Neural dynamics of human working memory networks

项目总结/摘要 有意和灵活的行为，通常被称为“认知控制”，需要保持和选择与更广泛的背景和更高层次的目标相一致的感知，记忆和反应表征。神经科学中最具挑战性的问题之一是确定自愿的，目标导向的行为是如何从大脑中数十亿神经元的分布活动中产生的。为了解决这个问题，人们必须了解工作记忆（WM）的认知和神经机制，这是目标导向行为的基本能力。然而，工作记忆的研究只从其他领域经历的神经动力学革命中获益甚微。WM神经动力学的发现是特别重要的，因为WM需要多个大脑系统的相互作用，特别是外侧PFC（LPFC）和后处理系统。因此，确定LPFC功能的神经机制，灵长类动物中最复杂的新皮层区域，以及WM，仍然是神经科学研究的基本目标。为了实现这一目标，本研究将在人类受试者执行WM任务时采用三种不同的方法- ECoG，fMRI和TMS。这将提供一个收敛的方法，测试关于WM的时空基础的假设，并将能够确定电生理和神经影像学结果的因果关系。虽然不是该提案的主要焦点，但ECoG数据也将提供与猴子神经生理学和fMRI BOLD信号的神经驱动器的联系。关于WM和额叶功能的基本知识可以提供大量影响PFC功能的精神和神经系统疾病的本质的实质性见解，如精神分裂症，痴呆症，中风和创伤性脑损伤;以及许多其他条件，如注意力缺陷障碍，物质成瘾和正常衰老，提出涉及额叶脑系统的选择性功能障碍。此外，认知和行为缺陷PFC损伤是特别具有挑战性的治疗。更好地了解额叶功能是必要的，以制定有效的治疗干预措施。

PROJECT SUMMARY/ABSTRACT Intentional and flexible behavior, often called “cognitive control”, requires the maintenance and selection of perceptual, mnemonic, and response representations consistent with the broader context and higher-level goals. One of the most challenging problems in neuroscience is determining how voluntary, goal-directed behavior arises from the distributed activity of billions of neurons in the brain. To tackle this problem, one must understand the cognitive and neural mechanisms of working memory (WM), a fundamental ability underlying goal-directed behavior. The study of WM, however, has only minimally benefited from the revolution in neural dynamics that has been experienced in other fields. Discovery of WM neural dynamics is particularly important given that WM requires the interaction of multiple brain systems, notably the lateral PFC (lPFC) and posterior processing systems. Thus, a determination of the neural mechanisms underlying lPFC function, the most elaborated neocortical region in primates, and WM, remains a fundamental goal of neuroscience research. To achieve this goal, three different methods will be implemented in human subjects in this proposal during the performance of WM task – ECoG, fMRI and TMS. This will provide a convergent approach that tests hypotheses regarding the spatio-temporal basis of WM and will be able to determine the causality of the electrophysiological and neuroimaging findings. Although not the prime focus of the proposal, the ECoG data will also provide a link to monkey neurophysiology and the neural drivers of the fMRI BOLD signal. Basic knowledge about WM and frontal lobe function can provide substantial insights into the nature of a large number of psychiatric and neurological disorders affecting PFC function such as schizophrenia, dementia, stroke and traumatic brain injury; as well as many other conditions such as attention-deficit disorder, substance addiction and normal aging, that are proposed to involve selective dysfunction of frontal brain systems. Moreover, cognitive and behavioral deficits from PFC damage are particularly challenging to treat. A greater understanding of frontal lobe function is necessary for developing effective therapeutic interventions.