Parkinson's Disease Patients Research Articles

Subthalamic nucleus deep brain stimulation modulates speech graphs in patients with Parkinson’s disease

Graph theory enables a direct quantification of topological properties of any arbitrary network. Its application in neuroscience has unveiled topological changes of brain networks associated with various neurodegenerative diseases. This study used the graph theory to understand speech deficits in patients with Parkinson’s disease (PD). In particular, this study investigated the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on the topology of speech graphs. Sixty patients with PD completed a standard semantic fluency test with DBS switched ON and OFF. A control group of sixty matched nonsurgical PD patients completed the test once. All verbal responses were recorded, transcripted, and transformed into directed speech graphs. Volumes of tissue activated (VTA) were estimated for three STN subregions, including sensorimotor, associative, and limbic parts. First, the patients with DBS OFF produced smaller and denser speech graphs than nonsurgical patients, showing fewer nodes, higher density, shorter diameter, and shorter average shortest path. Second, DBS partially reversed the effect of surgery, leading to larger and sparser speech graphs with more nodes, lower density, longer diameter, and longer average shortest path (ON versus OFF). Third, however, the left associative VTA negatively correlated with the DBS-induced diameter and average shortest path changes (ON versus OFF), suggesting that the patients with greater left associative STN stimulation tended to produce smaller and denser speech graphs. This study demonstrates that STN-DBS can partially restore the topological structure of speech graphs in PD patients. However, stimulating the left associative STN appears to disrupt speech graphs.

Changes of upper-limb kinematics during practice of a redundant motor task in patients with Parkinson’s disease

The ability to learn novel motor skills is essential for patients with Parkinson’s disease (PD) to regain activities of daily living. However, the underlying mechanisms of motor learning in PD remain unclear. To identify motor features that are distinctively manifested in PD during motor learning, we quantified a rich set of variables reflecting various aspects of the learning process in a virtual throwing task. While the performance outcome improved similarly over 3 days of practice for both PD patients and age-matched controls, further analysis revealed distinct learning processes between the two groups. PD patients initially performed with a slow release velocity and gradually increased it as practice progressed, whereas the control group began with an unnecessarily rapid release velocity, which they later stabilized at a lower value. Performance characteristics related to the timing of ball release and the inter-release interval did not show significant group differences, although they were modulated across practice in both groups. After one week, both groups retained the performance outcomes and underlying kinematics developed over practice. This study underscores the importance of analyzing the multi-faceted learning process to characterize motor skill learning in PD. The findings may provide insights into PD pathophysiology and inform rehabilitation strategies.

Identifying and Predicting Risk for Hospital Admission among Patients with Parkinsonism.

Patients with parkinsonism are more likely than age-matched controls to be admitted to hospital. It may be possible to reduce the cost and negative impact by identifying patients at highest risk and intervening to reduce hospital-related costs. Predictive models have been developed in nonparkinsonism populations. The aims were to (1) describe the reasons for admission, (2) describe the rates of hospital admission/emergency department attendance over time, and (3) use routine data to risk stratify unplanned hospital attendance in people with parkinsonism. This retrospective cohort study used Clinical Practice Research Datalink GOLD, a large UK primary care database, linked to hospital admission and emergency department attendance data. The primary diagnoses for nonelective admissions were categorized, and the frequencies were compared between parkinsonism cases and matched controls. Multilevel logistic and negative binomial regression models were used to estimate the risk of any and multiple admissions, respectively, for patients with parkinsonism. There were 9189 patients with parkinsonism and 45,390 controls. The odds of emergency admission more than doubled from 2010 to 2019 (odds ratio [OR] 2.33; 95% confidence interval [CI] 1.96, 2.76; P-value for trend <0.001). Pneumonia was the most common reason for admission among cases, followed by urinary tract infection. Increasing age, multimorbidity, parkinsonism duration, deprivation, and care home residence increased the odds of admission. Rural location was associated with reduced OR for admission (OR 0.79; 95% CI 0.70, 0.89). Our risk stratification tool may enable empirical targeting of interventions to reduce admission risk for parkinsonism patients.

Altered gait speed and brain network connectivity in Parkinson's disease.

