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Background: Coherent alpha electroencephalogram (EEG) rhythms in the frontal cortex have been correlated with the hypnotic effects of propofol and dexmedetomidine, but less is known about frontal connectivity as a state-specific correlate of unresponsiveness as compared with long-range connectivity. We aimed to distinguish dose- and state-dependent effects of dexmedetomidine and propofol on EEG connectivity.Methods: Forty-seven healthy males received either dexmedetomidine (n=23) or propofol (n=24) as target-controlled infusion with stepwise increments until loss of responsiveness (LOR). We attempted to arouse participants during constant dosing (return of responsiveness [ROR]), and the target concentration was then increased 50% to achieve presumed loss of consciousness. We collected 64-channel EEG data and prefrontal-frontal and anterior-posterior functional connectivity in the alpha band (8-14 Hz) was measured using coherence and weighted phase lag index (wPLI). Directed connectivity was measured with directed phase lag index (dPLI).Results: Prefrontal-frontal EEG-based connectivity discriminated the states at the different drug concentrations. At ROR, prefrontal-frontal connectivity reversed to the level observed before LOR, indicating that connectivity changes were related to unresponsiveness rather than drug concentration. Unresponsiveness was associated with emergence of frontal-to-prefrontal dominance (dPLI: -0.13 to -0.40) in contrast to baseline (dPLI: 0.01-0.02). Coherence, wPLI, and dPLI had similar capability to discriminate the states that differed in terms of responsiveness and drug concentration. In contrast, anterior-posterior connectivity in the alpha band did not differentiate LOR and ROR.Conclusions: Local prefrontal-frontal EEG-based connectivity reflects unresponsiveness induced by propofol or dexmedetomidine, suggesting its utility in monitoring the anaesthetised state with these agents.Clinical Trial Registration: NCT01889004. [ABSTRACT FROM AUTHOR]

Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level. We compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N =39) received dexmedetomidine (n =20) or propofol (n =19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N =37) were also later interviewed after NREM sleep awakenings. Most subjects were rousable, with no difference between anaesthetic agents (P =0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P =0.007) and propofol (P =0.002) but not with recall of experiences in either drug group (dexmedetomidine: P =0.543; propofol: P =0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P =0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P >0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P =0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P =0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state. Anaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content. Clinical trial registration. This study was part of a larger study registered at ClinicalTrials.gov (NCT01889004). [ABSTRACT FROM AUTHOR]