Neural mechanisms of reward processing and emotion

眶额皮层和前扣带皮层与处理情绪信息、产生适当的自主反应和指导行为密不可分。 这两个区域通过与杏仁核和与内脏功能相关的大脑结构的相互联系来完成这些功能。 最近的神经生理学报告表明，这两个区域的单个神经元的活动与不同决定的情感或奖励性质有关。 然而，不太清楚的是，眶额皮层和前扣带皮层中单个神经元的奖赏相关活动如何在行为过程中驱动身体感觉，以及这种神经和自主活动如何在杏仁核受损后发生改变。 本研究探讨杏仁核对眶额皮层和前扣带皮层功能的影响，以及杏仁核对奖励期望的自主反应的影响。 具体而言，眶额皮质和前扣带皮质的单细胞记录已与自主措施（瞳孔直径，心率和皮肤电导）相结合，而受试者进行两种奖励引导的任务。 在一项任务中，受试者在两种刺激中做出选择，他们知道这两种刺激会产生不同的奖励;在另一项任务中，他们了解一种新的刺激会产生多少奖励。 我们假设，在完整的大脑中，眶额和前扣带皮层神经元和自主输出的活动将反映奖励的大小，但杏仁核病变后，这些信号将减弱或消失。 这个项目还处于早期阶段，但到目前为止，我们已经证实了以前的报告，即单个眶额皮层神经元的活动和自主反应都反映了受试者可以预测不同决策的奖励数量。 我们还发现，杏仁核的损伤会阻断在大奖励之前发生的自主觉醒，这反映在瞳孔直径上。 这些结果表明杏仁核在调节与奖励期望相关的情绪中的作用。 我们未来的神经生理学分析应该会揭示杏仁核是否也会将这些信息传递到眶额和前扣带皮层。 该项目的另一个重要的初步发现是，虽然杏仁核病变消除了自主信号和奖励幅度之间的关系，但受试者的任务表现并未因病变而改变。 自主输出和行为的这种分离表明，眶额皮层的不同部分（或同一部分内的不同神经元）扮演着不同的角色：杏仁核损伤后，控制自主输出的神经元不再反映预期的奖励幅度，而与受试者决策相关的细胞继续编码这些信息。 我们现在正在实验中验证这一预测。 这个项目代表了一个重要的新范式，研究杏仁核与额叶皮层的相互作用，一个应该产生重要的见解的功能定位和机制的情绪，奖励期望和评价。 在一项关于杏仁核在奖励和情绪中作用的功能性磁共振成像研究中，我们正在与Hadj-Bouziane和NIMH大脑与认知实验室的其他人合作。 众所周知，当受试者看到情绪化的面部表情时（与非情绪化的面部表情相比），视觉皮层区域（如下颞叶皮层）的局部脑血流量会有更大的增加。 我们已经验证了一个假设，即杏仁核损伤会消除导致这种效应的视觉皮层的情感反馈。 面部选择性区域被确定在颞叶下皮层在对照组和杏仁核病变的主题。 在对照组中，与中性面孔相比，具有情绪表达的面孔在这些区域产生了增强的反应，正如预期的那样。 在杏仁核损伤的受试者中，这些效应被破坏。 在杏仁核损伤最严重的大脑半球，颞叶下皮层的面部选择性斑块不受面部表情的影响。 总的来说，我们的研究结果支持杏仁核是视觉皮层中与情绪相关的信号来源的观点，这一发现产生了重要的预测，可以用上述神经生理学范式进行测试。

The orbitofrontal and anterior cingulate cortex are inextricably linked with processing emotional information, generating appropriate autonomic responses and guiding behavior. Both areas accomplish these functions via reciprocal connections with the amygdala and brain structures related to visceral function. Recent neurophysiological reports have shown that the activity of single neurons in both areas is related to the emotional or rewarding nature of different decisions. What is less clear, however, is how the reward related activity of single neurons in the orbitofrontal cortex and the anterior cingulate cortex drives bodily sensations during behavior and how this activity, both neural and autonomic, may be altered following damage to the amygdala. This project probes the contribution of the amygdala to orbitofrontal and anterior cingulate cortex function and to autonomic responses based on reward expectation. Specifically, single-cell recording in orbitofrontal cortex and the anterior cingulate cortex have been combined with autonomic measures (pupil diameter, heart rate, and skin conductance) while subjects performed two kinds of reward-guided tasks. In one task, subjects choose between two stimuli that they know will yield different amounts of reward; in the other they learn how much reward a novel stimulus will yield. We hypothesize that, in intact brains, the activity of orbitofrontal and anterior cingulate cortex neurons and autonomic outputs will reflect reward magnitude, but following amygdala lesions these signals will be attenuated or absent. This project is in its early stages, but so far we have confirmed previous reports that both the activity of single orbitofrontal cortex neurons and autonomic responses reflect the amount of reward the subjects can predict for different decisions. We have also found that lesions of the amygdala block the autonomic arousal that occurs before large rewards, as reflected in pupillary diameter. These results indicate a role for the amygdala in mediating the emotions related to reward expectation. Our future neurophysiological analysis should reveal whether the amygdala relays this information to the orbitofrontal and anterior cingulate cortex, as well. Another important initial finding from this project is that while amygdala lesions abolish the relationship between autonomic signals and reward magnitude, the subjects task performance is unaltered by the lesion. This uncoupling of autonomic output and behavior suggests that distinct parts of orbitofrontal cortex (or distinct neurons within the same parts) play different roles: those controlling autonomic output cease to reflect anticipated reward magnitude after amygdala lesions, whereas cells correlated with the subjects decisions continue to encode this information. We are now testing this prediction experimentally. This project represents an important new paradigm for studying the interactions of the amygdala with the frontal cortex, one that should yield important insights into the functional localization and mechanisms of emotion, reward expectation, and valuation. In an fMRI study of the role of the amygdala in reward and emotion, we are collaborating with Hadj-Bouziane and others in the Laboratory of Brain and Cognition, NIMH. As is well known, when subjects view emotional facial expressions (compared to unemotional faces), there is a greater increase in regional cerebral blood flow in areas of visual cortex, such as the inferior temporal cortex. We have tested the hypothesis that amygdala lesions would eliminate the emotional feedback to the visual cortex that causes this effect. Face-selective regions were identified in the inferior temporal cortex in both control subjects and subjects with amygdala lesions. In controls, faces with emotional expressions produced enhanced responses in these regions relative to neutral faces, as expected. In subjects with amygdala lesions, these effects were disrupted. In the hemisphere with the most complete amygdala lesion, face-selective patches in inferior temporal cortex were unaffected by facial expressions. Overall, our results support the idea that the amygdala is the source of emotion-related signals seen in the visual cortex, a finding that yields important predictions that can be tested with the neurophysiological paradigm described above.