Visual Perception Laboratory, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Berlin Center for Advanced Neuroimaging (BCAN), Charité - Universitätsmedizin Berlin, Berlin, Germany.
Brain. 2017 Apr 1;140(4):1147-1157. doi: 10.1093/brain/awx025.
According to current concepts, major depressive disorder is strongly related to dysfunctional neural processing of motivational information, entailing impairments in reinforcement learning. While computational modelling can reveal the precise nature of neural learning signals, it has not been used to study learning-related neural dysfunctions in unmedicated patients with major depressive disorder so far. We thus aimed at comparing the neural coding of reward and punishment prediction errors, representing indicators of neural learning-related processes, between unmedicated patients with major depressive disorder and healthy participants. To this end, a group of unmedicated patients with major depressive disorder (n = 28) and a group of age- and sex-matched healthy control participants (n = 30) completed an instrumental learning task involving monetary gains and losses during functional magnetic resonance imaging. The two groups did not differ in their learning performance. Patients and control participants showed the same level of prediction error-related activity in the ventral striatum and the anterior insula. In contrast, neural coding of reward prediction errors in the medial orbitofrontal cortex was reduced in patients. Moreover, neural reward prediction error signals in the medial orbitofrontal cortex and ventral striatum showed negative correlations with anhedonia severity. Using a standard instrumental learning paradigm we found no evidence for an overall impairment of reinforcement learning in medication-free patients with major depressive disorder. Importantly, however, the attenuated neural coding of reward in the medial orbitofrontal cortex and the relation between anhedonia and reduced reward prediction error-signalling in the medial orbitofrontal cortex and ventral striatum likely reflect an impairment in experiencing pleasure from rewarding events as a key mechanism of anhedonia in major depressive disorder.
根据目前的概念，重度抑郁症与动机信息的神经处理功能障碍密切相关，这涉及到强化学习的损伤。虽然计算模型可以揭示神经学习信号的确切性质，但迄今为止，它尚未用于研究未经药物治疗的重度抑郁症患者与学习相关的神经功能障碍。因此，我们旨在比较未经药物治疗的重度抑郁症患者和健康参与者之间，代表神经学习相关过程的奖励和惩罚预测误差的神经编码。为此，一组未经药物治疗的重度抑郁症患者（n = 28）和一组年龄和性别匹配的健康对照组参与者（n = 30）在功能磁共振成像期间完成了一项涉及金钱收益和损失的工具性学习任务。两组在学习表现上没有差异。患者和对照组参与者在前脑岛和腹侧纹状体中表现出相同水平的预测误差相关活动。相比之下，内侧眶额皮质中的奖励预测误差的神经编码在患者中减少。此外，内侧眶额皮质和腹侧纹状体中的神经奖励预测误差信号与快感缺失的严重程度呈负相关。使用标准的工具性学习范式，我们没有发现未经药物治疗的重度抑郁症患者强化学习整体受损的证据。然而，重要的是，内侧眶额皮质中奖励的神经编码减弱，以及内侧眶额皮质和腹侧纹状体中快感缺失与减少的奖励预测误差信号之间的关系，可能反映了体验奖励事件的愉悦感的损伤，这是重度抑郁症中快感缺失的一个关键机制。
