scholarly journals The Association between DRD3 Ser9Gly Polymorphism and Depression Severity in Parkinson’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Yan Zhi ◽  
Yongsheng Yuan ◽  
Qianqian Si ◽  
Min Wang ◽  
Yuting Shen ◽  
...  

More and more evidence suggests that dopamine receptor D3 gene (DRD3) plays an important role in the clinical manifestations and the treatment of Parkinson’s disease (PD). DRD3 Ser9Gly polymorphism is the most frequently studied variant point. Our aim was to investigate the potential effect of DRD3 Ser9Gly polymorphism on modulating resting-state brain function and associative clinical manifestations in PD patients. We consecutively recruited 61 idiopathic PD patients and 47 healthy controls (HC) who were evaluated by clinical scales, genotyped for variant Ser9Gly in DRD3, and underwent resting-state functional magnetic resonance imaging. Based on DRD3 Ser9Gly polymorphism, PD patients and HCs were divided into four subgroups. Then, two-way analysis of covariance (ANCOVA) was applied to investigate main effects and interactions of PD and DRD3 Ser9Gly polymorphism on the brain function via amplitude of low-frequency fluctuations (ALFF) approach. The association between DRD3 Ser9Gly-modulated significantly different brain regions, and clinical manifestations were detected by Spearman’s correlations. PD patients exhibited decreased ALFF values in the right inferior occipital gyrus, lingual gyrus, and fusiform gyrus. A significant difference in the interaction of “groups × genotypes” was observed in the right medial frontal gyrus. The ALFF value of the cluster showing significant interactions was positively correlated with HAMD-17 scores (r=0.489, p=0.011) and anhedonia scores (r=0.512, p=0.008) in PD patients with the Ser/Gly or Gly/Gly genotypes. Therefore, D3 gene Ser9Gly polymorphism might be associated with the severity of depression characterized by anhedonia in PD patients.

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Yu-Ting Shen ◽  
Yong-Sheng Yuan ◽  
Min Wang ◽  
Yan Zhi ◽  
Jian-Wei Wang ◽  
...  

Abstract Alterations in brain function in Parkinson’s disease (PD) patients with diphasic dyskinesia have not been investigated. We aimed to explore the alterations in regional brain function. Each of 53 levodopa (LD)-treated PD patients had two resting-state functional magnetic resonance imaging (rs-fMRI) scans in the same morning, before and after taking LD. The regional homogeneity (ReHo) approach was used to reveal local synchronization changes. Two-way factorial repeated measures analysis of covariance, with group as a between-subject factor and LD effect as a within-subject factor, was performed to explore the two main effects and interaction. Interactive analysis was used to show outcomes that combined disease status and LD effect. Spearman’s correlations were used to detect associations between interactive brain regions and severity of dyskinetic symptoms, assessed by the Unified Dyskinesia Rating Scale (UDyRS) scores, along with moderation analyses. There was no significant difference in the main group effect analysis. Significantly different clusters obtained from main LD effect analysis were in left caudate nucleus and putamen. ReHo values decreased in the caudate nucleus and increased in the putamen during the ON state after taking LD. Interaction between group and LD effect was found in left medial superior frontal gyrus (mSFG), where there were the lowest ReHo values, and was negatively correlated with UDyRS scores in the diphasic dyskinetic group during the ON state. The relationship was independent of LD dose. Abnormal local synchronization in the mSFG is closely associated with the development of diphasic dyskinesia in PD patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Kai Li ◽  
Hong Zhao ◽  
Chun-Mei Li ◽  
Xin-Xin Ma ◽  
Min Chen ◽  
...  

