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@ARTICLE{Kruppa:856981,
      author       = {Kruppa, Jana and Gossen, Anna and Weiß, Eileen Oberwelland
                      and Kohls, Gregor and Großheinrich, Nicola and Cholemkery,
                      Hannah and Freitag, Christine M. and Karges, Wolfram and
                      Wölfle, Elke and Sinzig, Judith and Fink, Gereon Rudolf and
                      Herpertz-Dahlmann, Beate and Konrad, Kerstin and
                      Schulte-Rüther, Martin},
      title        = {{N}eural modulation of social reinforcement learning by
                      intranasal oxytocin in male adults with high-functioning
                      autism spectrum disorder: a randomized trial},
      journal      = {Neuropsychopharmacology},
      volume       = {44},
      number       = {4},
      issn         = {0893-133X},
      address      = {Basingstoke},
      publisher    = {Nature Publishing Group84063},
      reportid     = {FZJ-2018-06270},
      pages        = {749-756},
      year         = {2019},
      abstract     = {Reduced social motivation is a hallmark of individuals with
                      autism spectrum disorders (ASDs). Although the exact neural
                      mechanisms are unclear, oxytocin has been shown to enhance
                      motivation and attention to social stimuli, suggesting a
                      potential to augment social reinforcement learning as the
                      central mechanism of behavioral interventions in ASD. We
                      tested how reinforcement learning in social contexts and
                      associated reward prediction error (RPE) signals in the
                      nucleus accumbens (NAcc) were modulated by intranasal
                      oxytocin. Male adults with a childhood diagnosis of ASD
                      (n = 15) and healthy controls (n = 24; aged 18–26
                      years) performed a probabilistic reinforcement learning task
                      during functional magnetic resonance imaging in a
                      single-center (research center in Germany), randomized
                      double-blind, placebo-controlled cross-over trial. The
                      interventions were intranasal oxytocin (Syntocinon®,
                      Novartis; 10 puffs = 20 international units (IUs) per
                      treatment) and placebo spray. Using computational modeling
                      of behavioral data, trial-by-trial RPE signals were assessed
                      and related to brain activation in NAcc during reinforcing
                      feedback in social and non-social contexts. The order of
                      oxytocin/placebo was randomized for 60 participants.
                      Twenty-one participants were excluded from analyses, leaving
                      39 for the final analysis. Behaviorally, individuals with
                      ASD showed enhanced learning under oxytocin when the
                      learning target as well as feedback was social as compared
                      to non-social (social vs. non-social target: $87.09\%$ vs.
                      $71.29\%,$ $95\%$ confidence interval (CI): 7.28–24.33,
                      p = .003; social vs. non-social feedback: $81.00\%$ vs.
                      $71.29\%,$ $95\%$ CI: 2.81–16.61, p = .027).
                      Correspondingly, oxytocin enhanced the correlation of the
                      RPE signal with NAcc activation during social (vs.
                      non-social) feedback in ASD (3.48 vs. −1.12, respectively,
                      $95\%$ CI: 2.98–6.22, p = .000), whereas in controls,
                      this effect was found in the placebo condition (2.90 vs.
                      −1.14, respectively, $95\%$ CI: 1.07–7.01,
                      p = .010). In ASD, a similar pattern emerged when the
                      learning target was social (3.00 vs. −0.64, respectively,
                      $95\%$ CI: −0.13 to 7.41, p = .057), whereas controls
                      showed a reduced correlation for social learning targets
                      under oxytocin (−0.70 vs. 2.72, respectively, $95\%$ CI:
                      −5.86 to 0.98, p = .008). The current data suggest
                      that intranasal oxytocin has the potential to enhance social
                      reinforcement learning in ASD. Future studies are warranted
                      that investigate whether oxytocin can potentiate social
                      learning when combined with behavioral therapies, resulting
                      in greater treatment benefits than traditional behavior-only
                      approaches.},
      cin          = {INM-3},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572)},
      pid          = {G:(DE-HGF)POF3-572},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30390065},
      UT           = {WOS:000458386200012},
      doi          = {10.1038/s41386-018-0258-7},
      url          = {https://juser.fz-juelich.de/record/856981},
}