Enantiomorphic Site-Assisted Chain End Control Stereospecific Alternating Copolymerization of Chiral Cyclic Diesters.

Stereospecific alternating copolymerization of different chiral cyclic esters is one feasible approach to enrich the structural diversity of copolyesters and tailor their properties. However, dramatically different reactivities of different cyclic esters let a perfectly stereospecific alternating polymerization of these cyclic esters be a challenge, thus the catalyst is required to balance their reactivities. Herein, a remarkable enantiomorphic site effect on chain end control was discovered and successfully utilized to balance the reactivities of highly reactive S, S-lactide (S, S-LA) and low reactive R, R-ethylglycolide (R, R-EG)/R, R-propylglycolide (R, R-PG) during their heterospecific alternating copolymerization. The enantiomorphic site of R, R-SalenAl complex can increase the relative reactivity of R, R-EG/R, R-PG and suppress that of S, S-LA, then a perfectly alternating sequence of the copolymer of S, S-LA and R, R-EG/R, R-PG can be achieved (Palt = 0.96/0.91); inversely, using S, S-SalenAl complex, the significant enantiomorphic site effect enlarges the reactivity difference of two monomers, the alternating level was just 0.70/0.68 even to 0.61. Poly(S, S-LA-alt-R, R-EG) with a high alternating regularity exhibits lower glass transition temperatures and a dramatically higher elongation at break (εB = 449 ± 51% (Palt = 0.96) vs εB = 6 ± 1% (Palt = 0.70)).

Tetrabutylammonium Halides as Selectively Bifunctional Catalysts Enabling the Syntheses of Recyclable High Molecular Weight Salicylic Acid-Based Copolyesters.

To synthesize high molecular weight poly(phenolic ester) via a living ring-opening polymerization (ROP) of cyclic phenolic ester monomers remains a critical challenge due to serious transesterification and back-biting reactions. Both phenolic ester bonds in monomer and polymer chains are highly active, and it is difficult so far to distinguish them. In this work, an unprecedented selectively bifunctional catalytic system of tetra-n-butylammonium chloride (TBACl) was discovered to mediate the syntheses of high molecular weight salicylic acid-based copolyesters via a living ROP of salicylate cyclic esters (for poly(salicylic methyl glycolide) (PSMG), Mn =361.8 kg/mol, Ð<1.30). Compared to previous catalysis systems, the side reactions were suppressed remarkably in this catalysis system because phenolic ester bond in monomer can be selectively cleaved over that in polymer chains during ROP progress. Mechanistic studies reveal that the halide anion and alkyl-quaternaryammonium cation work synergistically, where the alkyl-quaternaryammonium cation moiety interacts with the carbonyl group of substrates via non-classical hydrogen bonding. Moreover, these salicylic acid-based copolyesters can be recycled to dimeric monomer under solution condition, and can be recycled to original monomeric monomers without catalyst under sublimation condition.

Impaired Ocular Tracking and Cortical Atrophy in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of synucleinopathies. Patients with synucleinopathies frequently display eye movement abnormalities. However, whether patients with iRBD have eye movement abnormalities remains unknown. OBJECTIVE: The aim of this study was to assess eye movement abnormalities and related gray matter alterations and explore whether such abnormalities can serve as biomarkers to indicate phenoconversion to synucleinopathies in iRBD. METHODS: Forty patients with iRBD with early disease progression and 35 healthy control subjects participated in a 15-minute ocular-tracking task that evaluated their control of eye movement abilities. They also underwent clinical assessments for olfactory function, nonmotor symptoms, and autonomic symptoms, all of which are biomarkers to predict phenoconversion to synucleinopathies in iRBD. A subgroup of the participants (20 patients with iRBD and 20 healthy control subjects) also participated in structural magnetic resonance imaging. RESULTS: The ocular-tracking ability in patients with iRBD was inferior to that of healthy control subjects in two aspects: pursuit initiation and steady-state tracking. Cortical thinning in the right visual area V4 in patients with iRBD is coupled with impaired pursuit initiation. Furthermore, prolonged pursuit initiation in patients with iRBD exhibits a trend of correlation with olfactory loss, the earliest biomarker that develops prior to other prodromal biomarkers. CONCLUSIONS: We found ocular-tracking abnormalities in patients with iRBD even early in their disease progression that have not been reported before. These abnormalities are coupled with atrophy of brain areas involved in the perception of object motion and might indicate phenoconversion to synucleinopathies in iRBD. © 2022 International Parkinson and Movement Disorder Society.

