Timing, reward processing and choice

项目总结 冲动的选择涉及到在数量和延迟之间进行权衡，通过交付更小-更快(SS)与 较大-较晚(LL)奖励。当个人频繁地选择党卫军时，就会出现冲动的选择 这样做并不是最好的。冲动的选择被认为是一种跨疾病过程，因为他们的 与多种疾病和障碍有关，包括药物滥用、赌博、肥胖、 以及注意力缺陷/多动障碍。冲动的选择既可以是光标的前置，也可以是 适应不良的行为。我们研究计划的首要目标是确定潜在的 通过干预来促进自我控制的冲动选择机制，并针对这些机制。时间歧视缺陷和延迟不耐受可预测稳定的个体差异 在大鼠临床前模型中的冲动选择。据称，时机不佳和不容忍拖延。 注意缺陷/多动障碍的内表型，提供了与啮齿动物临床前模型的重要联系。基于时间的干预成功地缓和了冲动的选择并改善了 啮齿动物的时间辨别能力。以时间为基础的干预在促进自我控制方面最为成功 在最冲动的人身上。最重要的是，涉及积极等待的干预措施 所需时间辨别是最有效的，这表明计时过程在 以时间为基础的干预。在前人研究成果的基础上，时间功能障碍模型(TDM)提出 冲动的选择产生于扭曲的计时过程，这可能导致不精确或不准确 时机到了。失灵的计时过程可能会导致冲动的选择。因此，TDM建议 计时过程是治疗干预的主要候选方法。此外，不同的 神经生物学机制可能对特定时间的不同贡献负责 冲动的选择的过程。目标1将演示特定计时过程的不同角色 促进自制力。这一目标将确定TDM，并明确基于时间的机制 干预对未来神经科学和翻译研究的冲动选择的影响。目标2将 评估干预措施对皮质-纹状体通路结构连通性的影响，这是最重要的 基于时间的干预对时间选择和冲动选择的影响。这一目标将使用 扩散张量成像(DTI)用于测量结构连通性。AIM 3将使用设计者受体 仅由特制药物(DREADD)激活，以抑制神经生物学通路中的活动， 很可能是基于时间的干预效应的候选者。这三个目标将确定具体的认知 以及基于时间的干预的神经机制。这项研究意义重大，因为迫切需要 有效的干预措施来缓和冲动的选择。作为一个跨疾病的过程，冲动的选择有 对人类健康具有广泛的相关性，并与NIMH任务具有重大相关性。

PROJECT SUMMARY Impulsive choices involve trade-offs between amount and delay by delivering smaller-sooner (SS) versus larger-later (LL) rewards. Impulsive choices occur when individuals frequently choose the SS when it is suboptimal to do so. Impulsive choices have been identified as a trans-disease process due to their association with a wide range of diseases and disorders including substance abuse, gambling, obesity, and attention-deficit/hyperactivity disorder. Impulsive choice can be both a pre-cursor to and product of maladaptive behaviors. The overarching goal of our research program is to identify the underlying mechanisms of impulsive choices and target those mechanisms using interventions to promote self-control. Time discrimination deficits and delay intolerance predicted stable individual differences in impulsive choice in the rat pre-clinical model. Poor timing and delay intolerance are purported endophenotypes in attention-deficit/hyperactivity disorder, providing important links with the rodent pre-clinical model. Time-based interventions have successfully moderated impulsive choices and improved time discrimination in rodents. Time-based interventions were most successful in promoting self-control in the most impulsive individuals. Most importantly, interventions that involved active waiting and that required time discrimination were most effective, suggesting a causal role for timing processes in the time-based interventions. Based on the previous results, the timing dysfunction model (TDM) proposes that impulsive choices arise from distorted timing processes, which may result in imprecise or inaccurate timing. Dysfunctional timing processes can lead to impulsive choices. Thus, the TDM proposes that timing processes are a primary candidate for therapeutic interventions. In addition, different neurobiological mechanisms may be responsible for the different contributions of specific timing processes to impulsive choices. Aim 1 will demonstrate distinct roles for specific timing processes in promoting self-control. This aim will confirm the TDM and pinpoint the mechanisms of time-based intervention effects on impulsive choices for future neuroscientific and translational research. Aim 2 will assess effects of the interventions on structural connectivity in cortico-striatal pathways, which are prime candidates for the time-based intervention effects on timing and impulsive choices. This aim will use diffusion tensor imaging (DTI) to measure structural connectivity. Aim 3 will use Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to depress activity in neurobiological pathways that are likely candidates for the time-based intervention effects. The three aims will identify specific cognitive and neural mechanisms of time-based interventions. This research is significant due the critical need for effective interventions to moderate impulsive choices. As a trans-disease process, impulsive choice has broad relevance for human health and is of significant relevance to the NIMH mission.