title: Intrinsic functional connectivity differentiates minimally conscious from unresponsive patients.
abstract: Despite advances in resting state functional magnetic resonance imaging investigations, clinicians remain with the challenge of how to implement this paradigm on an individualized basis. Here, we assessed the clinical relevance of resting state functional magnetic resonance imaging acquisitions in patients with disorders of consciousness by means of a systems-level approach. Three clinical centres collected data from 73 patients in minimally conscious state, vegetative state/unresponsive wakefulness syndrome and coma. The main analysis was performed on the data set coming from one centre (Liège) including 51 patients (26 minimally conscious state, 19 vegetative state/unresponsive wakefulness syndrome, six coma; 15 females; mean age 49 ± 18 years, range 11-87; 16 traumatic, 32 non-traumatic of which 13 anoxic, three mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised was congruent with positron emission tomography scanning. Group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks using a multiple-seed correlation approach. Between-group inferential statistics and machine learning were used to identify each network's capacity to discriminate between patients in minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Data collected from 22 patients scanned in two other centres (Salzburg: 10 minimally conscious state, five vegetative state/unresponsive wakefulness syndrome; New York: five minimally conscious state, one vegetative state/unresponsive wakefulness syndrome, one emerged from minimally conscious state) were used to validate the classification with the selected features. Coma Recovery Scale-Revised total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. All networks had a high discriminative capacity (>80%) for separating patients in a minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Among them, the auditory network was ranked the most highly. The regions of the auditory network which were more functionally connected in patients in minimally conscious state compared to vegetative state/unresponsive wakefulness syndrome encompassed bilateral auditory and visual cortices. Connectivity values in these three regions discriminated congruently 20 of 22 independently assessed patients. Our findings point to the significance of preserved abilities for multisensory integration and top-down processing in minimal consciousness seemingly supported by auditory-visual crossmodal connectivity, and promote the clinical utility of the resting paradigm for single-patient diagnostics.
authors.affiliation: 1 Coma Science Group, GIGA-Research & Cyclotron Research Centre, University and CHU University Hospital of Liège, Liège, Belgium a.demertzi@ulg.ac.be.
authors.forename: Athena
authors.initials: A
authors.lastname: Demertzi
authors.affiliation: 1 Coma Science Group, GIGA-Research & Cyclotron Research Centre, University and CHU University Hospital of Liège, Liège, Belgium.
authors.forename: Georgios
authors.initials: G
authors.lastname: Antonopoulos
authors.affiliation: 1 Coma Science Group, GIGA-Research & Cyclotron Research Centre, University and CHU University Hospital of Liège, Liège, Belgium.
authors.forename: Lizette
authors.initials: L
authors.lastname: Heine
authors.affiliation: 2 Department of Radiology and Citigroup Biomedical Imaging Centre, Weill Cornell Medical College, New York, USA.
authors.forename: Henning U
authors.initials: HU
authors.lastname: Voss
authors.affiliation: 3 Department of Psychology and Centre for Neurocognitive Research, Salzburg, Austria 4 Neuroscience Institute and Centre for Neurocognitive Research, Christian-Doppler-Klinik, Paracelsus Private Medical University, Salzburg, Austria 5 Department of Neurology, Christian-Doppler-Klinik, Paracelsus Private Medical University, Salzburg, Austria.
authors.forename: Julia Sophia
authors.initials: JS
authors.lastname: Crone
authors.affiliation: 6 Martinos Imaging Centre at McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge MA, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: de Los Angeles
authors.affiliation: 7 Cyclotron Research Centre, University of Liège, Liège, Belgium.
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: Bahri
authors.affiliation: 1 Coma Science Group, GIGA-Research & Cyclotron Research Centre, University and CHU University Hospital of Liège, Liège, Belgium.
authors.forename: Carol
authors.initials: C
authors.lastname: Di Perri
authors.affiliation: 8 Department of Algology and Palliative Care, CHU University Hospital of Liège, Liège, Belgium.
authors.forename: Audrey
authors.initials: A
authors.lastname: Vanhaudenhuyse
authors.affiliation: 1 Coma Science Group, GIGA-Research & Cyclotron Research Centre, University and CHU University Hospital of Liège, Liège, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Charland-Verville
authors.affiliation: 3 Department of Psychology and Centre for Neurocognitive Research, Salzburg, Austria 4 Neuroscience Institute and Centre for Neurocognitive Research, Christian-Doppler-Klinik, Paracelsus Private Medical University, Salzburg, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Kronbichler
authors.affiliation: 5 Department of Neurology, Christian-Doppler-Klinik, Paracelsus Private Medical University, Salzburg, Austria.
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
authors.affiliation: 7 Cyclotron Research Centre, University of Liège, Liège, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Phillips
authors.affiliation: 9 Computer Science Department, Universidad Central de Colombia, Bogota, Colombia.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gomez
authors.affiliation: 10 Department of Radiology, CHU University Hospital of Liège, Liège, Belgium.
authors.forename: Luaba
authors.initials: L
authors.lastname: Tshibanda
authors.affiliation: 11 Brain and Mind Institute, Department of Physics and Astronomy, Western University, London, Ontario, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Soddu
authors.affiliation: 12 Department of Neuroscience, Weill Cornell Graduate School of Medical Sciences, New York, USA 13 Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, USA.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Schiff
authors.affiliation: 6 Martinos Imaging Centre at McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge MA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Whitfield-Gabrieli
authors.affiliation: 1 Coma Science Group, GIGA-Research & Cyclotron Research Centre, University and CHU University Hospital of Liège, Liège, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Laureys
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D002648:Child; D003128:Coma / Q000473:pathology; D003244:Consciousness Disorders / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000098:blood supply* / Q000473:pathology; D010100:Oxygen / Q000097:blood; D018458:Persistent Vegetative State / Q000473:pathology*; D012146:Rest; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: anoxia; consciousness; resting state connectivity; sensory systems; traumatic brain injury