Increased free water in the substantia nigra in idiopathic REM sleep behaviour disorder.

Imaging markers sensitive to neurodegeneration in the substantia nigra are critically needed for future disease-modifying trials. Previous studies have demonstrated the utility of posterior substantia nigra free water as a marker of progression in Parkinson's disease. In this study, we tested the hypothesis that free water is elevated in the posterior substantia nigra of idiopathic REM sleep behaviour disorder, which is considered a prodromal stage of synucleinopathy. We applied free-water imaging to 32 healthy control subjects, 34 patients with idiopathic REM sleep behaviour disorder and 38 patients with Parkinson's disease. Eighteen healthy control subjects and 22 patients with idiopathic REM sleep behaviour disorder were followed up and completed longitudinal free-water imaging. Free-water values in the substantia nigra were calculated for each individual and compared among groups. We tested the associations between posterior substantia nigra free water and uptake of striatal dopamine transporter in idiopathic REM sleep behaviour disorder. Free-water values in the posterior substantia nigra were significantly higher in the patients with idiopathic REM sleep behaviour disorder patients than in the healthy control subjects, but were significantly lower in patients with idiopathic REM sleep behaviour disorder than in patients with Parkinson's disease. In addition, we observed significantly negative associations between posterior substantia nigra free-water values and dopamine transporter striatal binding ratios in the idiopathic REM sleep behaviour disorder patients. Longitudinal free-water imaging analyses were conducted with a linear mixed-effects model, and showed a significant Group × Time interaction in posterior substantia nigra, identifying increased mean free-water values in posterior substantia nigra of idiopathic REM sleep behaviour disorder over time. These results demonstrate that free water in the posterior substantia nigra is a valid imaging marker of neurodegeneration in idiopathic REM sleep behaviour disorder, which has the potential to be used as an indicator in disease-modifying trials.

Photoinduced Promiscuity of Cyclohexanone Monooxygenase for the Enantioselective Synthesis of α-Fluoroketones.

The development of mild, efficient, and enantioselective methods for preparing chiral fluorinated compounds has been a long-standing challenge. Herein, we report a promiscuous cyclohexanone monooxygenase (CHMO) for the photoinduced synthesis of chiral α-fluoroketones via enantioselective reductive dehalogenation of α,α-halofluoroketones. Wild-type CHMO from Acinetobacter sp. possesses this promiscuous ability innately; however, the yield and stereoselectivity are low. A structure-guided rational design of CHMO improved the yield and stereoselectivity remarkably. Mechanistic studies and molecular simulations demonstrated that this photoinduced CHMO catalyzes the reductive dehalogenation via a novel electron transfer (ET)/proton transfer (PT) mechanism, distinct from that of previously reported reductases with similar promiscuity. This methodology was expanded to various substrates, and desirable chiral α-fluoroketones were obtained in high yields (up to 99 %) and e.r. values (up to 99:1).

Isotactic-Alternating, Heterotactic-Alternating, and ABAA-Type Sequence-Controlled Copolyester Syntheses via Highly Stereoselective and Regioselective Ring-Opening Polymerization of Cyclic Diesters.

Synthesizing different types of sequence-controlled copolyesters can enrich the diversity of copolyesters and modify their properties more precisely, but it is still a challenge to synthesize a complicated sequence-controlled copolyester using different hydroxy acids in a living polymerization manner. In this work, a highly regioselective and stereoselective catalytic system was developed to synthesize biorenewable and biodegradable copolyesters of mandelic acid and lactic acid with isotactic-alternating, heterotactic-alternating, and ABAA-type precise and complicated sequences. Because of the regular incorporation of mandelic acid into polylactide, these sequence-controlled copolymers of mandelic acid and lactic acid show higher glass-transition temperatures than polylactide and a random copolymer. A stereocomplexation interaction between two opposite enantiomeric isotactic polymer chains was also discovered in the isotactic-alternating copolymer.

Altered structure and functional connectivity of the central autonomic network in idiopathic rapid eye movement sleep behaviour disorder.

