Topography of Regional Cerebral GABA A Receptor Availability in Parkinson's Disease Patients With Freezing of Gait

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ABSTRACT We aimed to explore the relationship between regional gamma‐aminobutyric acid (GABA A ) receptor availability, measured with [ 11 C]‐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 [ 11 C]‐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 GABA A 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 GABA A 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 GABA A inverse agonists for novel investigation of FOG treatment in Parkinson's disease.

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