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@ARTICLE{Michely:189310,
author = {Michely, J. and Vol, L. J. and Barbe, Michael and
Hoffstaedter, Felix and Viswanathan, Shivakumar and
Timmermann, L. and Eickhoff, Simon and Fink, Gereon Rudolf
and Grefkes, Christian},
title = {{D}opaminergic modulation of motor network dynamics in
{P}arkinson’s disease},
journal = {Brain},
volume = {138},
number = {Pt3},
issn = {0006-8950},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {FZJ-2015-02488},
pages = {664-678},
year = {2015},
abstract = {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.},
cin = {INM-3 / INM-1},
ddc = {610},
cid = {I:(DE-Juel1)INM-3-20090406 / I:(DE-Juel1)INM-1-20090406},
pnm = {572 - (Dys-)function and Plasticity (POF3-572)},
pid = {G:(DE-HGF)POF3-572},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000351510700023},
pubmed = {pmid:25567321},
doi = {10.1093/brain/awu381},
url = {https://juser.fz-juelich.de/record/189310},
}