Introduction Directional connectivity from anterior to posterior brain regions (or “feedback” connectivity) has been shown to be inhibited by the gamma-aminobutyric acid agonists propofol and sevoflurane. In this study we 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 (2mg/kg); electroencephalography of the frontal and parietal regions was acquired. We used normalized symbolic transfer entropy, a computational method based in 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, we 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 & anesthesia: 0.0074±0.003 & 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 & anesthesia: 0.0041±0.0015 & 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 Three major classes of 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.

BackgroundPropofol and barbiturates are both known to protect cells of several organs against ischemia/reperfusion injury, but there are few reports on any possible protective effects on human hepatocytes. We investigated the activities of both agents on human hepatic SNU761 cells under hydrogen peroxide (H2O2)-induced oxidative stress.MethodsTo determine whether propofol and pentobarbital protect hepatocytes from H2O2-induced toxicity, we used SNU761 cells, a human hepatocellular carcinoma (HCC) cell line. Cells were pretreated with different dosages (1, 10, 50 µM) of propofol or pentobarbital (1, 10, 50, 100, 400 µM) 30 min before H2O2 application. Lactate dehydrogenase (LDH) was measured to assess and quantify cell death. To determine the nature of cell death, treated hepatocytes were doubly stained with fluorescein isothiocyanate (FITC)-labeled Annexin V and propidium iodide (PI), and analyzed by flow cytometry.ResultsPretreatment with propofol, but not pentobarbital, suppressed H2O2-induced LDH release. In Annexin V-FITC/PI binding analysis, propofol decreased the number of necrotic and late apoptotic cells, but no significant decreases in such cell numbers were seen when pentobarbital was used.ConclusionsUnlike pentobarbital, propofol, at clinical concentrations, protected SNU-761 HCC cells against oxidative stress.