title: Intrinsic Functional Connectivity Patterns Predict Consciousness Level and Recovery Outcome in Acquired Brain Injury.
abstract: For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI.
  
  
  CONCLUSIONS
  Varying degrees of consciousness loss and recovery are commonly observed in acquired brain injury patients, yet the underlying neurobiological mechanisms remain elusive. Using a large sample of patients with varying degrees of consciousness loss, we demonstrate that intrinsic functional connectivity strength in many brain regions, especially in the posterior cingulate cortex and precuneus, significantly correlated with consciousness level and recovery outcome. We further demonstrate that the functional connectivity pattern of these regions can predict patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%. Our study thus provides potentially important biomarkers of acquired brain injury in clinical diagnosis, prediction of recovery outcome, and decision making for treatment strategies for patients with severe loss of consciousness.
authors.affiliation: Departments of Neurosurgery and.
authors.forename: Xuehai
authors.initials: X
authors.lastname: Wu
authors.affiliation: Center for MRI Research and Beijing City Key Laboratory of Medical Physics and Engineering, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Departments of Neurosurgery and.
authors.forename: Jin
authors.identifier: http://orcid.org/0000-0002-0504-960X
authors.initials: J
authors.lastname: Hu
authors.affiliation: Radiology, Huashan Hospital, Fudan University, Shanghai 200040, People's Republic of China.
authors.forename: Weijun
authors.identifier: http://orcid.org/0000-0002-3726-5243
authors.initials: W
authors.lastname: Tang
authors.affiliation: Departments of Neurosurgery and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Neurosurgical Department, Shanghai No.10 Hospital, Shanghai 200072, People's Republic of China.
authors.forename: Liang
authors.identifier: http://orcid.org/0000-0002-6325-4636
authors.initials: L
authors.lastname: Gao
authors.affiliation: Departments of Neurosurgery and.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Departments of Neurosurgery and.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Departments of Neurosurgery and.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Neurosurgical Department, Huajia Hospital, Shanghai 200433, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Neurosurgical Department, Huajia Hospital, Shanghai 200433, People's Republic of China.
authors.forename: Yaojun
authors.identifier: http://orcid.org/0000-0001-7537-1496
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Neurosurgical Department, Huajia Hospital, Shanghai 200433, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, People's Republic of China, Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing 100875, People's Republic of China.
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Center for MRI Research and Beijing City Key Laboratory of Medical Physics and Engineering, Peking University, Beijing 100871, People's Republic of China, McGovern Institute for Brain Research, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Gao
authors.affiliation: Center for Cognition and Brain Disorders and The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang 310015, People's Republic of China.
authors.forename: Xuchu
authors.identifier: http://orcid.org/0000-0001-5266-160X
authors.initials: X
authors.lastname: Weng
authors.affiliation: Departments of Neurosurgery and lfzhouc@126.com yihongyang@mail.nih.gov.
authors.forename: Liangfu
authors.identifier: http://orcid.org/0000-0002-0675-7720
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario K1Z 7K4, Canada.
authors.forename: Georg
authors.initials: G
authors.lastname: Northoff
authors.affiliation: Spaulding Rehabilitation Hospital and Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts 02129, and.
authors.forename: Joseph T
authors.identifier: http://orcid.org/0000-0002-7916-9698
authors.initials: JT
authors.lastname: Giacino
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, People's Republic of China, Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing 100875, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224 lfzhouc@126.com yihongyang@mail.nih.gov.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001925:Brain Damage, Chronic / Q000209:etiology / Q000503:physiopathology / Q000523:psychology / Q000534:rehabilitation; D001930:Brain Injuries / Q000503:physiopathology* / Q000523:psychology / Q000534:rehabilitation; D063132:Connectome; D003243:Consciousness / Q000502:physiology; D003244:Consciousness Disorders / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology / Q000534:rehabilitation; D005260:Female; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D010296:Parietal Lobe / Q000503:physiopathology*; D011379:Prognosis; D020127:Recovery of Function; D016896:Treatment Outcome; D055815:Young Adult
keywords: acquired brain injury; hub; posterior cingulate cortex/precuneus; prediction; recovery outcome; resting state fMRI