The neural bases of placebo effects and their relation to regulatory processes

描述（由申请人提供）：安慰剂效应是指不是由治疗的生物学作用引起的治疗效应，而是由归因于它的含义引起的。安慰剂治疗许多精神和身体疾病已被证明对健康和福祉有积极影响，因此了解产生这些效应的大脑和心理机制非常重要。最近的功能磁共振成像证据表明，安慰剂诱导的镇痛预期增加前额叶皮层的活动时，疼痛的预期和减少大脑的反应疼痛的刺激。这项研究的建议检查安慰剂对大脑的影响和行为措施的疼痛，焦虑，和其他负面的情感反应，使用功能磁共振成像。事件相关的功能磁共振成像设计用于隔离大脑对预期和疼痛刺激的反应，从而能够调查准备过程和体验过程之间的相互作用。两个实验研究了安慰剂反应的神经和神经化学基础。一项实验比较了安慰剂和阿片类镇痛药对大脑对疼痛刺激的反应的影响，并测试了药物是否像安慰剂本身一样，部分通过激活积极的预期来发挥作用。第二个实验比较了有和没有阿片类拮抗剂药物的大脑安慰剂反应，并测试阻断阿片类药物是否消除了安慰剂诱导的大脑活动。为了检验行为、心理和神经安慰剂效应的广度，两个实验比较了安慰剂减少疼痛和安慰剂减少负面影响的机制。最后一个实验使用功能磁共振成像来比较安慰剂的镇痛效果和分心的镇痛效果，以测试这两种有效缓解疼痛技术的神经机制的相似性。总的来说，这些研究探讨了镇痛的大脑机制如何与更普遍地减少负面影响的机制相关，为减少和管理几种心理健康障碍中的负面影响提供了潜在的见解，包括焦虑症，抑郁症和帕金森氏症（所有这些都受益于安慰剂治疗）。此外，一些药物治疗精神障碍的有效性已被证明部分取决于药物和预期之间的相互作用。该提案旨在从心理和大脑系统层面分析阿片类药物与预期相互作用的机制。

DESCRIPTION (provided by applicant): Placebo effects are treatment effects caused not by the biological action of the treatment, but by the meaning ascribed to it. Placebo treatments for a number of mental and physical disorders have been shown to have positive effects on health and well-being, making it important to understand the brain and psychological mechanisms through which these effects are produced. Recent fMRI evidence suggests that placebo-induced expectations of analgesia increase prefrontal cortex activity when pain is expected and decrease the brain's response to painful stimulation. The studies in this proposal examine placebo effects on brain and behavioral measures of pain, anxiety, and other negative affective responses using fMRI. Event- related fMRI designs are used to isolate brain responses to expectancy and painful stimulation, enabling an investigation of the interactions between preparatory and experiential processes. Two experiments examine the neural and neurochemical bases of the placebo response. One experiment compares the effects of placebo and an opiate analgesic drug on brain responses to painful stimulation, and tests whether the drug, like the placebo itself, works in part by activating positive expectancies. A second experiment compares brain placebo responses with and without an opioid antagonist drug, and tests whether blocking opioids eliminates placebo-induced activity in the brain. To examine the breadth of behavioral, psychological, and neural placebo effects, two experiments compare the mechanisms of placebo reductions in pain with placebo reductions in negative affect. A final experiment uses fMRI to compare the analgesic effects of placebo with analgesic effects of distraction, which tests the similarity in the neural mechanisms of these two effective pain-relieving techniques. Collectively, the studies examine how the brain mechanisms of analgesia relate to mechanisms for reducing negative affect more generally, providing potential insight into the reduction and management of negative affect in several mental health disorders, including anxiety disorders, depression, and Parkinson's (all of which benefit from placebo treatment). Further, the effectiveness of some pharmacological treatments for mental disorders has been shown to depend in part on interactions between drugs and expectancies. This proposal seeks to provide insight into the mechanisms of opioid-expectancy interactions at the psychological and brain systems levels of analysis.