迁移性安慰剂效应的多模态机制 ：从痛觉到情绪的行为、ERP和fMRI研究

Although studies on placebo effect proved the placebo expectation established by pain-alleviating treatment could significantly alleviate later pain perception, or the placebo expectation established by anxiety-reducing treatment could significantly reduce the intensity of induced negative feelings, it is still unclear whether or not the placebo effect can occur in a transferable manner. That is, we still don’t know if the placebo expectation derived from pain-alleviating can significantly reduce later negative emotional arousal or not. Experiment 1: We compared the effect of the verbal expectation (purely verbal induction and without pain-alleviating reinforcement) with the reinforced expectation (building the belief in the placebo’s ataractic efficiency on unpleasant picture processing by secret reduction of the intensity of the pain-evoking stimulus) on the negative emotion. The results showed that the expectation, which was reinforced by actual analgesia, was transferable and could produce significant placebo effect on negative emotional arousal. However, the expectation that was merely induced by verbal instruction did not have such power. Experiment 2 both examined the direct analgesic effect of the placebo on the sensory pain (how strong is the pain stimulus) and emotional pain (how disturbing is the pain stimulus) and the transferable ataractic effect of the placebo on the negative emotion (how disturbing is the emotional picture stimulus), and further proved that the placebo expectation that was established from pain-reducing reinforcement not only induced significant placebo effect on pain, but also significant placebo effect on unpleasant feeling. These results support the viewpoint that the reduction of affective pain based on the conditioning mechanism plays an important role in the placebo analgesia, but can’t explain the transferred placebo effect on visual unpleasantness. Experiment 3 continued to use the paradigm of the reinforced expectation group and recorded the EEG activities, the data showed that the transferable placebo treatment was accompanied with decreased P2 amplitude and increased N2 distributed, and significant differences between the transferable placebo condition and the control condition (i.e., P2 and N2) were observed within the first 150-300 ms, a duration brief enough to rule out the possibility that differences between the two conditions merely reflect a bias “to try to please the investigator. In Experiment 4, we selected the placebo responders in the pre-experiment and let them to go through the formal fMRI scan. The results found that the transferable placebo treatment reduced the negative emotional response, emotion-responsive regions such as the amygdala, insula, anterior cingulate cortex and the thalamus showed an attenuated activation. And in the placebo condition, there was an enhanced activation in the subcollosal gyrus, which may be involved in emotional regulation. In conclusion, the transferable placebo treatment induced the reliable placebo effect on the behavior, EEG activity and bold signal, and we attempted to discuss the pychophysiological mechanism based on the positive expectancy.

过去的安慰剂镇痛研究，都是通过镇痛药物强化，诱导被试建立对于特定处理能够镇痛的信念，然后研究对应的安慰剂镇痛反应；安慰剂镇静作用的研究则是在镇静药物强化之后研究对应的安慰剂镇静效应。但安慰剂预期是否能够从痛觉领域向情绪发生迁移尚不清楚。本研究尝试探讨从痛觉到情绪的安慰剂的迁移性模式，即与无治疗信念相比，从痛觉治疗中获得的治疗信念是否会使负性情绪体验及相应脑活动产生影响。实验一：比较单纯的言语预期和迁移的治疗预期两种安慰剂实施方式对被试负性情绪体验的影响有何不同。结果发现单纯的言语性安慰剂预期没有使被试的负性情绪体验发生显著变化，而迁移的安慰剂预期使被试的负性情绪体验显著降低。实验二既检验迁移性安慰剂信念对疼痛感觉（有多疼）和疼痛情绪（有多烦恼）影响，也检验其对负性情绪体验的影响，结果发现疼痛感觉的变化和疼痛情绪的变化相关显著，但二者与负性情绪的变化均无显著相关，表明负性图片情绪中诱发的安慰剂效应不能由安慰剂引起的疼痛感觉和疼痛情绪变化来解释。实验三采用实验一中强化预期组的实验范式同时记录脑电，结果发现与控制条件相比，迁移性安慰剂条件下负性情绪图片诱发更低幅度的P2和更高幅度的N2，并进一步证明安慰剂效应在感觉信息的早期加工阶段（300ms内）就已发生，不支持安慰剂效应产生于后期评价偏向的观点。实验四筛选出安慰剂反应者进入核磁实验。结果发现，迁移性安慰剂条件下与负性情绪加工密切相关的杏仁核、脑岛、腹侧丘脑和前扣带激活减弱，眶部前额叶则表现为激活增强。说明迁移性安慰剂效应确实缓解了负性情绪，这种安慰剂调控可能是通过眶部前额叶进行的。研究表明：迁移性安慰剂效应确实存在，可靠诱发了行为、脑电和Bold信号的变化，并初步探明对安慰剂疗效的积极预期可能是调控情绪的心理机制。