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

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 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 Additional Supporting Information may be found in the online version of this article. 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. Hum Brain Mapp 00:000-000, 2015.V C 2015 Wiley Periodicals, Inc.

Functional networks in prolonged disorders of consciousness

“…It could be speculated that the ECN constitutes a crucial neural substrate of the global workspace that enables consciousness control. Moreover, it has been suggested that the reduced functional connectivity between the DLPFC and precuneus enables the former a popular therapeutic target for non-invasive brain stimulation in prolonged DoC as to restore the disrupted balance between the ECN and DMN (Qin et al, 2015b;O'Neal et al, 2021).…”

Posterior cingulate cross-hemispheric functional connectivity predicts the level of consciousness in traumatic brain injury

“…Then, during nuisance signal regression, 6 head motion-related regressors and the average signals from the CSF and white matter were regressed out 17 , 30 , 31 . After the PCC seed was chosen, the PCC seed-based functional connectivity map was acquired.…”

The Role of Neuroimaging Techniques in Establishing Diagnosis, Prognosis and Therapy in Disorders of Consciousness

“…The technique allowed to correctly identify 93% of MCS patients and correctly predict consciousness recovery in 74% of patients with disorders of consciousness [ 27 ]. In the same line, a preliminary study in patients with disorders of consciousness using [ 11 C ] Flumazenil PET reported reduced global GABA-A receptor binding and decreased local-to-global ratio in the supragenual anterior cingulate that correlated with behavioral improvement after three months [ 52 ].…”