderate sedation; behavioral responsiveness; effect-site propofol concentration; and time-to-loss-of-consciousness.

Results At moderate sedation, participants who remained responsive showed paradoxical increases in LZC and decreases in SC, whereas unresponsive participants exhibited the opposite pattern. Baseline SC correlated negatively with both the change in SC (r = –0.88) and behavioural responsiveness, indicating that intrinsic brain dynamics influence individual susceptibility to sedation. CECP trajectories revealed a reproducible inflection point demarcating paradoxical excitation from suppression.

Conclusions Mapping EEG trajectories on the CECP bridges anesthetic state transitions with underlying neural dynamics. Baseline neural complexity indexes individual sensitivity to propofol, determining whether brain dynamics transiently enter excitation or direct suppression.

The authors have declared no competing interest.

NCT01911195

CM received funding from Fondation pour la recherche medicale (SPF202409019374). SBM is supported through the Natural Sciences and Engineering Research Council (NSERC) of Canada Discovery Grant (RGPIN-2023-03619); and a Canada Research Chair of Consciousness and Personhood Technology.

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