The Neural Basis of Decision-Making: Cortical & Subcortical Mechanisms

描述（由申请人提供）：您希望在12个月内获得20美元，还是在13个月内获得22美元？大多数人会多等一个月，以获得额外的2美元。365天后问自己同样的问题：今天20美元还是一个月后22美元，你更喜欢哪一个？现在大多数人会选择直接获得20美元；偏好的逆转。坐在诊所里，大多数吸毒者表示倾向于避免在一天的晚些时候吸毒。几个小时后，面对一种立即可用的药物，他们的偏好会发生逆转。这些观察结果表明，人类通过比较奖励的主观价值来做出选择，而这些价值不仅取决于奖励的大小，还取决于何时获得奖励。满足被推迟的时间越长；不那么理想的奖赏出现了。经验数据表明，这种可取性的下降在短延迟时发生得最突然，随着延迟的增加而逐渐发生。也许同样有趣的是，观察到基本上所有脊椎动物似乎都表现出类似的模式。那么，为延迟奖励设定主观价值的神经机制是什么呢？决策的神经生物学研究在很大程度上避免了这个问题。在这个应用中，我们建议将现有的决策神经生物学研究扩展到及时选择的领域。我们建议结合行为、生理和功能磁共振成像技术进行这项研究，并检验两个试图解释及时选择的假设：一个标准的生理模型和经济理论中占主导地位的双系统模型。具体来说，我们建议测试这两种模型中的任何一种都可以解释后顶叶皮层和腹侧纹状体在一系列条件下的活动的假设。延迟对决策的病理影响在疾病中是普遍存在的。拖延会扭曲患有注意力缺陷障碍、病态赌徒、吸毒者、吸烟者、酗酒者、可卡因和海洛因成瘾者的决定。尽管对延迟的异常敏感性控制着所有这些患者群体的行为，但对这种疾病的机制几乎一无所知。我们提出了一系列的实验，旨在阐明病理决策的基本机制，标志着不适当的选择。

DESCRIPTION (provided by applicant): Which would you prefer, a gain of $20 in 12 months or of $22 in 13 months? Most people would wait the extra month to gain the extra $2. Ask yourself the same question 365 days later: which would you prefer, $20 today or $22 in a month? Now most people would select the immediate gain of $20; a reversal in preferences. Sitting in a clinic, most drug users state a preference for avoiding drug use later in the day. Hours later, confronting an immediately available drug, their preferences reverse. These observations reveal that humans make choices by comparing the subjective values of rewards and that these values depend not just on how large a reward is but when that reward will be received. The longer gratification is delayed; the less desirable a reward appears. Empirical data suggests that this decrease in desirability occurs most abruptly at short delays and more gradually as delays increase. Perhaps just as interesting is the observation that essentially all vertebrates appear to show a similar pattern. What then, is the neural mechanism that sets a subjective value on delayed rewards? Neurobiological studies of decision-making have largely avoided this issue. In this application we propose to extend existing neurobiological studies of decision-making into the domain of choice-in-time. We propose to undertake this study with a combination of behavioral, physiological and functional magnetic resonance imaging techniques and to test two hypotheses that seek to explain choice-in-time: a standard physiological model and the dominant two-system model of economic theory. Specifically, we propose to test the hypothesis that either of these models can account for the activity of the posterior parietal cortex and the ventral striatum under a range of conditions. Pathological influences of delays on decision making are pervasive in disease. Delays distort the decisions made by children with attention-deficit disorder, pathological gamblers, drug abusers, smokers, alcoholics, cocaine and heroin addicts. Despite the fact that an abnormal sensitivity to delays controls the behavior of all of these patient groups, almost nothing is known about the mechanism of this disorder. We propose a series of experiments aimed at elucidating the basic mechanism that underlies the pathological decision making that marks inappropriate choice-in-time.