Alterations of mean diffusivity of pedunculopontine nucleus pathway in Parkinson's disease patients with freezing of gait

Abstract

Background: Although freezing of gait (FOG) is a common and disabling symptom in Parkinson's disease (PD), the underlying mechanism of FOG has not been clearly elucidated. Using analysis of diffusion tensor imaging (DTI), we investigated anatomic structures associated with FOG in PD patients. Methods: We enrolled 33 controls and 42 PD patients (19 patients with FOG and 23 without FOG). DTI data were compared between PD patients and controls, and also between PD patients with and without FOG. Whole brain voxel-based analysis and regions of interest analysis in the pedunculopontine nucleus were used for DTI analysis. Results: Compared with normal controls, PD patients showed microstructural changes in various subcortical structures (substantia nigra, globus pallidum and thalamus), frontal and insula cortex. PD patients with FOG demonstrated altered mean diffusivities in subcortical structures connected with pedunculopontine nucleus, such as basal ganglia, thalamus and cerebellum in voxel-based analysis. Using region of interest analysis of pedunculopontine nucleus, fractional anisotropy values were reduced and mean diffusivity values were increased bilaterally in PD patients with FOG. In correlation analysis, the fractional anisotropy value of the right pedunculopontine nucleus was moderately correlated with the severity of FOG. Conclusions: Based on our results, microstructural changes of pedunculopontine nucleus and connected subcortical structures are closely related with FOG in PD patients.