Neural dynamics of human working memory networks

项目摘要/摘要 有意而灵活的行为，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水平的目标一致的知觉、助记和反应表征。神经科学中最具挑战性的问题之一是确定大脑中数十亿个神经元的分布活动如何产生自愿的、目标导向的行为。要解决这个问题，我们必须了解工作记忆(WM)的认知和神经机制，这是目标导向行为背后的一种基本能力。然而，WM的研究只从神经动力学的革命中获得了极小的好处，而这场革命在其他领域已经经历过。WM神经动力学的发现尤其重要，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功能和WM的神经机制仍然是神经科学研究的基本目标。LPFC是灵长类动物中最复杂的新皮质区域。为了实现这一目标，在本方案中，将在执行WM任务的过程中，在被试身上实施三种不同的方法-ECoG、fMRI和TMS。这将提供一种融合的方法来测试关于WM的时空基础的假设，并将能够确定电生理和神经成像发现的因果关系。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信号的神经驱动因素的联系。WM和额叶功能的基本知识可以为大量影响PFC功能的精神和神经疾病的性质提供实质性的见解，如精神分裂症、痴呆症、中风和创伤性脑损伤，以及许多其他疾病，如注意力缺陷障碍、物质成瘾和正常衰老，这些被认为涉及额叶大脑系统的选择性功能障碍。此外，PFC损伤造成的认知和行为障碍尤其难以治疗。对额叶功能的更多了解对于开发有效的治疗干预措施是必要的。

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.