Evidence suggests peripheral autonomic structures may contribute to autonomic dysfunction in idiopathic rapid eye movement sleep behaviour disorder (iRBD). However, whether the central autonomic network (CAN) is affected in iRBD remains unclear. Magnetic resonance imaging data were acquired from 65 participants (32 patients with iRBD and 33 matched healthy controls). We investigated the CAN in patients with iRBD using a combined voxel-based morphometry and resting-state functional connectivity analysis and characterised the relationships between alterations of the CAN and autonomic symptoms. Patients with iRBD had significantly reduced grey matter volume in the brainstem, anterior cingulate and insula compared with healthy controls. Functional connectivity analysis revealed reduced functional connectivity between the brainstem and the cerebellum posterior lobe, temporal lobe and anterior cingulate in patients with iRBD. In patients with iRBD, both reduced grey matter volume and decreased functional connectivity of the CAN were negatively correlated with the Scales for Outcomes in Parkinson's Disease-Autonomic scores. The present study demonstrated that both the structure and the functional connectivity of the CAN were abnormal in patients with iRBD. In addition, correlation analysis suggested that CAN abnormalities may also play a role in the development of autonomic symptoms in iRBD.

Dendrobium officinale flos increases neurotrophic factor expression in the hippocampus of chronic unpredictable mild stress-exposed mice and in astrocyte primary culture and potentiates NGF-induced neuronal differentiation in PC12 cells.

Dendrobium officinale flos (DOF) is the flower of Dendrobium officinale Kimura et Migo, which is usually regarded as a by-product of Dendrobii Offcinalis Caulis. Based on its use as an alternative medicine, we evaluated the antidepressant-like effect of DOF extracts on chronic, unpredictable, mild stress-induced, depression-like behaviour in mice and tested the effects of DOF on the regulation of neurotrophic factors in mouse astrocyte primary cultures and PC12 cell lines. Oral treatment with DOF ethanol extract (DOF-E) could alleviate depression-like behaviours in stress-exposed mice, as evidenced by increased sucrose consumption and decreased immobile time in a forced swim test. In the hippocampus, DOF extracts increased the expression of NGF and BDNF, both at the transcriptional and protein levels. In astrocytes, DOF-E increased the expression of NGF and BDNF via a cAMP-dependent mechanism and regulated plasminogen and matrix metallopeptidase 9 (MMP-9), which are related to the metabolic regulation of neurotrophic factors. In PC12 cells, DOF-E induced the expression of neurofilaments and potentiated the induction of neurite outgrowth upon treatment with a low dose of NGF. Based on these findings, DOF might be used as a supplement for antidepressant therapy in patients with depression.

Autonomic dysfunction in Parkinson's disease: Implications for pathophysiology, diagnosis, and treatment.

Parkinson's disease (PD) is a neurodegenerative disease with a 200 year-long research history. Our understanding about its clinical phenotype and pathogenesis remains limited, although dopaminergic replacement therapy has significantly improved patient outcomes. Autonomic dysfunction is an essential category of non-motor phenotypes that has recently become a cutting edge field that directs frontier research in PD. In this review, we initially describe the epidemiology of dysautonomic symptoms in PD. Then, we perform a meticulous analysis of the pathophysiology of autonomic dysfunction in PD and propose that the peripheral autonomic nervous system may be a key route for α-synuclein pathology propagation from the periphery to the central nervous system. In addition, we recommend that constipation, orthostatic hypotension, urinary dysfunction, erectile dysfunction, and pure autonomic failure should be viewed as prodromal dysautonomic markers in PD prediction and diagnosis. Finally, we summarize the strategies currently available for the treatment of autonomic dysfunction in PD and suggest that high-quality, better-designed, randomized clinical trials should be conducted in the future.

CXCL12 is involved in α-synuclein-triggered neuroinflammation of Parkinson's disease.

