Neural Substrates of Reward Processing and Emotion

奖励处理和情绪的神经基础

• 批准号: 10266609
• 负责人: ELISABETH A MURRAY
• 金额: $ 127.08万
• 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/10266609
• 关键词: Affect; Amygdaloid structure; Animal Testing; Animals; Anterior; Anxiety; Area; Arousal; Attention; Behavior; Behavioral; Bilateral; Bipolar Disorder; Brain; Caliber; Cerebrovascular Circulation; Clinical Research; Code; Control Groups; Cues; Data; Decision Making; Deep Brain Stimulation; Disease; Electrophysiology (science); Emotions; Excitotoxic lesion; Eye; Food; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Genetic; Goals; Health; Human; Image; Impairment; Individual; Intervention; Juice; Knowledge; Learning; Lesion; Limbic System; Link; Liquid substance; Major Depressive Disorder; Maps; Measures; Medial; Mental disorders; Methodology; Methods; Modeling; Molecular; Mood Disorders; Nature; Neurons; Obsessive-Compulsive Disorder; Operative Surgical Procedures; Outcome; Panic Attack; Patients; Pattern; Performance; Peripheral; Phobias; Physiological; Postoperative Period; Prefrontal Cortex; Property; Psychological reinforcement; Pupil; Quality of life; Research; Retrieval; Rewards; Role; Saccades; Satiation; Schizophrenia; Sensory; Social support; Stimulus; Structure; Structure-Activity Relationship; Testing; Time; Training; Translating; Vision; Visual; Work; attentional modulation; autism spectrum disorder; base; cingulate cortex; excitotoxicity; expectation; experimental study; gaze; improved; interest; neural circuit; neuroimaging; preference; reduce symptoms; relating to nervous system; response; reward processing; sample fixation; social; social cognition

Neurons in the orbitofrontal cortex (OFC) encode the sensory properties, magnitude and subjective value of expected and received rewarding outcomes. In addition, the activity of OFC neurons reflects anticipatory arousal, as measured by pupil diameter. OFC neuronal activity is also modulated by attention. It is not well understood yet how gaze and/or attentional modulation of neuronal activity in OFC guides behavior, and in what circumstances OFC neuronal activity is necessary. To investigate the causal contribution of OFC to visual exploration of valuable objects, we trained animals with bilateral excitotoxic OFC lesions and controls on a preferential viewing task. The experiment occurred in two stages: stimulus-reward association training and preferential viewing test. The stimulus-reward training established thirty high-value images and thirty low-value images. When the training stage was completed, we administered a preferential viewing test. On each trial, two images -- one high-value image and one low-value image -- were presented simultaneously and the animals freely viewed them for 4 s. In this stage, an intermediate amount of fluid was delivered at the end of every trial. Both groups showed a consistent preference for the high-value images. During the preferential viewing test, when both a high- and a low-value image were available, animals looked at the high-value image first on 80% of trials. In addition, they viewed the high-value images 3.7 times longer and made 3.5 times more fixations relative to the low-value images. There was no group difference on any of these measures. Our findings indicate that, at least when