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

描述(申请人提供)：安慰剂效应不是由治疗的生物作用引起的，而是由赋予它的意义引起的治疗效果。一些精神和身体疾病的安慰剂治疗已被证明对健康和福祉有积极影响，因此了解产生这些影响的大脑和心理机制非常重要。最近的fMRI证据表明，安慰剂诱导的止痛预期会在预期疼痛时增加前额叶皮质的活动，并降低大脑对疼痛刺激的反应。这项建议中的研究使用功能磁共振成像检查安慰剂对大脑的影响，以及疼痛、焦虑和其他负面情感反应的行为测量。事件相关功能磁共振成像设计用于分离大脑对预期刺激和痛苦刺激的反应，从而能够研究准备过程和经验过程之间的相互作用。两个实验检验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止痛药对大脑对痛苦刺激的反应的影响，并测试了这种药物是否像安慰剂本身一样，部分通过激活积极的预期发挥作用。第二个实验比较了使用和不使用阿片类拮抗剂药物时的大脑安慰剂反应，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。为了检查行为、心理和神经安慰剂效应的广度，两个实验比较了安慰剂减轻疼痛的机制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止痛效果和分心的止痛效果，测试这两种有效止痛技术在神经机制上的相似性。总而言之，这些研究检查了大脑的止痛机制如何与更普遍的减少负面影响的机制有关，为减少和管理几种精神健康障碍的负面情绪提供了潜在的见解，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。这一建议试图在心理和大脑系统分析水平上对阿片类药物与预期相互作用的机制提供洞察。

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.