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@ARTICLE{Asendorf:1037239,
author = {Asendorf, Adrian L. and Theis, Hendrik and Tittgemeyer,
Marc and Timmermann, Lars and Fink, Gereon R. and Drzezga,
Alexander and Eggers, Carsten and Ruppert-Junck, Marina C.
and Pedrosa, David J. and Hoenig, Merle C. and van Eimeren,
Thilo},
title = {{D}ynamic properties in functional connectivity changes and
striatal dopamine deficiency in {P}arkinson's disease},
journal = {Human brain mapping},
volume = {45},
number = {10},
issn = {1065-9471},
address = {New York, NY},
publisher = {Wiley-Liss},
reportid = {FZJ-2025-00572},
pages = {e26776},
year = {2024},
note = {Deutsche Forschungsgemeinschaft (DFG,German Research
Foundation), Grant/AwardNumbers: 431549029, 413543196},
abstract = {Recent studies in Parkinson's disease (PD) patients
reported disruptions in dynamic functional connectivity
(dFC, i.e., a characterization of spontaneous fluctuations
in functional connectivity over time). Here, we assessed
whether the integrity of striatal dopamine terminals
directly modulates dFC metrics in two separate PD cohorts,
indexing dopamine-related changes in large-scale brain
network dynamics and its implications in clinical features.
We pooled data from two disease-control cohorts reflecting
early PD. From the Parkinson's Progression Marker Initiative
(PPMI) cohort, resting-state functional magnetic resonance
imaging (rsfMRI) and dopamine transporter (DaT)
single-photon emission computed tomography (SPECT) were
available for 63 PD patients and 16 age- and sex-matched
healthy controls. From the clinical research group 219 (KFO)
cohort, rsfMRI imaging was available for 52 PD patients and
17 age- and sex-matched healthy controls. A subset of 41 PD
patients and 13 healthy control subjects additionally
underwent 18F-DOPA-positron emission tomography (PET)
imaging. The striatal synthesis capacity of 18F-DOPA PET and
dopamine terminal quantity of DaT SPECT images were
extracted for the putamen and the caudate. After rsfMRI
pre-processing, an independent component analysis was
performed on both cohorts simultaneously. Based on the
derived components, an individual sliding window approach
(44 s window) and a subsequent k-means clustering were
conducted separately for each cohort to derive dFC states
(reemerging intra- and interindividual connectivity
patterns). From these states, we derived temporal metrics,
such as average dwell time per state, state attendance, and
number of transitions and compared them between groups and
cohorts. Further, we correlated these with the respective
measures for local dopaminergic impairment and clinical
severity. The cohorts did not differ regarding age and sex.
Between cohorts, PD groups differed regarding disease
duration, education, cognitive scores and L-dopa equivalent
daily dose. In both cohorts, the dFC analysis resulted in
three distinct states, varying in connectivity patterns and
strength. In the PPMI cohort, PD patients showed a lower
state attendance for the globally integrated (GI) state and
a lower number of transitions than controls. Significantly,
worse motor scores (Unified Parkinson's Disease Rating Scale
Part III) and dopaminergic impairment in the putamen and the
caudate were associated with low average dwell time in the
GI state and a low total number of transitions. These
results were not observed in the KFO cohort: No group
differences in dFC measures or associations between dFC
variables and dopamine synthesis capacity were observed.
Notably, worse motor performance was associated with a low
number of bidirectional transitions between the GI and the
lesser connected (LC) state across the PD groups of both
cohorts. Hence, in early PD, relative preservation of motor
performance may be linked to a more dynamic engagement of an
interconnected brain state. Specifically, those large-scale
network dynamics seem to relate to striatal dopamine
availability. Notably, most of these results were obtained
only for one cohort, suggesting that dFC is impacted by
certain cohort features like educational level, or disease
severity. As we could not pinpoint these features with the
data at hand, we suspect that other, in our case untracked,
demographical features drive connectivity dynamics in PD.
PRACTITIONER POINTS: Exploring dopamine's role in brain
network dynamics in two Parkinson's disease (PD) cohorts, we
unraveled PD-specific changes in dynamic functional
connectivity. Results in the Parkinson's Progression Marker
Initiative (PPMI) and the KFO cohort suggest motor
performance may be linked to a more dynamic engagement and
disengagement of an interconnected brain state. Results only
in the PPMI cohort suggest striatal dopamine availability
influences large-scale network dynamics that are relevant in
motor control.Keywords: DAT SPECT; F‐DOPA PET; dynamic
functional connectivity; imaging; network; resting‐state
fMRI.},
cin = {INM-3 / INM-2},
ddc = {610},
cid = {I:(DE-Juel1)INM-3-20090406 / I:(DE-Juel1)INM-2-20090406},
pnm = {5251 - Multilevel Brain Organization and Variability
(POF4-525) / DFG project G:(GEPRIS)431549029 - SFB 1451:
Schlüsselmechanismen normaler und krankheitsbedingt
gestörter motorischer Kontrolle (431549029) / 5253 -
Neuroimaging (POF4-525)},
pid = {G:(DE-HGF)POF4-5251 / G:(GEPRIS)431549029 /
G:(DE-HGF)POF4-5253},
typ = {PUB:(DE-HGF)16},
pubmed = {38958131},
UT = {WOS:001260701700001},
doi = {10.1002/hbm.26776},
url = {https://juser.fz-juelich.de/record/1037239},
}