Neural substrates of reward processing and emotion

该项目的先前研究表明，基于价值的决策需要OFC和杏仁核。我们使用了两种类型的任务来研究它们的机制：(1)标准概率和确定性2和3选择视觉辨别学习任务和(2)要求受试者做出与不同价值奖励相关的选择的任务（贬值任务）。我们发现，当受试者需要根据当前奖励的价值做出选择时，杏仁核和OFC都是必要的，而不是简单地根据奖励的可获得性做出选择。我们早期的研究结果表明，当一种食物的价值因受试者吃到饱而降低时，对照组受试者表现出与贬值食物相关的行为减少。相比之下，杏仁核或OFC双侧损伤的受试者没有表现出这种贬值效应。在当前的回顾期内，我们通过研究杏仁核和OFC的手术交叉断开对同一测试的影响，扩展了这些结果。初步结果表明，杏仁核与OFC的功能相互作用对于基于当前估值的选择是必不可少的。

Previous work on this project has shown that value-based decision making requires both the OFC and the amygdala. We have used two kinds of tasks to investigate their mechanisms: (1) standard probabilistic and deterministic 2- and 3-choice visual discrimination learning tasks and (2) tasks that require subjects to make choices associated with rewards of different value (the devaluation task). We have found that both the amygdala and OFC are necessary when subjects need to make choices based on the current value of rewards, but not for choices based simply on the availability of rewards. Our earlier results indicated that when the value of one food was reduced by the subject consuming it to satiety, control subjects showed a reduction in actions associated with the devalued food. In contrast, subjects with either bilateral damage to the amygdala or the OFC failed to show this devaluation effect. In the current review period, we have extended these results by studying the effect of surgical crossed-disconnections of the amygdala and the OFC on the same test. Preliminary results indicate that the functional interaction of the amygdala with the OFC is essential for choices based on current valuations. We recently found that damage limited to cells in the OFC, but sparing fibers, did not affect performance on standard tests of visual discrimination learning and reversal. This led us to reject the influential idea that the primary function of the OFC involves inhibitory control. Although the loss of neurons in OFC per se is not responsible for the impairment, some other part(s) of the frontal cortex is presumably responsible. Accordingly, future studies will seek to identify the specific frontal areas that mediate reward-based choices, as well as the location of white-matter pathways which are disrupted by OFC lesions. Because these findings contradict previous ideas about the function of the OFC, we explored the role of OFC in more demanding reversal learning tasks. We tested subjects on two separate probabilistic tasks. In one test, they saw two stimuli on a touch screen; one option had a 0.75 probability of producing a reward and the other had a 0.25 probability. Once the subjects consistently selected the high-probability option, the stimulus-reward contingencies were reversed. In the second test, subjects saw 3 different stimuli, each with a probability of receiving a reward that fluctuated during a session. On both tasks, subjects with selective lesions of the OFC performed as well as controls. All of our subjects tracked the probability of reward associated with the 3 options and selected the one with highest reward probability. Taken together, these results show that the OFC is not necessary for probabilistic learning and reversal: measures of reward availability as opposed to the current value of a reward. Like these recent findings for the OFC, the amygdala is not necessary for object reversal learning in the standard task. Indeed, amygdala damage leads to a slight facilitation in this form of stimulus-reward learning. Past studies have assessed the performance of subjects when they first experienced reversals as opposed to much later, when performance had reached an asymptote, and they exclusively used deterministic rewards. As such, it is not clear how the amygdala contributes to reversal learning when behavioral strategies are stable and feedback is probabilistic. To address these issues, we examined the role of the amygdala in reversal learning when subjects expected a reversal in the stimulus-reward contingencies. Subjects with bilateral amygdala damage and controls were assessed in two ways. In the first, subjects initially learned to choose between two novel, deterministically rewarded options and the tasks progression was tied to reaching a criterion level of performance after each reversal. In the second, subjects learned to choose between two choice options, but the reversal randomly occurred. Preliminary results show that amygdala damage compromises the ability to reverse stimulus-reward associations by disrupting reinforcement learning when tested in these new ways. Subjects with amygdala damage show heightened sensitivity to negative feedback, compared to controls. Thus, amygdala damage causes erratic choice behavior and heightened sensitivity to negative feedback, which can either enhance or impair decisions depending on the stability of behavioral strategies and knowledge of prior probabilities, in a Bayesian manner. Finally, a considerable body of evidence has suggested a role for the amygdala in processing emotionally salient information in faces. For example, patients with amygdala damage fix their gaze on the eye region of faces to a lesser extent than controls. To evaluate amygdala contributions to social displays of emotion, we had subjects perform an attentional capture task in which they viewed pictures of a socially relevant portion of a subject face (eye, nose, or mouth) or nonsocial pictures. When the stimulus appeared at the subjects fixation point, they had to make a saccade away from it as quickly as possible. For comparison, we also permitted free viewing, during which subjects looked at faces voluntarily. In the free viewing condition, like previously published data, subjects with amygdala lesions spent less time than controls exploring faces, specifically the eye region. In the attentional capture task, we found that all subjects, lesioned and controls, made saccades more slowly when they saw social (vs. nonsocial) stimuli. We also found that saccade latency varied according to the facial feature displayed. Saccade latency was significantly faster in subjects with amygdala damage, compared to controls, especially on trials with a threatening expression formed by the mouth. These data indicate that subjects with amygdala damage have an impairment in attending to certain social cues. Unlike in the free viewing condition, the effect of amygdala damage on the attentional capture task was driven by the mouth region, as opposed to the eyes. These data indicate that the amygdala plays a crucial role in processing and attending to social cues.