title: Role of the medial prefrontal cortex in impaired decision making in juvenile attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  Attention-deficit/hyperactivity disorder (ADHD) has been associated with deficient decision making and learning. Models of ADHD have suggested that these deficits could be caused by impaired reward prediction errors (RPEs). Reward prediction errors are signals that indicate violations of expectations and are known to be encoded by the dopaminergic system. However, the precise learning and decision-making deficits and their neurobiological correlates in ADHD are not well known.
  
  
  OBJECTIVE
  To determine the impaired decision-making and learning mechanisms in juvenile ADHD using advanced computational models, as well as the related neural RPE processes using multimodal neuroimaging.
  
  
  METHODS
  Twenty adolescents with ADHD and 20 healthy adolescents serving as controls (aged 12-16 years) were examined using a probabilistic reversal learning task while simultaneous functional magnetic resonance imaging and electroencephalogram were recorded.
  
  
  METHODS
  Learning and decision making were investigated by contrasting a hierarchical Bayesian model with an advanced reinforcement learning model and by comparing the model parameters. The neural correlates of RPEs were studied in functional magnetic resonance imaging and electroencephalogram.
  
  
  RESULTS
  Adolescents with ADHD showed more simplistic learning as reflected by the reinforcement learning model (exceedance probability, Px = .92) and had increased exploratory behavior compared with healthy controls (mean [SD] decision steepness parameter β: ADHD, 4.83 [2.97]; controls, 6.04 [2.53]; P = .02). The functional magnetic resonance imaging analysis revealed impaired RPE processing in the medial prefrontal cortex during cue as well as during outcome presentation (P < .05, family-wise error correction). The outcome-related impairment in the medial prefrontal cortex could be attributed to deficient processing at 200 to 400 milliseconds after feedback presentation as reflected by reduced feedback-related negativity (ADHD, 0.61 [3.90] μV; controls, -1.68 [2.52] μV; P = .04).
  
  
  CONCLUSIONS
  The combination of computational modeling of behavior and multimodal neuroimaging revealed that impaired decision making and learning mechanisms in adolescents with ADHD are driven by impaired RPE processing in the medial prefrontal cortex. This novel, combined approach furthers the understanding of the pathomechanisms in ADHD and may advance treatment strategies.
authors.affiliation: University Clinics for Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland3Wellcome Trust Centre for Neuroimaging, University College London, Londo.
authors.forename: Tobias U
authors.initials: TU
authors.lastname: Hauser
authors.affiliation: University Clinics for Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland4Doctoral Program in Integrative Molecular Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Iannaccone
authors.affiliation: University Clinics for Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland.
authors.forename: Juliane
authors.initials: J
authors.lastname: Ball
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, London, England5Max Planck University College London Centre for Computational Psychiatry and Ageing Research, London, England6Translational Neuromodeling Unit, Institute for Biomedical Eng.
authors.forename: Christoph
authors.initials: C
authors.lastname: Mathys
authors.affiliation: University Clinics for Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland7Zurich Center for Integrative Human Physiology, University of Zurich, Zu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brandeis
authors.affiliation: University Clinics for Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland7Zurich Center for Integrative Human Physiology, University of Zurich, Zu.
authors.forename: Susanne
authors.initials: S
authors.lastname: Walitza
authors.affiliation: University Clinics for Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Brem
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology* / Q000523:psychology; D001921:Brain / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D003657:Decision Making / Q000502:physiology*; D004569:Electroencephalography; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D007858:Learning / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D017397:Prefrontal Cortex / Q000503:physiopathology*