Disruption of frontal-parietal communication by ketamine, propofol, and sevoflurane

Anesthesiology. 2013 Jun;118(6):1264-75. doi: 10.1097/ALN.0b013e31829103f5.


Introduction: Directional connectivity from anterior to posterior brain regions (or "feedback" connectivity) has been shown to be inhibited by propofol and sevoflurane. In this study the authors tested the hypothesis that ketamine would also inhibit cortical feedback connectivity in frontoparietal networks.

Methods: Surgical patients (n = 30) were recruited for induction of anesthesia with intravenous ketamine (2 mg/kg); electroencephalography of the frontal and parietal regions was acquired. The authors used normalized symbolic transfer entropy, a computational method based on information theory, to measure directional connectivity across frontal and parietal regions. Statistical analysis of transfer entropy measures was performed with the permutation test and the time-shift test to exclude false-positive connectivity. For comparison, the authors used normalized symbolic transfer entropy to reanalyze electroencephalographic data gathered from surgical patients receiving either propofol (n = 9) or sevoflurane (n = 9) for anesthetic induction.

Results: Ketamine reduced alpha power and increased gamma power, in contrast to both propofol and sevoflurane. During administration of ketamine, feedback connectivity gradually diminished and was significantly inhibited after loss of consciousness (mean ± SD of baseline and anesthesia: 0.0074 ± 0.003 and 0.0055 ± 0.0027; F(5, 179) = 7.785, P < 0.0001). By contrast, feedforward connectivity was preserved during exposure to ketamine (mean ± SD of baseline and anesthesia: 0.0041 ± 0.0015 and 0.0046 ± 0.0018; F(5, 179) = 2.07; P = 0.072). Like ketamine, propofol and sevoflurane selectively inhibited feedback connectivity after anesthetic induction.

Conclusions: Diverse anesthetics disrupt frontal-parietal communication, despite molecular and neurophysiologic differences. Analysis of directional connectivity in frontal-parietal networks could provide a common metric of general anesthesia and insight into the cognitive neuroscience of anesthetic-induced unconsciousness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics / pharmacology
  • Anesthetics, Inhalation / pharmacology
  • Anesthetics, Intravenous / pharmacology
  • Electroencephalography
  • Female
  • Frontal Lobe / drug effects*
  • Humans
  • Ketamine / pharmacology*
  • Male
  • Methyl Ethers / pharmacology*
  • Middle Aged
  • Parietal Lobe / drug effects*
  • Propofol / pharmacology*
  • Sevoflurane
  • Young Adult


  • Analgesics
  • Anesthetics, Inhalation
  • Anesthetics, Intravenous
  • Methyl Ethers
  • Sevoflurane
  • Ketamine
  • Propofol