Functional Magnetic Resonance Imaging Of Emotion As Rela

最近情绪神经生物学的许多研究都将情绪分为积极情绪和消极情绪两类。积极情绪涉及高水平的唤醒，通常发生在预期奖励的背景下，而消极情绪，也涉及高水平的唤醒，通常发生在预期惩罚的背景下。此外，比较研究表明腹侧前脑多巴胺能通路参与奖赏的预期，大多数药物滥用动物模型都非常关注中脑边缘多巴胺投射在药物渴求神经回路中的重要性。因此，我们试图描述与奖励和惩罚的预期相关的神经活动，特别是在大脑多巴胺系统中。为了研究奖励和惩罚的神经基础，我们使用功能性磁共振成像（fMRI）来测量人类在金钱奖励的接近和回避行为中的大脑激活。具体来说，我们研究腹侧前脑多巴胺投射区是否在运动行为之前被激活，在奖励和惩罚的预期期间，而不是在奖励和惩罚之后的反应期间。在接近任务中，受试者看到一个提示，表明他们可以赢钱或不，等待一个可变的延迟，然后按下一个按钮，以响应呈现的目标。如果受试者在目标消失之前做出反应，他们会赢得5.00美元、1.00美元或0.20美元，而他们对中性目标的反应不会影响他们的总数。在主动回避任务中，受试者被给予20.00美元，并对遵循惩罚线索或中性线索的目标做出反应。如果他们在目标消失之前没有做出反应，他们会损失5美元、1美元或0.20美元，而他们对中性目标的反应不会影响他们的总数。使用1.5或3.0特斯拉GE系统采集T2* 加权梯度回波平面MR容积，描绘血氧水平依赖（BOLD）对比度。校正平面内运动后，使用AFNI软件包将个体体素激活与对应于预期激活时间过程的理想波形相关联。理想的波形包括与血流动力学响应函数卷积的任务开-关波形。对奖赏的预期激活了纹状体区域（尾状核、壳核）和内侧前脑区域（前扣带回、内侧前额叶皮质和丘脑区域）。相对于没有金钱结果的预期，对惩罚的预期也激活了这些区域。然而，对奖励而不是惩罚的预期在丘脑核中产生激活。当提示信号发出金钱奖励时，丘脑底核激活的幅度预测了受试者报告的积极情绪的量。我们还分别研究了奖励预期和结果与事件相关的功能磁共振成像。这项研究证实，神经核主要是通过预期金钱奖励来招募的。这种激活消退期间提供奖励的结果，而且，核脑桥的活动受到抑制时，预期的奖励没有得到。奖励预期没有激活腹内侧前额叶皮层（VMFC），但预期奖励的不发生抑制VMFC活动。失活的这些地区在奖励nondelivery是一致的灵长类动物的电生理记录显示减少中脑多巴胺神经放电在奖励遗漏。目前正在进行研究，以比较有和没有酗酒或药物滥用家族史的青少年对工作以获得奖励或避免惩罚的预期的大脑反应。这些研究表明，青少年在预期为奖励而工作时会激活与成年人相同的大脑回路，但激活的程度低于成年人。此外，青少年儿童的酗酒者似乎有更少的激活腹侧纹状体在奖励预期比控制青少年。这些结果表明，大脑奖励和动机回路功能低下可能是酗酒发展的一个危险因素。此外，我们还开始比较酗酒者和对照组的大脑激励回路。这项工作的初步结果表明，在最后一次饮酒三周后研究的酗酒者在预期为奖励而工作时，丘脑核也表现出迟钝的反应。在成年酗酒者中的发现与在有酗酒风险的儿童中的发现是一致的，进一步加强了这样一种认识，即一个不活跃的动机系统可能参与了酗酒的病理生理学，也许还有其他形式的物质滥用。

Much of the recent work in the neurobiology of emotion has divided emotion into two categories of positive and negative emotion. Positive emotions involving high levels of arousal often occur in the context of the anticipation of reward, while negative emotions, which also involve high levels of arousal often occur in the context of the anticipation of punishment. In addition, comparative studies have implicated a ventral forebrain dopaminergic pathway in the anticipation of reward, and most of the animal models of substance abuse focus heavily on the importance of mesolimbic dopamine projections in the neural circuitry underlying drug craving. Thus, we have sought to characterize neural activity associated with the anticipation of rewards and punishments, particularly in brain dopamine system. In order to investigate the neural basis of reward and punishment we have used functional magnetic resonance imaging (fMRI) to measure brain activation during monetarily rewarded approach and avoidance behavior in humans. Specifically, we examined whether ventral forebrain dopamine projection areas were activated prior to motor behavior, during anticipation of reward and punishment, as opposed to during responses following reward and punishment. During the approach task, subjects saw a cue indicating that they could either win money or not, waited a variable delay, and then pressed a button in response presentation of a target. If subjects responded before the target following the reward cue disappeared, they won $5.00, $1.00, or $.20 whereas their response to the neutral target did not affect their total. During the active avoidance task, subjects were given $20.00 and responded to targets that followed either a punishment cue or a neutral cue. If they failed to respond before the disappearance of the target following the punishment cue, they lost $5.00, $1.00, or $.20 whereas their response to the neutral target again did not affect their total. T2*-weighted gradient echoplanar MR volumes depicting blood oxygenation level dependent (BOLD)-contrast were acquired using a 1.5 or 3.0 Tesla GE System. After correcting for in-plane motion, individual voxel activations were correlated with an ideal waveform corresponding to the expected activation time course using the AFNI software package. The ideal waveform consisted of the task On-Off waveform convoluted with the hemodynamic response function. Anticipation of reward activated striatal areas (caudate, putamen) and mesial forebrain areas (anterior cingulate, mesial prefrontal cortex, and thalamic regions). Anticipation of punishment also activated these regions relative to anticipation of no monetary outcome. However, anticipation of reward but not punishment produced activation in the nucleus accumbens. Magnitude of nucleus accumbens activation predicted the amount of positive emotion subjects reported feeling when the cues signaling monetary reward. We also separately examined reward anticipation and outcomes with event-related fMRI. This study confirmed that the nucleus accumbens was primarily recruited by anticipation of monetary reward. This activation subsided during delivery of rewarding outcomes, and moreover, nucleus accumbens activity was suppressed when anticipated rewards were not obtained. Reward anticipation did not activate the ventro-medial prefrontal cortex (VMFC), but nonoccurrence of anticipated rewards did suppress VMFC activity. Deactivation of these regions during reward nondelivery is consistent with primate electrophysiological recordings showing decreased midbrain dopamine neural firing during reward omission. Studies are currently ongoing to compare the brain response to anticipation of working to gain reward or to avoid punishment in adolescents with and without a family history of alcoholism or substance abuse. These studies have shown that adolescents activate the same brain circuit during anticipation of working for reward as adults do, but that the magnitude of the activation is less than the magnitude seen in adults. Furthermore, adolescent children of alcoholics appear to have even less activation of the ventral striatum during reward anticipation than the control adolescents do. These results suggest that hypofunction of brain reward and motivation circuits may be a risk factor in the development of alcoholism. In addition, we have also begun comparing brain motivation circuits in alcoholics and controls. Initial results from this work suggest that alcoholics studied three weeks from their last drink also shown a blunted response in the nucleus accumbens during the anticipation of working for reward. The finding in adult alcoholics is consistent with the findings in children at risk for alcoholism further strenghtening the arguement that an underactive motivational system may be involved in the pathophysiology of alcoholism and perhaps other forms of substance abuse.