Slow gait speed and disrupted brain network connectivity are common in patients with Parkinson's disease (PD). This study aimed to clarify the relationship between gait speed and clinical characteristics in PD, and explore the underlying brain network mechanisms. Forty-two PD patients and 20 healthy controls (HC) were recruited. Statistical independent component analysis and correlation analysis were employed to investigate underlying neural mechanisms and relationships. PD patients exhibited significantly slower gait speed, which showed a significant negative correlation with postural instability and gait disturbance scores. Network connectivity analysis revealed decreased intranetwork functional connectivity (FC) within visual network (VN) and cerebellum network (CN), but increased internetwork FC between CN and both sensorimotor network (SMN) and frontoparietal network (FPN) in PD patients compared to HC. The slow gait speed PD subgroup demonstrated increased intranetwork FC within SMN and VN, along with decreased FC between VN and both FPN and default mode network. Correlation analyses revealed negative correlation between gait speed and FC of CN and positive correlation to FC of CN-SMN. Our study identified relationships between gait speed and clinical characteristics, and corresponding network connectivity alterations in PD patients, providing insights into the neural mechanisms underlying gait impairments in PD.

Insulin Resistance Is a Modifying Factor for Parkinson's Disease.

Parkinson's disease (PD) is the second most common, and the fastest-growing neurodegenerative disorder with unclear etiology in most cases. Therefore, the identification of non-genetic risk factors for PD pathology is crucial to develop effective preventative or therapeutic strategies. An increasing number of evidence suggests that central insulin resistance might have an essential role in PD pathology. Nevertheless, it is not clear whether insulin resistance arises from external factors/lifestyle, comorbidities such as type 2 diabetes or it can occur in a PD patient's brain independently from peripheral insulin resistance. We aimed to investigate insulin resistance and its role in GBA1mutation-associated PD pathogenesis and phenotype severity. Midbrain organoids, generated from induced pluripotent stem cells (iPSCs) of PD patients carrying the GBA1-N370S heterozygous mutation (GBA-PD) and healthy donors, were exposed to different insulin concentrations to modify insulin signaling function. Transcriptomics analysis was performed to explore insulin signaling gene expression patterns in GBA-PD and to find a potential target for GBA-PD-associated phenotype rescue. The insulin signaling pathway genes show dysregulation in GBA-PD. Particularly, we highlight that a knockdown of FOXO1 mitigates the loss of dopaminergic neurons and cellular death in GBA-PD. Additionally, our findings suggest a promising therapeutic potential of the anti-diabetic drug Pioglitazone in decreasing dopaminergic neuron loss associated with GBA-PD. Local insulin signaling dysfunction plays a substantial role in GBA-PD pathogenesis, exacerbating dopaminergic neuron death. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Disgust-specific impairment of facial emotion recognition in Parkinson's disease patients with mild cognitive impairment.

This study investigated the association between cognitive function and facial emotion recognition (FER) in patients with Parkinson's disease (PD) and mild cognitive impairment (PD-MCI). We enrolled 126 participants from Taiwan, including 63 patients with idiopathic PD and 63 matched healthy controls. The PD group was divided into two groups: those with normal cognitive function (PD-NC) and those with MCI (PD-MCI). Participants underwent a modality emotion recognition test and comprehensive cognitive assessment. Our findings reveal that patients with PD-MCI exhibit significantly impaired FER, especially in recognizing "disgust," compared with patients with PD-NC and healthy adults (P = .001). This deficit correlates with executive function, attention, memory, and visuospatial abilities. Attention mediates the relationship between executive function and "disgust" FER. The findings highlight how patients with PD-MCI are specifically challenged when recognizing "disgust" and suggest that cognitive training focusing on cognitive flexibility and attention may improve their FER abilities. This study contributes to our understanding of the nuanced relationship between cognitive dysfunction and FER in patients with PD-MCI, emphasizing the need for targeted interventions.

Understanding Parkinson disease in Spain: Genetic and clinical insights.

