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Hum Brain Mapp. 2015 Oct;36(10):3867-77. doi: 10.1002/hbm.22883. Epub 2015 Jul 3.

GABAA receptor deficits predict recovery in patients with disorders of consciousness: A preliminary multimodal [(11) C]Flumazenil PET and fMRI study.

Qin P1,2,3, Wu X4, Duncan NW1,2,3,5, Bao W6, Tang W7, Zhang Z6, Hu J4, Jin Y4, Wu X4, Gao L4, Lu L8, Guan Y6, Lane T2,3, Huang Z2, Bodien YG9, Giacino JT9, Mao Y4, Northoff G1,2,3,5,10.

Author information

1
Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan.
2
Institute of Mental Health Research, University of Ottawa, Ottawa, Canada.
3
Brain and Consciousness Research Centre, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
4
Neurosurgery Department, Huashan Hospital, Fudan University, Shanghai, China.
5
Centre for Cognition and Brain Disorders (CCBD), Hangzhou Normal University, Hangzhou, China.
6
PET/CT Centre, Huashan Hospital, Fudan University, Shanghai, China.
7
Radiologic Department of Huashan Hospital, Fudan University, Shanghai, China.
8
Antai Hospital, Shanghai, China.
9
Spaulding Rehabilitation Hospital, Charlestown, Massachusetts.
10
Research Centre for Mind, Brain and Learning, National Chengchi University, Taipei, Taiwan.

Abstract

OBJECTIVES:

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.

EXPERIMENTAL DESIGN:

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.

PRINCIPAL OBSERVATIONS:

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.

KEYWORDS:

Zolpidem; default-mode network; executive-control network; functional connectivity; minimally conscious state; salience network; unresponsive wakefulness syndrome; vegetative state

PMID:
26147065
DOI:
10.1002/hbm.22883
[Indexed for MEDLINE]

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