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@ARTICLE{Kasper:1002271,
      author       = {Kasper, Jan and Eickhoff, Simon B and Caspers, Svenja and
                      Peter, Jessica and Dogan, Imis and Wolf, Robert Christian
                      and Reetz, Kathrin and Dukart, Juergen and Orth, Michael},
      title        = {{L}ocal synchronicity in dopamine-rich caudate nucleus
                      influences {H}untington’s disease motor phenotype},
      journal      = {Brain},
      volume       = {146},
      number       = {8},
      issn         = {0006-8950},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {FZJ-2023-01253},
      pages        = {3319–3330},
      year         = {2023},
      abstract     = {Structural grey and white matter changes precede the
                      manifestation of clinical signs of Huntington's disease by
                      many years. Conversion to clinically manifest disease
                      therefore likely reflects not merely atrophy but a more
                      wide-spread breakdown of brain function. Here, we
                      investigated the structure - function relationship close to
                      and after the clinical onset testing for its co-localization
                      with specific neurotransmitter/receptor systems and
                      important regional brain hubs, in particular caudate nucleus
                      and putamen that are central to maintain normal motor
                      behavior. In two independent cohorts of patients with
                      premanifest Huntington's disease close to onset and very
                      early manifest Huntington's disease (total n = 84; n = 88
                      matched controls) we used structural and resting state
                      functional MRI. We show that measures of functional activity
                      and local synchronicity within cortical and subcortical
                      regions remain normal in the premanifest Huntington's
                      disease phase despite clear evidence of brain atrophy. In
                      manifest Huntington's disease, homeostasis of synchronicity
                      was disrupted in subcortical hub regions such as caudate
                      nucleus and putamen, but also in cortical hub regions, for
                      instance the parietal lobe. Cross-modal spatial correlations
                      of functional MRI data with receptor/neurotransmitter
                      distribution maps showed that Huntington's disease specific
                      alterations co-localize with dopamine receptors D1, D2, as
                      well as dopamine and serotonin transporters. Caudate nucleus
                      synchronicity significantly improved models predicting the
                      severity of the motor phenotype or predicting the
                      classification into premanifest Huntington's disease or
                      motor manifest Huntington's disease. Our data suggest that
                      the functional integrity of the dopamine receptor rich
                      caudate nucleus is key to maintain network function. The
                      loss of caudate nucleus functional integrity affects network
                      function to a degree that causes a clinical phenotype. These
                      insights into what happens in Huntington's disease could
                      serve as a model for what might be a more general
                      relationship between brain structure and function in
                      neurodegenerative diseases in which other brain regions are
                      vulnerable.},
      cin          = {INM-7 / INM-1 / INM-11},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-7-20090406 / I:(DE-Juel1)INM-1-20090406 /
                      I:(DE-Juel1)INM-11-20170113},
      pnm          = {5251 - Multilevel Brain Organization and Variability
                      (POF4-525) / HBP SGA3 - Human Brain Project Specific Grant
                      Agreement 3 (945539)},
      pid          = {G:(DE-HGF)POF4-5251 / G:(EU-Grant)945539},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {36795496},
      UT           = {WOS:000954320200001},
      doi          = {10.1093/brain/awad043},
      url          = {https://juser.fz-juelich.de/record/1002271},
}