title: Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness.
abstract: Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α₂-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness.
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Akeju
authors.affiliation: MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States.
authors.forename: Marco L
authors.initials: ML
authors.lastname: Loggia
authors.affiliation: MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Catana
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Pavone
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Rafael
authors.initials: R
authors.lastname: Vazquez
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: James
authors.initials: J
authors.lastname: Rhee
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Violeta
authors.initials: V
authors.lastname: Contreras Ramirez
authors.affiliation: MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Chonde
authors.affiliation: MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States.
authors.forename: David
authors.initials: D
authors.lastname: Izquierdo-Garcia
authors.affiliation: MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States.
authors.forename: Grae
authors.initials: G
authors.lastname: Arabasz
authors.affiliation: MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States.
authors.forename: Shirley
authors.initials: S
authors.lastname: Hsu
authors.affiliation: Clinical Research Center, Massachusetts General Hospital, Boston, United States.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Habeeb
authors.affiliation: MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.affiliation: MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Charlestown, United States.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Napadow
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Purdon
mesh_terms: D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D003243:Consciousness / Q000502:physiology; D020927:Dexmedetomidine / Q000494:pharmacology; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D013788:Thalamus / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D014474:Unconsciousness / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D018712:Analgesics, Non-Narcotic; D020927:Dexmedetomidine
keywords: consciousness; cortico-cortical; default mode network; dexmedetomidine; functional connectivity; human; neuroscience; thalamo-cortical