Pavlovian learning, attention and decisions

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质下介导的享乐和情绪学习过程，以及皮质依赖性决策。药物滥用决策偏差的一个重要来源来自巴甫洛夫刺激和背景，凭借其与滥用药物的关联获得激励显着性和影响行为的力量。在成瘾者中，仅仅暴露于与药物相关的线索就可以激发进一步的药物消费，甚至在戒断一段时间后引发复发。尽管这些巴甫洛夫效应对认知决策很重要，但其神经机制仍不清楚。最近，我们发现巴甫洛夫学习强烈地影响与注意力和眼球运动相关的活动在皮层联合区，外侧顶内区（LIP）的猴子。预测奖励的条件刺激（“好消息”）吸引注意力，并在LIP的空间注意力图中产生局部兴奋;预测无奖励的条件刺激（“坏消息”）将注意力从其位置上排斥，并在LIP中产生局部抑制。就像啮齿动物和人类中描述的效果一样，我们研究中的效果自动出现并持续存在，即使它们干扰了表现;此外，经过长时间的训练，效果增加并成为习惯性的，部分抵抗上下文控制。我们的目标是扩展这些研究结果，测试是否，除了偏置简单的定向，巴甫洛夫刺激也偏置更复杂的决定，空间上不相关的线索。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（传统上使用药理学和行为方法在啮齿动物中进行）和决策形成研究（传统上使用单神经元记录在猴子中进行）。因此，他们将提供洞察情绪学习和决策形成之间的相互作用，在正常行为和药物滥用，并可能建议认知策略，克服情绪学习的力量时，这种学习有不良的，适应不良的影响。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起着重要作用。与滥用药物有关的线索或环境获得了激励的显著性和引发渴望的力量，可能有助于药物消费的维持或复发。为了了解这些影响的机制，我们测试的影响，巴甫洛夫学习注意使用单神经元记录在顶叶区有关的注意和决策形成的恒河猴。长期目标是了解正常行为和药物成瘾中情绪学习和认知决策之间的相互作用。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