Expected value and prediction error abnormalities in depression and schizophrenia
Expected value and prediction error abnormalities in depression and schizophrenia
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DOI：
10.1093/brain/awr059
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发表时间：
2011-06-01
期刊：
影响因子：
14.5
通讯作者：
Steele, J. Douglas
中科院分区：
文献类型：
--
作者：
Gradin, Victoria B.;Kumar, Poornima;Steele, J. Douglas
多巴胺系统与抑郁症的快感缺失以及精神分裂症的阳性和阴性症状有关，但尚不清楚多巴胺功能障碍如何与观察到的症状存在机械联系。有相当多的证据表明，时相多巴胺信号编码预测误差(预期结果和实际结果之间的差异)，强化学习理论基于预测误差中介的联想学习。有人假设，神经预测错误信号的异常编码可能是抑郁症的快感缺失和精神分裂症的负面症状的基础，因为它扰乱了学习，削弱了奖励事件的显著程度，并通过促进异常知觉和妄想的形成而导致精神病症状。为了验证这一点，我们使用基于模型的功能磁共振成像和工具性奖励学习任务来研究抑郁症患者(n=15)、精神分裂症患者(n=14)和健康对照组(n=17)预测误差与期望奖励值的神经相关性。两组患者在神经预测误差方面都表现出异常，但异常的空间模式不同，异常的程度与证候严重程度相关。具体地说，在抑郁症患者中，纹状体和中脑的预测错误减少，双侧尾状核、伏隔核和中脑的信号减少程度与快感缺失的严重程度相关。在精神分裂症患者中，尾状核、丘脑、脑岛和杏仁-海马复合体的预测错误信号减少，中脑的预测错误有减少的趋势，岛叶、杏仁-海马复合体和中脑的预测错误编码的钝化程度与精神症状的严重程度相关。精神分裂症还与双侧杏仁核-海马区复合体和海马旁回预期奖励值的编码中断有关，中断的程度与精神病症状的严重程度相关。精神分裂症患者神经信号异常与阴性症状严重程度无关。这些发现支持这样一种观点，即预测错误信号的编码中断导致了抑郁症的快感缺失症状。在精神分裂症中，这一发现支持了错误依赖的推论和信念更新中异常的假设，这些推断和信念驱动了精神病症状。根据我们对多巴胺富集区预测错误异常的观察，给出了多巴胺编码预测错误的证据，提示抑郁症和精神分裂症的相性多巴胺异常。这一发现与精神症状反映了神经评估和激励显著形成的不同障碍的观点是一致的，这有助于弥合生物学和现象学水平之间的理解差距。
The dopamine system has been linked to anhedonia in depression and both the positive and negative symptoms of schizophrenia, but it remains unclear how dopamine dysfunction could mechanistically relate to observed symptoms. There is considerable evidence that phasic dopamine signals encode prediction error (differences between expected and actual outcomes), with reinforcement learning theories being based on prediction error-mediated learning of associations. It has been hypothesized that abnormal encoding of neural prediction error signals could underlie anhedonia in depression and negative symptoms in schizophrenia by disrupting learning and blunting the salience of rewarding events, and contribute to psychotic symptoms by promoting aberrant perceptions and the formation of delusions. To test this, we used model based functional magnetic resonance imaging and an instrumental reward-learning task to investigate the neural correlates of prediction errors and expected-reward values in patients with depression (n = 15), patients with schizophrenia (n = 14) and healthy controls (n = 17). Both patient groups exhibited abnormalities in neural prediction errors, but the spatial pattern of abnormality differed, with the degree of abnormality correlating with syndrome severity. Specifically, reduced prediction errors in the striatum and midbrain were found in depression, with the extent of signal reduction in the bilateral caudate, nucleus accumbens and midbrain correlating with increased anhedonia severity. In schizophrenia, reduced prediction error signals were observed in the caudate, thalamus, insula and amygdala-hippocampal complex, with a trend for reduced prediction errors in the midbrain, and the degree of blunting in the encoding of prediction errors in the insula, amygdala-hippocampal complex and midbrain correlating with increased severity of psychotic symptoms. Schizophrenia was also associated with disruption in the encoding of expected-reward values in the bilateral amygdala-hippocampal complex and parahippocampal gyrus, with the degree of disruption correlating with psychotic symptom severity. Neural signal abnormalities did not correlate with negative symptom severity in schizophrenia. These findings support the suggestion that a disruption in the encoding of prediction error signals contributes to anhedonia symptoms in depression. In schizophrenia, the findings support the postulate of an abnormality in error-dependent updating of inferences and beliefs driving psychotic symptoms. Phasic dopamine abnormalities in depression and schizophrenia are suggested by our observation of prediction error abnormalities in dopamine-rich brain areas, given the evidence for dopamine encoding prediction errors. The findings are consistent with proposals that psychiatric syndromes reflect different disorders of neural valuation and incentive salience formation, which helps bridge the gap between biological and phenomenological levels of understanding.