Causal dynamics in neural networks underlying top-down modulation

描述（由申请人提供）：注意力（或自上而下）控制使我们能够专注于任务目标并屏蔽干扰。如果不能正确地使用这些自上而下的机制，就会导致内存性能下降，因为不相关的信息会使有限的内存容量过载。虽然注意力控制缺陷在所有健康成年人中周期性发生（例如，注意力分散、走神），但随着年龄的增长，它变得更加普遍，并且是精神疾病、神经退行性疾病和脑损伤患者的一个突出因素。不幸的是，目前尚不清楚自上而下的控制是如何在大脑中实施的，因此限制了治疗干预。值得注意的是，大脑通过招募额外的神经区域和重新连接神经网络来保持表现能力，从而对神经衰退具有天然的弹性。然而，人们对这些重组特性和大脑在功能障碍存在时保留自上而下控制信号的潜力知之甚少。该研究项目的基本科学目标是描述自上而下的信号在何时何地被传递，以及它们与注意力和记忆过程的关系。从翻译的角度来看，平行的目标是评估神经代偿机制在脑功能扰动后保持表现能力的潜力。为了实现这些目标，年轻人将参与两个涉及注意力和记忆过程的实验。第一次会议将使用功能性磁共振成像（fMRI）来识别参与任务的神经网络中假定的自上而下的控制区域。第二阶段将利用经颅磁刺激（TMS）来扰乱从第一阶段确定的自上而下控制区域内的神经功能。在TMS之后，当参与者从事与第一阶段相同的任务时，将通过fMRI或脑电图（EEG）获取神经数据。将评估皮层功能的时间和空间测量，重点是网络连接。将经颅磁刺激、假经颅磁刺激和经颅磁刺激与非任务相关区域进行比较，将从因果角度阐明这些控制区域的作用，有助于表征神经重组的潜力，并为理解注意和记忆之间的机制关系提供基础。除了推进这一重要领域的有限工作外，我们预计这种独特的“扰动和记录”方法方法和实验设计将对该领域产生重大影响。这些知识将用于指导有针对性的康复计划的发展，针对广泛的认知能力和易受注意力和记忆功能下降影响的临床人群。

DESCRIPTION (provided by applicant): Attentional (or top-down) control enables us to focus on task goals and block out interference. Failing to properly engage these top-down mechanisms results in decreased memory performance by overloading our limited memory capacity with irrelevant information. While deficient attentional control periodically occurs in al healthy adults (e.g., distraction, mind wandering), it becomes more prevalent with age and is a prominent factor in those with psychiatric disorders, neurodegenerative disease, and brain injury. Unfortunately, it is unclear exactly how top-down control is implemented in the brain, thereby limiting therapeutic interventions. Remarkably, the brain is naturally resilient to neural decline by recruiting additional neural regions and rewiring neural networks to retain performance abilities. However, little is known about these reorganizational properties and the brain's potential to retain top-down control signals in the presence of dysfunction. The basic science goals of the proposed research project are to characterize where and when top-down signals are communicated and how they pertain to attention and memory processes. From a translational perspective, parallel goals are to assess the potential for neural compensatory mechanisms to retain performance abilities following the perturbation of brain function. To accomplish these goals, young adults will participate in two- session experiments that engage attention and memory processes. The first session will implement functional magnetic resonance imaging (fMRI) to identify putative top-down control regions within the neural networks involved in the task. The second session will utilize transcranial magnetic stimulation (TMS) to perturb neural function within the top-down control regions that were identified from the first session. Following TMS, neural data will be acquired via fMRI or electroencephalography (EEG) while participants are engaged in the same task as the first session. Temporal and spatial measures of cortical function, with an emphasis on network connectivity, will be evaluated. Comparisons between TMS, sham TMS, and TMS to areas not involved in the task will elucidate the role of these control regions from a causal perspective, help characterize the potential for neural reorganization, and offer a basis to understand the mechanistic relationship between attention and memory. In addition to advancing the limited work in this important area, we anticipate that this unique "perturb and record" methodological approach and experimental design will have a major impact on the field. This knowledge will be used to guide the targeted development of rehabilitation programs directed at the broad range of cognitive abilities and clinical populations that are susceptible to decline in attention and memory function.