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

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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EEG-Derived Functional Connectivity Patterns Associated with Mild Cognitive Impairment in Parkinson’s Disease

Behavioral Sciences ◽

10.3390/bs11030040 ◽

2021 ◽

Vol 11 (3) ◽

pp. 40

Author(s):

Alejandro Armando Peláez Suárez ◽

Sheila Berrillo Batista ◽

Ivonne Pedroso Ibáñez ◽

Enrique Casabona Fernández ◽

Marinet Fuentes Campos ◽

...

Keyword(s):

Parkinson’S Disease ◽

Working Memory ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Functional Connectivity ◽

Path Length ◽

Clustering Coefficient ◽

Eyes Closed ◽

The Mean

Objective: To evaluate EEG-derived functional connectivity (FC) patterns associated with mild cognitive impairment (MCI) in Parkinson’s disease (PD). METHODS: A sample of 15 patients without cognitive impairment (PD-WCI), 15 with MCI (PD-MCI), and 26 healthy subjects were studied. The EEG was performed in the waking functional state with eyes closed, for the functional analysis it was used the synchronization likelihood (SL) and graph theory (GT). RESULTS: PD-MCI patients showed decreased FC in frequencies alpha, in posterior regions, and delta with a generalized distribution. Patients, compared to the healthy people, presented a decrease in segregation (lower clustering coefficient in alpha p = 0.003 in PD-MCI patients) and increased integration (shorter mean path length in delta (p = 0.004) and theta (p = 0.002) in PD-MCI patients). There were no significant differences in the network topology between the parkinsonian groups. In PD-MCI patients, executive dysfunction correlated positively with global connectivity in beta (r = 0.47) and negatively with the mean path length at beta (r = −0.45); alterations in working memory were negatively correlated with the mean path length at beta r = −0.45. CONCLUSIONS: PD patients present alterations in the FC in all frequencies, those with MCI show less connectivity in the alpha and delta frequencies. The neural networks of the patients show a random topology, with a similar organization between patients with and without MCI. In PD-MCI patients, alterations in executive function and working memory are related to beta integration.

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Functional connectivity in Parkinson’s disease candidates for deep brain stimulation

npj Parkinson s Disease ◽

10.1038/s41531-021-00268-6 ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Luigi Albano ◽

Federica Agosta ◽

Silvia Basaia ◽

Camilla Cividini ◽

Tanja Stojkovic ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Basal Ganglia ◽

Functional Connectivity ◽

Brain Stimulation ◽

Regional Analysis ◽

Clustering Coefficient ◽

Clinical Indication ◽

Deep Brain

AbstractThis study aimed to identify functional neuroimaging patterns anticipating the clinical indication for deep brain stimulation (DBS) in patients with Parkinson’s disease (PD). A cohort of prospectively recruited patients with PD underwent neurological evaluations and resting-state functional MRI (RS-fMRI) at baseline and annually for 4 years. Patients were divided into two groups: 19 patients eligible for DBS over the follow-up and 41 patients who did not meet the criteria to undergo DBS. Patients selected as candidates for DBS did not undergo surgery at this stage. Sixty age- and sex-matched healthy controls performed baseline evaluations. Graph analysis and connectomics assessed global and local topological network properties and regional functional connectivity at baseline and at each time point. At baseline, network analysis showed a higher mean nodal strength, local efficiency, and clustering coefficient of the occipital areas in candidates for DBS over time relative to controls and patients not eligible for DBS. The occipital hyperconnectivity pattern was confirmed by regional analysis. At baseline, a decreased functional connectivity between basal ganglia and sensorimotor/frontal networks was found in candidates for DBS compared to patients not eligible for surgery. In the longitudinal analysis, patient candidate for DBS showed a progressively decreased topological brain organization and functional connectivity, mainly in the posterior brain networks, and a progressively increased connectivity of basal ganglia network compared to non-candidates for DBS. RS-fMRI may support the clinical indication to DBS and could be useful in predicting which patients would be eligible for DBS in the earlier stages of PD.

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Global efficiency of the motor network is decreased in Parkinson's disease in comparison with essential tremor and healthy controls

Brain and Behavior ◽

10.1002/brb3.2178 ◽

2021 ◽

Author(s):

Natalia Pelizari Novaes ◽

Joana Bisol Balardin ◽

Fabiana Campos Hirata ◽

Luciano Melo ◽

Edson Amaro ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Essential Tremor ◽

Healthy Controls ◽

Global Efficiency ◽

Motor Network

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Functional connectivity of the tremor network in essential tremor plus and tremor dominant Parkinson's disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2020.06.413 ◽

2020 ◽

Vol 79 ◽

pp. e114

Author(s):

S. Prasad ◽

J. Saini ◽

R.D. Bharath ◽

P.K. Pal

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Essential Tremor

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Altered intrinsic brain functional connectivity in drug-naïve Parkinson’s disease patients with LRRK2 mutations

Neuroscience Letters ◽

10.1016/j.neulet.2018.03.038 ◽

2018 ◽

Vol 675 ◽

pp. 145-151 ◽

Cited By ~ 5

Author(s):

Yanbing Hou ◽

Chunyan Luo ◽

Jing Yang ◽

Ruwei Ou ◽

Wei Song ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Drug Naïve ◽

Brain Functional Connectivity

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Implications of dopaminergic medication withdrawal in Parkinson’s disease

Journal of Neural Transmission ◽

10.1007/s00702-021-02389-x ◽

2021 ◽

Author(s):

J. Koschel ◽

K. Ray Chaudhuri ◽

L. Tönges ◽

M. Thiel ◽

V. Raeder ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Medication ◽

Medication Withdrawal

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Bringing Advanced Therapies for Parkinson’s Disease to the Clinic: The Scientist’s Perspective

Journal of Parkinson s Disease ◽

10.3233/jpd-212685 ◽

2021 ◽

pp. 1-6

Author(s):

Mark Tomishima ◽

Agnete Kirkeby

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Trials ◽

Phase I Clinical Trials ◽

Preclinical Models ◽

Preclinical Development ◽

Dopaminergic Medication ◽

Gene Therapies ◽

Advanced Therapies ◽

New Phase

After many years of preclinical development, cell and gene therapies have advanced from research tools in the lab to clinical-grade products for patients, and today they constitute more than a quarter of all new Phase I clinical trials for Parkinson’s disease. Whereas efficacy has been convincingly proven for many of these products in preclinical models, the field is now entering a new phase where the functionality and safety of these products will need to stand the test in clinical trials. If successful, these new products can have the potential to provide patients with a one-time administered treatment which may alleviate them from daily symptomatic dopaminergic medication.

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