BACKGROUND: The mechanisms underlying the pathogenesis and progression of Parkinson's disease (PD) remain elusive, but recent opinions and perspectives have focused on whether the inflammation process induced by microglia contributes to α-synuclein-mediated toxicity. Migration of microglia to the substantia nigra (SN) could precede neurodegeneration in A53T mice. We hypothesized that CXCL12 could be a mediator in the α-synuclein-induced migration of microglia. METHODS: After establishing appropriate animal and cell culture models, we explored the relationship between α-synuclein and CXCL12 in A53T mice, primary microglia, and BV-2 cell lines. We also explored the mechanisms of these interactions and the signaling processes involved in neuroinflammation. RESULTS: We confirmed the positive correlation between α-synuclein and CXCL12 in the postmortem brain tissue of PD patients and the upregulated CXCR4 expression in SN microglia of A53T mice. In addition, as expected, α-synuclein increased the production of CXCL12 in microglia via TLR4/IκB-α/NF-κB signaling. Importantly, CXCL12/CXCR4/FAK/Src/Rac1 signaling was shown to be involved in α-synuclein-induced microglial accumulation. CONCLUSIONS: Our study suggests that CXCL12 could be a novel target for the prevention of α-synuclein-triggered ongoing microglial responses. Blocking CXCL12/CXCR4 may be a potential therapeutic approach for PD progression.

Volume Stability and Frost Resistance of High-Ductility Magnesium Phosphate Cementitious Concrete.

To address the issue of pavement cracking due to brittle concrete in road and bridge engineering, this study explores the use of high-ductility magnesium phosphate cementitious concrete (HD-MPCC) for rapid repairs. The deformation and frost properties of HD-MPCC are analyzed to assess its suitability for this application. Deformation properties were tested for HD-MPCC specimens cured in both air and water. Subsequent tests focused on the frost performance and mechanical properties after freeze-thaw cycles. A mercury penetration technique was utilized to examine the pore structure. The findings reveal that the expansion deformation of HD-MPCC increases with curing age in both air and water conditions, and the quantitative relationship between the expansion deformation and curing age of HD-MPCC was analyzed. Additionally, the freeze-thaw cycles led to a decrease in mass loss, the relative dynamic elastic modulus, the ultimate tensile strength, the ultimate tensile strain, the flexural strength, and the peak deflection. The volume fraction of harmless and less harmful pores gradually decreased as the freeze-thaw cycle increased, while the volume fraction of more harmful pores increased, resulting in a decrease in the strength, ultimate tensile strain, and peak deflection.

Neuronal-enriched small extracellular vesicles trigger a PD-L1-mediated broad suppression of T cells in Parkinson's disease.

Many clinical studies indicate a significant decrease of peripheral T cells in Parkinson's disease (PD). There is currently no mechanistic explanation for this important observation. Here, we found that small extracellular vesicles (sEVs) derived from in vitro and in vivo PD models suppressed IL-4 and INF-γ production from both purified CD4+ and CD8+ T cells and inhibited their activation and proliferation. Furthermore, neuronal-enriched sEVs (NEEVs) isolated from plasma of A53T-syn mice and culture media of human dopaminergic neurons carrying A53T-syn mutation also suppressed Th1 and Th2 differentiation of naive CD4+ T cells. Mechanistically, the suppressed phenotype induced by NEEVs was associated with altered programmed death ligand 1 (PD-L1) level in T cells. Blocking PD-L1 with an anti-PD-L1 antibody or a small molecule inhibitor BMS-1166 reversed T cell suppression. Our study provides the basis for exploring peripheral T cells in PD pathogenesis and as biomarkers or therapeutic targets for the disease.

MAPT rs17649553 T allele is associated with better verbal memory and higher small-world properties in Parkinson's disease.

Currently, over 90 genetic loci have been found to be associated with Parkinson's disease (PD) in genome-wide association studies, nevertheless, the effects of these genetic variants on the clinical features and brain structure of PD patients are largely unknown. This study investigated the effects of microtubule-associated protein tau (MAPT) rs17649553 (C>T), a genetic variant associated with reduced PD risk, on the clinical manifestations and brain networks of PD patients. We found MAPT rs17649553 T allele was associated with better verbal memory in PD patients. In addition, MAPT rs17649553 significantly shaped the topology of gray matter covariance network and white matter network. Both the network metrics in gray matter covariance network and white matter network were correlated with verbal memory, however, the mediation analysis showed that it was the small-world properties in white matter network that mediated the effects of MAPT rs17649553 on verbal memory. These results suggest that MAPT rs17649553 T allele is associated with higher small-world properties in structural network and better verbal memory in PD.

Effect of Ambient Temperature on the Mechanical Properties of High Ductility Concrete.

