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  Dopaminergic modulation of motor network compensatory mechanisms in Parkinson's disease

Jastrzębowska, M. A., Marquis, R., Melie‐García, L., Lutti, A., Kherif, F., Herzog, M. H., et al. (2019). Dopaminergic modulation of motor network compensatory mechanisms in Parkinson's disease. Human Brain Mapping. doi:10.1002/hbm.24710.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-50BB-F Version Permalink: http://hdl.handle.net/21.11116/0000-0004-644A-9
Genre: Journal Article

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 Creators:
Jastrzębowska, Maya A.1, 2, Author
Marquis, Renaud2, 3, Author
Melie‐García, Lester2, Author
Lutti, Antoine2, Author
Kherif, Ferath2, Author
Herzog, Michael H.1, Author
Draganski, Bogdan2, 4, Author              
Affiliations:
1Laboratory of Psychophysics, Brain Mind Institute, Swiss Federal Institute of Technology in Lausanne, Switzerland, ou_persistent22              
2Département des Neurosciences Cliniques, Laboratoire de Recherche en Neuroimagerie (LREN), Centre hospitalier universitaire vaudois, Lausanne, Switzerland, ou_persistent22              
3EEG and Epilepsy Unit, University Hospital of Geneva, Switzerland, ou_persistent22              
4Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              

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Free keywords: Dynamic causal modeling; Effective connectivity; fMRI; Lateralization; Parametric empirical Bayes; Parkinson's disease
 Abstract: The dopaminergic system has a unique gating function in the initiation and execution of movements. When the interhemispheric imbalance of dopamine inherent to the healthy brain is disrupted, as in Parkinson's disease (PD), compensatory mechanisms act to stave off behavioral changes. It has been proposed that two such compensatory mechanisms may be (a) a decrease in motor lateralization, observed in drug‐naïve PD patients and (b) reduced inhibition ‐ increased facilitation. Seeking to investigate the differential effect of dopamine depletion and subsequent substitution on compensatory mechanisms in non‐drug‐naïve PD, we studied 10 PD patients and 16 healthy controls, with patients undergoing two test sessions — “ON” and “OFF” medication. Using a simple visually‐cued motor response task and fMRI, we investigated cortical motor activation — in terms of laterality, contra‐ and ipsilateral percent BOLD signal change and effective connectivity in the parametric empirical Bayes framework. We found that decreased motor lateralization persists in non‐drug‐naïve PD and is concurrent with decreased contralateral activation in the cortical motor network. Normal lateralization is not reinstated by dopamine substitution. In terms of effective connectivity, disease‐related changes primarily affect ipsilaterally‐lateralized homotopic cortical motor connections, while medication‐related changes affect contralaterally‐lateralized homotopic connections. Our findings suggest that, in non‐drug‐naïve PD, decreased lateralization is no longer an adaptive cortical mechanism, but rather the result of maladaptive changes, related to disease progression and long‐term dopamine replacement. These findings highlight the need for the development of noninvasive therapies, which would promote the adaptive mechanisms of the PD brain.

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Language(s): eng - English
 Dates: 2019-05-282019-02-152019-06-272019-07-10
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1002/hbm.24710
Other: Epub ahead of print
PMID: 31291039
 Degree: -

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Project name : -
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Funding organization : Fondation Leenaards
Project name : -
Grant ID : -
Funding program : -
Funding organization : Roger De Spoelberch Foundation
Project name : Human Brain Project Specific Grant Agreement 1 / HBP SGA1
Grant ID : -
Funding program : Horizon 2020
Funding organization : European Commission (EC)
Project name : -
Grant ID : -
Funding program : -
Funding organization : Partridge Foundation
Project name : -
Grant ID : 32003B_135679 ; 32003B_159780
Funding program : -
Funding organization : Swiss National Science Foundation
Project name : NCCR Synapsy
Grant ID : 125759 ; 565593
Funding program : -
Funding organization : Swiss National Science Foundation

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Title: Human Brain Mapping
Source Genre: Journal
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Publ. Info: New York : Wiley-Liss
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1065-9471
CoNE: https://pure.mpg.de/cone/journals/resource/954925601686