Investigations of the dynamic nature of intrinsic brain networks

描述(申请人提供)：大脑具有惊人的能力，能够根据不断变化的环境的需求灵活地使用不同的功能网络。有时，作用于内在基线环境的力是暂时的，例如日常生活中动态的认知需求。在其他时候，它们是较长期的，有时是永久性的，例如由于衰老、脑损伤或精神障碍而发生的变化。最近，使用功能磁共振成像(FMRI)来测量休息时大脑区域网络的内在功能连通性已经成为一个焦点。将来自数学领域的图论工具应用于这些固有的大脑网络允许对网络属性进行量化，例如大脑区域组将其自身分隔成基本上独立的网络(或模块)的程度，并识别各个大脑区域的角色，例如对于跨多个大脑区域和网络的通信而言，区域是否是完整的，或者区域是否将其交互限制为单个网络内的大脑区域的一小部分。这一建议旨在将这种对内在大脑网络的描述扩展到其他背景下，以评估大脑在不同背景下的可塑性潜力。因此，这项拟议的研究将在两个不同的背景下调查全球大脑组织的重新配置和单个大脑区域从内在网络配置中角色的变化：1)由于以下原因造成的功能中断 局灶性脑损伤，以及2)由于不同认知任务条件的管理而产生的特定认知需求。方法：本研究方案将应用最先进的方法和分析来解决具体目标。第一个实验将分析从脑局灶性病变患者和年龄匹配的健康对照组收集的数据，以评估脑损伤后网络重构的程度。我假设，如果网络中遭受脑损伤的完整组织的作用变得更类似于受损组织在健康的、内在的脑组织中所起的作用，那么自适应网络重新配置就会发生。我预测，与单纯关注解剖上接近受损组织的完整组织(即，病变周围组织)或未受损(即，对侧)半球同源区域的完整组织相比，网络内适应是表征脑组织代偿性变化的更准确的方式。第二个实验将考察健康年轻人的大脑在不同认知环境下的重新配置能力。我假设，自适应网络重新配置将通过将网络组织改变为单一的特定于上下文的网络来发生，该网络由认知上相关的区域和跨独立的内在网络的连接组成。关键的是，这种重新配置的适应性将通过将行为性能与任务性能的区域积分对于该特定背景网络内的通信的重要程度相关联来评估。 与公共健康相关：这项研究将进一步了解成人大脑由于其固有的基线环境的变化而产生的可塑性潜力，包括大脑损伤、衰老和动态变化环境的认知需求。有人提出，神经可塑性的一个潜在机制是单个大脑区域为了适应当前环境的需求而改变角色，这种可塑性导致适应性的重新配置(如通过网络组织在脑损伤后接近健康状态以及健康网络中认知表现期间重新配置与性能之间的关系进行评估)。至关重要的是，这种增加的知识可以导致对以适应性重构为目标的认知受损或脑损伤个人进行认知训练和康复治疗。

DESCRIPTION (provided by applicant): The brain has an amazing ability to flexibly engage different functional networks based on the demands of a constantly changing environment. Sometimes forces acting on an intrinsic, baseline environment are transient, such as the dynamic cognitive demands of daily life. At other times they are longer term, and occasionally permanent, such as the changes that occur due to aging, brain damage, or psychiatric disorders. Recently there has been a focus on measuring the intrinsic functional connectivity of networks of brain regions during rest using functional MRI (fMRI). The application of graph theoretical tools taken from the field of mathematics to these intrinsic brain networks allows for the quantification of network properties, such as the degree to which groups of brain regions separate themselves into largely independent networks (or modules), and the identification of the role of individual brain regions, such as whether a region is integral for communication across multiple brain regions and networks, or whether a region limits its interactions to a small subset of brain regions within a single network. This proposal aims to extend this characterization of intrinsic brain networks to other contexts to assess the brain's potential for plasticity in different contexts. The proposed research, therefore, will investigate both the reconfiguration of global brain organization and the changing roles of individual brain regions from intrinsic network configuration in two different contexts: 1) disruption of functioning due to focal brain lesions, and 2) specific cognitive demands due to administration of different conditions of a cognitive task. METHOD: This research proposal will apply state-of-the-art methodologies and analyses to address the specific aims. The first experiment will analyze data that was collected from patients with focal brain lesions and age-matched healthy controls to assess the extent of network reconfiguration after brain damage. I hypothesize that adaptive network reconfiguration will occur if the role of intact tissue within the network that sustained te brain damage changes to be more similar to the role that the damaged tissue had in healthy, intrinsic brain organization. I predict that within-network adaptation is a more accurate manner of characterizing compensatory changes in brain organization than is focusing purely on intact tissue anatomically close to the damaged tissue (i.e., perilesional tissue) or on intact tissue in homologous regions in the undamaged (i.e., contralesional) hemisphere. The second experiment will examine the brain's ability to reconfigure in different cognitive contexts in healty young adults. I hypothesize that adaptive network reconfiguration will occur by changing network organization toward a single context-specific network made up of cognitively relevant regions and connections across separate intrinsic networks. Critically, the adaptive nature of this reconfiguration will be assessed by relating behavioral performance to the degree to which regions integral for task performance are important for communication within that context-specific network. PUBLIC HEALTH RELEVANCE: This research will further knowledge of the adult brain's potential for plasticity due to changes to its intrinsic, baseline environment, including brain damage, aging, and the cognitive demands of a dynamically altering environment. It is proposed that a potential mechanism underlying neural plasticity is the changing role of individual brain regions to adapt to the demands of the current environment and that this plasticity results in reconfiguration that is adaptive (as assessed by network organization close to a healthy state after brain damage and a relationship between reconfiguration and performance in healthy networks during cognitive performance). Crucially, this increased knowledge can lead to treatments involving cognitive training and rehabilitation in cognitively impaired or brain-damaged individuals that target adaptive reconfiguration.