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

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 [¹¹C]Flumazenil positron emission tomography to establish global GABA_A 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 GABA_A 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 GABA_A receptor binding, functional connectivity did not correlate with behavioral improvement. Conclusions: Our preliminary findings point toward GABA_A receptor binding being a marker of consciousness recovery in DoC.