Objective. Motor symptoms are usually asymmetric in Parkinson’s disease (PD), and asymmetry in PD may involve widespread brain areas. We sought to evaluate the effect of asymmetry on the whole brain spontaneous activity using the measure regional homogeneity (ReHo) through resting-state functional MRI. Methods. We recruited 30 PD patients with left onset (LPD), 27 with right side (RPD), and 32 controls with satisfactory data. Their demographic, clinical, and neuropsychological information were obtained. Resting-state functional MRI was performed, and ReHo was used to determine the brain activity. ANCOVA was utilized to analyze between-group differences in ReHo and the associations between abnormal ReHo, and various clinical and neuropsychological variables were explored by Spearman’s correlation. Results. LPD patients had higher ReHo in the right temporal pole than the controls. RPD patients had increased ReHo in the right temporal pole and decreased ReHo in the primary motor cortex and premotor area, compared with the controls. Directly comparing LPD and RPD patients did not show a significant difference in ReHo. ReHo of the right temporal pole was significantly correlated with depression and anxiety in RPD patients. Conclusions. Both LPD and RPD have increased brain activity synchronization in the right temporal pole, and only RPD has decreased brain activity synchronization in the right frontal motor areas. The changed brain activity in the right temporal pole may play a compensatory role for depression and anxiety in PD, and the altered cerebral function in the right frontal motor area in RPD may represent the reorganization of the motor system in RPD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Su ◽  
Kai Li ◽  
Chun-Mei Li ◽  
Xin-Xin Ma ◽  
Hong Zhao ◽  
...  

Objective: The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that lateralization affects cortico-striatal functional connectivity in PD. The present study sought to evaluate the effect of lateralization on various cortico-striatal circuits through resting-state functional magnetic resonance imaging (fMRI).Methods: Thirty left-onset Parkinson's disease (LPD) patients, 27 right-onset Parkinson's disease (RPD) patients, and 32 normal controls with satisfactory data were recruited. Their demographic, clinical, and neuropsychological information was collected. Resting-state fMRI was performed, and functional connectivity changes of seven subdivisions of the striatum were explored in the two PD groups. In addition, the associations between altered functional connectivity and various clinical and neuropsychological characteristics were analyzed by Pearson's or Spearman's correlation.Results: Directly comparing the LPD and RPD patients demonstrated that the LPD patients had lower FC between the left dorsal rostral putamen and the left orbitofrontal cortex than the RPD patients. In addition, the LPD patients showed aberrant functional connectivity involving several striatal subdivisions in the right hemisphere. The right dorsal caudate, ventral rostral putamen, and superior ventral striatum had decreased functional connectivity with the cerebellum and parietal and occipital lobes relative to the normal control group. The comparison between RPD patients and the controls did not obtain significant difference in functional connectivity. The functional connectivity between the left dorsal rostral putamen and the left orbitofrontal cortex was associated with contralateral motor symptom severity in PD patients.Conclusions: Our findings provide new insights into the distinct characteristics of cortico-striatal circuits in LPD and RPD patients. Lateralization of motor symptoms is associated with lateralized striatal functional connectivity.


2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Juan Shen ◽  
Chao Xu

This paper uses resting-state functional magnetic resonance imaging to observe the changes in local consistency of brain activity in patients with Parkinson’s disease (PD). Both healthy volunteers and Parkinson’s disease patients were scanned for resting brain functional imaging, and the collected raw data were processed using resting functional magnetic resonance data processing toolkit software. This study adopted the use of Regional Homogeneity (ReHo). The postprocessing method of RS-fMRI is to study the spontaneous brain activity changes of patients with Parkinson’s disease and cognitive impairment and to explore the changes in the function of their brain regions in the hope of providing help for the treatment of Parkinson’s disease cognitive impairment. The results showed that, compared with the normal control group, the brain regions with increased ReHo values in the PD group were the right central anterior gyrus, the right lingual gyrus, the left middle occipital gyrus, and the bilateral anterior cuneiform lobes. The results show that PD patients have abnormal brain nerve activities in the resting state, and these abnormal brain nerve activities may be related to PD cognitive and behavioral dysfunction.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7957
Author(s):  
Lina Wang ◽  
Yongsheng Yuan ◽  
Jianwei Wang ◽  
Yuting Shen ◽  
Yan Zhi ◽  
...  

