Neural dynamics of directly and indirectly conditioned placebo/nocebo effect

 描述(由申请人提供)：安慰剂和NOCEBO已经在直接条件/情境学习范例中进行了深入的探索。然而，日常生活和临床环境中的大多数学习都是间接进行的(例如，观察性/社会性学习)，对高度相关的背景线索做出反应，并可能不仅有意识地，而且在潜意识中诱导安慰剂/非安慰剂效应。尽管间接学习无处不在，并有可能利用它，但人们对间接学习线索诱导的安慰剂/非安慰剂的大脑机制知之甚少。本研究的目的是研究直接和间接、有意识和潜意识的安慰剂/非安慰剂学习和提取的神经机制。通过应用具有毫秒分辨率的脑磁图，我们将能够研究1)由有意识和无意识线索引起的安慰剂/无脑反应；2)参与语境学习和安慰剂/无脑效应的大脑网络；3)直接/间接学习和有意识/无意识激活语境线索之间相互作用的振荡动力学。使用假药名作为提示，将进一步加深我们对药物标签对安慰剂/NOCEBO反应的影响的理解。所有受试者都将接受经典条件反射(体验不同的线索和不同程度的疼痛)和社会观察条件反射(观察他人对线索和疼痛的反应)。然后，我们将比较主观疼痛评级和MEG信号变化，这些变化是由相同的疼痛引起的，前面有高或低，直接或观察性地学习伪药名称，有意识或无意识地感知。所获得的结果将有助于开发利用安慰剂/nocebo效应的新方法，以及理解临床环境中直接和间接学习的机制。揭示通过社会观察获得的“看不见的”线索的调制作用，将揭示无意识观察性学习的一般机制，这可以扩展到其他精神病学研究领域，如成瘾和创伤后应激障碍，在这些领域，线索激活不想要的记忆或渴望是相关的。

 DESCRIPTION (provided by applicant): Placebo and nocebo have been intensively explored in direct conditioning/ context learning paradigms. However, most learning in daily life and clinical settings takes place indirectly (e.g., observational / social learning) in response to higly relevant contextual cues and may induce placebo/nocebo effects not only consciously but also subconsciously. Despite the ubiquity of indirect learning and the potential promise of harnessing it, little is known about the brain mechanisms of indirectly learned cue-induced placebo/nocebo. The goal of this proposal is to investigate the neural mechanism of direct and indirect, conscious and subliminal placebo/nocebo learning and retrieval. By applying MEG, featuring millisecond resolution, we will be able to study 1) placebo/nocebo responses evoked with conscious and non-conscious cues; 2) brain networks involved in context learning and placebo / nocebo effect; 3) the oscillatory dynamics underlying the interaction between direct / indirect learning and conscious / non- conscious activation of contextual cues. The use of pseudo drug names as cues will further enhance our understanding of the influence of medication labels on placebo/nocebo response. All subjects will undergo both a classical conditioning (experiencing different cues with different levels of pain intensity) and social observation conditioning (observing others' response to cues and pain). We will then compare subjective pain ratings and MEG signal changes evoked by identical pain preceded by high or low directly or observationally learned pseudo drug names, perceived consciously or non-consciously. The results obtained will shed light on developing new methods of harnessing placebo/nocebo effects, as well as understanding the mechanisms of direct and indirect learning in a clinical setting. Revealing the modulation effects of 'unseen' cues learned through social observation will unveil general mechanisms of non-conscious observational learning, which can be extended to other fields of psychiatric research such as addiction and Post-Traumatic Stress Disorder, where cue-activation of unwanted memories or cravings is relevant.