Parkinson disease (PD) is a complex and heterogeneous neurodegenerative disorder with a broad spectrum of clinical manifestations, determined by a complex interplay of environmental and genetic factors. This study aimed to investigate genetic variants associated with PD and assess their impact on the disease phenotype through genotype-phenotype correlations. We employed a targeted resequencing panel to analyze 27 genes linked to PD in a cohort of 1185 PD patients from southern Spain. Variants were categorized based on the American College of Medical Genetics and Genomics pathogenicity criteria. Demographic and clinical data were also collected. Among the patients analyzed, 13.5% carried potential disease-causing pathogenic or likely pathogenic variants in 12 different genes, indicating significant genetic heterogeneity. The most frequently affected genes were LRRK2, PRKN, and GBA1 (accounting for 72.1% of positive cases). Sex-specific differences were observed, with a higher proportion of female patients carrying LRRK2 variants. Differences in age at onset and clinical features were also observed among the different mutated genes. Notably, variants in genes associated with atypical parkinsonism presented distinct clinical presentations, highlighting the importance of genetic factors in the differential diagnosis. Our study provides valuable information on the genetic landscape of PD and its clinical manifestations. The observed genotype-phenotype correlations, along with sex-specific differences, emphasize the complexity of PD pathogenesis, underlining the importance of personalized approaches to PD diagnosis and treatment. Further investigations into genetic interactions and population-specific effects are warranted to enhance our understanding of PD etiology and improve patient care.

Depressive symptoms in Brazilian Parkinson’s disease patients treated with subthalamic nucleus deep brain stimulation: A Cross-Sectional study

Parkinson’s disease (PD) is a neurological disorder that primarily affects movement and is often accompanied by depressive symptoms. Subthalamic nucleus (STN) deep brain stimulation (DBS) has emerged as a therapeutic intervention for PD, although its impact on depressive symptoms remains complex. This study investigates the relationship between PD, DBS, and depressive symptoms, focusing on how DBS influences cognitive function and mood among PD patients in Brazil. The study involved two cohorts: one in 2019 with 46 participants and another in 2022 with 31 patients. Distinct assessment instruments, including the Geriatric Depression Scale-15 and Beck Depression Inventory-II, were employed to evaluate depressive symptoms. The results revealed no significant correlation between participants’ gender and the presence of DBS, but substantial differences were observed in age, disease duration, and Activities of Daily Living scores. Patients undergoing DBS showed notably poorer cognitive performance compared to those treated solely with medication. Furthermore, the use of DBS was associated with higher scores on depressive symptoms scales within one of the cohorts. These findings underscore the intricate interplay among PD, DBS treatment, and depressive symptoms, highlighting the necessity for tailored approaches to patient care.

Reliable change indices for the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson’s disease patients

Background. The present study aimed at deriving regression-based reliable change indices (RCIs) for the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented Parkinson’s disease (PD) patients.MethodsN = 33 consecutive, non-demented PD patients were followed-up at a 5-to-8-month interval (M = 6.6; SD = 0.6) with the MoCA. Practice effects and test-retest reliability were assessed via dependent-sample t-tests and intra-class correlation (ICC) coefficients, respectively. RCIs were derived separately for raw and demographically adjusted MoCA scores according to a standardized regression-based approach by accounting for both baseline confounders (i.e., demographics, disease duration and Unified Parkinson’s Disease Rating Scale scores) and retest interval.ResultsNo practice effects were found (t(32) = 0.29; p = .778), with acceptable test-retest reliability being detected (ICC = 0.67). MoCA scores at T0 proved to be the only significant predictor of T1 MoCA performances within both the model addressing raw scores and that addressing adjusted scores (ps < 0.001).ConclusionsThe present study provides Italian practitioners and researchers with regression-based RCIs for the MoCA in non-demented PD patients, which can be reliably adopted for retest interval ≥ 5 and ≤ 8 months without encountering any practice effect.

Metabolic biomarkers of appetite control in Parkinson's disease patients with and without cognitive impairment

