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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Behavior
  • Brain Injuries / complications
  • Consciousness Disorders / diagnostic imaging*
  • Consciousness Disorders / genetics*
  • Consciousness Disorders / pathology
  • Female
  • Flumazenil
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Persistent Vegetative State / diagnostic imaging
  • Persistent Vegetative State / pathology
  • Persistent Vegetative State / psychology
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Receptors, GABA-A / deficiency*
  • Receptors, GABA-A / metabolism
  • Recovery of Function
  • Young Adult


  • Radiopharmaceuticals
  • Receptors, GABA-A
  • Flumazenil