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We aimed to explore the relationship between regional gamma-aminobutyric acid (GABAA) receptor availability, measured with [11C]-flumazenil brain positron emission tomography (PET) and freezing of gait in patients with Parkinson's disease. Freezing of gait is a significant mobility impairment with limited effectiveness to L-DOPA in advancing disease implying a role for other neurotransmitters, such as GABA. Imaging studies using [11C]-flumazenil PET and magnetic resonance imaging (MRI) were conducted in 33 patients with Parkinson's disease (9F/24M; age 68.34 ± 6.38, disease duration 8.03 ± 4.73, motor Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores 44.01 ± 14.85). Patients were classified into two groups: "freezers" (n = 8) and "nonfreezers" (n = 25), based on the MDS-UPDRS Part III off state examination. Whole brain voxel-based t-tests group comparisons were performed using SPM12. Reduced GABAA binding was observed in the cerebellum vermis, esp. vermis lobule VI, left posterior cingulum, posterior parahippocampal gyrus/fimbriae, medial occipital-temporal gyrus and the right gyrus rectus, right anterior cingulum, and adjacent right superior frontal gyrus that demonstrated significantly reduced GABAA receptor availability in the individuals with freezing as compared to those without. In addition, reductions were also seen in the left posterior putamen and pallidum. Findings may augur a role for GABAA inverse agonists for novel investigation of FOG treatment in Parkinson's disease.
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