Neural substrates of reward processing and emotion

奖励处理和情绪的神经基质

• 批准号: 8745735
• 负责人: ELISABETH A MURRAY
• 金额: $ 99.89万
• 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/8745735
• 关键词: Address; Affect; Affective; Agreement; Amygdaloid structure; Anxiety; Area; Attention; Behavior; Behavior Control; Behavioral; Bilateral; Biological; Brain; Cells; Clinical; Clinical Research; Complement; Consumption; Cues; Data; Decision Making; Deep Brain Stimulation; Depressed mood; Disease; Eating; Electrophysiology (science); Emotional; Emotions; Equilibrium; Excitotoxic lesion; Exhibits; Eye; Face; Failure; Fiber; Food; Foundations; Fright; Functional disorder; Future; Genetic; Goals; Health; Impairment; Influentials; Intervention; Knowledge; Learning; Lesion; Literature; Major Depressive Disorder; Measures; Mediating; Memory; Mental disorders; Methodology; Methods; Molecular; Nature; Operative Surgical Procedures; Oral cavity; Panic Attack; Patients; Perception; Performance; Phobic anxiety disorder; Play; Process; Psychological Theory; Quality of life; Regulation; Research; Reversal Learning; Rewards; Role; Running; Saccades; Satiation; Shapes; Snakes; Social Behavior; Stimulus; Stress; Structure; Structure-Activity Relationship; Syndrome; Testing; Time; Training; Translating; Translational Research; Update; Work; base; conditioned fear; design; dysphoria; emotion regulation; emotional stimulus; feeding; flexibility; follow-up; frontal lobe; improved; neuroimaging; neuron loss; neuropsychiatry; novel; operation; receptor; relating to nervous system; research study; reward processing; social; theories; touchscreen

Work on this project has demonstrated that value-based decision making requires both the OFC and the amygdala for normal operations. We use a decision-making task that requires subjects to make choices associated with rewards of different value. In this task, the value of rewards is varied by prior consumption of a food item that serves as a reward. Eating a certain kind of food leads to a selective satiation that temporarily decreases the value of that food. We found that the OFC and the amygdala both play a necessary, causal role in the rapid updating of valuations, based on current biological needs. Our previous work had emphasized the valuation of objects, but traditional psychological theory has focused on the valuation of actions rather than of objects. Specifically, the learning-theory literature stresses the valuation of actions to guide goal-directed behavior. To investigate the role of the amygdala in updating the valuation of actions, we designed a novel task. Subjects were trained to perform two different actions on a touch screen. Repetitive tapping produced one food; constant holding produced a different food. Subjects were fed one of the foods to satiety, which lowered its value. Control subjects showed a reduction in the action associated with obtaining the devalued food. This result, called the devaluation effect, is a hallmark of goal-directed behavior. Subjects with bilateral lesions of either OFC or the amygdala exhibited significantly reduced devaluation effects. These results show that both OFC and the amygdala play an essential, causal role in goal-directed behavior that depend on the valuation of actions, which complements our earlier findings on the valuation of objects. Notably, these findings challenge the idea that the OFC and MFC are specialized for object- and action valuation, respectively. They also