Neural mechanisms of reward processing and emotion

杏仁核、眶额皮层和前额叶皮层在一定程度上通过评估反馈来促进学习。为了扩展我们对情感处理的生理机制的理解，我们开发了一种fMRI范式来揭示血氧水平依赖（BOLD）的视觉图像信号奖励的反应。每周，受试者学习将新物体的图像与水奖励的高或低概率联系起来。响应于最近学习的奖励预测图像的值的区域包括MFC区域10 m/32、腹外侧前额叶皮层区域12和下颞视觉皮层（IT）。杏仁核和眶额皮层都被认为与价值编码有关，但几乎没有这种影响。相反，这两个区域主要分别对视觉刺激和奖励接收做出反应。我们的研究结果表明，腹外侧前额叶皮层，MFC和IT在代表最近学习的视觉图像的价值的重要性。 口味及其相关的价值驱动食物消费，影响选择行为。为了了解奖励引导决策和价值学习的神经机制，我们用fMRI表征了受试者的味觉系统，同时测量舔来控制口腔运动，并评估偏好。尽管解剖学数据表明来自丘脑腹后内侧核（VPMpc）的味觉信息进入味觉皮层，但对味觉的生理反应广泛存在于皮层，包括体感皮层和眶额皮层。为了识别味觉反应皮层，我们以随机顺序递送少量（0.1ml）蔗糖、柠檬酸或蒸馏水，而没有任何预测线索（例如，视觉刺激），同时使用事件相关的功能磁共振成像。此外，我们使用了MRI兼容的舔传感器来测量受试者在扫描过程中的舔。在没有流体输送的情况下与舔相关的fMRI信号用于掩盖对流体输送/接收和相关舔的反应。将每种促味剂在不存在液体递送和液体接收时间的情况下的舔食并入一般线性模型中以分析fMRI数据。通过将BOLD对甜味或酸味的反应与蒸馏水的反应进行对比，并在没有液体输送的情况下用与舔相关的BOLD信号进行掩蔽，我们在三名受试者中确定了味觉皮层、腹外侧前额叶皮层12 o区、OFC 13 b区和体感皮层3b区的味觉反应。通过所有味道相对于基线的对比所定义的流体递送激活的区域一般包括内侧OFC区14、腹侧纹状体、腹侧苍白球、杏仁核基底核和嗅周皮质。我们的味觉反应的研究结果与单单位神经生理记录一致。全脑功能磁共振成像结合舔行为的量化和受试者对不同口味的选择偏好将用于识别信号值的大脑区域。 我们小组以前的工作表明，前扣带皮层的膝下部分在预期积极（奖励）事件时有助于自主唤醒。由于眶额皮层参与了基于刺激的奖励学习，我们想知道这个区域是否也有助于学习或维持与积极事件相关的自主觉醒。因此，我们评估了自主神经反应的受试者，持续双边兴奋性损伤的OFC和控制。受试者接受训练的任务中，巴甫洛夫条件反射的刺激奖励协会叠加在仪器条件反射的主动视觉固定。在一些试验中，两个巴甫洛夫刺激（CS+，CS-）之一，在4秒的注视期间，在监视器屏幕上显示1秒。CS+之后总是有大量的流动奖励; CS-导致没有奖励。我们记录瞳孔大小作为自主反应的测量。与对CS-的反应相比，对照组在几个训练期内表现出对CS+的瞳孔大小增加（2 +/-1），并且在至少4个连续的训练期内继续表现出预期奖励的条件化瞳孔反应。相比之下，OFC损伤的受试者需要更多的训练（20 +/- 7次）来获得条件性自主反应，四分之三的受试者即使在延长的训练期（50次）也无法持续4次连续训练。用第二组刺激进行训练也产生了类似的结果。因此，目前的研究结果表明，OFC参与获得适当的自主反应的线索预测积极的事件。

The amygdala, OFC and MFC contribute to learning, in part, by evaluating feedback. In an effort to extend our understanding of the physiological mechanisms underlying affective processing, we developed an fMRI paradigm to reveal blood-oxygen-level dependent (BOLD) responses to visual images that signal reward. Each week, subjects learned to associate images of novel objects with a high or low probability of water reward. Areas responding to the value of recently learned reward-predictive images included MFC area 10m/32, ventrolateral prefrontal cortex area 12, and inferior temporal visual cortex (IT). The amygdala and OFC, each thought to be involved in value encoding, showed little such effect. Instead, these two areas primarily responded to visual stimulation and reward receipt, respectively. Our findings demonstrate the importance of ventrolateral prefrontal cortex, MFC, and IT in representing the values of recently learned visual images. Tastes and their associated values drive food consumption and influence choice behavior. To understand the neural mechanisms underlying reward-guided decision making and value learning, we characterized the gustatory system in subjects with fMRI while measuring licking to control for oral movements, and to assess preferences. Though anatomical data indicate that taste information from the ventroposteromedial nucleus of the thalamus (VPMpc) goes to gustatory cortex, physiological responses to taste are widespread in cortex, including in somatosensory cortex and OFC. To identify taste-responsive cortex, we delivered small quantities (0.1ml) of sucrose, citric acid, or distilled water in random order without any predictive cues (e.g., visual stimuli) to subjects while using event-related fMRI. In addition, we used an MRI-compatible lick sensor to measure subjects licking during the scans. fMRI signals associated with licking in the absence of fluid delivery were used to mask responses to fluid delivery/receipt and associated licking. Licking in the absence of fluid delivery and fluid receipt times for each tastant were incorporated into a general linear model to analyze fMRI data. By contrasting BOLD responses to either sweet or sour tastes to those from distilled water, and masking with BOLD signals associated with licking in the absence of fluid delivery, we identified taste responses in gustatory cortex, ventrolateral prefrontal cortex area 12o, OFC area 13b and somatosensory cortex area 3b in three subjects. Areas activated by fluid delivery in general as defined by a contrast of all tastes relative to baseline included medial OFC area 14, the ventral striatum, the ventral pallidum, the basal nucleus of amygdala, and the perirhinal cortex. Our findings of gustatory responses are in agreement with single unit neurophysiological recordings. Whole brain fMRI in combination with quantification of licking behavior and subjects choice preferences for different tastes will be used to identify brain regions that signal value. Previous work from our group has shown that the subgenual portion of the anterior cingulate cortex contributes to autonomic arousal during anticipation of positive (rewarding) events. Because the OFC is involved in stimulus-based reward learning, we wondered whether this region, too, contributed to either the learning or maintenance of autonomic arousal associated with positive events. Accordingly, we evaluated autonomic responses in subjects that had sustained bilateral excitotoxic lesions of OFC and controls. Subjects were trained on a task in which Pavlovian conditioning of stimulus-reward associations was superimposed on instrumental conditioning of active visual fixation. On some trials, one of two Pavlovian stimuli (CS+, CS-) was presented on the monitor screen for 1 s during the 4-s fixation period. The CS+ was always followed by a large fluid reward; the CS- led to no reward. We recorded pupil size as a measure of autonomic response. Controls exhibited an increased pupil size to the CS+, compared to the response to the CS-, within a couple of training sessions (2 +/- 1) and continued to show the conditioned pupil response in anticipation of reward across at least 4 consecutive sessions. By contrast, subjects with OFC lesions required more sessions (20 +/- 7 sessions) to acquire the conditioned autonomic response and three out of four failed to sustain it for 4 consecutive sessions even with an extended period of training (50 sessions). Training with a second set of stimuli yielded a similar result. Thus, the present results suggest that OFC is involved in acquiring appropriate autonomic responses to cues predicting positive events.