title: Disruption of posteromedial large-scale neural communication predicts recovery from coma.
abstract: OBJECTIVE
  We hypothesize that the major consciousness deficit observed in coma is due to the breakdown of long-range neuronal communication supported by precuneus and posterior cingulate cortex (PCC), and that prognosis depends on a specific connectivity pattern in these networks.
  
  
  METHODS
  We compared 27 prospectively recruited comatose patients who had severe brain injury (Glasgow Coma Scale score <8; 14 traumatic and 13 anoxic cases) with 14 age-matched healthy participants. Standardized clinical assessment and fMRI were performed on average 4 ± 2 days after withdrawal of sedation. Analysis of resting-state fMRI connectivity involved a hypothesis-driven, region of interest-based strategy. We assessed patient outcome after 3 months using the Coma Recovery Scale-Revised (CRS-R).
  
  
  RESULTS
  Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with PCC, globally notwithstanding etiology. The functional connectivity strength between PCC and medial prefrontal cortex (mPFC) was significantly different between comatose patients who went on to recover and those who eventually scored an unfavorable outcome 3 months after brain injury (Kruskal-Wallis test, p < 0.001; linear regression between CRS-R and PCC-mPFC activity coupling at rest, Spearman ρ = 0.93, p < 0.003).
  
  
  CONCLUSIONS
  In both etiology groups (traumatic and anoxic), changes in the connectivity of PCC-centered, spontaneously synchronized, large-scale networks account for the loss of external and internal self-centered awareness observed during coma. Sparing of functional connectivity between PCC and mPFC may predict patient outcome, and further studies are needed to substantiate this potential prognosis biomarker.
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland. silva.s@chu-toulouse.fr.
authors.forename: Stein
authors.initials: S
authors.lastname: Silva
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: de Pasquale
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland.
authors.forename: Corine
authors.initials: C
authors.lastname: Vuillaume
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Riu
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Loubinoux
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Geeraerts
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Seguin
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bounes
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fourcade
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Demonet
authors.affiliation: From the Critical Care Unit (S.S., B.R.), Critical Care and Anaesthesiology Department (S.S., C.V., B.R., T.G., T.S., O.F.), and SAMU 31 (V.B.), University Teaching Hospital of Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9; INSERM U825 (S.S., C.V., I.L., P.P.), CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France; Department of Radiology (F.d.P.), Santa Lucia Foundation, Rome; ITAB (F.d.P.), Department of Neuroscience Imaging and Clinical Science, G. D'Annunzio University, Chieti, Italy; and Leenaards Memory Center (J.-F.D.), Department of Clinical Neuroscience CHUV and University of Lausanne, Switzerland.
authors.forename: Patrice
authors.initials: P
authors.lastname: Péran
mesh_terms: D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D003128:Coma / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism*; D003243:Consciousness / Q000502:physiology; D005260:Female; D015600:Glasgow Coma Scale; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000378:metabolism*; D010296:Parietal Lobe / Q000378:metabolism*; D011237:Predictive Value of Tests; D020127:Recovery of Function / Q000502:physiology*