BackgroundAppetite dysregulation in Parkinson’s Disease (PD) appears to be linked to physical and cognitive deterioration. PD patients with and without cognitive impairment (CI) were compared to an age-matched control group to explore predictors of appetite control in fasting and post-prandial conditions. MethodsFifty-five patients were recruited and divided into three groups: twenty controls (age: 74y, BMI: 25.8kg/m2), nineteen PD patients without CI (72.5y, 25.1kg/m2) and sixteen PD patients with CI (74.3y, 24.0kg/m2). Self-reported appetite perception and circulating blood metabolic biomarkers were measured in fasting and over a three-hour post-prandial period. Biomarkers included glucose, insulin, tumour necrosis factor alpha (TNF-α), leptin, acyl-ghrelin, total ghrelin, peptide YY (PYY), glucagon like peptide 1 (GLP-1), insulin growth factor 1 (IGF-1), growth factor (GF) and triglycerides. Patients were then provided with a mixed meal to eat ad libitum with the aim to evaluate links between metabolic biomarkers and control of energy intake. ResultsPD patients with CI had a significant lower protein intake (7.4±2.5g, p=0.01) compared to controls (21.9±3.1g) and PD patients without CI (14.3±3.0g). Post-prandial plasma GLP-1 concentrations were associated with decreased hunger perception (B±SE, -5.3±2.4mm·hour-1, p=0.04). PYY concentrations were significantly associated with GLP-1 in fasting (r=0.40, p=0.005) and post-prandial (r=0.46, p<0.001) conditions. In a multivariate model, post-prandial PYY concentrations were a significant predictor of ad libitum energy intake in all subjects (B±SE, -87.5±34.9kcal, p=0.01) and in patients with PD (B±SE, -106.8±44.9kcal, p=0.04). ConclusionsPYY and GLP-1 appeared to influence appetite control in PD patients and their roles merit further investigation.

TMEM16F regulates pathologic α-synuclein secretion and spread in cellular and mouse models of Parkinson's disease.

One of the main hallmarks of Parkinson's disease (PD) pathology is the spread of the aggregate-prone protein α-synuclein (α-syn), which can be detected in the plasma and cerebrospinal fluid of patients as well as in the extracellular environment of neuronal cells. The secreted α-syn can exhibit "prion-like" behavior and transmission to naïve cells can promote conformational changes and pathology. The precise role of plasma membrane proteins in the pathologic process of α-syn is yet to be fully resolved. The TMEM16 family of lipid scramblases and ion channels has been recently associated with cancer and infectious diseases but is less known for its role in aging-related diseases. To elucidate the role of TMEM16F in α-syn spread, we transduced neurons derived from TMEM16F knockout mice with a reporter system that enables the distinction between donor and recipient neurons of pathologic α-synA53T. We found that the spread of α-synA53T was reduced in neurons derived from TMEM16F-knockout mice. These findings were recapitulated invivo in a mouse model of PD, where attenuated α-synA53T spread was observed when TMEM16F was ablated. Moreover, we identified a single nucleotide polymorphism in TMEM16F of Ashkenazi Jewish PD patients resulting in a missense Ala703Ser mutation with enhanced lipid scramblase activity. This mutation is associated with altered regulation of α-synA53T extracellular secretion in cellular models of PD. Our study highlights TMEM16F as a novel regulator of α-syn spread and as a potential therapeutic target in synucleinopathies.

LRRK2 Inhibitors as Promising Treatment for Parkinson's Disease.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, with current treatments offering only temporary symptomatic relief. There is an urgent need for the development of novel therapeutic approaches. Abnormal increases in LRRK2 kinase activity have been identified in both sporadic and familial PD patients, suggesting that inhibiting LRRK2 kinase activity presents a promising avenue for the pursuit of effective PD treatment strategies. In this Viewpoint, we discuss the exciting new insights regarding the development of LRRK2 kinase inhibitors as a treatment for Parkinson's disease.

Higher Serum Galectin‑3 Levels Were Associated with More Severe Motor Performance in Parkinson's Disease.

Parkinson's disease (PD) is a movement disorder that lacks proven biomarkers. Case-control genome-wide association studies revealed the potential effect of galectin‑3 (GAL3) on motor progression in PD patients. Based on this finding, our study aimed to explore the correlation between serum GAL3 levels and motor performance in PD patients. Five hundred PD patients and 200healthy controls were recruited. The serum levels of GAL3 were measured in participants by enzyme linked immunosorbent assay (ELISA). The baseline characteristics of the participants were collected, and the associated scale scores were obtained. Compared with healthy controls, the serum levels of GAL3 were greatly increased in PD patients. These levels could distinguish between PD patients and healthy controls with a sensitivity of 0.798 and a specificity of 0.815 (AUC = 0.795, 95% CI 0.757-0.834, P < 0.001). Patients with age >60 years tended to have higher serum GAL3 levels, disease duration, Hoehn-Yahr stage, MDS-UPDRS III total score, tremor subscores, rigid subscores, and bradykinesia subscores than those with age ≤60 years. When adjusting for confounders, higher GAL3 level was significantly correlated with MDS-UPDRS III total score and rigid subscores. In men with PD, GAL3 was significantly correlated with MDS-UPDRS III total score; but the association between GAL3 and bradykinesia subscores was found in women. Moreover, the associations between GAL3 with MDS-UPDRS III total score and bradykinesia subscores were significant in patients with age >60 years. Higher GAL3 level was related to more severe motor performance in patients with age >60 years, and it may be a potential predictive biomarker for motor performance in PD patients.

