Mechanisms of Neuroplasticity in Functional Brain Networks

描述（由申请人提供）：大脑在快速变化的环境中灵活地参与不同功能网络的潜力对于促进各种各样的行为和损伤后的自适应重组都是至关重要的。这种网络可塑性可以通过功能网络中局部连接强度的变化和整个大脑的更全球化的网络结构来实现。最近的一系列研究使用功能性MRI（fMRI）评估了休息时大脑区域局部网络的内在功能连接。现在可以使用图论工具来量化这种复杂大脑组织的全局属性，其中大脑区域被定义为节点，区域之间的连接被定义为边缘。这个提议的广泛目标是应用局部的、网络特定的连接测量以及全局的、图论的方法来研究两种不同背景下的神经可塑性的能力：皮质功能的破坏（急性和慢性）和特定的认知任务需求。关于脑损伤对网络组织的影响的研究主要集中在局部的、网络特定的损伤效应上，通常发现对网络的一部分的损伤会影响连接但未受损的区域。全球大脑组织的局灶性损伤的后果主要是研究与模拟病变数据，它提出了大脑区域特别重要的跨网络的信息整合，是最关键的保持网络的完整性。在这里，我们将测试这一预测，通过使用静息状态fMRI数据收集的患者与局灶性脑病变和健康的参与者后，经颅磁刺激（TMS）。我们将检验这样一个假设，即大脑内在组织的扰动导致了局部和局部的 减少受影响的网络和大脑模块的全球重新配置。此外，我们假设在脑损伤后重新配置的网络中节点的作用是补偿性的。研究网络重构的另一种方法是比较休息时的大脑组织与认知任务期间的大脑组织。因此，我们也将测试的假设，类似的适应性重组后的损害，特定的任务需求将导致网络组织在全球和本地水平的快速变化。这一建议将进一步了解大脑组织及其在各种情况下的可塑性潜力，如脑损伤和日常生活的动态认知需求。此外，我们提出，网络方法，如本建议中所应用的方法，可以提供经验数据，以协调严格的本地化与分配主义的大脑功能的帐户。与NIH的使命相关，在拟议的研究中确定的脑可塑性的神经机制可以作为诊断生物标志物的开发目标，以及用于脑损伤患者的认知治疗干预，以康复流行的神经系统疾病，如中风和创伤性脑损伤。

DESCRIPTION (provided by applicant): The brain's potential to flexibly engage different functional networks in a rapidly changing environment is crucial both for facilitating a wide variety of behaviors and adaptively reorganizing following damage. This network plasticity can emerge through both changes in the local connectivity strengths within functional networks and the more global network structure of the whole brain. A recent surge of studies has assessed the intrinsic functional connectivity of local networks of brain regions during rest using functionl MRI (fMRI). Quantifying the global properties of this complex brain organization is now possible using graph theoretical tools, in which brain regions are defined as nodes and connections between regions are defined as edges. The broad goal of this proposal is to apply local, network-specific connectivity measurements as well as global, graph theoretical methods to examine the capacity for neuroplasticity under two different contexts: disruption of cortical function (acute and chronic) and specific cognitive task demands. Studies of the effect of brain damage on network organization have focused on the local, network specific effects of damage, generally finding that damage to one portion of a network effects connected but undamaged regions. The consequence of focal damage on global brain organization has primarily been examined with simulated lesion data and it is proposed that brain regions particularly important for integrating information across networks, are most critical to maintaining network integrity. Here we will test this prediction by using resting state fMRI data collected from patients with focal brain lesions and healthy participants following transcranial magnetic stimulation (TMS). We will test the hypothesis that perturbation of intrinsic brain organization results in both local decreases in the affected network and global reconfiguration of brain modules. Moreover, we hypothesize that the roles of nodes within networks that have reconfigured following brain damage is compensatory. Another approach for investigating network reconfiguration is to compare brain organization at rest to that during a cognitive task. Thus, we will also test the hypothesis that, similar to the adaptive reorganization after damage, specific task demands will result in rapid alteration of network organization at both the global and local level. This proposa will further knowledge about brain organization and its potential for plasticity in various context, such as brain damage and the dynamics cognitive demands of daily life. Moreover, we propose that network approaches such as those applied in this proposal can provide empirical data to reconcile strictly localizationalist vs. distributionist accounts of brain function. Relevant to th NIH mission, the neural mechanisms underlying brain plasticity identified in the proposed studies can serve as targets for the development of diagnostic biomarkers as well as cognitive therapy interventions for rehabilitation of patients with brain damage from prevalent neurological disorders such as stroke and traumatic brain injury.