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.

与不治疗相比，安慰剂治疗可以产生显着的临床益处但安慰剂治疗本身是药理学的。和身体惰性：他们的好处来自于活跃的大脑和心理反应神经科学研究已经证实安慰剂治疗会产生影响。与期望相关的皮质-皮质下脑通路和神经化学系统，对个人和社会意义的评估以及价值驱动的学习也是如此。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 续订资助了一项正在进行的研究计划，该计划做出了基础性贡献它还确定了对这些文献特别重要的几个重大差距。将安慰剂研究与心理健康联系起来的一个差距是我们对大脑的理解。安慰剂效应的机制几乎完全来自对疼痛的研究。研究扩展了之前的工作，研究安慰剂对焦虑产生影响的大脑通路和社会排斥，消极情感过程与多种心理健康直接相关模式识别（机器学习）分析可识别与症状最相关的疾病。途径，并测试安慰剂和其他背景干预措施对这些途径的影响。 1（实验1-3），我们开发跨多种情感症状的模型，解析情感分为特定症状的途径和跨多种症状的普遍途径我们还讨论了与内源性阿片类药物密切相关的作用。安慰剂镇痛，在其他负面情感体验中的另一个差距是大多数以前的。研究驱动强烈安慰剂效应的背景变量——包括社会影响，治疗历史——尚未主要在大脑水平上进行研究。在目标 2 中，我们研究了几种有前景的情境干预措施背后的大脑通路可以增强安慰剂效应，包括成功或不成功治疗反应的社会模型，治疗成功或失败的初步经验，以及安慰剂建议之间的匹配以及一个人接受它们的倾向。