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Depth of sedation with dexmedetomidine modulates cortical excitability non-linearly

Background Cortical excitability changes across conscious states, being higher in unconsciousness compared to normal wakefulness. Anaesthesia offers controlled manipulation to investigate conscious processes and underlying brain dynamics. Among commonly used anaesthetic agents, dexmedetomidine (DEX) effects are not completely known. In this study, we investigated cortical excitability as a function of DEX sedation depth. Methods Transcranial magnetic stimulation coupled with electroencephalography was recorded in 20 healthy subjects undergoing DEX sedation in four conditions (baseline, light sedation, deep sedation, recovery). Frontal and parietal cortices were stimulated using a neuronavigation system. Cortical excitability was inferred by slope, amplitude, positive and negative peak latencies of the first component (0-30 ms) of the TMS-evoked potential. Four Generalized Linear Mixed Models (GLMM) were used to test the effect of condition and brain region over cortical excitability. Results Dexmedetomidine modulated amplitude (P<0.001), slope (P=0.0001) and positive peak (P=0.042), while the targeted brain region affected amplitude (P<0.001), slope (P<0.001), and negative peak (P=0.001). The interaction between dexmedetomidine and region had an effect over amplitude (P=0.004), and slope (P=0.009) such that cortical excitability was higher during all conditions where DEX was present as compared to the baseline. Conclusions Cortical excitability changes non-linearly as a function of the depth of DEX sedation, with a paradoxical non dose-dependent increase. The effect is region-specific, being present in the frontal but not in the parietal region. Future research should extend the current results with other anaesthetics to better understand the link between cortical excitability and depth of sedation.