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@ARTICLE{Hammes:860706,
      author       = {Hammes, Jochen and Theis, Hendrik and Giehl, Kathrin and
                      Hoenig, Merle C and Greuel, Andrea and Tittgemeyer, Marc and
                      Timmermann, Lars and Fink, Gereon Rudolf and Drzezga,
                      Alexander and Eggers, Carsten and van Eimeren, Thilo},
      title        = {{D}opamine metabolism of the nucleus accumbens and
                      fronto-striatal connectivity modulate impulse control},
      journal      = {Brain},
      volume       = {142},
      number       = {3},
      issn         = {1460-2156},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {FZJ-2019-01371},
      pages        = {733-743},
      year         = {2019},
      abstract     = {Impulsive-compulsive behaviours like pathological gambling
                      or hypersexuality are a frequent side effect of dopamine
                      replacement therapy in patients with Parkinson’s disease.
                      Multiple imaging studies suggest a significant reduction of
                      presynaptic dopamine transporters in the nucleus accumbens
                      to be a predisposing factor, reflecting either a reduction
                      of mesolimbic projections or, alternatively, a lower
                      presynaptic dopamine transporter expression per se. Here, we
                      aimed to test the hypothesis of fewer mesolimbic projections
                      as a risk factor by using dopamine synthesis capacity as a
                      proxy of dopaminergic terminal density. Furthermore,
                      previous studies have demonstrated a reduction of
                      fronto-striatal connectivity to be associated with increased
                      risk of impulsive-compulsive behaviour in Parkinson’s
                      disease. Therefore, another aim of this study was to
                      investigate the relationship between severity of
                      impulsive-compulsive behaviour, dopamine synthesis capacity
                      and fronto-striatal connectivity. Eighty participants
                      underwent resting state functional MRI and anatomical
                      T1-weighted images [mean age: 68 ± 9.9 years, $67\%$ male
                      (patients)]. In 59 participants, 18F-DOPA-PET was obtained
                      and voxel-wise Patlak slopes indicating dopamine synthesis
                      capacity were calculated. All participants completed the
                      QUIP-RS questionnaire, a well validated test to quantify
                      severity of impulsive-compulsive behaviour in Parkinson’s
                      disease. A voxel-wise correlation analysis between dopamine
                      synthesis capacity and QUIP-RS score was calculated for
                      striatal regions. To investigate the relationship between
                      symptom severity and functional connectivity, voxel-wise
                      correlations were performed. A negative correlation was
                      found between dopamine synthesis capacity and QUIP-RS score
                      in the nucleus accumbens (r = −0.57, P = 0.001), a region
                      functionally connected to the rostral anterior cingulate
                      cortex. The connectivity strength was modulated by QUIP-RS,
                      i.e. patients with more severe impulsive-compulsive
                      behaviours had a weaker functional connectivity between
                      rostral anterior cingulate cortex and the nucleus accumbens.
                      In addition, cortical thickness and severity of
                      impulsive-compulsive behaviour were positively correlated in
                      the subgenual rostral anterior cingulate cortex. We found
                      three factors to be associated with severity of
                      impulsive-compulsive behaviour: (i) decreased dopamine
                      synthesis capacity in the nucleus accumbens; (ii) decreased
                      functional connectivity of the rostral anterior cingulate
                      cortex with the nucleus accumbens; and (iii) increased
                      cortical thickness of the subgenual rostral anterior
                      cingulate cortex. Rather than a downregulation of dopamine
                      transporters, a reduction of mesolimbic dopaminergic
                      projections in conjunction with a dysfunctional rostral
                      anterior cingulate cortex—a region known to play a key
                      role in impulse control—could be the most crucial
                      neurobiological risk factor for the development of
                      impulsive-compulsive behaviours in patients with
                      Parkinson’s disease under dopamine replacement therapy.},
      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:30753324},
      UT           = {WOS:000512724900026},
      doi          = {10.1093/brain/awz007},
      url          = {https://juser.fz-juelich.de/record/860706},
}