The effectiveness and safety of botulinum toxin injections for managing motor disorders of patients with Parkinson's disease: A meta-analysis of randomized controlled trials.

This study aimed to assess the effectiveness and safety of botulinum toxin (BTX) injections for managing motor disorders in patients with Parkinson's disease (PD). An electronic search was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from available randomized controlled trials (RCTs) assessing BTX injections for motor disorders in PD patients were extracted for meta-analysis. Ultimately, 215 patients from eight RCTs were enrolled. Pooled analyses indicated that BTX was more effective than placebo in improving tremor (standardized mean difference [SMD] = 0.96, 95% CI [0.34, 1.58], p < 0.01), whereas no notable differences were observed between BTX and placebo regarding freezing of gait (SMD = 0.66, 95% CI [-0.26, 1.58], p = 0.162), United Parkinson's Disease Rate Scale (UPDRS) III score (SMD = -0.20, 95% CI [-1.17, 0.76], p = 0.68) and clinical global impression (CGI) score (SMD = 0.84, 95% CI [-0.74, 2.42], p = 0.298). Adverse events related to BTX injections were comparable to placebo (OR = 1.74, 95% CI [0.59, 5.14], p = 0.32). The current evidence suggests that BTX is effective and safe in treating PD tremor but fails to provide therapeutic benefits for freezing of gait and motor functional scores in PD patients. Furthermore, the limited number of included studies and heterogeneity in BTX intervention protocols suggest more research is needed, with additional standardized RCTs, to better understand and optimize BTX injections for motor disorders in PD.

Deficits in or Preservation of Basic Number Processing in Parkinson's Disease? A Registered Report.

Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health care system. Until now, diagnosis of mild cognitive impairments in PD has been established based on domain-general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD-immanent deterioration of domain-general functions and domain-specific numerical areas suggests mechanisms of both primary and secondary dyscalculia. The current study systematically investigated basic number processing performance in PD patients for the first time, targeting domain-specific cognitive representations of numerosity and the influence of domain-general factors. The overall sample consisted of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients were stratified into patients with normal cognition (PD-NC) or mild cognitive impairment (level I-PD-MCI based on cognitive screening). Basic number processing was assessed using transcoding, number line estimation, and (non-) symbolic number magnitude comparison tasks. Discriminant analysis was employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants were subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Results indicate a profile of preserved (verbal representation) and impaired (magnitude representation, place × value activation) function in PD-MCI, hinting at basal ganglia dysfunction affecting numerical cognition in PD. Numerical deficits could not be explained by domain-general cognitive impairments, so that future research needs to incorporate domain-specific tasks of sufficient difficulty.

Choroidal thickness in the eyes of Parkinson's disease patients measured using optical coherence tomography: A systematic review and meta-analysis

BackgroundParkinson's disease (PD) presents a complex etiology involving genetics and environmental factors. Non-motor symptoms often precede motor manifestations. Dopaminergic neuron degeneration, oxidative stress, and vascular changes characterize PD. Retinal changes are studied as potential biomarkers, yet choroidal involvement remains unclear. This review aims to clarify choroidal thickness's role in PD progression for diagnostic advancements. MethodsWe examined PubMed, Scopus, and Embase databases. Depending on the heterogeneity, an appropriate model was used for the meta-analysis. Additionally, meta-regression, publication bias, subgroup analyses, and quality evaluation were carried out. ResultsWe evaluated twelve studies involving 442 PD patients and 608 healthy controls. This study found insignificant differences in choroidal thickness between PD patients and healthy controls. ConclusionChoroidal thickness is influenced by age, axial length, and intraocular pressure, with PD potentially impacting thickness through neurodegenerative mechanisms. However, inconsistencies exist in the findings, warranting further investigation. Future studies should explore the impact of disease severity, medication effects, and other confounding variables on choroidal thickness in PD patients. Additionally, advanced imaging modalities like optical coherence tomography angiography (OCTA) may provide more comprehensive evaluations of choroidal vascular changes in PD.