Aims We sought to explore the role of the SLC6A3 rs393795 allelic variant in cerebral spontaneous activity and clinical features in Parkinson’s disease (PD) via imaging genetic approach. Methods Our study recruited 50 PD and 45 healthy control (HC) participants to provide clinical, genetic, and resting state functional magnetic resonance imaging (rs-fMRI) data. All subjects were separated into 16 PD-AA, 34 PD-CA/CC, 14 HC-AA, and 31 HC-CA/CC four subgroups according to SLC6A3 rs393795 genotyping. Afterwards, main effects and interactions of groups (PD versus HC) and genotypes (AA versus CA/CC) on cerebral function reflected by regional homogeneity (ReHo) were explored using two-way analysis of covariance (ANCOVA) after controlling age and gender. Finally, Spearman’ s correlations were employed to investigate the relationships between significantly interactive brain regions and clinical manifestations in PD subgroups. Results Compared with HC subjects, PD patients exhibited increased ReHo signals in left middle temporal gyrus and decreased ReHo signals in left pallidum. Compared with CA/CC carriers, AA genotype individuals showed abnormal increased ReHo signals in right inferior frontal gyrus (IFG) and supplementary motor area (SMA). Moreover, significant interactions (affected by both disease factor and allelic variation) were detected in right inferior temporal gyrus (ITG). Furthermore, aberrant increased ReHo signals in right ITG were observed in PD-AA in comparison with PD-CA/CC. Notably, ReHo values in right ITG were negatively associated with Tinetti Mobility Test (TMT) gait subscale scores and positively related to Freezing of Gait Questionnaire (FOG-Q) scores in PD-AA subgroup. Conclusions Our findings suggested that SLC6A3 rs393795 allelic variation might have a trend to aggravate the severity of gait disorders in PD patients by altering right SMA and IFG function, and ultimately result in compensatory activation of right ITG. It could provide us with a new perspective for exploring deeply genetic mechanisms of gait disturbances in PD.


2021 ◽  
pp. 1-15
Author(s):  
Rafail Matzaras ◽  
Kuangyu Shi ◽  
Artemios Artemiadis ◽  
Panagiotis Zis ◽  
Georgios Hadjigeorgiou ◽  
...  

Background: REM-sleep behaviour disorder (RBD) is a parasomnia and a common comorbidity in Parkinson’s disease (PD). There is evidence that the presence of RBD is associated with more severe PD. The differences in the clinical manifestations and the natural history are likely to imply underlying differences in the pathophysiology among PD patients with and without RBD. The increasing number of neuroimaging studies support this notion. Objective: Our primary objective was to review the current evidence regarding the brain neuroimaging findings in PD patients with RBD (PDRBD). Methods: A systematic review of articles, published in PubMed between January 1, 2000 and September 23, 2020 was performed. We evaluate previous studies that assessed PD patients with RBD using various brain structural and functional magnetic resonance imaging (MRI) techniques and brain nuclear medicine imaging. Results: Twenty-nine studies, involving a total of 3,347 PD subjects among which 912 subjects with PDRBD, met the selection criteria and were included. The presence of RBD in PD patients is associated with structural and functional alterations in several brain regions, mainly in brainstem, limbic structures, frontotemporal cortex, and basal ganglia, raising the hypothesis of a PDRBD neuroimaging phenotype. Conclusion: The current review provides up-to-date knowledge in this field and summarizes the neurobiological/neuroimaging substrate of RBD in PD.


2021 ◽  
Vol 13 ◽  
Author(s):  
Junli Li ◽  
Haiyan Liao ◽  
Tianyu Wang ◽  
Yuheng Zi ◽  
Lin Zhang ◽  
...  

