Computational models of reinforcement learning have helped dissect discrete components of reward-related function and characterize neurocognitive deficits in psychiatric illnesses. Stimulus novelty biases decision-making, even when unrelated to choice outcome, acting as if possessing intrinsic reward value to guide decisions toward uncertain options. Heightened novelty seeking is characteristic of attention deficit hyperactivity disorder, yet how this influences reward-related decision-making is computationally encoded, or is altered by stimulant medication, is currently uncertain. Here we used an established reinforcement-learning task to model effects of novelty on reward-related behaviour during functional MRI in 30 adults with attention deficit hyperactivity disorder and 30 age-, sex- and IQ-matched control subjects. Each participant was tested on two separate occasions, once ON and once OFF stimulant medication. OFF medication, patients with attention deficit hyperactivity disorder showed significantly impaired task performance (P = 0.027), and greater selection of novel options (P = 0.004). Moreover, persistence in selecting novel options predicted impaired task performance (P = 0.025). These behavioural deficits were accompanied by a significantly lower learning rate (P = 0.011) and heightened novelty signalling within the substantia nigra/ventral tegmental area (family-wise error corrected P < 0.05). Compared to effects in controls, stimulant medication improved attention deficit hyperactivity disorder participants’ overall task performance (P = 0.011), increased reward-learning rates (P = 0.046) and enhanced their ability to differentiate optimal from non-optimal novel choices (P = 0.032). It also reduced substantia nigra/ventral tegmental area responses to novelty. Preliminary cross-sectional evidence additionally suggested an association between long-term stimulant treatment and a reduction in the rewarding value of novelty. These data suggest that aberrant substantia nigra/ventral tegmental area novelty processing plays an important role in the suboptimal reward-related decision-making characteristic of attention deficit hyperactivity disorder. Compared to effects in controls, abnormalities in novelty processing and reward-related learning were improved by stimulant medication, suggesting that they may be disorder-specific targets for the pharmacological management of attention deficit hyperactivity disorder symptoms.

中文翻译：

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奖励和新颖性处理以及精神兴奋剂在注意力缺陷多动障碍中的作用的神经计算解释

强化学习的计算模型有助于剖析奖励相关功能的离散组件，并描述精神疾病中的神经认知缺陷。即使与选择结果无关，刺激的新颖性也会使决策产生偏见，就好像拥有内在的奖励价值来引导决策朝着不确定的选择方向发展一样。高度的新奇寻求是注意力缺陷多动障碍的特征，但是这如何影响与奖励相关的决策是计算编码的，或者是由兴奋剂药物改变的，目前尚不确定。在这里，我们使用已建立的强化学习任务来模拟 30 名患有注意力缺陷多动障碍的成年人和 30 名年龄、性别和智商匹配的对照受试者在功能 MRI 期间新颖性对奖励相关行为的影响。每个参与者都在两个不同的场合进行了测试，一次是使用兴奋剂药物，一次是关闭兴奋剂药物。停药后，注意力缺陷多动障碍患者的任务表现明显受损（P = 0.027），以及更多的新选择（P = 0.004）。此外，坚持选择新选项预示着任务绩效受损（P = 0.025）。这些行为缺陷伴随着显着降低的学习率（P = 0.011）和黑质/腹侧被盖区域内的新奇信号增强（家庭错误校正P < 0.05）。与对照组的效果相比，兴奋剂药物改善了注意力缺陷多动障碍参与者的整体任务表现（P = 0.011），提高了奖励学习率（P = 0.046）并增强了他们区分最佳和非最佳新选择的能力（P = 0.032）。它还减少了黑质/腹侧被盖区域对新奇事物的反应。初步的横断面证据还表明，长期兴奋剂治疗与新颖性的奖励价值降低之间存在关联。这些数据表明，异常的黑质/腹侧被盖区域新奇加工在注意力缺陷多动障碍的次优奖赏相关决策特征中起重要作用。与对照组的效果相比，兴奋剂药物改善了新奇加工和奖励相关学习的异常，这表明它们可能是注意力缺陷多动障碍症状的药理学管理的疾病特异性目标。