Normal-sized basal ganglia perivascular space related to motor phenotype in Parkinson freezers

Lv, Wen; Yue, Yumei; Shen, Ting; Hu, Xingyue; Chen, Lili; Xie, Fei; Zhang, Wenying; Zhang, Baorong; Gui, Yaxing; Lai, Hsin-Yi; Ba, Fang

doi:10.18632/aging.203343

Cited by 10 publications

(5 citation statements)

References 66 publications

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“…Notably, the current study showed alterations mainly in the right hemisphere of PD-FOG patients, which is consistent with a growing body of literature demonstrating that the right hemisphere appears to be selectively affected in FOG ( Fling et al, 2013 ; Peterson et al, 2014 ; Bharti et al, 2020 ; Lv et al, 2021 ; Song et al, 2021 ; Lench et al, 2022 ). The laterality of imaging abnormalities in PD-FOG patients is likely related to the fact that the right hemisphere plays a strong role in visuospatial function in right-handed subjects ( Joseph, 1988 ).…”

Section: Discussionsupporting

confidence: 92%

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

Kou

Wang²,

Zheng³

et al. 2022

Front. Aging Neurosci.

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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.

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Section: Discussionsupporting

confidence: 92%

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

Kou

Wang²,

Zheng³

et al. 2022

Front. Aging Neurosci.

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“…An increased PVS burden indicates dysfunctional endothelial walls and impaired ISF exchange 41 , and would further lead to glymphatic dysfunction. Our previous studies have shown a higher PVS burden in PD patients 25,35 , with such burden in BG as a candidate biomarker to evaluate PD motor severity 24 . Increased PVS burden is one of the manifestations of an impaired perivascular clearance system, and mainly indicates a structural abnormality in the glymphatic system.…”

Section: Discussionmentioning

confidence: 99%

“…These findings suggest the potential of the DTI-ALPS index as a non-invasive imaging biomarker in evaluating the integrity of the glymphatic system. Ultra-high field 7 T MRI, with increased spatial resolution, contrast and signal-to-noise ratio, improved the visualization and detection rate of PVS, especially small-sized PVS that might be neglected using conventional MRI technology 25,26,35 . Moreover, for DTI studies, 7 T MRI enables visualization of the white matter orientations and making sharp turns into the cortex, which are more difficult to see with the 3 T scanner 36 .…”

Section: Introductionmentioning

confidence: 99%

Diffusion along perivascular spaces as marker for impairment of glymphatic system in Parkinson’s disease

Shen

Yue

et al. 2022

npj Parkinsons Dis.

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The brain glymphatic system is involved in the clearance of misfolding α-synuclein, the impaired glymphatic system may contribute to the progression of Parkinson’s disease (PD). We aimed to analyze the diffusion tensor image along the perivascular space (DTI-ALPS) and perivascular space (PVS) burden to reveal the relationship between the glymphatic system and PD. A cross-sectional study using a 7 T MRI of 76 PD patients and 48 controls was performed to evaluate the brain’s glymphatic system. The DTI-ALPS and PVS burden in basal ganglia were calculated. Correlation analyses were conducted between DTI-ALPS, PVS burden and clinical features. We detected lower DTI-ALPS in the PD subgroup relative to controls, and the differences were more pronounced in patients with Hoehn & Yahr stage greater than two. The decreased DTI-ALPS was only evident in the left hemisphere in patients in the early stage but involved both hemispheres in more advanced PD patients. Decreased DTI-ALPS were also correlated with longer disease duration, higher Unified Parkinson’s Disease Rating Scale motor score (UPDRS III) and UPDRS total scores, as well as higher levodopa equivalent daily dose. Moreover, the decreased DTI-ALPS correlated with increased PVS burden, and both indexes correlated with PD disease severity. This study demonstrated decreased DTI-ALPS in PD, which might initiate from the left hemisphere and progressively involve right hemisphere with the disease progression. Decreased DTI-ALPS index correlated with increased PVS burden, indicating that both metrics could provide supporting evidence of an impaired glymphatic system. MRI evaluation of the PVS burden and diffusion along PVS are potential imaging biomarkers for PD for disease progression.

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“…It is believed that the abnormal function of the basal ganglia–cortical loop may play an important role in the occurrence and development of FOG ( Bartels and Leenders, 2008 ; Snijders et al, 2016 ). For example, Lv et al (2021) examined the association between basal ganglia perivascular spaces and FOG using high resolution 7T-magnetic resonance imaging (MRI), and found that basal ganglia perivascular spaces were significantly greater during frozen episodes. Although neuroimaging studies provide adequate coverage and spatial resolution, they do not reflect the dynamic response to FOG events.…”

Section: Introductionmentioning

confidence: 99%

Synchronized Intracranial Electrical Activity and Gait Recording in Parkinson’s Disease Patients With Freezing of Gait

et al. 2022

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BackgroundThis study aimed to describe a synchronized intracranial electroencephalogram (EEG) recording and motion capture system, which was designed to explore the neural dynamics during walking of Parkinson’s disease (PD) patients with freezing of gait (FOG). Preliminary analysis was performed to test the reliability of this system.MethodsA total of 8 patients were enrolled in the study. All patients underwent bilateral STN-DBS surgery and were implanted with a right subdural electrode covering premotor and motor area. Synchronized electrophysiological and gait data were collected using the Nihon Kohden EEG amplifier and Codamotion system when subjects performed the Timed Up and Go (TUG) test. To verify the reliability of the acquisition system and data quality, we calculated and compared the FOG index between freezing and non-freezing periods during walking. For electrophysiological data, we first manually reviewed the scaled (five levels) quality during waking. Spectra comprising broadband electrocorticography (ECoG) and local field potential (LFP) were also compared between the FOG and non-FOG states. Lastly, connectivity analysis using coherence between cortical and STN electrodes were conducted. In addition, we also use machine learning approaches to classified FOG and non-FOG.ResultsA total of 8 patients completed 41 walking tests, 30 of which had frozen episodes, and 21 of the 30 raw data were level 1 or 2 in quality (70%). The mean ± SD walking time for the TUG test was 85.94 ± 47.68 s (range: 38 to 190.14 s); the mean ± SD freezing duration was 12.25 ± 7.35 s (range: 1.71 to 27.50 s). The FOG index significantly increased during the manually labeled FOG period (P < 0.05). The beta power of STN LFP in the FOG period was significantly higher than that in the non-FOG period (P < 0.05), while the band power of ECoG did not exhibit a significant difference between walking states. The coherence between the ECoG and STN LFP was significantly greater in high beta and gamma bands during the FOG period compared with the shuffled surrogates (P < 0.05). Lastly, STN-LFP band power features showed above-chance performance (p < 0.01, permutation test) in identifying FOG epochs.ConclusionIn this study, we established and verified the synchronized ECoG/LFP and gait recording system in PD patients with FOG. Further neural substrates underlying FOG could be explored using the current system.

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Normal-sized basal ganglia perivascular space related to motor phenotype in Parkinson freezers

Cited by 10 publications

References 66 publications

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

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

Diffusion along perivascular spaces as marker for impairment of glymphatic system in Parkinson’s disease

Synchronized Intracranial Electrical Activity and Gait Recording in Parkinson’s Disease Patients With Freezing of Gait

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