Objectives: This study aimed to investigate alterations in regional homogeneity (ReHo) in early Parkinson’s disease (PD) at different Hoehn and Yahr (HY) stages and to demonstrate the relationships between altered brain regions and clinical scale scores.Methods: We recruited 75 PD patients, including 43 with mild PD (PD-mild; HY stage: 1.0–1.5) and 32 with moderate PD (PD-moderate; HY stage: 2.0–2.5). We also recruited 37 age- and sex-matched healthy subjects as healthy controls (HC). All subjects underwent neuropsychological assessments and a 3.0 Tesla magnetic resonance scanning. Regional homogeneity of blood oxygen level-dependent (BOLD) signals was used to characterize regional cerebral function. Correlative relationships between mean ReHo values and clinical data were then explored.Results: Compared to the HC group, the PD-mild group exhibited increased ReHo values in the right cerebellum, while the PD-moderate group exhibited increased ReHo values in the bilateral cerebellum, and decreased ReHo values in the right superior temporal gyrus, the right Rolandic operculum, the right postcentral gyrus, and the right precentral gyrus. Reho value of right Pre/Postcentral was negatively correlated with HY stage. Compared to the PD-moderate group, the PD-mild group showed reduced ReHo values in the right superior orbital gyrus and the right rectus, in which the ReHo value was negatively correlated with cognition.Conclusion: The right superior orbital gyrus and right rectus may serve as a differential indicator for mild and moderate PD. Subjects with moderate PD had a greater scope for ReHo alterations in the cortex and compensation in the cerebellum than those with mild PD. PD at HY stages of 2.0–2.5 may already be classified as Braak stages 5 and 6 in terms of pathology. Our study revealed the different patterns of brain function in a resting state in PD at different HY stages and may help to elucidate the neural function and early diagnosis of patients with PD.


2021 ◽  
Vol 12 (1) ◽  
pp. 415-424
Author(s):  
Yirong Wang ◽  
Shushan Zhang ◽  
Haodi Yang ◽  
Xin Zhang ◽  
Shijia He ◽  
...  

Abstract Introduction Damage to the cerebellar functional network may underlie anxiety symptoms in patients with Parkinson’s disease (PD). Herein we investigated the regional homogeneity (ReHo) and functional connectivity (FC) patterns of cerebellar and clinical correlates in PD patients with anxiety and explored their clinical significance. Methods We enrolled 50 newly diagnosed drug-naïve PD patients and 30 normal controls (NCs). Twenty-six PD patients with anxiety symptoms (PD-A) and 24 PD patients without anxiety symptoms (PD-NA) were sorted into groups based on the Hamilton Anxiety Scale (HAMA). All included participants underwent rest-state functional magnetic resonance imaging (rs-fMRI) scanning. Cerebellar FC based on the seed-based method was used to investigate regional and whole brain function in PD-A, PD-NA, and NCs, and the relationship between the abnormal brain function and anxiety symptoms in PD patients was also detected. Results Compared with the PD-NA group and the NCs, the ReHo value of the PD-A group was significantly decreased in the left medial frontal gyrus and increased in the left cerebellum. Further, left-cerebellum-based FC patterns were used to detect the decreased FC in the right cerebellum, while FC was increased in the right caudate nucleus, and the right anterior cingulate cortex (ACC) in the PD-A group was compared with that in the PD-NA group. Further, the altered FC between the left cerebellum and the right cerebellum was significantly associated with anxiety symptoms in the PD-A group. Conclusion The present study found abnormal regional cerebellum function as well as disruptions in the connectivity network within the cerebellum, caudate, and ACC in patients with PD-A. In addition, the FC between the left cerebellum and the right cerebellum was associated with anxiety symptoms in patients with PD. The present study indicated that cerebellar functional damage may be associated with anxiety symptoms in PD patients.


2022 ◽  
Author(s):  
Sule Tinaz ◽  
Serageldin Kamel ◽  
Sai S Aravala ◽  
Mohamed Elfil ◽  
Ahmed Bayoumi ◽  
...  

