Institute of Cognitive Neuroscience, University College London, London, UK.
Neuroimage. 2010 Apr 1;50(2):657-64. doi: 10.1016/j.neuroimage.2009.11.075. Epub 2009 Dec 5.
Theories of the positive symptoms of schizophrenia hypothesize a role for aberrant reinforcement signaling driven by dysregulated dopamine transmission. Recently, we provided evidence of aberrant reward learning in symptomatic, but not asymptomatic patients with schizophrenia, using a novel paradigm, the Salience Attribution Test (SAT). The SAT is a probabilistic reward learning game that employs cues that vary across task-relevant and task-irrelevant dimensions; it provides behavioral indices of adaptive and aberrant reward learning. As an initial step prior to future clinical studies, here we used functional magnetic resonance imaging to examine the neural basis of adaptive and aberrant reward learning during the SAT in healthy volunteers. As expected, cues associated with high relative to low reward probabilities elicited robust hemodynamic responses in a network of structures previously implicated in motivational salience; the midbrain, in the vicinity of the ventral tegmental area, and regions targeted by its dopaminergic projections, i.e. medial dorsal thalamus, ventral striatum and prefrontal cortex (PFC). Responses in the medial dorsal thalamus and polar PFC were strongly correlated with the degree of adaptive reward learning across participants. Finally, and most importantly, differential dorsolateral PFC and middle temporal gyrus (MTG) responses to cues with identical reward probabilities were very strongly correlated with the degree of aberrant reward learning. Participants who showed greater aberrant learning exhibited greater dorsolateral PFC responses, and reduced MTG responses, to cues erroneously inferred to be less strongly associated with reward. The results are discussed in terms of their implications for different theories of associative learning.
精神分裂症阳性症状的理论假设，多巴胺传递失调导致异常强化信号是其产生的原因。最近，我们利用新颖的突显归因测试（SAT）为有症状但无症状的精神分裂症患者提供了异常奖励学习的证据。SAT 是一种概率奖励学习游戏，它采用了跨任务相关和任务无关维度变化的线索；它提供了适应性和异常奖励学习的行为指标。作为未来临床研究的初步步骤，我们使用功能磁共振成像检查了健康志愿者在 SAT 期间适应性和异常奖励学习的神经基础。正如预期的那样，与高相对低奖励概率相关的线索引起了一组先前涉及动机突显的结构的强烈血流反应；中脑，在腹侧被盖区附近，以及其多巴胺能投射的目标区域，即内侧背侧丘脑、腹侧纹状体和前额叶皮层（PFC）。内侧背侧丘脑和极性 PFC 的反应与参与者之间适应性奖励学习的程度强烈相关。最后，也是最重要的，对具有相同奖励概率的线索的背外侧前额叶皮层和颞中回（MTG）的差异反应与异常奖励学习的程度非常强烈相关。表现出更大异常学习的参与者对错误推断为与奖励相关性较弱的线索表现出更大的背外侧前额叶皮层反应，以及减少的 MTG 反应。结果讨论了它们对不同联想学习理论的意义。
