EAGER: Modifying human cognition using targeted non-invasive stimulation of large-scale brain networks

认知能力因人而异。这些差异存在于健康状况不同的个人中，但也存在于看似相同的队列中，如健康的年轻人。认知上的个体差异通常是根据不同的加工领域(例如，长期记忆、执行功能、语言、知觉)来区分的。这些差异被认为是人脑中可分离系统或网络的功能专门化的结果。这个项目调查特定的认知能力是否可以通过直接操纵其相应的大脑系统来改变。这项研究涉及开发和应用“网络引导”的非侵入性脑刺激，以增强健康年轻人的特定认知能力，特别是执行功能和长期情景记忆。这项研究的结果将有助于我们理解个体认知差异的生物学根源，并可能为调整个体的认知能力提供一种途径。通过这样做，该项目将帮助我们进一步了解在整个生命周期中调节受损个体认知功能障碍的大脑机制，并可能允许应用该研究计划来延迟甚至预防脆弱个体的认知功能障碍，使用脑刺激。该项目包括指导一名博士后研究员，分享与该项目相关的工具和方法，以及参与与公众的外联和教育活动。以前的工作是使用大脑刺激来改变大脑中许多目标位置的认知的各个方面。这些研究的结果和成功是多变的，但令人鼓舞。在已经注意到与刺激相关的认知能力提高的地方，很少有证据将行为变化与潜在的神经生理学变化联系起来，从而在我们对变化的潜在机制的理解上留下了空白。这项拟议的研究旨在阐明对人脑的非侵入性刺激是否以及如何增强特定领域的认知(执行功能和长期情景记忆)。经颅磁刺激(TMS)将针对涉及每个认知领域的两个功能大脑系统(分别为额顶控制系统和默认系统)中的关键区域(网络节点)。为了表征认知和大脑的变化，这项研究将包括广泛的认知测试，并使用功能磁共振成像(FMRI)对大脑网络组织进行测量，这些测试是在多次TMS会话之前和之后收集的。为了实现提议的目标，该项目汇集了PI帮助开创的方法进步。这些方法允许在逐个受试者的基础上精确地表征大脑刺激目标，以及用于表征和评估在个体中观察到的大脑网络组织的变化的正式方法。通过瞄准大脑组织的特定特征并测量它们在刺激后的变化，拟议工作的更广泛目标是更深入地了解大脑刺激可能如何改变认知和大脑的功能网络组织。

Cognitive abilities differ across individuals. These differences are present across individuals with different status of health, but also within seemingly homogenous cohorts such as healthy young adults. Individual differences in cognition are typically differentiated according to distinct domains of processing (e.g., long-term memory, executive function, language, perception). These distinctions are thought to be a result of the functional specialization of dissociable systems, or networks, in the human brain. This project investigates whether a specific cognitive ability can be modified by directly manipulating its corresponding brain system. The study involves the development and application of "network-guided" non-invasive brain-stimulation to enhance specific cognitive abilities in healthy young adults; specifically, executive function and long-term episodic memory. The results of the research will inform our understanding of the biological source of individual differences in cognition and possibly provide an approach for modifying cognitive ability within an individual. In doing so the project will help us further understand the brain mechanisms that mediate cognitive dysfunction in impaired individuals across the lifespan, and may allow application of the research program towards delaying or even preventing cognitive dysfunction in vulnerable individuals, using brain stimulation. The project includes mentorship to a post-doctoral fellow, sharing of tools and methods that are developed in relation to the project, and engagement in outreach and education activities with the general public.Previous work has used brain stimulation to modify various aspects of cognition across numerous target locations in the brain. The outcome and success of these studies have been variable but encouraging. Where stimulation-associated gains in cognitive ability have been noted, there has been sparse evidence linking the behavioral change to changes in the underlying neurophysiology, thus leaving a gap in our understanding of the underlying mechanism of change. The proposed research aims to elucidate whether and how non-invasive stimulation of the human brain can enhance specific domains of cognition (executive function and long-term episodic memory). Transcranial magnetic stimulation (TMS) sessions will target critical areas (network nodes) within two functional brain systems that have been implicated in each cognitive domain (frontal-parietal control system and default system, respectively). To characterize cognitive and brain changes, the study will incorporate extensive cognitive testing and measurement of brain network organization using functional magnetic resonance imaging (fMRI), collected both prior to and following the multiple TMS sessions. To accomplish the proposed aims, the project brings together methodological advances that the PI has helped pioneer. These methods allow precise characterization of brain stimulation targets on a subject-by-subject basis, and formal methods for characterizing and assessing changes in brain network organization observed at rest in an individual. By targeting specific features of brain organization and measuring their change as a result of stimulation, the broader goal of the proposed work is to gain a deeper understanding of how brain stimulation may modify cognition and the brain's functional network organization.