Memory Monitoring and Declarative Memory: Behavior and Brain

描述(申请人提供)：人类有意识地监控记忆内容的能力一直无法在动物模型中进行研究。可被监控的记忆通常被称为外显的或陈述性的。相比之下，内隐或无意识的记忆不能被主观监控，但在行为中仍然很明显。例如，可能不能口头报告键盘上字母的位置的人仍然可以在不看键的情况下准确而快速地打字。监控记忆的能力是元认知的一种形式，这种能力在自闭症、与年龄相关的认知衰退以及注意力和冲动控制障碍(如ADHD)中受到损害。中风、阿尔茨海默病、S病和其他大脑侮辱导致的记忆力丧失严重损害了包括学习、计划和适应性决策在内的高级认知过程。需要动物模型来识别参与记忆监测的特定大脑结构，以便我们能够开发出改善人类认知障碍的治疗方法。 在解决这些问题时，使用动物模型的主要挑战是，动物无法提供通常用于识别人类记忆监控的口头报告。为了克服这一障碍，我们将实施新的行为范式，在这种范式中，下降测试？选项允许受试者选择进行哪些记忆测试以及避免哪些测试。准确的记忆监控在操作上被定义为选择在记住项目时进行测试，而在没有记住项目时避免测试，从而提供了这一关键人类能力的模型。这项拟议的工作是首次将动物模型中的记忆监测范例与神经解剖学技术相结合，这些技术将确定接受监测的记忆的神经基础。由于受监视和未受监视的内存同时运行以产生自适应行为，因此拟议的研究旨在确定这些内存类型如何协同工作。被称为过程分离程序的方法被设计来量化多个记忆系统的同时行动，并将从人类认知文献中改编用于本项目。 我将使用这些新的行为技术来实现三个具体目标：1)在记忆测试中量化监控和非监控记忆对绩效的独立贡献，2)确定监控和非监控记忆在神经解剖学上是否是不同的，以及3)测试识别记忆绩效的双加工/双系统理论。这种动物模型系统的发展将推进认知的生理学、神经化学和遗传学方面的工作，并将有助于影响高级认知功能的疾病的治疗。 公共卫生相关性：这项研究与人类健康相关，因为它承诺在人类认知的一个重要动物模型中的记忆研究方面取得实质性进展。记忆监测针对的是中风、阿尔茨海默病和其他影响高级认知功能的大脑侮辱中最常受损的记忆类型。这一模型系统的开发将允许在生理学、神经化学和记忆遗传学方面的进一步工作，这将有助于治疗这些毁灭性的人类疾病。

DESCRIPTION (provided by applicant): The human ability to consciously monitor the contents of memory has not been accessible to study in animal models. Memories that are accessible to monitoring are often called explicit or declarative. In contrast implicit or unconscious memories cannot be subjectively monitored, but are still evident in behavior. For example, a person who may not be able to verbally report the locations of the letters on a keyboard may nonetheless type accurately and rapidly without looking at the keys. The ability to monitor memory is a form of metacognition, which is impaired in autism, age-related cognitive decline, and attention and impulse control disorders such as ADHD. Loss of memory from stroke, Alzheimer?s disease, and other brain insults severely impairs higher cognitive processes including learning, planning, and adaptive decision-making. Animal models are needed to identify the specific brain structures involved in memory monitoring so that we can develop improved treatments for cognitive impairment in humans. In addressing these problems, the main challenge in the use of animal models is that animals cannot provide the verbal reports often used to identify memory monitoring in humans. To overcome this obstacle, we will implement new behavioral paradigms in which a ?decline test? option allows subjects to select which memory tests to take and which to avoid. Accurate memory monitoring is operationally defined as choosing to take tests when the item is remembered and avoiding tests when it is not remembered, thus providing a model of this crucial human capacity. The proposed work is the first to combine memory monitoring paradigms in an animal model with neuroanatomical techniques that will identify the neural basis of memories that are subject to monitoring. Because monitored and unmonitored memory operate simultaneously to produce adaptive behavior, the proposed studies are designed to determine how these memory types work together. Methodology called Process Dissociation Procedure is designed to quantify the simultaneous action of multiple memory systems and will be adapted from the human cognitive literature for use in the present project. I will use these new behavioral techniques to achieve three specific aims: 1) quantify the independent contributions of monitored and unmonitored memories to performance in memory tests, 2) determine whether monitored and unmonitored memories are neuroanatomically distinct, and 3) test the dual process/dual system theory of recognition memory performance. Development of this animal model system will advance work on the physiology, neurochemistry, and genetics of cognition and will contribute to the treatment of diseases affecting higher cognitive function. PUBLIC HEALTH RELEVANCE: This research is relevant to human health because it promises substantial progress in the study of memory in an important animal model of human cognition. Memory monitoring targets the type of memory most often compromised in stroke, Alzheimer's disease, and other brain insults affecting higher cognitive function. Development of this model system will permit further work on the physiology, neurochemistry, and genetics of memory that will contribute to the treatment of these devastating human conditions.