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Dopaminergic modulation of motor network dynamics in Parkinson’s disease

Although characteristic motor symptoms of Parkinson’s disease such as bradykinesia typically improve under dopaminergic medication, deficits in higher motor control are less responsive. We here investigated the dopaminergic modulation of network dynamics underlying basic motor performance, i.e. fing...

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Autores principales: Michely, Jochen, Volz, Lukas J., Barbe, Michael T., Hoffstaedter, Felix, Viswanathan, Shivakumar, Timmermann, Lars, Eickhoff, Simon B., Fink, Gereon R., Grefkes, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339773/
https://www.ncbi.nlm.nih.gov/pubmed/25567321
http://dx.doi.org/10.1093/brain/awu381
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author Michely, Jochen
Volz, Lukas J.
Barbe, Michael T.
Hoffstaedter, Felix
Viswanathan, Shivakumar
Timmermann, Lars
Eickhoff, Simon B.
Fink, Gereon R.
Grefkes, Christian
author_facet Michely, Jochen
Volz, Lukas J.
Barbe, Michael T.
Hoffstaedter, Felix
Viswanathan, Shivakumar
Timmermann, Lars
Eickhoff, Simon B.
Fink, Gereon R.
Grefkes, Christian
author_sort Michely, Jochen
collection PubMed
description Although characteristic motor symptoms of Parkinson’s disease such as bradykinesia typically improve under dopaminergic medication, deficits in higher motor control are less responsive. We here investigated the dopaminergic modulation of network dynamics underlying basic motor performance, i.e. finger tapping, and higher motor control, i.e. internally and externally cued movement preparation and selection. Twelve patients, assessed ON and OFF medication, and 12 age-matched healthy subjects underwent functional magnetic resonance imaging. Dynamic causal modelling was used to assess effective connectivity in a motor network comprising cortical and subcortical regions. In particular, we investigated whether impairments in basic and higher motor control, and the effects induced by dopaminergic treatment are due to connectivity changes in (i) the mesial premotor loop comprising the supplementary motor area; (ii) the lateral premotor loop comprising lateral premotor cortex; and (iii) cortico-subcortical interactions. At the behavioural level, we observed a marked slowing of movement preparation and selection when patients were internally as opposed to externally cued. Preserved performance during external cueing was associated with enhanced connectivity between prefrontal cortex and lateral premotor cortex OFF medication, compatible with a context-dependent compensatory role of the lateral premotor loop in the hypodopaminergic state. Dopaminergic medication significantly improved finger tapping speed in patients, which correlated with a drug-induced coupling increase of prefrontal cortex with the supplementary motor area, i.e. the mesial premotor loop. In addition, only in the finger tapping condition, patients ON medication showed enhanced excitatory influences exerted by cortical premotor regions and the thalamus upon the putamen. In conclusion, the amelioration of bradykinesia by dopaminergic medication seems to be driven by enhanced connectivity within the mesial premotor loop and cortico-striatal interactions. In contrast, medication did not improve internal motor control deficits concurrent to missing effects at the connectivity level. This differential effect of dopaminergic medication on the network dynamics underlying motor control provides new insights into the clinical finding that in Parkinson’s disease dopaminergic drugs especially impact on bradykinesia but less on executive functions.
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spelling pubmed-43397732015-06-26 Dopaminergic modulation of motor network dynamics in Parkinson’s disease Michely, Jochen Volz, Lukas J. Barbe, Michael T. Hoffstaedter, Felix Viswanathan, Shivakumar Timmermann, Lars Eickhoff, Simon B. Fink, Gereon R. Grefkes, Christian Brain Original Articles Although characteristic motor symptoms of Parkinson’s disease such as bradykinesia typically improve under dopaminergic medication, deficits in higher motor control are less responsive. We here investigated the dopaminergic modulation of network dynamics underlying basic motor performance, i.e. finger tapping, and higher motor control, i.e. internally and externally cued movement preparation and selection. Twelve patients, assessed ON and OFF medication, and 12 age-matched healthy subjects underwent functional magnetic resonance imaging. Dynamic causal modelling was used to assess effective connectivity in a motor network comprising cortical and subcortical regions. In particular, we investigated whether impairments in basic and higher motor control, and the effects induced by dopaminergic treatment are due to connectivity changes in (i) the mesial premotor loop comprising the supplementary motor area; (ii) the lateral premotor loop comprising lateral premotor cortex; and (iii) cortico-subcortical interactions. At the behavioural level, we observed a marked slowing of movement preparation and selection when patients were internally as opposed to externally cued. Preserved performance during external cueing was associated with enhanced connectivity between prefrontal cortex and lateral premotor cortex OFF medication, compatible with a context-dependent compensatory role of the lateral premotor loop in the hypodopaminergic state. Dopaminergic medication significantly improved finger tapping speed in patients, which correlated with a drug-induced coupling increase of prefrontal cortex with the supplementary motor area, i.e. the mesial premotor loop. In addition, only in the finger tapping condition, patients ON medication showed enhanced excitatory influences exerted by cortical premotor regions and the thalamus upon the putamen. In conclusion, the amelioration of bradykinesia by dopaminergic medication seems to be driven by enhanced connectivity within the mesial premotor loop and cortico-striatal interactions. In contrast, medication did not improve internal motor control deficits concurrent to missing effects at the connectivity level. This differential effect of dopaminergic medication on the network dynamics underlying motor control provides new insights into the clinical finding that in Parkinson’s disease dopaminergic drugs especially impact on bradykinesia but less on executive functions. Oxford University Press 2015-03 2015-01-07 /pmc/articles/PMC4339773/ /pubmed/25567321 http://dx.doi.org/10.1093/brain/awu381 Text en © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Michely, Jochen
Volz, Lukas J.
Barbe, Michael T.
Hoffstaedter, Felix
Viswanathan, Shivakumar
Timmermann, Lars
Eickhoff, Simon B.
Fink, Gereon R.
Grefkes, Christian
Dopaminergic modulation of motor network dynamics in Parkinson’s disease
title Dopaminergic modulation of motor network dynamics in Parkinson’s disease
title_full Dopaminergic modulation of motor network dynamics in Parkinson’s disease
title_fullStr Dopaminergic modulation of motor network dynamics in Parkinson’s disease
title_full_unstemmed Dopaminergic modulation of motor network dynamics in Parkinson’s disease
title_short Dopaminergic modulation of motor network dynamics in Parkinson’s disease
title_sort dopaminergic modulation of motor network dynamics in parkinson’s disease
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339773/
https://www.ncbi.nlm.nih.gov/pubmed/25567321
http://dx.doi.org/10.1093/brain/awu381
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