Neural mechanisms of reward processing and emotion

奖励处理和情绪的神经机制

• 批准号: 9357294
• 负责人: ELISABETH A MURRAY
• 金额: $ 104.63万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9357294
• 关键词: Achievement; Affective; Agreement; Amygdaloid structure; Anterior; Anxiety Disorders; Area; Arousal; Basal Ganglia; Behavior; Bilateral; Brain; Brain region; Cell Nucleus; Choice Behavior; Citric Acid; Cues; Data; Decision Making; Emotional; Emotions; Event; Excitotoxic lesion; Exhibits; Feedback; Functional Magnetic Resonance Imaging; Functional disorder; Future; Globus Pallidus; Goals; Image; Inferior; Learning; Lesion; Linear Models; Liquid substance; Magnetic Resonance Imaging; Maintenance; Major Depressive Disorder; Masks; Measures; Medial; Mental disorders; Methods; Monitor; Mood Disorders; Movement; Neurons; Obsessive-Compulsive Disorder; Ocular Fixation; Operant Conditioning; Oral; Panic Attack; Photic Stimulation; Physiological; Play; Prefrontal Cortex; Probability; Process; Pupil; Reaction; Rewards; Role; Scanning; Signal Transduction; Somatosensory Cortex; Stimulus; Sucrose; Syndrome; Taste Perception; Thalamic structure; Time; Training; Ventral Striatum; Visual; Visual Cortex; Water; Work; autonomic conditioning; base; blood oxygen level dependent; cingulate cortex; classical conditioning; food consumption; frontal lobe; improved; neuromechanism; neurophysiology; neuropsychological; novel; preference; response; reward anticipation; reward processing; sample fixation; sensor; taste system; theories; visual learning; visual stimulus

The amygdala, OFC and MFC contribute to learning, in part, by evaluating feedback. In an effort to extend our understanding of the physiological mechanisms underlying affective processing, we developed an fMRI paradigm to reveal blood-oxygen-level dependent (BOLD) responses to visual images that signal reward. Each week, subjects learned to associate images of novel objects with a high or low probability of water reward. Areas responding to the value of recently learned reward-predictive images included MFC area 10m/32, ventrolateral prefrontal cortex area 12, and inferior temporal visual cortex (IT). The amygdala and OFC, each thought to be involved in value encoding, showed little such effect. Instead, these two areas primarily responded to visual stimulation and reward receipt, respectively. Our findings demonstrate the importance of ventrolateral prefrontal cortex, MFC, and IT in representing the values of recently learned visual images. Tastes and their associated values drive food consumption and influence choice behavior. To understand the neural mechanisms underlying reward-guided decision making and value learning, we characterized the gustatory system in subjects with fMRI while measuring licking to control for oral movements, and to assess preferences. Though anatomical data indicate that taste information from the ventroposteromedial nucleus of the thalamus (VPMpc) goes to gustatory cortex, physiological responses to taste are widespread in cortex, including in somatosensory cortex and OFC. To identify taste-responsive cortex, we delivered small quantities (0.1ml) of sucrose, citric acid, or distilled water in random order without any predictive cues (e.g., visual stimuli) to subjects while using event-related fMRI. In addition, we used an MRI-compatible lick sensor to measure subjects licking during the scans. fMRI signals associated with licking in the absence of fluid delivery were used to mask responses to fluid delivery/receipt and associated licking. Licking in the absence of fluid delivery and fluid receipt times for each tastant were incorporated into a general linear model to analyze fMRI data. By contrasting BOLD responses to either sweet or sour tastes to those from distilled water, and masking with BOLD signals associated with licking in the absence of fluid delivery, we identified taste responses in gustatory cortex, ventrolateral prefrontal cortex area 12o, OFC area 13b and somatosensory cortex area 3b in three subjects. Areas activated by fluid delivery in general as defined by a contrast of all tastes relative to baseline included medial OFC area 14, the ventral striatum, the ventral pallidum, the basal nucleus of amygdala, and the perirhinal cortex. Our findings of gustatory responses are in agreement with single unit neurophysiological recordings. Whole brain fMRI in combination with quantification of licking behavior and subjects choice preferences for different tastes will be used to identify brain regions that signal value. Previous work from our group has shown that the subgenual portion of the anterior cingulate cortex contributes to autonomic arousal during anticipation of positive (rewarding) events. Because the OFC is involved in stimulus-based reward learning, we wondered whether this region, too, contributed to either the learning or maintenance of autonomic arousal associated with positive events. Accordingly, we evaluated autonomic responses in subjects that had sustained bilateral excitotoxic lesions of OFC and controls. Subjects were trained on a task in which Pavlovian conditioning of stimulus-reward associations was superimposed on instrumental conditioning of active visual fixation. On some trials, one of two Pavlovian stimuli (CS+, CS-) was presented on the monitor screen for 1 s during the 4-s fixation period. The CS+ was always followed by a large fluid reward; the CS- led to no reward. We recorded pupil size as a measure of autonomic response. Controls exhibited an increased pupil size to the CS+, compared to the response to the CS-, within a couple of training sessions (2 +/- 1) and continued to show the conditioned pupil response in anticipation of reward across at least 4 consecutive sessions. By contrast, subjects with OFC lesions required more sessions (20 +/- 7 sessions) to acquire the conditioned autonomic response and three out of four failed to sustain it for 4 consecutive sessions even with an extended period of training (50 sessions). Training with a second set of stimuli yielded a similar result. Thus, the present results suggest that OFC is involved in acquiring appropriate autonomic responses to cues predicting positive events.