stimulus-value associations are acquired postoperatively, OFC is not necessary for guiding the eyes to valuable images. Lesion studies suggest dissociable functions of medial prefrontal cortex (MFC) and orbitofrontal cortex (OFC), with MFC being essential for social cognition and OFC being essential for value-based decision making. Although bilateral amygdala damage also results in impairments in these domains, it is not known whether the dissociable functional roles of MFC and OFC critically depend on interactions with the amygdala. To test this possibility, we compared the performance of animals with crossed surgical disconnection of the prelimbic cortex, a subregion of MFC, and amygdala (PL x AMY) and animals with surgical disconnection of the OFC and amygdala (OFC x AMY), to a group of controls (CON). All animals were assessed for food-retrieval latency while viewing videos of social stimuli (a test of social interest) and object choices based on current food value (devaluation task, a test of value-based decision making). Compared to the CON group, group PL x AMY, but not group OFC x AMY, showed significantly reduced latencies to reach for a reward in the presence of videos of conspecifics, indicating reduced social valuation and/or reduced social interest. In a test of value-based decision making, however, the opposite pattern was observed; group OFC x AMY, but not group PL x AMY, displayed severe deficits on object choice following selective satiation. These data indicate that MFC and OFC interact with the amygdala to subserve distinct behavioral contributions in the domains of social cognition and decision making, respectively. The MFC has been identified as encoding not only reward value but also features of conspecifics and of ones self. Physiological studies in animals and fMRI studies in humans have identified MFC as supporting social cognition. Relatedly, a growing body of evidence suggests that some species find the sight of another individual receiving a reward reinforcing, called vicarious reinforcement, and that this capacity is supported by a network of brain areas including the MFC. Indeed, single neurons in MFC selectively code reward delivery to the self, a partner, both animals, or neither animal. We used a vicarious reinforcement task to measure prosocial tendencies in animals. Two animals participated in each test session: an actor and a recipient. Actors learned that three different visual cues mapped onto three distinct reward outcomes: to Self, the Other animal, or Neither animal. On each trial, actors saw a cue that predicted one of the three juice offers and could accept the offer by making a saccade to a peripheral target or reject the offer by breaking fixation. All six actors displayed prosocial preferences, indicated by their greater tendency to give reward to Other relative to Neither. To determine whether the MFC contribution to social cognition is essential, we tested animals on the vicarious reinforcement task before and after they sustained MFC lesions. Specifically, half of the actors received selective, bilateral, excitotoxic lesions of the anterior cingulate cortex (ACC), a part of the MFC, and the other half served as unoperated controls. After surgery, all animals retained the social preferences they had demonstrated with the preoperatively learned