Background: Parkinson's disease (PD) causes difficulty with maintaining the speed, size, and vigor of movements, especially when they are internally generated. We previously proposed that the insula is important in motivating intentional movement via its connections with the dorsomedial frontal cortex (dmFC). We demonstrated that subjects with PD can increase the right insula-dmFC functional connectivity using fMRI-based neurofeedback (NF) combined with kinesthetic motor imagery (MI). The current study is a randomized clinical trial testing whether NF-guided kinesthetic MI training can improve motor performance and increase task-based and resting-state right insula-dmFC functional connectivity in subjects with PD. Methods: We assigned nondemented subjects with mild PD (Hoehn & Yahr stage ≤ 3) to the experimental kinesthetic MI with NF (MI-NF, n=22) and active control visual imagery (VI, n=22) groups. Only the MI-NF group received NF-guided MI training (10-12 runs). The NF signal was based on the right insula-dmFC functional connectivity strength. All subjects also practiced their respective imagery tasks at home daily for 4 weeks. Post-training changes in 1) task-based and resting-state right insula-dmFC functional connectivity were the imaging outcomes, and 2) MDS-UPDRS motor exam and motor function scores were the clinical outcomes. Results: The MI-NF group did not show significant NF regulation and was not significantly different from the VI group in any of the imaging or clinical outcome measures. The MI-NF group reported subjective improvement in kinesthetic body awareness. There was significant and comparable improvement only in motor function scores in both groups. This improvement correlated with NF regulation of the right insula-dmFC functional connectivity only in the MI-NF group. Both groups showed specific training effects in whole-brain functional connectivity with distinct neural circuits supporting kinesthetic motor and visual imagery (exploratory outcome). Conclusions: The functional connectivity-based NF regulation was unsuccessful in our cohort with mild PD. However, kinesthetic MI practice by itself or in combination with other imagery techniques is a promising tool in motor rehabilitation in PD.


2021 ◽  
Author(s):  
Sunita Gudwani ◽  
Prabhakar Upadhyay ◽  
Kamlesh Sharma ◽  
Rajesh Sagar ◽  
S. Senthil Kumaran ◽  
...  

AbstractBackgroundSwallowing is complex phenomena comprising oral (preparatory and pre-swallow positioning), oropharyngeal, pharyngeal and esophageal phases. The timing of these phases is controlled by brain stem pattern generators including reflex for oropharyngeal propulsion and transit. Dysphagia in Parkinson’s disease (PD) commonly observed at late stages with aspiration, pneumonia and hospitalization.ObjectiveCan subtle oromotor signs (if any) be observed for planning early interventions in PDMethodsThe present study investigated oromotor function in fourteen early PD (onset ≤2years; H&Y score ≤2.5) with dynamic MRI using saline (water) bolus and compared with seven age-matched healthy controls.ResultsAll the patients with PD were non-symptomatic for dysphagia by self-reporting, and on clinical assessment (Part-II MDS-UPDRS, Swallowing disturbance questionnaire, SDQ and Clinical assessment of dysphagia in neurodegeneration, CADN). Qualitatively MR images visualized, differences in PD compared to healthy controls for tongue-wave, velar-closure or release, bolus placement, oropharyngeal reflex-initiation, transit-time, epiglottic-closure-coordination and post-swallow oral or pharyngeal residue. Descriptive analysis showed higher variability of velar-closure, oropharyngeal- and pharygoesophageal-transit time in patient with PD. Group analysis (two-sample) show significant difference for velar-closure.ConclusionMultiple lingual-waves, reverse-tongue thrust, with delayed velar control attributed to incoordinated muscular rhythm. Variable oropharyngeal transit time (0.64 to 2.25 msec) in PD ascribed to brainstem degenerative changes. Findings imply that subtle observable early oromotor signs as pre-clinical manifestation when evaluated with non-invasive, non-contrast dynamic MRI support early intervention, to prevent late-stage aspiration episodes and consequent hospitalizations.


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