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  Modulatory effects of levodopa on cerebellar connectivity in Parkinson’s disease

Mueller, K., Jech, R., Ballarini, T., Holiga, Š., Růžička, F., Piecha, F., et al. (2019). Modulatory effects of levodopa on cerebellar connectivity in Parkinson’s disease. The Cerebellum, 18(2), 212-224. doi:10.1007/s12311-018-0981-y.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-650A-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-F314-3
Genre: Journal Article


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Mueller, Karsten1, Author              
Jech, Robert2, 3, Author
Ballarini, Tommaso4, Author              
Holiga, Štefan1, Author              
Růžička, Filip 2, Author
Piecha, Fabian1, Author
Möller, Harald E.1, Author              
Vymazal, Josef 3, Author
Růžička, Evžen 2, Author
Schroeter, Matthias L.4, 5, Author              
1Methods and Development Unit Nuclear Magnetic Resonance, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634558              
2Center for Interventional Therapy of Movement Disorders, Department of Neurology, First Faculty of Medicine, Charles University, Prague, Czech Republic, , ou_persistent22              
3Department of Radiology, Na Homolce Hospital, Prague, Czech Republic, ou_persistent22              
4Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
5Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              


Free keywords: Dopaminergic treatment; L-dopa; Levodopa; Parkinson’s disease; Resting-state magnetic resonance imaging; Eigenvector centrality; Brain connectivity; Functional connectivity; Nexopathy; Cerebellum Cerebellar networks; Brainstem
 Abstract: Levodopa has been the mainstay of symptomatic therapy for Parkinson’s disease (PD) for the last five decades. However, it is associated with the development of motor fluctuations and dyskinesia, in particular after several years of treatment. The aim of this study was to shed light on the acute brain functional reorganization in response to a single levodopa dose. Functional magnetic resonance imaging (fMRI) was performed after an overnight withdrawal of dopaminergic treatment and 1 h after a single dose of 250 mg levodopa in a group of 24 PD patients. Eigenvector centrality was calculated in both treatment states using resting-state fMRI. This offers a new data-driven and parameter-free approach, similar to Google’s PageRank algorithm, revealing brain connectivity alterations due to the effect of levodopa treatment. In all PD patients, levodopa treatment led to an improvement of clinical symptoms as measured with the Unified Parkinson’s Disease Rating Scale motor score (UPDRS-III). This therapeutic effect was accompanied with a major connectivity increase between cerebellar brain regions and subcortical areas of the motor system such as the thalamus, putamen, globus pallidus, and brainstem. The degree of interconnectedness of cerebellar regions correlated with the improvement of clinical symptoms due to the administration of levodopa. We observed significant functional cerebellar connectivity reorganization immediately after a single levodopa dose in PD patients. Enhanced general connectivity (eigenvector centrality) was associated with better motor performance as assessed by UPDRS-III score. This underlines the importance of considering cerebellar networks as therapeutic targets in PD.


Language(s): eng - English
 Dates: 2018-10-082019-04
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1007/s12311-018-0981-y
PMID: 30298443
Other: Epub ahead of print
 Degree: -



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Project name : -
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Funding organization : Max Planck Society
Project name : -
Grant ID : 16-13323S
Funding program : -
Funding organization : Czech Science Foundation “Micro and Macro-Connectomics of the STN nucleus”
Project name : Czech Republic Progres Q27/LF1
Grant ID : -
Funding program : -
Funding organization : Charles University
Project name : -
Grant ID : -
Funding program : (PDF-IRG-1307)
Funding organization : Parkinson’s Disease Foundation
Project name : -
Grant ID : -
Funding program : (MJFF-11362)
Funding organization : Michael J. Fox Foundation

Source 1

Title: The Cerebellum
Source Genre: Journal
Publ. Info: New York, NY : Springer
Pages: - Volume / Issue: 18 (2) Sequence Number: - Start / End Page: 212 - 224 Identifier: ISSN: 1473-4222
CoNE: https://pure.mpg.de/cone/journals/resource/1473-4222