Freezing of gait in Parkinson’s disease is associated with the microstructural and functional changes of globus pallidus internus

Abstract

BackgroundFreezing of gait (FOG) is a common motor symptom in advanced Parkinson’s disease (PD). However, the pathophysiology mechanism of FOG is not fully understood. The purpose of this study was to investigate microstructural abnormalities in subcortical gray matter and alterations in functional connectivity of the nuclei with microstructural changes. In addition, the correlations between these microstructural and functional changes and the severity of FOG were measured.Materials and methodsTwenty-four patients with FOG (PD-FOG), 22 PD patients without FOG (PD-nFOG), and 27 healthy controls (HC) were recruited. FOG Questionnaire (FOGQ) and Gait and Falling Questionnaire (GFQ) were assessed, and Timed Up and Go (TUG) tests were performed in PD-FOG patients. All subjects underwent diffusion tensor imaging (DTI) and resting-state functional MRI scanning. The DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were extracted and measured from basal ganglia, thalamus, and substantia nigra. The nuclei with microstructural alterations were selected as seed regions to perform the seed-based resting-state functional connectivity.ResultsThe MD and RD values of the right globus pallidus internus (GPi) were significantly higher in patients with PD-FOG compared with PD-nFOG patients and HC. In PD-FOG patients, the MD and RD values of the right GPi were significantly correlated with the time of the TUG test in both ON and OFF states. The MD values were also correlated with the GFQ scores in PD-FOG patients. Resting-state functional connectivity between the right GPi and left middle occipital gyri decreased significantly in PD-FOG patients compared to PD-nFOG patients, and was negatively correlated with GFQ scores as well as the time of ON state TUG in PD-FOG patients.ConclusionMicrostructural alterations in the right GPi and functional connectivity between the right GPi and visual cortex may be associated with the pathophysiological mechanisms of FOG in PD patients.

Quantitative Susceptibility Mapping Changes Relate to Gait Issues in Parkinson’s Disease

“…Recent studies have showed that diffusion changes in the globus pallidus are associated with FOG. 39,40 Within the landscape of susceptibility MRI studies in PD investigating the relationship between susceptibility and gait, our study aligns with another study demonstrating susceptibility changes in the putamen and globus pallidus. 10 Our study complements these susceptibility and diffusion MRI studies by showing that susceptibility changes in the globus pallidus are also implicated in FOG.…”

“…Recent studies have showed that diffusion changes in the globus pallidus are associated with FOG. 39,40…”

Differential Cortical and Subcortical Activations during Different Stages of Muscle Control: A Functional Magnetic Resonance Imaging Study

“…The direct pathway facilitates the intended movements, while the indirect pathway inhibits the neural responses of the thalamus, making excitation of the motor cortex less likely, hence inhibiting action. Studies of Parkinson's disease have shown that patients are characterized by slowness of movement (bradykinesia), possibly due to dysfunction in the direct pathway [22][23][24][25][26][27]29,30]. Conversely, Huntington's disease is associated with rapid, jerky motions with no clear purpose, possibly due to dysfunction in the indirect pathway [22].…”