杏仁核、OFC和MFC在一定程度上通过评估反馈来促进学习。为了扩展我们对情感加工背后的生理机制的理解，我们开发了一种fMRI范式，以揭示对发出奖赏信号的视觉图像的血氧水平依赖(BOLD)反应。每周，受试者都会学会将新奇物体的图像与水奖励的概率高低联系在一起。对最近学习的奖赏预测图像做出反应的区域包括MFC区10m/32、前额叶皮质腹外侧区12和颞叶下部视觉皮质(IT)。杏仁核和OFC都被认为与价值编码有关，但几乎没有表现出这样的效果。相反，这两个区域主要分别对视觉刺激和奖励接收做出反应。我们的发现证明了腹外侧额叶皮质、MFC和IT在代表新近学习的视觉图像的价值方面的重要性。 口味及其相关价值观驱动着食物消费，影响着人们的选择行为。为了理解奖励引导决策和价值学习背后的神经机制，我们用fMRI表征了受试者的味觉系统，同时测量舔来控制口腔运动，并评估偏好。虽然解剖学数据表明，来自丘脑腹后内侧核(VPMPC)的味觉信息进入味觉皮质，但味觉的生理反应在皮质广泛存在，包括在躯体感觉皮质和OFC。为了识别味觉反应皮层，我们在使用事件相关功能磁共振的同时，以随机顺序向受试者提供了少量(0.1毫升)的蔗糖、柠檬酸或蒸馏水，而没有任何预测性线索(例如视觉刺激)。此外，我们使用了与MRI兼容的舔唇传感器来测量受试者在扫描过程中舔舔的情况。在没有液体输送的情况下，与舔相关的fMRI信号被用来掩盖对液体输送/接收和相关舔的反应。每个受试者在没有液体输送的情况下舔水和接受液体的时间被纳入一个一般的线性模型来分析fMRI数据。通过将对甜味或酸味的大胆反应与蒸馏水的反应进行对比，并在没有液体输送的情况下用与舔东西相关的大胆信号进行掩蔽，我们在三名受试者的味觉皮质、腹外侧额叶皮质120区、OFC区13b和体感皮质3b区识别了味觉反应。根据所有味觉相对于基线的对比，液体输送所激活的区域一般包括内侧OFC区14、腹侧纹状体、腹侧苍白球、杏仁基底核和虹周皮质。我们对味觉反应的发现与单个单位的神经生理记录是一致的。全脑功能磁共振成像结合对舔食行为的量化和受试者对不同口味的选择偏好，将被用来识别大脑中发出信号的区域。 我们小组之前的工作表明，在对积极(奖励)事件的预期中，前扣带回皮质的膝下部有助于自主神经的唤醒。因为OFC参与基于刺激的奖赏学习，我们想知道这个区域是否也有助于学习或维持与积极事件相关的自主神经唤醒。因此，我们评估了持续双侧OFC兴奋毒性损害的受试者和对照组的自主神经反应。受试者接受了一项任务的训练，在这项任务中，刺激-奖赏联系的巴甫洛夫条件反射被叠加到主动视觉注视的工具性条件反射上。在一些实验中，两个巴甫洛夫刺激(CS+，CS-)之一出现在监视器屏幕上，显示在4-S注视期间的1-S。CS+之后总是有一大笔流动的奖励；CS-不会带来奖励。我们记录了瞳孔大小作为自主神经反应的衡量标准。在两个训练阶段(2+/-1)中，与对CS-的反应相比，控制组对CS+表现出更大的瞳孔大小，并在至少连续4个训练阶段继续显示对奖赏的条件瞳孔反应。相比之下，患有OFC病变的受试者需要更多的训练(20+/-7次)才能获得条件自主神经反应，而且四分之三的受试者即使在较长的训练期(50次)下也无法维持连续四次的自主神经反应。用第二组刺激进行训练也产生了类似的结果。因此，目前的结果表明，OFC参与了对预测积极事件的线索的适当自主反应。