cues, but this preference was reduced in the animals with ACC lesions. Critically, none of the animals in the ACC lesion group acquired social preferences with a new set of cues introduced after surgery. These data indicate that the ACC is necessary for acquisition of prosocial preferences from vicarious reinforcement. At the same time, analyses of autonomic arousal have been increasingly used to contextualize and guide neural research, especially for studies of reward processing. We therefore collected pupil diameter while animals performed the vicarious reinforcement task. Contrary to our expectations, we found that pupils were widest in anticipation of juice to the self, moderately-sized in anticipation of juice to nobody, and narrowest in anticipation of juice to a social partner. The seemingly paradoxical pupil effect can be explained by a model in which pupil size tracks outcome salience, prosocial tendencies track outcome valence, and the relation between salience and valence is U-shaped. Although ACC lesions disrupted animals social decision making, as evidenced by altered acquisition of prosocial tendencies, there was no effect on autonomic arousal in anticipation of those same outcomes. Thus, our results indicate that the ACC is not part of the neural circuitry responsible for producing the socially modulated pupil response seen during vicarious reinforcement.

眶额皮质 (OFC) 中的神经元对预期和收到的奖励结果的感觉特性、大小和主观价值进行编码。此外，OFC 神经元的活动反映了预期的唤醒，通过瞳孔直径来测量。 OFC 神经元活动也受到注意力的调节。目前尚不清楚 OFC 神经元活动的凝视和/或注意调节如何指导行为，以及在什么情况下 OFC 神经元活动是必要的。为了研究 OFC 对有价值物体的视觉探索的因果贡献，我们训练了双侧兴奋性毒性 OFC 损伤的动物和优先观看任务的对照。实验分两个阶段进行：刺激-奖励关联训练和偏好观看测试。刺激奖励训练建立了三十个高价值图像和三十个低价值图像。训练阶段完成后，我们进行了优先观看测试。在每次试验中，同时呈现两张图像（一张高价值图像和一张低价值图像），动物自由观看它们 4 秒。在此阶段，每次试验结束时输送中等量的液体。两组人都对高价值图像表现出一致的偏好。在优先观看测试中，当高价值图像和低价值图像都可用时，80% 的试验中动物首先查看高价值图像。此外，相对于低价值图像，他们观看高价值图像的时间要长 3.7 倍，注视时间要多 3.5 倍。这些措施中的任何一项都没有组间差异。我们的研究结果表明，至少当术后获得刺激-价值关联时，OFC 并不是引导眼睛看到有价值图像所必需的。 病变研究表明内侧前额叶皮层 (MFC) 和眶额叶皮层 (OFC) 的分离功能，其中 MFC 对于社会认知至关重要，而 OFC 对于基于价值的决策至关重要。尽管双侧杏仁核损伤也会导致这些区域的损伤，但尚不清楚 MFC 和 OFC 的可分离功能作用是否主要取决于与杏仁核的相互作用。为了测试这种可能性，我们将前边缘皮质（MFC 的一个分区）和杏仁核交叉手术断开的动物（PL x AMY）以及 OFC 和杏仁核手术断开（OFC x AMY）的动物与一组对照组（CON）进行了比较。所有动物在观看社交刺激视频（社会兴趣测试）和基于当前食物价值的对象选择（贬值任务，基于价值的决策测试）时评估食物检索延迟。与 CON 组相比，PL x AMY 组（而非 OFC x AMY 组）在存在同种人视频的情况下表现出显着降低的获得奖励的延迟，表明社会评价降低和/或社会兴趣降低。然而，在基于价值的决策测试中，观察到了相反的模式。 OFC x AMY 组（而非 PL x AMY 组）在选择性饱足后的物体选择上表现出严重缺陷。这些数据表明，MFC 和 OFC 与杏仁核相互作用，分别促进社会认知和决策领域的不同行为贡献。 MFC 被认为不仅编码奖励价值，还编码同种人和自我的特征。动物生理学研究和人类功能磁共振成像研究已确定 MFC 支持社会认知。与此相关的是，越来越多的证据表明，某些物种发现另一个个体收到奖励强化，称为替代强化，并且这种能力得到了包括 MFC 在内的大脑区域网络的支持。事实上，MFC 中的单个神经元选择性地编码将奖励传递给自己、伴侣、两只动物或都不给动物。 我们使用替代强化任务来测量动物的亲社会倾向。每次测试都有两只动物参加：一名演员和一名接受者。演员们了解到，三种不同的视觉线索映射到三种不同的奖励结果：自我、其他动物或两者都不是。在每次试验中，演员都会看到一个提示，该提示可以预测三个果汁提议中的一个，并且可以通过向外围目标进行扫视来接受该提议，或者通过打破固定来拒绝该提议。所有六名演员都表现出亲社会偏好，这表明他们更倾向于给予其他人相对于“两者都不是”的奖励。 为了确定 MFC 对社会认知的贡献是否至关重要，我们在动物遭受 MFC 损伤之前和之后测试了动物的替代强化任务。具体来说，一半的演员接受了前扣带皮层（ACC）（MFC 的一部分）的选择性、双侧、兴奋性毒性损伤，另一半则作为未手术的对照。手术后，所有动物都保留了它们通过术前习得的线索所表现出的社交偏好，但这种偏好在 ACC 损伤的动物中有所降低。关键的是，ACC 损伤组中没有一只动物通过手术后引入的一组新线索获得了社会偏好。这些数据表明 ACC 对于从替代强化中获得亲社会偏好是必要的。 与此同时，自主神经唤醒的分析越来越多地用于情境化和指导神经研究，特别是奖励处理的研究。因此，我们在动物执行替代强化任务时收集了瞳孔直径。与我们的预期相反，我们发现学生对自己喝果汁的期望值最大，对没有人喝果汁的期望值中等，对社会伙伴喝果汁的期望值最窄。看似矛盾的瞳孔效应可以用一个模型来解释，其中瞳孔大小跟踪结果显着性，亲社会倾向跟踪结果效价，显着性和效价之间的关系呈 U 形。尽管 ACC 损伤扰乱了动物的社会决策，正如亲社会倾向的改变所证明的那样，但对预期相同结果的自主神经唤醒没有影响。因此，我们的结果表明 ACC 不是负责产生替代强化期间看到的社会调节瞳孔反应的神经回路的一部分。