title: GABAA circuit mechanisms are associated with ether anesthesia-induced unconsciousness.
abstract: OBJECTIVE
  An emerging paradigm for understanding how anesthetics induce altered arousal is relating receptor targeting in specific neural circuits to electroencephalogram (EEG) activity. Enhanced gamma amino-butyric acid A (GABAA) inhibitory post-synaptic currents (IPSCs) manifest with large-amplitude slow (0.1-1Hz) and frontally coherent alpha (8-12Hz) EEG oscillations during general anesthesia. Therefore, we investigated the EEG signatures of modern day derivatives of ether (MDDE) anesthesia to assess the extent to which we could obtain insights into MDDE anesthetic mechanisms.
  
  
  METHODS
  We retrospectively studied cases from our database in which patients received isoflurane anesthesia vs. isoflurane/ketamine anesthesia (n=10 each) or desflurane anesthesia vs. desflurane/ketamine anesthesia (n=9 each). We analyzed the EEG recordings with spectral power and coherence methods.
  
  
  RESULTS
  Similar to known GABAA circuit level mechanisms, we found that MDDE anesthesia induced large amplitude slow and frontally coherent alpha oscillations. Additionally, MDDE anesthesia also induced frontally coherent theta (4-8Hz) oscillations. Reduction of GABAergic IPSCs with ketamine resulted in beta/gamma (13-40Hz) oscillations, and significantly reduced MDDE anesthesia-induced slow, theta and alpha oscillation power.
  
  
  CONCLUSIONS
  Large amplitude slow oscillations and coherent alpha and theta oscillations are moderated by ketamine during MDDE anesthesia.
  
  
  CONCLUSIONS
  These observations are consistent with the notion that GABAA circuit-level mechanisms are associated with MDDE anesthesia-induced unconsciousness.
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: oluwaseun.akeju@mgh.harvard.edu.
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Akeju
authors.affiliation: Harvard Medical School, Boston, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Allison E
authors.initials: AE
authors.lastname: Hamilos
authors.affiliation: Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Song
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Pavone
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Purdon
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
mesh_terms: D000328:Adult; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D058256:Brain Waves / Q000187:drug effects*; D000077335:Desflurane; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology*; D006801:Humans; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D018685:Anesthetics, Inhalation; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D007649:Ketamine; D000077335:Desflurane; D007530:Isoflurane
keywords: Alpha oscillations; Desflurane; EEG; Isoflurane; Ketamine; Slow oscillations