confirm our previous results showing that the amygdala plays an important role in positive valuations and emotions, which balances the overemphasis in the literature on negative valuations and emotions. To build on these findings, and to investigate whether the amygdala and either the OFC or MFC interact to guide goal-directed behavior, we are currently examining the effect of surgical crossed-disconnections of the amygdala and the frontal lobe on the performance of the same test of goal directed behavior described above. We are studying both amygdala-MFC and amygdala-OFC interactions. Our preliminary data suggest that functional interaction of the amygdala with OFC, but not MFC, is essential for goal-directed behavior. For decades, both clinical and experimental work on the OFC have been dominated by the idea that it regulates emotion and enhances behavioral flexibility through inhibitory control. In support of this idea, profoundly altered emotion regulation is a hallmark of damage or dysfunction within OFC. In addition, OFC damage yields an impairment in the ability to rapidly alter object-reward associations, as assessed in the object reversal learning task, a finding taken to support the role of OFC in inhibitory control. This influential result has been replicated many times, but our research has shown that the interpretation of this finding has been incorrect. Our earlier work showed that subtotal fiber-sparing, excitotoxic lesions of OFC failed to produce the expected changes in behavioral flexibility and emotion regulation. This failure, however, may have resulted because complete OFC lesions are needed to produce the classic behavioral effects. Alternatively, however, the effects of OFC damage may have depended on inadvertent damage to fiber tracts running near or through OFC and not on the function of OFC per se. To examine these possibilities we assessed subjects with excitotoxic lesions of OFC on two tests of inhibitory control (object reversal learning and snake fear) and one of updating object valuations, like the tasks described above. Unlike aspirations lesions of OFC, damage limited to cells in this area, but sparing fibers, did not affect either behavioral flexibility, as measured by object reversal learning, or emotion regulation, as reflected in measures of snake fear. These complete, excitotoxic lesions of OFC did, however, cause the same impairment in updating valuations that follows aspiration lesions of the same area. In a follow-up experiment, aspiration of a narrow strip of cortex in the posterior OFC reproduced the often-replicated impairments in object reversal learning and the blunting of snake fear caused by aspiration lesions of the entire OFC. Taken together, these findings show that inadvertent damage to fibers passing near or through OFC causes the impairments in behavioral flexibility and emotion regulation typically attributed to OFC. The results also support the idea that the OFC performs a more specific function in reward-guided behavior and emotion than currently thought, and indicate that this function includes the updating of object valuations according to current motivational states. We can reject the influential idea that the primary function of the OFC involves inhibitory control. Although loss of neurons in OFC per se is not responsible for the impairment in reversal learning or the dysregulation of snake fear, loss of neurons in some other parts of the frontal cortex presumably causes these classic