The Neural Bases of Placebo Effects and their Relation to Regulatory Processes

描述（由申请人提供）：纵观历史，安慰剂效应一直被认为是医生对易受骗的人开的玩笑，也是强大但神秘的治疗力量。随着对人类大脑功能的直接测量的出现，现代科学已经表明，安慰剂效应两者都不是。相反，它们反映了心理和大脑过程对大脑和身体疾病的原则性影响。安慰剂效应代表着一个机会——因为它们为研究影响健康的大脑内部过程提供了一个窗口——同时也是一个挑战，因为数十项临床试验现在都未能显示常用处方药比安慰剂的优越性，这给医疗保健提供者和消费者带来了巨大的成本。这可能不是由于药物无效，而是似乎与高安慰剂反应率有关。对安慰剂效应背后的大脑机制的研究可以提供有价值的见解，让我们了解大脑如何积极地预测、回应和学习积极的治疗方法，以及这些过程对疼痛和健康其他方面的影响。在此资助的前一阶段，功能性磁共振成像（fMRI）对安慰剂和阿片类药物效应的研究有助于确定安慰剂治疗影响疼痛的神经生物学，包括对与疼痛体验最密切相关的大脑皮层和皮层下区域的影响。该研究还提供了一些关于大脑中产生安慰剂效应的相互作用的第一手证据，并证明了前额叶皮层-皮层下-脑干系统和内源性阿片系统的参与。出现的观点是，安慰剂治疗涉及与概念性思维（显性信念）和学习过程相关的大脑系统，这些系统改变了分配给治疗线索和疼痛本身的价值。在这个更新申请中，我们建立在这个基础上，来解决在安慰剂效应被理解，在治疗中被利用，并在临床试验和实践中与药物效应完全分离之前需要解决的许多未解之谜。这些基本问题包括：a)……的性质

DESCRIPTION (provided by applicant): Throughout history, placebo effects have been variously considered as tricks played upon the gullible by medical practitioners and powerful but mysterious healing forces. With the advent of direct measurements of human brain function, modern science has shown that placebo effects are neither of these. Rather, they reflect the principled impact of psychological and brain processes on diseases of the brain and body. Placebo effects represent an opportunity-because they provide a window into internal brain processes that influence health- and a challenge, because dozens of clinical trials have now failed to show the superiority of commonly prescribed drugs to placebo, at great cost to health care providers and consumers. This may not be due to the ineffectiveness of the medications, but rather seems to be related to high placebo response rates. Studies of the brain mechanisms underlying placebo effects can provide valuable insight into how the brain actively anticipates, responds to, and learns about active treatments, and the effects of these processes on pain and other aspects of health. In the previous period of this grant, functional magnetic resonance imaging (fMRI) of placebo and opiate drug effects was instrumental in establishing that placebo treatments impact the neurobiology of pain, including effects on the cortical and subcortical brain regions most closely associated with pain experience. The research also provided some of the first evidence on the interactions in the brain that give rise to placebo effects, and demonstrated the involvement of prefrontal cortical-subcortical-brainstem systems and the endogenous opioid system. The view that emerged is that placebo treatments engage brain systems related to both conceptual thought (explicit beliefs) and learning processes that change the value assigned to treatment cues and pain itself. In this Renewal application, we build on this foundation to address some of the many unanswered questions that need to be addressed before placebo effects are understood, harnessed in therapy, and separated cleanly from drug effects in clinical trials and practice. These include fundamental questions about a) the nature of the "pain-related" processes regulated by placebos (are they specific to pain, or general affective processes?) and b) the critical conditions required to create placebo analgesia. Our working hypothesis is that conceptual and learning processes interact, and that both are critical. Learning systems fundamentally shape the motivational value of pain and modulate nociception in subcortical-brainstem systems, and conceptual processes are needed to attribute perceived benefits to the placebo treatment and engage learning. To better understand these systems, we bring to bear new computational machine-learning tools that can identify and test placebo effects on patterns of brain activity specific to pain. We also test the involvement of several neurochemical systems-opioids, dopamine, and oxytocin-and their relationships with specific brain and psychological aspects of the placebo response-generation process.