title: Anesthesia-induced Suppression of Human Dorsal Anterior Insula Responsivity at Loss of Volitional Behavioral Response.
abstract: BACKGROUND
  It has been postulated that a small cortical region could be responsible for the loss of behavioral responsiveness (LOBR) during general anesthesia. The authors hypothesize that any brain region demonstrating reduced activation to multisensory external stimuli around LOBR represents a key cortical gate underlying this transition. Furthermore, the authors hypothesize that this localized suppression is associated with breakdown in frontoparietal communication.
  
  
  METHODS
  During both simultaneous electroencephalography and functional magnetic resonance imaging (FMRI) and electroencephalography data acquisition, 15 healthy volunteers experienced an ultraslow induction with propofol anesthesia while a paradigm of multisensory stimulation (i.e., auditory tones, words, and noxious pain stimuli) was presented. The authors performed separate analyses to identify changes in (1) stimulus-evoked activity, (2) functional connectivity, and (3) frontoparietal synchrony associated with LOBR.
  
  
  RESULTS
  By using an FMRI conjunction analysis, the authors demonstrated that stimulus-evoked activity was suppressed in the right dorsal anterior insula cortex (dAIC) to all sensory modalities around LOBR. Furthermore, the authors found that the dAIC had reduced functional connectivity with the frontoparietal regions, specifically the dorsolateral prefrontal cortex and inferior parietal lobule, after LOBR. Finally, reductions in the electroencephalography power synchrony between electrodes located in these frontoparietal regions were observed in the same subjects after LOBR.
  
  
  CONCLUSIONS
  The authors conclude that the dAIC is a potential cortical gate responsible for LOBR. Suppression of dAIC activity around LOBR was associated with disruption in the frontoparietal networks that was measurable using both electroencephalography synchrony and FMRI connectivity analyses.
authors.affiliation: Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom (C.E.W., M.S., R.N.M., R.R., S.J., I.T.); Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom (C.E.W., M.S., R.N.M., R.R., J.S., I.T.); Department of Anaesthetics, University of Edinburgh, Edinburgh, United Kingdom (M.S.); and Department of Anaesthesia, University of Auckland, Waikato Hospital, Hamilton, New Zealand (J.S.).
authors.forename: Catherine Elizabeth
authors.initials: CE
authors.lastname: Warnaby
authors.forename: Marta
authors.initials: M
authors.lastname: Seretny
authors.forename: Roísín
authors.initials: R
authors.lastname: Ní Mhuircheartaigh
authors.forename: Richard
authors.initials: R
authors.lastname: Rogers
authors.forename: Saad
authors.initials: S
authors.lastname: Jbabdi
authors.forename: Jamie
authors.initials: J
authors.lastname: Sleigh
authors.forename: Irene
authors.initials: I
authors.lastname: Tracey
mesh_terms: D000328:Adult; D000768:Anesthesia, General; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001307:Auditory Perception / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D058748:Pain Perception / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D012016:Reference Values; D055815:Young Adult
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol