BACKGROUND:In experimental placebo and nocebo studies, neutral control treatments are often administered for comparison with active treatments, but are of little interest, as, on average, they result in little change. Yet, when considered at an individual level, they fluctuate between baseline and subsequent measurements and may reveal important information about participants' placebo/nocebo responding tendencies.

METHODS:In a paradigm involving application of creams paired with positive, negative and neutral expectations, some subjects rated identical stimuli in the neutral condition as more painful while others as less painful after treatment with inert cream. We divided subjects into two groups based on the median split in these pre-post responses in the neutral control condition, and investigated (a) fMRI signal differences (post minus pre) between the two groups in neutral condition, and (b) seed-based resting state connectivity of the bilateral amygdala, known to be involved in emotional self-regulation, as well as ambiguous stimulus processing and aversive learning.

RESULTS:The results suggested that subjects who rated the same pain stimuli after treatment with explicitly neutral cream as more painful showed stronger fMRI activation of the amygdala during the experiment and had higher connectivity between the left amygdala and the striatum at rest. Neutral pre-post changes predicted behavioural placebo/nocebo response in this and two independent datasets.

CONCLUSION:These findings suggest that measuring pre-post change in the neutral control condition might provide important information about subjects' individual differences in placebo/nocebo response.

SIGNIFICANCE:Pre-post changes in pain ratings in neutral conditions are modulated by amygdala activity and connectivity and can be used to predict placebo/nocebo responses.

译文

背景:在实验性安慰剂和Nocebo研究中,通常将中性对照治疗与主动治疗进行比较,但兴趣不大,因为平均而言,它们的变化很小。但是,以个人水平考虑时,它们会在基线和后续测量之间波动,并可能揭示有关参与者安慰剂/ Nocebo反应趋势的重要信息。

方法:在涉及应用的范例中在对乳膏剂进行正面,负面和中性的期望配对后,有些受试者在惰性霜剂治疗后,在中性状态下对相同的刺激物评价为较痛苦,而另一些受试者对疼痛的评价则较小。我们根据中性对照条件下这些前后反应的中位数划分将受试者分为两组,并研究了(a)中性条件下两组之间的fMRI信号差异(减去前后),以及(b)基于双侧杏仁核的静息状态连通性,已知其参与情绪自我调节以及模棱两可的刺激处理和厌恶性学习。

结果:结果表明,在实验中,使用显着中性乳膏治疗的患者对相同的疼痛刺激评分更高,因为在实验过程中,更痛苦的显示杏仁核的功能磁共振成像激活更强,并且左侧杏仁核和静息纹状体之间的连通性更高。中性事前变化预测该行为和两个独立数据集中的行为安慰剂/ nocebo反应。

结论:这些发现表明,在中性对照条件下测量事前变化可提供重要的信息。有关受试者在安慰剂/ nocebo反应中个体差异的信息。

显着性:杏仁核的活动性和连通性可调节中性条件下疼痛等级的事前变化。安慰剂/ nocebo反应。

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