• Annalotta Scheinin, Roosa E Kallionpää, Duan Li, Minna Kallioinen, Kaike Kaisti, Jaakko Långsjö, Anu Maksimow, Tero Vahlberg, Katja Valli, George A Mashour, Antti Revonsuo, and Harry Scheinin.
• From the Turku PET Centre, University of Turku and the Hospital District of Southwest Finland, Turku, Finland (A.S., K.K., J.L., A.M., H.S.) the Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, Turku, Finland (A.S., R.E.K., M.K., A.M., H.S.) the Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center (R.E.K., K.V., A.R.) the Department of Pharmacology, Drug Development and Therapeutics (H.S.) University of Turku, Turku, Finland; the Department of Anesthesiology, Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, Michigan (D.L., G.A.M.) the Department of Anesthesiology and Intensive Care, Oulu University Hospital, Oulu, Finland (K.K.) the Department of Intensive Care, Tampere University Hospital, Tampere, Finland (J.L.) the Department of Clinical Medicine, Biostatistics, University of Turku and Turku University Hospital, Turku, Finland (T.V.) the Department of Cognitive Neuroscience and Philosophy, School of Bioscience, University of Skövde, Skövde, Sweden (K.V., A.R.).
• Anesthesiology. 2018 Jul 1; 129 (1): 22-36.

BackgroundDifferentiating 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.MethodsForty-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.ResultsEighteen (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.ConclusionsElectroencephalogram 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.

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