This study analyzes the mechanical properties of high ductility concrete (HDC) under different ambient temperatures to provide a parameter basis for the design of HDC bridge deck link slabs. Five temperatures (-30, 0, 20, 40, and 60 °C) were designed to investigate the compressive, tensile, and flexural properties of HDC after temperature treatment and analyze the pore structure. The results show that, compared with the HDC performance at room temperature (20 °C), the compressive strength, ultimate tensile strength, and flexural strength decreased after treatment at low temperatures (-30 and 0 °C), while the strength increased after treatment at high temperatures (40 and 60 °C). After experiencing low- and high-temperature treatments, the ultimate tensile strain and ultimate deflection of the HDC increased. The tensile and flexural failures of the HDC exhibited multiple cracking, and the stress-strain/deflection curve showed a strain/deflection hardening stage. The tensile constitutive relationship can be simplified as a bilinear two-stage relationship. As the temperature increased, the porosity of harmless and less harmful pores in HDC gradually increased, while the porosity of harmful and more harmful pores gradually decreased, resulting in an increase in HDC strength. Based on the influence of temperature on HDC properties, design parameters for the HDC bridge deck link slab structure are proposed.

Age and sex differentially shape brain networks in Parkinson's disease.

AIMS: Age and sex are important individual factors modifying the clinical symptoms of patients with Parkinson's disease (PD). Our goal is to evaluate the effects of age and sex on brain networks and clinical manifestations of PD patients. METHODS: Parkinson's disease participants (n = 198) receiving functional magnetic resonance imaging from Parkinson's Progression Markers Initiative database were investigated. Participants were classified into lower quartile group (age rank: 0%~25%), interquartile group (age rank: 26%~75%), and upper quartile group (age rank: 76%~100%) according to their age quartiles to examine how age shapes brain network topology. The differences of brain network topological properties between male and female participants were also investigated. RESULTS: Parkinson's disease patients in the upper quartile age group exhibited disrupted network topology of white matter networks and impaired integrity of white matter fibers compared to lower quartile age group. In contrast, sex preferentially shaped the small-world topology of gray matter covariance network. Differential network metrics mediated the effects of age and sex on cognitive function of PD patients. CONCLUSION: Age and sex have diverse effects on brain structural networks and cognitive function of PD patients, highlighting their roles in the clinical management of PD.

Amperometric immunosensor for carcinoembryonic antigen detection with carbon nanotube-based film decorated with gold nanoclusters.

A new amperometric immunosensor for the determination of carcinoembryonic antigen (CEA) was constructed. First, the uniform nanomultilayer film was fabricated via layer-by-layer (LBL) assembly of positively charged carbon nanotubes wrapped by poly(diallyldimethylammonium chloride) and negatively charged poly(sodium-p-styrene-sulfonate), which could provide a high accessible surface area and a biocompatible microenvironment. Subsequently, gold nanoclusters were electrodeposited on the electrode to immobilize anti-CEA. The fabricated process and electrochemical behaviors of the immunosensor were characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM). Under optimal conditions, the proposed immunosensor could detect CEA in two linear ranges from 0.1 to 2.0 ng mL(-1) and from 2.0 to 160.0 ng mL(-1), with a detection limit of 0.06 ng mL(-1).

Bienzyme bionanomultilayer electrode for glucose biosensing based on functional carbon nanotubes and sugar-lectin biospecific interaction.

Bienzyme bionanomultilayer electrode for glucose biosensing was constructed based on functional carbon nanotubes and sugar-lectin biospecific interaction through layer-by-layer (LBL) assembly. After being functionalized by wrapping with polyelectrolyte, multiwalled carbon nanotubes (MCNTs) were water soluble and positively charged. MCNT-bienzyme bionanomultilayer electrode was then fabricated by LBL assembly of horseradish peroxidase (HRP) and glucose oxidase (GOD) on functional MCNT modified electrode. The attachment of the MCNT-bienzyme bionanomultilayer with the underlying electrode and each layer in the bionanomultilayer was based on reliably electrostatic or sugar-lectin biospecific interaction. The developed bienzyme biosensor exhibited fast amperometric response for the determination of glucose. The linear response of the developed biosensor for the determination of glucose ranged from 2.0 x 10(-6) to 1.7 x 10(-4) M with a detection limit of 2.5 x 10(-7) M. The biosensor can be used directly to determine glucose in serum. The construction of the bienzyme biosensor showed potential for the preparation of MCNT-enzyme nanocomposite with controllability and high performance.

