Abstract
ObjectiveFreezing of gait (FOG) is a common disabling motor symptom in Parkinson’s disease (PD), but the potential pathogenic mechanisms are still unclear.MethodsA total of 22 patients with PD with FOG (PD-FOG), 28 patients with PD without FOG (PD-nFOG), and 33 healthy controls (HCs) were recruited in this study. Degree centrality (DC)—a graph theory-based measurement of global connectivity at the voxel level by measuring the number of instantaneous functional connections between one region and the rest of the brain—can map brain hubs with high sensitivity, specificity, and reproducibility. DC was used to explore alterations in the centrality of PD-FOG correlated with brain node levels. PD-FOG cognitive network dysfunction was further revealed via a seed-based functional connectivity (FC) analysis. In addition, correlation analyses were carried out between clinical symptoms and acquired connectivity measurement.ResultsCompared to the PD-nFOG group, the PD-FOG group showed remarkably increased DC values in the right middle frontal gyrus (RMFG). There were no significant differences in other gray matter regions. Importantly, the clinical severity of FOG was related to the mean DC values in the RMFG. This brain region served as a seed in secondary seed-based FC analysis, and we further found FC changes in the right precuneus, right inferior frontal gyrus, right superior frontal gyrus (SFG), and cerebellum.ConclusionIncreased RMFG activity and FC network alterations in the middle frontal cortex with the precuneus, inferior, and SFG, and the cerebellum may have great potential in brain dysfunction in PD with FOG.
Highlights
Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder mainly characterized by motor impairments (Kalia and Lang, 2015)
One surface-based morphometry (SBM) study based on 21 patients with PD-freezing of gait (FOG), 28 PD patients without FOG (PD-nFOG), and 19 healthy controls (HCs) revealed bilateral frontal, parietal, and occipital cortical thickness reductions in PD with FOG (PD-FOG), which were significant in the middle frontal cortex (Pietracupa et al, 2018)
We found in the current study that the right middle frontal gyrus (RMFG)-functional connectivity (FC) of the right superior frontal gyrus (SFG) and inferior frontal gyrus (IFG) showed decreased changes in PD-FOG, suggesting that their activity was reduced, reflecting the presence of pathological damage in the default mode network (DMN)
Summary
Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder mainly characterized by motor impairments (Kalia and Lang, 2015). A structural magnetic resonance imaging (sMRI) study involving voxel-based morphometry (VBM) found widespread gray matter (GM) volume atrophy in the frontal–parietal cortical areas and cerebellum in PD-FOG (Jha et al, 2015). A functional MRI (fMRI) study using amplitude of low-frequency fluctuation (ALFF) found abnormal ALFF in the frontal, parietal, and temporal areas and cerebellum in PD-FOG, and found a significant correlation between ALFF changes in the middle frontal gyrus and FOG severity (Mi et al, 2017). This finding suggested that executive function impairment in the frontal regions was involved in PD-FOG. Studies based on the resting state voxel-level whole-brain impaired neural networks are rare in literature, which has limited our understanding of PD-FOG
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