title: Multimodal study of default-mode network integrity in disorders of consciousness.
abstract: OBJECTIVE
  Understanding residual brain function in disorders of consciousness poses extraordinary challenges, and imaging examinations are needed to complement clinical assessment. The default-mode network (DMN) is known to be dysfunctional, although correlation with level of consciousness remains controversial. We investigated DMN activity with resting-state functional magnetic resonance imaging (rs-fMRI), alongside its structural and metabolic integrity, aiming to elucidate the corresponding associations with clinical assessment.
  
  
  METHODS
  We enrolled 119 consecutive patients: 72 in a vegetative state/unresponsive wakefulness state (VS/UWS), 36 in a minimally conscious state (MCS), and 11 with severe disability. All underwent structural MRI and rs-fMRI, and a subset also underwent18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Data were analyzed with manual and automatic approaches, in relation to diagnosis and clinical score.
  
  
  RESULTS
  Excluding the quartile with largest head movement, DMN activity was decreased in VS/UWS compared to MCS, and correlated with clinical score. Independent-component and seed-based analyses provided similar results, although the latter and their combination were most informative. Structural MRI and FDG-PET were less sensitive to head movement and had better diagnostic accuracy than rs-fMRI only when all cases were included. rs-fMRI indicated relatively preserved DMN activity in a small subset of VS/UWS patients, 2 of whom evolved to MCS. The integrity of the left hemisphere appears to be predictive of a better clinical status.
  
  
  CONCLUSIONS
  rs-fMRI of the DMN is sensitive to clinical severity. The effect is consistent across data analysis approaches, but heavily dependent on head movement. rs-fMRI could be informative in detecting residual DMN activity for those patients who remain relatively still during scanning and whose diagnosis is uncertain. Ann Neurol 2016;79:841-853.
authors.affiliation: Neuroradiology Unit, Carlo Besta Institute of Hospitalization and Scientific Care Foundation Neurological Institute, Milan, Italy.|Scientific Department, Carlo Besta Institute of Hospitalization and Scientific Care Foundation Neurological Institute, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rosazza
authors.affiliation: Neuroradiology Unit, Carlo Besta Institute of Hospitalization and Scientific Care Foundation Neurological Institute, Milan, Italy.
authors.forename: Adrian
authors.initials: A
authors.lastname: Andronache
authors.affiliation: Neurology, Public Health, Disability Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Sattin
authors.affiliation: Neuroradiology Unit, Carlo Besta Institute of Hospitalization and Scientific Care Foundation Neurological Institute, Milan, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bruzzone
authors.affiliation: Department of Nuclear Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Marotta
authors.affiliation: Neuroradiology Unit, Carlo Besta Institute of Hospitalization and Scientific Care Foundation Neurological Institute, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Nigri
authors.affiliation: Neuroradiology Unit, Carlo Besta Institute of Hospitalization and Scientific Care Foundation Neurological Institute, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferraro
authors.affiliation: Department of Neurophysiology, Epilepsy Center, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi Sebastiano
authors.affiliation: Laboratory of Methodology for Biomedical Research, Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Porcu
authors.affiliation: Cerebrovascular Disease Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bersano
authors.affiliation: Department of Nuclear Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Benti
authors.affiliation: Neurology, Public Health, Disability Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Leonardi
authors.affiliation: Neuroradiology Unit, Carlo Besta Institute of Hospitalization and Scientific Care Foundation Neurological Institute, Milan, Italy.
authors.forename: Ludovico
authors.initials: L
authors.lastname: D'Incerti
authors.affiliation: Scientific Department, Carlo Besta Institute of Hospitalization and Scientific Care Foundation Neurological Institute, Milan, Italy.
authors.forename: Ludovico
authors.initials: L
authors.lastname: Minati