Graph theory network function in Parkinson’s disease assessed with electroencephalography

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the elderly population. Similarly to other neurodegenerative diseases, the early diagnosis of PD is quite difficult. The current pilot study aimed to explore the differences in brain connectivity between PD and NOrmal eLDerly (Nold) subjects to evaluate whether connectivity analysis may speed up and support early diagnosis. A total of 26 resting state EEGs were analyzed from 13 PD patients and 13 age-matched Nold subjects, applying to cortical reconstructions the graph theory analyses, a mathematical representation of brain architecture. Results showed that PD patients presented a more ordered structure at slow-frequency EEG rhythms (lower value of SW) than Nold subjects, particularly in the theta band, whereas in the high-frequency alpha, PD patients presented more random organization (higher SW) than Nold subjects. The current results suggest that PD could globally modulate the cortical connectivity of the brain, modifying the functional network organization and resulting in motor and non-motor signs. Future studies could validate whether such an approach, based on a low-cost and non-invasive technique, could be useful for early diagnosis, for the follow-up of PD progression, as well as for evaluating pharmacological and neurorehabilitation treatments.

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Dopaminergic modulation of local non-oscillatory activity and global-network properties in Parkinson's disease: an EEG study

10.1101/2021.12.17.21267975 ◽

2021 ◽

Author(s):

Juanli Zhang ◽

Arno Villringer ◽

Vadim V. Nikulin

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Graph Theory ◽

Functional Connectivity ◽

Power Spectra ◽

Clustering Coefficient ◽

Spectral Slope ◽

Dopaminergic Medication ◽

Oscillatory Component ◽

Global Efficiency

Dopaminergic medication for Parkinson's disease (PD) modulates neuronal oscillations and functional connectivity across the basal ganglia-thalamic-cortical circuit. However, the non-oscillatory component of the neuronal activity, potentially indicating a state of excitation/inhibition balance, has not yet been investigated and previous studies have shown inconsistent changes of cortico-cortical connectivity as a response to dopaminergic medication. To further elucidate changes of regional non-oscillatory component of the neuronal power spectra, functional connectivity, and to determine which aspects of network organization obtained with graph theory respond to dopaminergic medication, we analyzed a resting-state EEG (Electroencephalogram) dataset including 15 PD patients during OFF and ON medication conditions. We found that the spectral slope, typically used to quantify the broadband non-oscillatory component of power spectra, steepened particularly in the left central region in the ON compared to OFF condition. In addition, using lagged coherence as a functional connectivity measure, we found that the functional connectivity in the beta frequency range between centro-parietal and frontal regions was enhanced in the ON compared to the OFF condition. After applying graph theory analysis, we observed that at the lower level of topology the node degree was increased, particularly in the centro-parietal area. Yet, results showed no significant difference in global topological organization between the two conditions: either in global efficiency or clustering coefficient for measuring global and local integration, respectively. Interestingly, we found a close association between local/global spectral slope and functional network global efficiency in the OFF condition, suggesting a crucial role of local non-oscillatory dynamics in forming the functional global integration which characterizes PD. These results provide further evidence and a more complete picture for the engagement of multiple cortical regions at various levels in response to dopaminergic medication in PD.

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Mechanisms of Motor Symptom Improvement by Long-Term Tai Chi Training in Parkinson's Disease Patients

10.21203/rs.3.rs-884753/v1 ◽

2021 ◽

Author(s):

