Gray matter atrophy and freezing of gait in Parkinson's disease: Is the evidence black-on-white?

OBJECTIVES: The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease (PD) is poorly understood. We tested whether gray matter (GM) atrophy contributes to FOG in PD. METHODS: Voxel-based morphometry quantified GM atrophy in 106 patients who were classified as freezers (n = 30) or nonfreezers (n = 76). Well-matched smaller subgroups were also studied. Balance, gait, and cognitive function were assessed, and we evaluated the relationship between GM, FOG severity, and symptoms associated with FOG. RESULTS: GM was significantly reduced in the inferior parietal lobe and angular gyrus in the matched freezers (n = 22), compared to nonfreezers (n = 22; P < 0.015, cluster-level corrected). In the entire cohort, FOG severity was related to bilateral caudate volumes. CONCLUSIONS: GM atrophy in cortical (i.e., parietal lobe and angular gyrus) and subcortical areas (i.e., caudate) are related to FOG. Disparities among the existing findings suggest that inferences regarding specific brain regions should be made with caution.