Tobias U Hauser1, Reto Iannaccone2, Juliane Ball3, Christoph Mathys4, Daniel Brandeis5, Susanne Walitza5, Silvia Brem6. 1. 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. 2. University Clinics for Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland4Doctoral Program in Integrative Molecular Medicine, University of Zurich, Zurich, Switzerland. 3. University Clinics for Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland. 4. 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. 5. 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. 6. University Clinics for Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland2Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
Abstract
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.
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