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

安慰剂效应的神经基础及其与调节过程的关系

基本信息

批准号：
10358505
负责人：
TOR D. WAGER
金额：
$ 71.46万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10358505
关键词：
Acupuncture Therapy Address Affect Affective Affective Symptoms Alcohol abuse Anxiety Area Brain Brain Diseases Cardiovascular Diseases Caring Cellular Phone Clinical Clinical Research Clinical Treatment Clinical Trials Cognitive Conceptions Deception Disease Drug abuse Emotions Expectancy Failure Functional Magnetic Resonance Imaging Funding Future Grant Individual Intervention Joints Learning Link Literature Machine Learning Major Depressive Disorder Masks Mediating Mediator of activation protein Mental Depression Mental Health Mental disorders Modeling Motivation Naloxone Neural Pathways Neurobiology Neurologic Neuronal Plasticity Operative Surgical Procedures Outcome Pain Parkinson Disease Participant Pathway interactions Patients Pattern Pattern Recognition Persons Pharmaceutical Preparations Pharmacological Treatment Pharmacology Pharmacotherapy Physiology Placebo Effect Placebos Predisposition Process Psyche structure Psychotherapy Public Health Randomized Recording of previous events Regulation Research Risk Factors Role Shapes Sleep Social Anxiety Disorder Substance Use Disorder Suggestion Symptoms System Taste Perception Testing Time Wages Work active method base brain pathway clinical pain clinical practice clinically relevant clinically significant endogenous opioids expectation experience experimental study follow-up gastrointestinal function improved negative affect neurochemistry neuroimaging neuromechanism neuroregulation patient expectation placebo analgesia prevent programs psychologic relating to nervous system resilience response social social influence social interventions social model success theories translational potential treatment response

项目摘要

Placebo treatments can induce clinically significant benefits, compared with no-treatment controls, across a variety of disorders. But placebo treatments themselves are pharmacologically and physically inert: Their benefits result from active brain and psychological responses to the treatment context. Neuroscientific studies have established that placebo treatments influence cortical-subcortical brain pathways and neurochemical systems relevant for expectation, appraisals of personal and social meaning, and value-driven learning. These systems are also related to symptom progression across mental health disorders and several other neurological and substance use disorders. Understanding the brain and psychological mechanisms of placebo effects will help improve psychological and neurological (e.g., neuromodulation-based) treatments across disorders. This R01 renewal funds an ongoing program of research that has made fundamental contributions to this literature. It has also identified several significant gaps that are particularly important for connecting placebo research to mental health. One gap is that our understanding of the brain mechanisms underlying placebo effects comes almost purely from studies of pain. The proposed studies extend previous work to study the brain pathways underlying placebo effects in anxiety and social rejection, negative affective processes directly relevant for multiple mental health disorders. Pattern-recognition (machine learning) analyses identify the most symptom-relevant pathways, and test effects of placebo and other context interventions on these pathways. In Aim 1 (Experiments 1-3), we develop models across multiple affective symptoms, parsing affective pathways into those that are symptom-specific and those that generalize across multiple symptoms and outcomes. We also address the role of endogenous opioids, strongly linked to placebo analgesia, in other negative affective experiences. Another gap is that most previous studies of the context variables that drive strong placebo effects—including social influences, treatment history—have not been studied extensively at the brain level. In Aim 2, we study the brain pathways underlying several promising context interventions that enhance the strength of placebo effects, including social modeling of successful or unsuccessful treatment response, initial experiences of treatment success or failure, and the match between placebo suggestions and a person’s predisposition to be receptive to them.

与未治疗相比，安慰剂治疗可以引起临床上的显着好处控制，各种疾病。但是安慰剂治疗本身就是药物和身体上的惰性：它们的益处是由主动的大脑和心理反应引起的治疗环境。神经科学研究已经确定安慰剂治疗会影响皮质增生的脑途径和神经化学系统与期望相关，评估个人和社会意义以及价值驱动的学习。这些系统也是与精神健康障碍和其他几种神经系统疾病的症状进展有关和药物使用障碍。了解安慰剂的大脑和心理机制效果将有助于改善心理和神经系统（例如，基于神经调节）跨疾病的治疗。 R01更新为正在进行的研究计划提供了基本贡献对此文学。它还确定了几个重大差距，对于将安慰剂研究与心理健康联系起来。一个差距是我们对大脑的理解安慰剂作用的机制几乎纯粹来自疼痛的研究。提议研究扩展了以前的工作，以研究焦虑中安慰剂效应的大脑途径和社会拒绝，负面情感过程与多重心理健康直接相关疾病。模式识别（机器学习）分析确定最症状与症状相关安慰剂和其他上下文干预对这些途径的途径以及测试影响。目标 1（实验1-3），我们开发跨多种情感症状，解析情感的模型进入症状特异性的途径，以及那些遍布多个症状的途径症状和结果。我们还解决了内源性阿片类药物的作用，与安慰剂镇痛，在其他负面情感经历中。另一个差距是大多数以前研究上下文变量，这些变量会带来强烈的安慰剂效应 - 包括社会影响，治疗史 - 没有在大脑一级进行广泛研究。在AIM 2中，我们研究大脑通路是几种应许的上下文干预措施的基础，以增强安慰剂效应，包括成功或失败的治疗反应的社会建模，治疗成功或失败的最初经验，以及安慰剂建议之间的匹配一个人倾向于接受他们的倾向。