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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., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22-59% of the participants. Thus, the Bayesian method was the most liberal and also showed the greatest concordance between the experimental paradigms (active/passive). ANOVA detected significant effect only in cases with converging evidence from other methods. The t-CWT and cluster-based method were the most conservative methods. As we show in the current study, different analysis methods provide results that do not completely overlap. The method of choice for determining the presence of an ERP component at single-subject level thus remains unresolved. Relying on a single statistical method may not be sufficient for drawing conclusions on single-subject ERPs., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Differentiating drug-related changes and state-related changes on the electroencephalogram during anesthetic-induced unconsciousness has remained a challenge. To distinguish these, we designed a rigorous experimental protocol with two drugs known to have distinct molecular mechanisms of action. We hypothesized that drug- and state-related changes can be separated., Methods: Forty-seven healthy participants were randomized to receive dexmedetomidine (n = 23) or propofol (n = 24) as target-controlled infusions until loss of responsiveness. Then, an attempt was made to arouse the participant to regain responsiveness while keeping the drug infusion constant. Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness. We conducted statistical comparisons between the drugs and different states of consciousness for spectral bandwidths, and observed how drug-induced electroencephalogram patterns reversed upon awakening. Cross-frequency coupling was also analyzed between slow-wave phase and alpha power., Results: Eighteen (78%) and 10 (42%) subjects were arousable during the constant drug infusion in the dexmedetomidine and propofol groups, respectively (P = 0.011 between the drugs). Corresponding with deepening anesthetic level, slow-wave power increased, and a state-dependent alpha anteriorization was detected with both drugs, especially with propofol. The slow-wave and frontal alpha activities were momentarily disrupted as the subjects regained responsiveness at awakening. Negative phase-amplitude coupling before and during loss of responsiveness frontally and positive coupling during the highest drug concentration posteriorly were observed in the propofol but not in the dexmedetomidine group., Conclusions: Electroencephalogram effects of dexmedetomidine and propofol are strongly drug- and state-dependent. Changes in slow-wave and alpha activity seemed to best detect different states of consciousness.