Pavlovian learning, attention and decisions

描述（由申请人提供）：药物滥用和成瘾是以过度和强迫性药物消费为特征的严重疾病，影响着西方世界数百万人。越来越多的证据表明，长期接触药物会影响皮层下介导的享乐和情绪学习过程，以及皮层依赖性决策。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环境，它们由于与滥用药物有关而获得了显著的激励和影响行动的力量。在成瘾的个体中，仅仅接触到与毒品有关的线索就能激发进一步的毒品消费，甚至在一段时间的戒断后引发复发。尽管巴甫洛夫效应对认知决策很重要，但其神经机制尚不清楚。最近，我们发现巴甫洛夫学习强烈地影响了与注意力和眼球运动相关的皮层关联区，即猴子的顶叶内外侧区（LIP）。预测奖励（“好消息”）的条件刺激在LIP的空间注意图中引起注意并产生局部兴奋；被预设为无回报（“坏消息”）的刺激会将注意力从其位置排斥，并在LIP中产生局部抑制。就像在啮齿动物和人类身上描述的影响一样，我们研究中的影响是自动产生的，即使它们干扰了表现，也会持续存在；此外，经过长时间的训练后，这种效果增强并成为习惯，部分地抵制了环境控制。我们的目标是通过测试巴甫洛夫刺激除了会影响简单定向外，是否也会影响与线索在空间上无关的更复杂的决策，来扩展这些发现。这些研究具有创新性，因为它们在两种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（传统上在啮齿动物中使用药理学和行为学方法进行）和决策形成研究（传统上在猴子中使用单神经元记录进行）。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有关的关系，并可能提出克服情绪学习的力量的认知策略，当这种学习具有不良的、不适应的影响时。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