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

认知能力因人而异。这些差异存在于不同健康状况的个体中，但也存在于看似同质的群体中，如健康的年轻人。认知中的个体差异通常根据不同的处理领域（例如，长期记忆、执行功能、语言、感知）。这些区别被认为是人类大脑中可分离系统或网络功能专业化的结果。该项目研究是否可以通过直接操纵相应的大脑系统来修改特定的认知能力。该研究涉及“网络引导”非侵入性脑刺激的开发和应用，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。研究结果将为我们了解认知个体差异的生物学来源提供信息，并可能提供一种改善个体认知能力的方法。 在这样做的过程中，该项目将帮助我们进一步了解在整个生命周期中介导受损个体认知功能障碍的大脑机制，并可能允许将研究计划应用于使用脑刺激延迟甚至预防脆弱个体的认知功能障碍。 该项目包括指导一名博士后研究员，分享与该项目有关的工具和方法，并与公众参与外联和教育活动。以前的工作使用脑刺激来修改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情况各不相同，但令人鼓舞。虽然已经注意到与刺激相关的认知能力的提高，但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，因此在我们对变化的潜在机制的理解中留下了空白。这项研究旨在阐明非侵入性刺激人脑是否以及如何增强特定的认知领域（执行功能和长期情景记忆）。经颅磁刺激（TMS）会话将针对两个功能性大脑系统内的关键区域（网络节点），这些系统涉及每个认知领域（分别为额顶叶控制系统和默认系统）。为了表征认知和大脑的变化，该研究将采用功能性磁共振成像（fMRI）对大脑网络组织进行广泛的认知测试和测量，这些测试和测量在多次TMS治疗之前和之后收集。为了实现拟议的目标，该项目汇集了PI帮助开拓的方法学进步。这些方法允许在逐个受试者的基础上精确表征脑刺激目标，以及用于表征和评估在个体中休息时观察到的脑网络组织变化的正式方法。通过针对大脑组织的特定特征并测量它们因刺激而发生的变化，拟议工作的更广泛目标是更深入地了解大脑刺激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.