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@ARTICLE{Ruppert:874734,
      author       = {Ruppert, Marina C and Greuel, Andrea and Tahmasian, Masoud
                      and Schwartz, Frank and Stürmer, Sophie and Maier,
                      Franziska and Hammes, Jochen and Tittgemeyer, Marc and
                      Timmermann, Lars and van Eimeren, Thilo and Drzezga,
                      Alexander and Eggers, Carsten},
      title        = {{N}etwork degeneration in {P}arkinson’s disease:
                      multimodal imaging of nigro-striato-cortical dysfunction},
      journal      = {Brain},
      volume       = {143},
      number       = {3},
      issn         = {1460-2156},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {FZJ-2020-01643},
      pages        = {944 - 959},
      year         = {2020},
      abstract     = {The spreading hypothesis of neurodegeneration assumes an
                      expansion of neural pathologies along existing neural
                      pathways. Multimodal neuroimaging studies have demonstrated
                      distinct topographic patterns of cerebral pathologies in
                      neurodegeneration. For Parkinson’s disease the hypothesis
                      so far rests largely on histopathological evidence of
                      α-synuclein spreading in a characteristic pattern and
                      progressive nigrostriatal dopamine depletion. Functional
                      consequences of nigrostriatal dysfunction on cortical
                      activity remain to be elucidated. Our goal was to
                      investigate multimodal imaging correlates of degenerative
                      processes in Parkinson’s disease by assessing dopamine
                      depletion and its potential effect on striatocortical
                      connectivity networks and cortical metabolism in relation to
                      parkinsonian symptoms. We combined 18F-DOPA-PET,
                      18F-fluorodeoxyglucose (FDG)-PET and resting state
                      functional MRI to multimodally characterize network
                      alterations in Parkinson’s disease. Forty-two patients
                      with mild-to-moderate stage Parkinson’s disease and 14
                      age-matched healthy control subjects underwent a multimodal
                      imaging protocol and comprehensive clinical examination. A
                      voxel-wise group comparison of 18F-DOPA uptake identified
                      the exact location and extent of putaminal dopamine
                      depletion in patients. Resulting clusters were defined as
                      seeds for a seed-to-voxel functional connectivity analysis.
                      18F-FDG metabolism was compared between groups at a
                      whole-brain level and uptake values were extracted from
                      regions with reduced putaminal connectivity. To unravel
                      associations between dopaminergic activity, striatocortical
                      connectivity, glucose metabolism and symptom severity,
                      correlations between normalized uptake values,
                      seed-to-cluster β-values and clinical parameters were
                      tested while controlling for age and dopaminergic
                      medication. Aside from cortical hypometabolism, 18F-FDG-PET
                      data for the first time revealed a hypometabolic midbrain
                      cluster in patients with Parkinson’s disease that
                      comprised caudal parts of the bilateral substantia nigra
                      pars compacta. Putaminal dopamine synthesis capacity was
                      significantly reduced in the bilateral posterior putamen and
                      correlated with ipsilateral nigral 18F-FDG uptake. Resting
                      state functional MRI data indicated significantly reduced
                      functional connectivity between the dopamine depleted
                      putaminal seed and cortical areas primarily belonging to the
                      sensorimotor network in patients with Parkinson’s disease.
                      In the inferior parietal cortex, hypoconnectivity in
                      patients was significantly correlated with lower metabolism
                      (left P = 0.021, right P = 0.018). Of note, unilateral
                      network alterations quantified with different modalities
                      corresponded with contralateral motor impairments. In
                      conclusion, our results support the hypothesis that
                      degeneration of nigrostriatal fibres functionally impairs
                      distinct striatocortical connections, disturbing the
                      efficient interplay between motor processing areas and
                      impairing motor control in patients with Parkinson’s
                      disease. The present study is the first to reveal trimodal
                      evidence for network-dependent degeneration in Parkinson’s
                      disease by outlining the impact of functional nigrostriatal
                      pathway impairment on striatocortical functional
                      connectivity networks and cortical metabolism.},
      cin          = {INM-3 / INM-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406 / I:(DE-Juel1)INM-2-20090406},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572)},
      pid          = {G:(DE-HGF)POF3-572},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32057084},
      UT           = {WOS:000522641900028},
      doi          = {10.1093/brain/awaa019},
      url          = {https://juser.fz-juelich.de/record/874734},
}