title: Isoflurane induces dose-dependent alterations in the cortical connectivity profiles and dynamic properties of the brain's functional architecture.
abstract: Despite their widespread use, the effect of anesthetic agents on the brain's functional architecture remains poorly understood. This is particularly true of alterations that occur beyond the point of induced unconsciousness. Here, we examined the distributed intrinsic connectivity of macaques across six isoflurane levels using resting-state functional MRI (fMRI) following the loss of consciousness. The results from multiple analysis strategies showed stable functional connectivity (FC) patterns between 1.00% and 1.50% suggesting this as a suitable range for anesthetized nonhuman primate resting-state investigations. Dose-dependent effects were evident at moderate to high dosages showing substantial alteration of the functional topology and a decrease or complete loss of interhemispheric cortical FC strength including that of contralateral homologues. The assessment of dynamic FC patterns revealed that the functional repertoire of brain states is related to anesthesia depth and most strikingly, that the number of state transitions linearly decreases with increased isoflurane dosage. Taken together, the results indicate dose-specific spatial and temporal alterations of FC that occur beyond the typically defined endpoint of consciousness. Future work will be necessary to determine how these findings generalize across anesthetic types and extend to the transition between consciousness and unconsciousness.
authors.affiliation: Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; Department of Psychology, Harvard University, Cambridge, Massachusetts; Center for Brain Science, Harvard University, Cambridge, Massachusetts.
authors.forename: R Matthew
authors.initials: RM
authors.lastname: Hutchison
authors.forename: Melina
authors.initials: M
authors.lastname: Hutchison
authors.forename: Kathryn Y
authors.initials: KY
authors.lastname: Manning
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Menon
authors.forename: Stefan
authors.initials: S
authors.lastname: Everling
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D005260:Female; D007530:Isoflurane / Q000494:pharmacology*; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D012146:Rest; D012815:Signal Processing, Computer-Assisted; D014474:Unconsciousness / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane
keywords: anesthesia; connectivity; consciousness; functional repertoire resting-state functional MRI