Dopaminergic modulation of motor network compensatory mechanisms in Parkinson's disease.
Adaptation, Physiological
/ drug effects
Aged
Bayes Theorem
Case-Control Studies
Connectome
Dominance, Cerebral
/ physiology
Dopamine
/ physiology
Dopamine Agonists
/ pharmacology
Female
Foot
/ physiopathology
Hand
/ physiopathology
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Models, Neurological
Motor Activity
/ physiology
Nerve Net
/ physiopathology
Parkinson Disease
/ drug therapy
Symptom Assessment
Parkinson's disease
dynamic causal modeling
effective connectivity
fMRI
lateralization
parametric empirical Bayes
Journal
Human brain mapping
ISSN: 1097-0193
Titre abrégé: Hum Brain Mapp
Pays: United States
ID NLM: 9419065
Informations de publication
Date de publication:
15 10 2019
15 10 2019
Historique:
received:
15
02
2019
revised:
28
05
2019
accepted:
27
06
2019
pubmed:
11
7
2019
medline:
21
4
2020
entrez:
11
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31291039
doi: 10.1002/hbm.24710
pmc: PMC6865418
doi:
Substances chimiques
Dopamine Agonists
0
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4397-4416Subventions
Organisme : Fondation Leenaards
Pays : International
Organisme : Fondation ROGER DE SPOELBERCH
Pays : International
Organisme : H2020 Future and Emerging Technologies
ID : 720270
Pays : International
Organisme : Partridge Foundation
Pays : International
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
ID : 32003B_135679
Pays : International
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
ID : 32003B_159780
Pays : International
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
ID : NCCR-Synapsy 125759
Pays : International
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
ID : NCCR-Synapsy 565593
Pays : International
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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