Neural Substrates of Reward Processing and Emotion

眼窝额叶皮层（OFC）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觉醒，通过瞳孔直径来测量。OFC神经元的活动也受到注意的调节。目前还不清楚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关系，我们对双侧兴奋性中毒性OFC病变的动物进行了优先观看任务的训练。实验分刺激-奖励联想训练和偏好观看测试两个阶段进行。刺激-奖励训练建立了30个高价值图像和30个低价值图像。当训练阶段完成后，我们进行了一次优先观看测试。在每次试验中，同时呈现两幅图像——一幅高价值图像和一幅低价值图像，动物自由地观看它们4秒。在这一阶段，每次试验结束时都要注入适量的液体。两组都表现出对高价值图像的一致偏好。在优先观看测试中，当高价值和低价值的图像都可用时，动物在80%的试验中首先看高价值的图像。此外，他们观看高价值图像的时间是低价值图像的3.7倍，注视的时间是3.5倍。在这些测量中没有任何组间差异。我们的研究结果表明，至少当术后获得刺激-价值关联时，OFC对于引导眼睛看到有价值的图像是不必要的。

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.