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@ARTICLE{Steidel:904884,
      author       = {Steidel, Kenan and Ruppert, Marina C. and Palaghia, Irina
                      and Greuel, Andrea and Tahmasian, Masoud and Maier,
                      Franziska and Hammes, Jochen and van Eimeren, Thilo and
                      Timmermann, Lars and Tittgemeyer, Marc and Drzezga,
                      Alexander and Pedrosa, David and Eggers, Carsten},
      title        = {{D}opaminergic pathways and resting-state functional
                      connectivity in {P}arkinson’s disease with freezing of
                      gait},
      journal      = {NeuroImage: Clinical},
      volume       = {32},
      issn         = {2213-1582},
      address      = {[Amsterdam u.a.]},
      publisher    = {Elsevier},
      reportid     = {FZJ-2022-00200},
      pages        = {102899 -},
      year         = {2021},
      abstract     = {Freezing of gait is a common phenomenon of advanced
                      Parkinson’s disease. Besides locomotor function per se, a
                      role of cognitive deficits has been suggested. Limited
                      evidence of associated dopaminergic deficits points to
                      caudatal denervation. Further, altered functional
                      connectivity within resting-state networks with importance
                      for cognitive functions has been described in freezers. A
                      potential pathophysiological link between both imaging
                      findings has not yet been addressed. The current study
                      sought to investigate the association between dopaminergic
                      pathway dysintegrity and functional dysconnectivity in
                      relation to FOG severity and cognitive performance in a
                      well-characterized PD cohort undergoing high-resolution
                      6-[18F]fluoro-L-Dopa PET and functional MRI. The freezing of
                      gait questionnaire was applied to categorize patients (n =
                      59) into freezers and non-freezers. A voxel-wise group
                      comparison of 6-[18F]fluoro-L-Dopa PET scans with focus on
                      striatum was performed between both well-matched and
                      neuropsychologically characterized patient groups.
                      Seed-to-voxel resting-state functional connectivity maps of
                      the resulting dopamine depleted structures and dopaminergic
                      midbrain regions were created and compared between both
                      groups. For a direct between-group comparison of
                      dopaminergic pathway integrity, a molecular connectivity
                      approach was conducted on 6-[18F]fluoro-L-Dopa scans. With
                      respect to striatal regions, freezers showed significant
                      dopaminergic deficits in the left caudate nucleus, which
                      exhibited altered functional connectivity with regions of
                      the visual network. Regarding midbrain structures, the
                      bilateral ventral tegmental area showed altered functional
                      coupling to regions of the default mode network. An
                      explorative examination of the integrity of dopaminergic
                      pathways by molecular connectivity analysis revealed
                      freezing-associated impairments in mesolimbic and
                      mesocortical pathways. This study represents the first
                      characterization of a link between dopaminergic pathway
                      dysintegrity and altered functional connectivity in
                      Parkinson’s disease with freezing of gait and hints at a
                      specific involvement of striatocortical and
                      mesocorticolimbic pathways in freezers.},
      cin          = {INM-7 / INM-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-7-20090406 / I:(DE-Juel1)INM-2-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34911202},
      UT           = {WOS:000726978300003},
      doi          = {10.1016/j.nicl.2021.102899},
      url          = {https://juser.fz-juelich.de/record/904884},
}