Translating from Rats to Humans: A Human Foraging Model of Decision-Making

 描述（由申请人提供）：成瘾的动物模型是精神病理学最受重视的模型之一。 因此，对人类的治疗通常是基于动物成瘾模型开发的。 然而，这些临床前模型和治疗结果之间仍然存在脱节。 一些研究人员认为，将临床前模型转化为临床模型的差距源于未经检验的假设，即不同物种在建模任务中招募相同的认知基质。 因此，有必要进行研究，以验证动物和人类的决策系统是可比的，这反过来又可以提高这些研究阶段的结果的普遍性。 有效的翻译范式需要测试跨物种认知过程的相似性（或差异）。 本提案介绍了一种新的经验觅食范式为人类，这是设计的基础上去/不去觅食范式大鼠（餐厅行）。 在餐馆行范例中，动物有固定的时间穿过圆形轨道，在不同的延迟时间之后从不同的“餐馆”收集食物奖励。“这种范式成功地捕捉到了偏好的个体差异，以及情绪结构的行为和神经特征（例如遗憾，失望）。 在提出的人类变体（称为网络冲浪任务）中，人类在视频画廊之间旅行时做出一系列去/不去的决定，这些视频画廊在可变延迟后呈现不同类型的视频剪辑。 人类变体的设计是为了模仿大鼠变体，同时也考虑到自然的人类行为学。 对人类受试者的初步分析表明，这两种范式捕获了相似的行为机制。 该项目的第一个目的是检验网络冲浪任务是否等同于测量情感结构，如后悔。 第一个目标也试图阐明是否在行为任务的表现映射到冲动性状的变化的个体差异。 该项目的第二个目的是确定网络冲浪任务是否捕获了大鼠中所见的审议和情绪处理的神经信号。 这将使用一般线性建模和机器学习方法来处理功能性神经成像数据。 这项任务对于缩小临床前研究和临床研究之间的差距至关重要，更重要的是，它可以促进人类成瘾治疗的发展。

 DESCRIPTION (provided by applicant): Animal models of addiction are some of the most highly regarded models of psychopathology. As a result, treatments for humans are often developed based on animal addiction models. However, there remains a disconnection between these pre-clinical models and treatment outcomes. Some researchers suggest that the gap in translating pre-clinical to clinical models stems from untested assumptions that different species recruit the same cognitive substrates on the modeled tasks. Therefore, there is a need for research than can verify that animal and human decision-making systems are comparable, which in turn, could improve the generalizability of results across these research stages. Effective translational paradigms are needed to test similarities (or differences) in cognitive processes across species. The present proposal introduces a novel experiential foraging paradigm for humans, which was designed based on a go/no-go foraging paradigm for rats (Restaurant Row). In the Restaurant Row paradigm, an animal has a fixed amount of time to traverse a circular track collecting food rewards after variable delay times from different "restaurants." This paradigm successfully captured individual differences in preference, as well as behavioral and neural signatures of emotional constructs (e.g. regret, disappointment). In the proposed human variant (called the Web-Surf task), humans make a series of go/no-go decisions as they travel between video galleries that present different types of video clips after variable delays. The human variant was designed to mimic the rat variant while also considering natural human ethology. Preliminary analyses in human subjects suggest the two paradigms capture similar behavioral mechanisms. The first aim of the proposed project is to examine whether the Web- Surf task equivalently measures emotional constructs, such as regret. The first aim also seeks to elucidate whether individual differences in behavioral task performance map onto variations in impulsive traits. The second aim of the proposed project is to determine whether the Web-Surf task captures neural signatures of deliberation and emotional processing as seen in rats. This will be accomplished using general linear modeling and machine learning approaches for processing functional neuroimaging data. This task could be pivotal in reducing the gap between pre-clinical and clinical research, and more importantly, advancing the development of addiction treatments for humans.