Background and Goal of Study: Current depth-of-anesthesia monitors cannot reliably differentiate unconsciousness from
deep sedation. In the search for better methods, we compared connectivity changes induced by dexmedetomidine and
propofol until loss of consciousness (LOC) in a highly standardized setting.
Materials and methods: Forty-seven healthy male subjects were randomized to receive dexmedetomidine (n=23) or
propofol (n=24) through TCI, starting from 1.0 ng/ml for dexmedetomidine and 1.0 μg/ml for propofol, and then titrated with
small increments at 7 min intervals until loss of responsiveness (LOR). LOR was defined as subjects' inability to press
handles upon requests. After achieving LOR, an attempt was made to awaken the subjects with a loud voice or mild
physical stimulation without changing the infusion. After possible awakening (return of responsiveness, ROR), the subjects
were permitted to subside (or maintain if unarousable) unresponsive, and the target was increased by 50 % to achieve
LOC. EEG signal was collected, and EEG spectra and weighted (wPLI) and directed phase lag index (dPLI) between
different brain areas processed offline using custom-written functions in MATLAB.
Results and discussion: The mean (SD) measured drug conc. for LOR was 2.10 (0.67) ng/ml dexmedetomidine and 1.67
(0.62) μg/ml for propofol. Eighteen (78%) and 10 (42%) subjects were arousable from the LOR state in the
dexmedetomidine and propofol groups, respectively. Apparent connectivity changes were seen in the alpha band (8-14
Hz), and topographic analysis revealed that especially in (pre)frontal areas the the measures showed state dependent
changes. Prefrontal-frontal wPLI increased and dPLI turned more negative (suggesting that prefrontal “lagged”) towards
LOC, and were reverted in subjects who could be aroused during constant infusion (p< 0.001, Figure). These findings are
intriguing as dexmedetomidine does not induce strong anteriorization or apparent hyper-coherence of the alpha band like
propofol.

Alpha band connectivity of the frontal EEG associates with consciousness during target controlled infusion of dexmedetomidine and propofol in healthy subjects