results. Future studies will need to identify the specific frontal areas that mediate behavioral flexibility and emotion regulation. We have also studied the contribution of the amygdala to emotional processes. Learning, memory, attention and perception are all influenced by amygdala activity when subjects are perceiving and encoding emotional stimuli. Lesion studies have shown that the perception of emotional content of stimuli is affected by amygdala damage. For example, previous work on this project has shown that amygdala damage disrupts snake fear. Nevertheless, there is little work that assesses the contribution of the amygdala to social behavior in a rigorous manner. Accordingly, we examined the role of the amygdala in an attention task with social and nonsocial stimuli. Subjects with bilateral amygdala damage and control subjects performed an attention task in which they viewed social stimuli (pictures of a socially relevant portion of a face, such as the eye or mouth) or nonsocial stimuli (such as a geometrical shape). After viewing the stimuli, the subjects made a saccade to a visible target. Control subjects showed a significantly higher latency to initiate a saccade when presented with a social stimulus compared to a nonsocial one. By contrast, subjects with amygdala lesions showed the same latency to saccade for social and nonsocial stimuli, thereby indicating a lack of attention to social cues. These data show that the amygdala plays a crucial role in attending to and recognizing social cues.

该项目的工作表明，基于价值的决策需要 OFC 和杏仁核才能正常运作。我们使用的决策任务要求受试者做出与不同价值的奖励相关的选择。在此任务中，奖励的价值因之前食用作为奖励的食物而异。吃某种食物会导致选择性饱足，从而暂时降低该食物的价值。我们发现，根据当前的生物需求，OFC 和杏仁核在估值的快速更新中都发挥着必要的因果作用。 我们之前的工作强调对物体的评价，但传统的心理学理论关注的是对行为的评价而不是对物体的评价。具体来说，学习理论文献强调对行动进行评估以指导目标导向的行为。为了研究杏仁核在更新行为评估中的作用，我们设计了一项新颖的任务。受试者接受训练在触摸屏上执行两种不同的操作。重复敲击产生一种食物；不断的持有产生了不同的食物。受试者被喂食其中一种食物至饱腹感，这降低了其价值。对照组受试者表现出与获取贬值食物相关的行为减少。这种结果称为贬值效应，是目标导向行为的标志。双侧 OFC 或杏仁核损伤的受试者表现出显着降低的贬值效应。这些结果表明，OFC 和杏仁核在依赖于行动评估的目标导向行为中发挥着重要的因果作用，这补充了我们之前关于物体评估的发现。值得注意的是，这些发现挑战了 OFC 和 MFC 分别专门用于对象和动作评估的观点。 他们还证实了我们之前的结果，即杏仁核在积极评价和情绪中发挥着重要作用，这平衡了文献中对消极评价和情绪的过分强调。 为了以这些发现为基础，并研究杏仁核与 OFC 或 MFC 是否相互作用来指导目标导向行为，我们目前正在研究手术交叉断开杏仁核和额叶对其性能的影响。测试上述目标导向行为。 我们正在研究杏仁核-MFC 和杏仁核-OFC 相互作用。我们的初步数据表明，杏仁核与 OFC（而非 MFC）的功能相互作用对于目标导向行为至关重要。 几十年来，OFC 的临床和实验工作一直被这样的观点所主导，即它通过抑制控制来调节情绪并增强行为灵活性。支持这一观点的是，情绪调节的深刻改变是 OFC 损伤或功能障碍的标志。此外，在物体逆转学习任务中评估，OFC 损伤会损害快速改变物体-奖励关联的能力，这一发现支持了 OFC 在抑制控制中的作用。这一有影响力的结果已被重复多次，但我们的研究表明，对这一发现的解释是错误的。 我们早期的工作表明，OFC 的次全纤维保留、兴奋性毒性损伤未能在行为灵活性和情绪调节方面产生预期的变化。然而，这种失败可能是因为需要完全的 OFC 损伤才能产生典型的行为效应。然而，OFC 损伤的影响可能取决于对靠近或穿过 OFC 的纤维束的无意损伤，而不是 OFC 本身的功能。为了检验这些可能性，我们通过两项抑制控制测试（对象反转学习和蛇恐惧）和一项更新对象评估测试（如上述任务）评估了 OFC 兴奋性毒性损伤的受试者。与 OFC 的吸入损伤不同，损伤仅限于该区域的细胞，但不影响纤维，不会影响行为灵活性（通过对象逆转学习测量）或情绪调节（通过蛇恐惧测量反映出来）。然而，OFC 的这些完整的兴奋性毒性损伤确实在更新同一区域的抽吸损伤后的评估时造成了同样的损害。在后续实验中，对后部 OFC 中的一条狭窄皮层的抽吸再现了物体反转学习中经常重复的损伤，以及由整个 OFC 的抽吸损伤引起的对蛇的恐惧减弱。总而言之，这些发现表明，对靠近或穿过 OFC 的纤维的无意损伤会导致通常归因于 OFC 的行为灵活性和情绪调节受损。结果还支持这样的观点，即 OFC 在奖励引导行为和情感方面发挥着比目前想象的更具体的功能，并表明该功能包括根据当前动机状态更新对象评估。我们可以拒绝这种有影响力的观点，即 OFC 的主要功能涉及抑制控制。 尽管 OFC 本身神经元的缺失并不导致逆向学习受损或对蛇的恐惧调节失调，但额叶皮层其他部分神经元的缺失可能会导致这些经典结果。未来的研究需要确定介导行为灵活性和情绪调节的特定额叶区域。 我们还研究了杏仁核对情绪过程的贡献。当受试者感知和编码情绪刺激时，学习、记忆、注意力和感知都会受到杏仁核活动的影响。损伤研究表明，杏仁核损伤会影响对刺激的情绪内容的感知。例如，该项目之前的工作表明，杏仁核损伤会扰乱对蛇的恐惧。然而，很少有工作以严格的方式评估杏仁核对社会行为的贡献。因此，我们研究了杏仁核在社交和非社交刺激的注意力任务中的作用。双侧杏仁核受损的受试者和对照组受试者执行一项注意力任务，其中他们观看社交刺激（面部与社交相关的部分的图片，例如眼睛或嘴巴）或非社交刺激（例如几何形状）。在看到刺激物后，受试者对可见目标进行扫视。与非社交刺激相比，对照组受试者在受到社交刺激时启动眼跳的潜伏期明显更高。相比之下，杏仁核受损的受试者在社交和非社交刺激下表现出相同的眼跳潜伏期，从而表明缺乏对社交线索的关注。这些数据表明杏仁核在关注和识别社交线索方面发挥着至关重要的作用。