Investigating Cognitive and Neural Bases of Working Memory

描述(申请人提供)：工作记忆是指当环境中不存在信息时，有意识地保留信息，对其进行操纵，并将其用于指导行为。工作记忆被认为是语言理解、学习、计划、推理和一般流动智力等基本认知功能和特性的关键贡献者。此外，工作记忆表现的个体差异可以预测一系列显著的“真实世界”结果指标，从阅读能力到标准化测试成绩，再到社会经济地位和个性特征。因此，了解工作记忆功能的认知和神经基础对于理解正常认知及其神经和精神功能障碍至关重要。PI的研究项目调查了工作记忆功能的认知和神经基础。它是在一个框架内做到这一点的，该框架认为工作记忆是一种新出现的属性，它是通过注意力对大脑系统进行协调招募而产生的，这些系统已经进化成完成与感觉、表征或动作相关的功能。本申请更新PI的R01的具体目标建立在这项工作的基础上，通过阐明比2003年提出的假设更强的推论(由于在PI的方法论基础上增加了用于测量功能连通性和重复的经颅磁刺激(RTMS)的新的多变量方法)，并通过测试PI最近的工作中出现的机械假设来实现。它们是：具体目标1：检验工作记忆存储是由广泛分布的、功能上连接的PFC后方区域网络支持的假设。具体目标2：检验工作记忆储存部分是通过长时记忆(LTM)表征的暂时激活完成的假设。具体目标3：验证前额眼场(FEF)是支持工作记忆存储的注意激活的来源的假说。与公共健康相关的工作记忆损害可见于许多神经、精神和发育障碍。因此，更好地了解工作记忆功能的认知和神经生物学组织，可能对这些障碍患者的诊断、临床治疗和认知康复具有重要意义。

DESCRIPTION (provided by applicant): Working memory refers to the retention of information in conscious awareness when this information is not present in the environment, to its manipulation, and to its use in guiding behavior. Working memory has been implicated as a critical contributor to such essential cognitive functions and properties as language comprehension, learning, planning, reasoning, and general fluid intelligence. Additionally, individual differences in working memory performance predict a remarkable array of "real world" outcome measures, from reading ability to standardized test performance to socioeconomic status to personality traits. Thus, understanding the cognitive and neural bases of working memory functions is central to understanding normal cognition, as well as its neurological and psychiatric dysfunctions. The PI's research program investigates the cognitive and neural bases of working memory function. It does so within a framework that holds that working memory is an emergent property that arises from the coordinated recruitment, via attention, of brain systems that have evolved to accomplish sensory-, representation-, or action-related functions. The Specific Aims of the present application for renewal of the PI's R01 build on this work by articulating hypotheses than will support stronger inference than could those proposed in 2003 (due to the addition of novel multivariate methods for measuring functional connectivity and of repetitive transcranial magnetic stimulation (rTMS) to the PI's methodological armamentarium), and by testing mechanistic hypotheses that have arisen from the PI's recent work. They are: Specific Aim 1: To test the hypothesis that working memory storage is supported by broadly distributed, functionally connected networks of regions posterior to the PFC. Specific Aim 2: To test the hypothesis that working memory storage is accomplished, in part, via the temporary activation of long-term memory (LTM) representations. Specific Aim 3: To test the hypothesis that the frontal eye fields (FEF) are a source of the attentional activation that supports working memory storage. PUBLIC HEALTH RELEVANCE Impairments of working memory are seen in many neurological, psychiatric, and developmental disorders. Achieving a better understanding of the cognitive and neurobiological organization of working memory functions, therefore, may have important implications for the diagnosis, clinical treatment, and cognitive rehabilitation of patients with these disorders.