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排除干扰。如果不能恰当地运用这些自上而下的机制，就会使我们有限的记忆容量因无关信息而超载，从而导致记忆性能下降。虽然注意力控制不足周期性地发生在所有健康的成年人中（例如，注意力分散，走神），它随着年龄的增长而变得更加普遍，并且是患有精神疾病，神经退行性疾病和脑损伤的人的突出因素。不幸的是，目前还不清楚自上而下的控制是如何在大脑中实施的，从而限制了治疗干预。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，从而自然地适应神经衰退。然而，人们对这些重组特性以及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。拟议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，以及它们如何与注意力和记忆过程相关。从翻译的角度来看，平行的目标是评估潜在的神经补偿机制，以保持性能的脑功能扰动后的能力。为了实现这些目标，年轻人将参加两个阶段的实验，参与注意力和记忆过程。第一次会议将实施功能性磁共振成像（fMRI），以确定参与任务的神经网络内假定的自上而下的控制区域。第二次会议将利用经颅磁刺激（TMS）来扰乱第一次会议确定的自上而下的控制区域内的神经功能。在TMS之后，当参与者从事与第一次会议相同的任务时，将通过fMRI或脑电图（EEG）获取神经数据。将评估皮质功能的时间和空间测量，重点是网络连接。TMS、假TMS和TMS与不参与任务的区域之间的比较将从因果关系的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，并为理解注意力和记忆之间的机械关系提供基础。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的康复计划的有针对性的发展。

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.