Pavlovian learning, attention and decisions

描述(申请人提供)：药物滥用和成瘾是一种严重的疾病，以过度和强迫的药物消费为特征，在西方世界影响着数百万人。越来越多的证据表明，长期接触毒品会影响皮层下调节的享乐性和情绪学习过程，以及皮质依赖的决定。药物滥用中决策偏差的一个重要来源来自巴甫洛夫刺激和背景，这些刺激和背景凭借其与滥用药物的关联而获得激励突出和影响行动的权力。在上瘾的人中，仅仅是接触到与药物有关的线索就会刺激进一步的药物消费，甚至在一段时间的戒断后引发复发。尽管这些巴甫洛夫效应对认知决策很重要，但它们的神经机制仍不清楚。最近，我们发现巴甫洛夫学习强烈地影响了与注意和眼球运动有关的大脑皮质关联区，即猴子的外侧顶内区(LIP)的活动。预测奖励的条件性刺激(“好消息”)吸引注意，并在嘴唇的空间注意图中产生局部兴奋；而预测没有奖励的条件刺激(“坏消息”)则将注意力从其所在位置排斥，并在嘴唇产生局部抑制。就像在啮齿类动物和人类身上描述的效果一样，我们研究中的效果会自动产生并持续存在，即使它们干扰了表现；此外，经过长时间的训练，这些效果会增加，并变得习惯性，部分抵抗环境控制。我们的目标是通过测试巴甫洛夫刺激除了偏向简单的定向外，是否还偏向于与线索空间无关的更复杂的决定，从而扩展这些发现。这些研究具有创新性，因为它们在两个截然不同的研究传统之间建立了新的联系--巴甫洛夫学习研究(传统上使用药理学和行为方法在啮齿类动物身上进行)和决策形成研究(传统上使用单神经元记录在猴子身上进行)。因此，他们将深入了解正常行为中情绪学习和决策形成之间的相互作用以及与药物滥用的关系，并可能建议在情绪学习具有不良的、不适应的影响时克服情绪学习力量的认知策略。1 公共卫生相关性：大量证据表明，巴甫洛夫学习在药物滥用中发挥着重要作用。与滥用药物相关的线索或环境获得诱因突显和引起渴望的能力，潜在地有助于维持或复发药物消费。为了了解这些效应的机制，我们测试了巴甫洛夫学习对注意力的影响，方法是在恒河猴的顶叶区域记录与注意力和决策形成相关的单个神经元。长期目标是了解正常行为和吸毒成瘾中情绪学习和认知决定之间的相互作用。1

DESCRIPTION (provided by applicant): Drug abuse and addiction are severe disorders characterized by excessive and compulsive drug consumption, affecting millions of individuals in the Western world. Converging evidence shows that long-term exposure to drugs affects subcortically mediated hedonic and emotional learning processes, as well as cortically dependent decisions. An important source of decision bias in drug abuse comes from Pavlovian stimuli and contexts which, by virtue of their association with drugs of abuse gain incentive salience and the power to influence actions. In addicted individuals, the mere exposure to drug-associated cues can motivate further drug consumption or even trigger relapse after a period of abstinence. Despite the importance of these Pavlovian effects on cognitive decisions, their neural mechanisms remain unknown. Recently we discovered that Pavlovian learning strongly affects activity related to attention and eye movements in a cortical association area, the lateral intraparietal area (LIP) of the monkey. Conditioned stimuli predicting reward ("good news") attract attention and produce local excitation in the spatial attention map in LIP; stimuli conditioned to predict no reward ("bad news") repel attention from their location and produce local inhibition in LIP. Like the effects described in rodents and humans, the effects in our study arose automatically and persisted even though they interfered with performance; moreover, after prolonged training the effects increased and became habitual, partly resistant to contextual control. We aim to extend these findings by testing whether, in addition to biasing simple orienting, Pavlovian stimuli also bias more complex decisions that are not spatially related to the cues. These studies are innovative because they establish a new link between two disparate research traditions - the study of Pavlovian learning (traditionally conducted in rodents using pharmacological and behavioral methods) and the study of decision formation (traditionally conduced in monkeys using single-neuron recordings). Thus, they will provide insight into interactions between emotional learning and decision formation in normal behavior and in relation to drug abuse, and may suggest cognitive strategies for overcoming the power of emotional learning when this learning has undesirable, maladaptive effects. 1 PUBLIC HEALTH RELEVANCE: Abundant evidence shows that Pavlovian learning plays an important role in drug abuse. Cues or environments associated with drugs of abuse gain incentive salience and the power to elicit cravings, potentially contributing to the maintenance or relapse of drug consumption. To understand the mechanisms of these effects we test the influence of Pavlovian learning on attention using single-neuron recording in a parietal area related to attention and decision formation in rhesus monkeys. The long-term goal is to understand interactions between emotional learning and cognitive decisions in normal behavior and drug addiction. 1