Alpha band frontal connectivity is a state-specific electroencephalographic correlate of unresponsiveness during exposure to dexmedetomidine and propofol

Br J Anaesth. 2020 Oct;125(4):518-528. doi: 10.1016/j.bja.2020.05.068. Epub 2020 Aug 7.

Abstract

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.

Keywords: anaesthesia; dexmedetomidine; directed connectivity; electroencephalogram; functional connectivity; propofol; responsiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dexmedetomidine / pharmacology*
  • Dose-Response Relationship, Drug
  • Electroencephalography / drug effects*
  • Frontal Lobe / drug effects
  • Frontal Lobe / physiology
  • Humans
  • Male
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology
  • Propofol / pharmacology*

Substances

  • Dexmedetomidine
  • Propofol

Associated data

  • ClinicalTrials.gov/NCT01889004