• Tobias U Hauser, Reto Iannaccone, Juliane Ball, Christoph Mathys, Daniel Brandeis, Susanne Walitza, and Silvia Brem.
• 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.
• JAMA Psychiatry. 2014 Oct 1; 71 (10): 1165-73.

ImportanceAttention-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.ObjectiveTo 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.Design, Setting, And ParticipantsTwenty 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.Main Outcomes And MeasuresLearning 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.ResultsAdolescents 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 And RelevanceThe 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.

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