title: GABAA receptor deficits predict recovery in patients with disorders of consciousness: A preliminary multimodal [(11) C]Flumazenil PET and fMRI study.
abstract: OBJECTIVE
  Disorders of consciousness (DoC)-that is, unresponsive wakefulness syndrome/vegetative state and minimally conscious state-are debilitating conditions for which no reliable markers of consciousness recovery have yet been identified. Evidence points to the GABAergic system being altered in DoC, making it a potential target as such a marker.
  
  
  METHODS
  In our preliminary study, we used [(11) C]Flumazenil positron emission tomography to establish global GABAA receptor binding potential values and the local-to-global (LTG) ratio of these for specific regions. These values were then compared between DoC patients and healthy controls. In addition, they were correlated with behavioral improvements for the patients between the time of scanning and 3 months later. Functional magnetic resonance imaging resting-state functional connectivity was also calculated and the same comparisons made.
  
  
  RESULTS
  lobal GABAA receptor binding was reduced in DoC, as was the LTG ratio in specifically the supragenual anterior cingulate. Both of these measures correlated with behavioral improvement after 3 months. In contrast to these measures of GABAA receptor binding, functional connectivity did not correlate with behavioral improvement.
  
  
  CONCLUSIONS
  Our preliminary findings point toward GABAA receptor binding being a marker of consciousness recovery in DoC.
authors.affiliation: Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan.|Institute of Mental Health Research, University of Ottawa, Ottawa, Canada.|Brain and Consciousness Research Centre, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
authors.forename: Pengmin
authors.initials: P
authors.lastname: Qin
authors.affiliation: Neurosurgery Department, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xuehai
authors.initials: X
authors.lastname: Wu
authors.affiliation: Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan.|Institute of Mental Health Research, University of Ottawa, Ottawa, Canada.|Brain and Consciousness Research Centre, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.|Centre for Cognition and Brain Disorders (CCBD), Hangzhou Normal University, Hangzhou, China.
authors.forename: Niall W
authors.initials: NW
authors.lastname: Duncan
authors.affiliation: PET/CT Centre, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Bao
authors.affiliation: Radiologic Department of Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Tang
authors.affiliation: PET/CT Centre, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Neurosurgery Department, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hu
authors.affiliation: Neurosurgery Department, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Neurosurgery Department, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Neurosurgery Department, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Gao
authors.affiliation: Antai Hospital, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: PET/CT Centre, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Institute of Mental Health Research, University of Ottawa, Ottawa, Canada.|Brain and Consciousness Research Centre, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
authors.forename: Timothy
authors.initials: T
authors.lastname: Lane
authors.affiliation: Institute of Mental Health Research, University of Ottawa, Ottawa, Canada.
authors.forename: Zirui
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Spaulding Rehabilitation Hospital, Charlestown, Massachusetts.
authors.forename: Yelena G
authors.initials: YG
authors.lastname: Bodien
authors.affiliation: Spaulding Rehabilitation Hospital, Charlestown, Massachusetts.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Giacino
authors.affiliation: Neurosurgery Department, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan.|Institute of Mental Health Research, University of Ottawa, Ottawa, Canada.|Brain and Consciousness Research Centre, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.|Centre for Cognition and Brain Disorders (CCBD), Hangzhou Normal University, Hangzhou, China.|Research Centre for Mind, Brain and Learning, National Chengchi University, Taipei, Taiwan.
authors.forename: Georg
authors.initials: G
authors.lastname: Northoff
mesh_terms: D000328:Adult; D001519:Behavior; D001930:Brain Injuries / Q000150:complications; D003244:Consciousness Disorders / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005442:Flumazenil; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018458:Persistent Vegetative State / Q000000981:diagnostic imaging / Q000473:pathology / Q000523:psychology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A / Q000172:deficiency* / Q000378:metabolism; D020127:Recovery of Function; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D005442:Flumazenil
keywords: Zolpidem; default-mode network; executive-control network; functional connectivity; minimally conscious state; salience network; unresponsive wakefulness syndrome; vegetative state