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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},
}