The Neurobiology of Uncertainty

不确定性的神经生物学

• 批准号: 6781895
• 负责人: GREGORY S. BERNS
• 金额: $ 29.88万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6781895
• 关键词: amygdala; association learning; behavior test; clinical research; conditioning; decision making; emotions; functional magnetic resonance imaging; hippocampus; human subject; neural information processing; neuroanatomy; neurobiology; quality of life; stimulus /response

DESCRIPTION (provided by applicant): Uncertainty has a major impact on emotional well-being. Its manifestations within psychiatric disorders are profound and range from the miscalculations of drug abuse to the ruminations of depression. Although most everyone can appreciate that uncertainty causes anxiety in normal individuals, the precise biological mechanisms by which this occurs is not known. Recent political and economic events have made it clear that we live in an unpredictable and uncertain era. The psychological effects of chronic uncertainty are powerful, and the broad aim of this proposal is to understand the neurobiological substrates of uncertainty. Using functional magnetic resonance imaging (fMRI), we propose to elucidate the brain circuitry associated with several aspects of uncertainty. We will use an objective framework for quantifying the amount of uncertainty in a particular circumstance and use several forms of Pavlovian conditioning to measure how uncertainty interacts with the brain's response. In general, we define three aspects of uncertainty: 1) uncertainty for "when"; 2) uncertainty for "what"; and 3) and higher-order (secondary) interactions. We will perform a series of simple classical conditioning experiments on healthy volunteers while they undergo fMRI scanning. We will focus on the activity in the striatal-amygdalar-hippocampal circuit, as these regions have been shown to be necessary for different forms of associative learning. More importantly, the specific roles of these structures in emotional processing are not clear, but our hypothesis is that they code the degree of uncertainty in a context-specific fashion. We will test this hypothesis with a series of 12 fMRI experiments using both pleasant and aversive stimuli. We will use variants of Pavlovian conditioning to associate pleasant oral stimuli (fruit juice) or unpleasant ones (quinine water) with different neutral cues. By varying both the predictability of temporal (when) and stimulus (what) pairings, we will be able to measure how uncertainty modulates the brain's response to this basic learning process. We hypothesize that both the amygdala and ventral striatum will be more active when uncertainty of any form is present. We will further quantify the level of this activation with autonomic measures of arousal. Finally we will investigate how these effects generalize to secondary associations. Ultimately we anticipate that this will suggest new therapies that can be targeted towards the effects of both acute and chronic uncertainty.

描述（由申请人提供）：不确定性对情绪健康产生重大影响。它在精神疾病中的表现非常深刻，范围从对药物滥用的错误计算到抑郁症的反省。尽管大多数人都可以欣赏到不确定性会引起正常人的焦虑，但尚不清楚发生这种情况的精确生物学机制。最近的政治和经济事件已经明确表明我们生活在一个不可预测和不确定的时代。慢性不确定性的心理影响是强大的，该提议的广泛目的是了解不确定性的神经生物学基质。使用功能磁共振成像（fMRI），我们建议阐明与不确定性的几个方面相关的脑电路。我们将使用一个客观的框架来量化特定情况下的不确定性量，并使用多种形式的Pavlovian条件来衡量不确定性与大脑反应的相互作用。通常，我们定义了不确定性的三个方面：1）“何时”的不确定性； 2）“什么”的不确定性； 3）和高阶（次要）相互作用。我们将在健康志愿者进行fMRI扫描时对健康志愿者进行一系列简单的经典调节实验。我们将重点关注纹状体 - 杏仁核 - 海马电路的活性，因为这些区域已被证明是不同形式的关联学习所必需的。更重要的是，这些结构在情感处理中的具体作用尚不清楚，但是我们的假设是它们以特定于上下文的方式对不确定性进行编码。我们将使用愉快和厌恶刺激进行一系列12个fMRI实验来检验这一假设。我们将使用Pavlovian调节的变体与具有不同中性提示的宜人的口服刺激（果汁）或不愉快的刺激（奎宁水）相关联。通过改变时间（何时）和刺激（什么）配对的可预测性，我们将能够衡量不确定性如何调节大脑对这个基本学习过程的反应。我们假设，当存在任何形式的不确定性时，杏仁核和腹纹状体都将更加活跃。我们将通过唤醒的自主措施进一步量化这种激活的水平。最后，我们将研究这些影响如何推广到二级关联。最终，我们预计这将提出可以针对急性和慢性不确定性影响的新疗法。