Dynamic functional connectivity impairments in idiopathic rapid eye movement sleep behavior disorder.

INTRODUCTION: Previous functional magnetic resonance imaging (fMRI) studies typically analyzed static functional connectivity (sFC) to reveal the pathophysiology of iRBD and overlooked the dynamic nature of brain activity. Thus, we aimed to explore whether iRBD showed abnormalities of brain network dynamics using the dynamic functional connectivity (dFC) approach. METHODS: Resting-state fMRI data from 33 iRBD patients and 38 matched healthy controls were analyzed using an independent component analysis, sliding window correlation and k-means clustering. Relationships between clinical symptoms and abnormal dFC were evaluated using Spearman's correlation analysis. RESULTS: Four distinct connectivity states were identified to characterize and compare dFC patterns. We demonstrated that iRBD had fewer occurrences and a shorter dwell time in the infrequent and strongly connected State 1, but with more occurrences and a longer dwell time in the frequent and sparsely connected State 2. In addition, iRBD patients showed significantly decreased FC in certain dFC states compared to healthy controls. More importantly, the impairments in the temporal properties of State 2 were found to be associated RBDSQ scores in the patient group. CONCLUSIONS: This study detected dFC impairments in iRBD patients and provided new insights into the pathophysiology of iRBD, which might contribute to the development of disease-modifying drugs in future clinical trials.

Abnormal intrinsic brain activity of the putamen is correlated with dopamine deficiency in idiopathic rapid eye movement sleep behavior disorder.

OBJECTIVES: To investigate the changes in spontaneous neuronal activity of the striatum in idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) patients using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analysis. Furthermore, we tested the association between abnormal spontaneous brain activity and dopamine deficit in patients with iRBD. METHODS: Fifteen iRBD patients and 15 matched healthy controls received resting state magnetic resonance imaging (MRI) and neuropsychological assessments. ReHo and ALFF in subregions of the striatum were calculated and compared between groups in a voxel-by-voxel manner. In addition, 15 iRBD patients and seven healthy controls underwent dopamine transporter single photon computed emission tomography (DAT-SPECT) imaging. Correlation analysis was also performed to investigate whether the altered spontaneous brain activity could be correlated with dopamine deficiency in iRBD patients. RESULTS: We found that iRBD patients, compared with healthy controls, exhibited significantly reduced ReHo in the bilateral putamen. Patients also had significantly decreased tracer uptake in the bilateral putamen and left caudate. In addition, a significantly positive correlation was observed between the mean ReHo value and the tracer uptake ratio in the left putamen of iRBD patients. CONCLUSIONS: We detected abnormal spontaneous brain activity of the bilateral putamen in iRBD patients. These findings could be complementary to the Braak staging model and could help to clarify the pathophysiology of iRBD.

Gait Characteristics and Brain Activity in Parkinson's Disease with Concomitant Postural Abnormalities.

To explore the underlying pathogenic mechanism of Parkinson's disease (PD) with concomitant postural abnormalities (PDPA) through the relationship between its gait and brain function characteristics. PD patients from the neurology outpatient clinic at Ruijin Hospital were recruited and grouped according to whether postural abnormalities (including camptocormia and Pisa syndrome) were present. PD-related scale assessments, three-dimensional gait tests and brain resting-state functional magnetic imaging were performed and analyzed. The gait characteristics independently associated with PDPA were decreased pelvic obliquity angle and progressive downward movement of the center of mass during walking. PDPA features included decreased functional connectivity between the left insula and bilateral supplementary motor area, which was significantly correlated with reduced Berg Balance Scale scores. Functional connectivity between the right insula and bilateral middle frontal gyrus was decreased and significantly correlated with a decreased pelvic obliquity angle and poor performance on the Timed Up and Go test. Moreover, through diffusion tensor imaging analysis, the average fractional anisotropy value of the fibers connecting the left insula and left supplementary motor area was shown to be decreased in PDPA. There is decreased functional connectivity among the insula, supplementary motor area and middle frontal gyrus with structural abnormalities between the left insula and the left supplementary motor area; these changes in brain connectivity are probably among the causes of gait dysfunction in PDPA and provide some clues regarding the pathogenic mechanisms of PDPA.