Microstructural and functional alterations of the ventral pallidum are associated with levodopa-induced dyskinesia in Parkinson's disease.

BACKGROUND AND PURPOSE: The ventral pallidum (VP) regulates involuntary movements, but it is unclear whether the VP regulates the abnormal involuntary movements in Parkinson's disease (PD) patients who have levodopa-induced dyskinesia (LID). To further understand the role of the VP in PD patients with LID (PD-LID), we explored the structural and functional characteristics of the VP in such patients using multimodal magnetic resonance imaging (MRI). METHODS: Thirty-one PD-LID patients, 39 PD patients without LID (PD-nLID), and 28 healthy controls (HCs) underwent T1-weighted MRI, quantitative susceptibility mapping, multi-shell diffusion MRI, and resting-state functional MRI (rs-fMRI). Different measures characterizing the VP were obtained using a region-of-interest-based approach. RESULTS: The left VP in the PD-LID group showed significantly higher intracellular volume fraction (ICVF) and isotropic volume fraction (IsoVF) compared with the PD-nLID and HC groups. Rs-MRI revealed that, compared with the PD-nLID group, the PD-LID group in the medication 'off' state had higher functional connectivity (FC) between the left VP and the left anterior caudate, left middle frontal gyrus and left precentral gyrus, as well as between the right VP and the right posterior ventral putamen and right mediodorsal thalamus. In addition, the ICVF values of the left VP, the FC between the left VP and the left anterior caudate and left middle frontal gyrus were positively correlated with Unified Dyskinesia Rating Scale scores. CONCLUSION: Our multimodal imaging findings show that the microstructural changes of the VP (i.e., the higher ICVF and IsoVF) and the functional change in the ventral striatum-VP-mediodorsal thalamus-cortex network may be associated with pathophysiological mechanisms of PD-LID.

Microstructural and functional impairment of the basal ganglia in Wilson's disease: a multimodal neuroimaging study.

Objectives: Magnetic susceptibility changes in brain MRI of Wilson's disease (WD) patients have been described in subcortical nuclei especially the basal ganglia. The objectives of this study were to investigate its relationship with other microstructural and functional alterations of the subcortical nuclei and the diagnostic utility of these MRI-related metrics. Methods: A total of 22 WD patients and 20 healthy controls (HCs) underwent 3.0T multimodal MRI scanning. Susceptibility, volume, diffusion microstructural indices and whole-brain functional connectivity of the putamen (PU), globus pallidus (GP), caudate nucleus (CN), and thalamus (TH) were analyzed. Receiver operating curve (ROC) was applied to evaluate the diagnostic value of the imaging data. Correlation analysis was performed to explore the connection between susceptibility change and microstructure and functional impairment of WD and screen for neuroimaging biomarkers of disease severity. Results: Wilson's disease patients demonstrated increased susceptibility in the PU, GP, and TH, and widespread atrophy and microstructural impairments in the PU, GP, CN, and TH. Functional connectivity decreased within the basal ganglia and increased between the PU and cortex. The ROC model showed higher diagnostic value of isotropic volume fraction (ISOVF, in the neurite orientation dispersion and density imaging model) compared with susceptibility. Severity of neurological symptoms was correlated with volume and ISOVF. Susceptibility was positively correlated with ISOVF in GP. Conclusion: Microstructural impairment of the basal ganglia is related to excessive metal accumulation in WD. Brain atrophy and microstructural impairments are useful neuroimaging biomarkers for the neurological impairment of WD.

Multimodal Imaging of Substantia Nigra in Parkinson's Disease with Levodopa-Induced Dyskinesia.

BACKGROUND: Degeneration of the substantia nigra (SN) may contribute to levodopa-induced dyskinesia (LID) in Parkinson's disease (PD), but the exact characteristics of SN in LID remain unclear. OBJECTIVE: To further understand the pathogenesis of patients with PD with LID (PD-LID), we explored the structural and functional characteristics of SN in PD-LID using multimodal magnetic resonance imaging (MRI). METHODS: Twenty-nine patients with PD-LID, 37 patients with PD without LID (PD-nLID), and 28 healthy control subjects underwent T1-weighted MRI, quantitative susceptibility mapping, neuromelanin-sensitive MRI, multishell diffusion MRI, and resting-state functional MRI. Different measures characterizing the SN were obtained using a region of interest-based approach. RESULTS: Compared with patients with PD-nLID and healthy control subjects, the quantitative susceptibility mapping values of SN pars compacta (SNpc) were significantly higher (P = 0.049 and P = 0.00002), and the neuromelanin contrast-to-noise ratio values in SNpc were significantly lower (P = 0.012 and P = 0.000002) in PD-LID. The intracellular volume fraction of the posterior SN in PD-LID was significantly higher compared with PD-nLID (P = 0.037). Resting-state fMRI indicated that PD-LID in the medication off state showed higher functional connectivity between the SNpc and putamen compared with PD-nLID (P = 0.031), and the functional connectivity changes in PD-LID were positively correlated with Unified Dyskinesia Rating Scale total scores (R = 0.427, P = 0.042). CONCLUSIONS: Our multimodal imaging findings highlight greater neurodegeneration in SN and the altered nigrostriatal connectivity in PD-LID. These characteristics provide a new perspective into the role of SN in the pathophysiological mechanisms underlying PD-LID. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Gait performance and non-motor symptoms burden during dual-task condition in Parkinson's disease.

INTRODUCTION: Impaired gait is observed in patients with Parkinson's disease (PD) in both single-task (ST) and dual-task (DT) conditions. Non-motor symptoms (NMSs), another vital symptom future experienced along the PD disease trajectory, contribute to gait performance in PD. However, whether DT gait performance is indicative of NMS burden (NMSB) remains unknown. This study investigated correlation between NMS and DT gait performance and whether NMSB is reflected in the DT effects (DTEs) of gait parameters in PD. METHODS: Thirty-three idiopathic PD participants were enrolled in this study; the median H-Y staging was 2.5. NMSB was assessed by Non-motor Symptoms Scale (NMSS). Spatiotemporal gait parameters under ST and DT conditions were evaluated by wearable sensors. Gait parameters under ST and DT conditions and DTEs of gait parameters were compared across NMSB groups. The associations between NMS and DTEs of gait parameters were analyzed by correlation analysis and linear regression models. RESULTS: Compared to PD patients with mild-moderate NMSB, the severe-very severe NMSB group showed slower gait speed and shorter stride length under both ST and DT conditions (p < 0.05). DT had significantly negative effect on gait parameters in PD patients, including gait speed, stride length, and gait cycle duration (p < 0.05). PD patients with mild-moderate NMSB showed larger DTEs of cadence and bilateral gait cycle duration (p < 0.05). DTEs of bilateral gait cycle duration and swing phase on the more affected (MA) side were significantly correlated with NMSS scores (∣rSp∣ ≥ 0.3, p < 0.05). Gait cycle duration on the less affected (LA) side explained 43% of the variance in NMSS scores, when accounting for demographic and clinical confounders (ß = - 1.095 95% CI - 4.061 ~ - 0.058, p = 0.044; adjusted R2 = 0.434). CONCLUSION: DT gait performance could reflect NMSB in PD patients at early stage, and gait cycle duration is a valuable gait parameter to further investigate and to provide more evidence for PD management.