Gen Li ◽

Pei Huang ◽

Shi-Shuang Cui ◽

Yu-Yan Tan ◽

Ya-Chao He ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Tai Chi ◽

Symptom Improvement ◽

Motor Symptoms ◽

Mrna Levels ◽

Brisk Walking ◽

Step Width ◽

Network Function

Abstract Background Tai Chi has been shown to improve motor symptoms in Parkinson’s disease (PD), but its long-term effects was not clear and the related mechanism was not elucidated. Therefore, we investigated the mechanism of long-term Tai Chi training on improving motor symptoms in PD. Methods 95 early-stage PD patients were enrolled and randomly divided into Tai Chi (N = 32), brisk walking (N = 31) and no-exercise group (N = 32). All subjects were assessed at baseline, 6 months and 12 months after one-year intervention. Motor symptoms were evaluated by Berg balance scale (BBS), Unified PD rating scale (UPDRS), Timed Up and Go test (TUG) and 3D gait analysis. Functional MRI, plasma cytokine and metabolomics, blood Huntingtin interaction protein 2 (HIP2) mRNA levels were analyzed to investigate the mechanisms of Tai Chi training at macro and molecular level. The longitudinal effects of self-changes were calculated using repeated measures ANOVA. Generalized estimating equations (GEE) was used to assess the association of longitudinal data of rating scales. Switch rates were used into the fMRI analysis. False discovery rate (FDR) correction was used to perform multiple correction. Results Tai Chi group had better performance in BBS, UPDRS, TUG and step width. Besides, Tai Chi had more advantages in improving BBS, step width than brisk walking. Improved BBS was correlated with enhanced visual network function and downregulation of IL-1β. Improvements in UPDRS were associated with enhanced default mode network function, decreased L-malic acid and 3-phosphoglyceric acid, increased adenosine and HIP2 mRNA levels. In addition, arginine biosynthesis, urea cycle, TCA cycle and beta oxidation of very long chain fatty acids were also improved by Tai Chi. Conclusions Long-term Tai Chi training improved motor function, especially gait and balance, in PD. Enhanced brain network function, reduced inflammation, improved amino acid metabolism, energy metabolism and neurotransmitters metabolism, decreased vulnerability to dopaminergic degeneration might be the mechanisms of Tai Chi effects. Trial registration: This study is registered at Chinese Clinical Trial Registry (Registration number: ChiCTR-OPC-16008074; Registration date: March 8, 2016).

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Oscillation-specific nodal alterations in early to middle stages Parkinson’s disease

Translational Neurodegeneration ◽

10.1186/s40035-019-0177-5 ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 2

Author(s):

Xiaojun Guan ◽

Tao Guo ◽

Qiaoling Zeng ◽

Jiaqiu Wang ◽

Cheng Zhou ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Graph Theory ◽

Oscillation Frequency ◽

Large Scale ◽

Early Stage ◽

Degree Centrality ◽

Middle Stage ◽

Network Analyses ◽

Oscillation Frequencies

Abstract Background Different oscillations of brain networks could carry different dimensions of brain integration. We aimed to investigate oscillation-specific nodal alterations in patients with Parkinson’s disease (PD) across early stage to middle stage by using graph theory-based analysis. Methods Eighty-eight PD patients including 39 PD patients in the early stage (EPD) and 49 patients in the middle stage (MPD) and 36 controls were recruited in the present study. Graph theory-based network analyses from three oscillation frequencies (slow-5: 0.01–0.027 Hz; slow-4: 0.027–0.073 Hz; slow-3: 0.073–0.198 Hz) were analyzed. Nodal metrics (e.g. nodal degree centrality, betweenness centrality and nodal efficiency) were calculated. Results Our results showed that (1) a divergent effect of oscillation frequencies on nodal metrics, especially on nodal degree centrality and nodal efficiency, that the anteroventral neocortex and subcortex had high nodal metrics within low oscillation frequencies while the posterolateral neocortex had high values within the relative high oscillation frequency was observed, which visually showed that network was perturbed in PD; (2) PD patients in early stage relatively preserved nodal properties while MPD patients showed widespread abnormalities, which was consistently detected within all three oscillation frequencies; (3) the involvement of basal ganglia could be specifically observed within slow-5 oscillation frequency in MPD patients; (4) logistic regression and receiver operating characteristic curve analyses demonstrated that some of those oscillation-specific nodal alterations had the ability to well discriminate PD patients from controls or MPD from EPD patients at the individual level; (5) occipital disruption within high frequency (slow-3) made a significant influence on motor impairment which was dominated by akinesia and rigidity. Conclusions Coupling various oscillations could provide potentially useful information for large-scale network and progressive oscillation-specific nodal alterations were observed in PD patients across early to middle stages.

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An Update on Gene Therapy Approaches for Parkinson’s Disease: Restoration of Dopaminergic Function

Journal of Parkinson s Disease ◽

10.3233/jpd-212724 ◽

2021 ◽

pp. 1-10

Author(s):

Amber D. Van Laar ◽

Victor S. Van Laar ◽

Waldy San Sebastian ◽

Aristide Merola ◽

J. Bradley Elder ◽

...

Keyword(s):

Parkinson’S Disease ◽

Gene Therapy ◽

Parkinson's Disease ◽

Genetic Material ◽

Unmet Need ◽

Surgical Approaches ◽

Nigrostriatal Pathway ◽

Neuronal Function ◽

Network Function ◽

Clinical Gene Therapy

At present there is a significant unmet need for clinically available treatments for Parkinson’s disease (PD) patients to stably restore balance to dopamine network function, leaving patients with inadequate management of symptoms as the disease progresses. Gene therapy is an attractive approach to impart a durable effect on neuronal function through introduction of genetic material to reestablish dopamine levels and/or functionally recover dopaminergic signaling by improving neuronal health. Ongoing clinical gene therapy trials in PD are focused on enzymatic enhancement of dopamine production and/or the restoration of the nigrostriatal pathway to improve dopaminergic network function. In this review, we discuss data from current gene therapy trials for PD and recent advances in study design and surgical approaches.

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