Blood-Based Nanoparticle-Enhanced Quaking-Induced Conversion (Nano-QuIC): Inhibitor-Resistant Detection of Seeding Activity in Patients Diagnosed with Parkinson's Disease.

A hallmark of α-synucleinopathies (e.g., Parkinson's disease) is the misfolding and aggregation of α-synuclein in tissues and biological fluids. Protein amplification assays like real-time quaking-induced conversion (RT-QuIC) are sensitive yet currently limited to semi-invasive sample types such as cerebrospinal fluid because more accessible samples, such as blood, contain inhibitors. Here, we show that Nanoparticle-enhanced Quaking-induced Conversion (Nano-QuIC) can double the speed of reactions spiked with misfolded α-synuclein while increasing sensitivity 100-fold in human plasma. Nano-QuIC detected spike concentrations down to 90 pg/mL in lysed whole blood, while reactions without nanoparticles (RT-QuIC) failed to have any detection due to the presence of strong inhibitors. Moreover, Nano-QuIC showed increased seeding activity in plasma samples from Parkinson's patients (n = 4) versus healthy controls (n = 4). This sets the groundwork for the noninvasive diagnostic use of Nano-QuIC, potentially enabling early disease detection and management through blood-based testing.

Protecting Parkinson's Patients: Hospital Care Standards to Avoid Preventable Harm

Protecting Parkinson's Patients: Hospital Care Standards to Avoid Preventable Harm

Regional gray matter volumes are not predictive of axial symptom response to subthalamic deep brain stimulation in Parkinsonian patients

IntroductionIn Parkinson’s disease (PD), axial symptom response to deep brain stimulation of the subthalamic nucleus (STN-DBS) is heterogeneous. This single-center, retrospective study aimed to assess imaging biomarkers of routine magnetic resonance imaging (MRI) to predict axial symptom response to STN-DBS, specifically by using an index of volumes of mesencephalon, pons, middle, and superior peduncle (“MR PIGD index”). MethodsWe investigated 94 PD patients pre- and three to six months postoperatively by using MDS-UPDRS III, Berg Balance Scale, Freezing of Gait Questionnaire (FOG-Q) and Ziegler Course, which were related to regional brain volumetry information using regression analysis and partial least squares correlation analysis. ResultsSTN-DBS led to significant, but heterogeneous improvement of axial PD symptoms. Neither the MR PIGD index nor other cortical brain volumes predicted the extent of the postoperative, axial symptom improvement. ConclusionsResponse to STN-DBS in PD cannot be predicted by MRI regional gray matter volumes.

Static and Dynamic Functional Network Connectivity inParkinson's Disease Patients With Postural Instability andGait Disorder.

The exact cause of the parkinsonism gait remains uncertain. We first focus on understanding the underlying neurological reasons for these symptoms through the examination of both static functional network connectivity (SFNC) and dynamic functional network connectivity (DFNC). We recruited 64 postural instability and gait disorder-dominated Parkinson's disease (PIGD-PD) patients, 31 non-PIGD-PD (nPIGD-PD) patients, and 54 healthy controls (HC) from Nanjing Brain Hospital. The GIFT software identified five distinct independent components: the basal ganglia (BG), cerebellum (CB), sensory networks (SMN), default mode network (DMN), and central executive network (CEN). We conducted a comparison between the SFNC and DFNC of the five networks and analyzed their correlations with postural instability and gait disorder (PIGD) symptoms. Compared with nPIGD-PD patients, the PIGD-PD patients demonstrated reduced connectivity between CEN and DMN while spending less mean dwell time (MDT) in state 4. This is characterized by strong connections. Compared with HC, PIGD-PD patients exhibited enhanced connectivity in the SFNC between CB and CEN, as well as the network between CB and DMN. Patients with PIGD-PD spent more MDT in state 1, which is characterized by few connections, and less MDT in state 4. In state 3, there was an increase in the functional connectivity between the CB and DMN in patients with PIGD-PD. The nPIGD patients showed increased SFNC connectivity between CB and DMN compared to HC. These patients spent more MDT in state 1 and less in state 4. The MDT and fractional windows of state 2 showed a positive link with PIGD scores. Patients with PIGD-PD exhibit a higher likelihood of experiencing reduced brain connectivity and impaired information processing. The enhanced connection between the cerebellum and DMN networks is considered a type of dynamic compensation.