Multimodal imaging of brain activity to investigate walking and mobility decline in older adults

大脑活动的多模态成像，以调查老年人的行走和行动能力下降

TODD MANINI (2018-09-30 to 2023-05-31) $4,820,481

Project ID: U01AG061389 (NIA)

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Abstract

Project Description: Mobility impairments in older adults decrease quality of life and are associated with high societal and economic burden. NIH RFA-AG-18-019 solicits applications ??to investigate the central neural control of mobility in older adults?using innovative and cutting-edge methods.? Current approaches to study the neural control of walking are limited by either the inability to measure people during walking (functional magnetic resonance imaging, fMRI) or the inability to measure activity below the cortex (functional near- infrared spectroscopy, fNIRS). We assert that a full and accurate understanding of the neural control of walking in older adults requires real time measurement of active regions throughout the brain during actual walking. We will achieve this by using innovative mobile brain imaging with high-density electroencephalography (EEG). This approach relies upon innovative hardware and software to deliver three-dimensional localization of active cortical and subcortical brain regions with high spatial and temporal resolution during walking. The result is unprecedented insight into the neural control of walking. Here, our overarching objective is to determine the central neural control of mobility in older adults by collecting EEG during walking and correlating these findings with a comprehensive set of diverse mobility outcomes (clinic-based walking, complex walking and community mobility measures). Our first aim is to evaluate the extent to which brain activity during actual walking explains mobility decline. In both cross sectional and longitudinal designs, we will determine whether poorer walking performance and steeper trajectories of decline are associated with the Compensation Related Utilization of Neural Circuits Hypothesis (CRUNCH). CRUNCH is a well-supported model of brain activity patterns that are seen when older individuals perform tasks of increasing complexity. CRUNCH describes the over-recruitment of frontoparietal brain networks that older adults exhibit in comparison to young adults, even at low levels of task complexity. CRUNCH also describes the limited reserve resources available in the older brain. These factors cause older adults to quickly reach a ceiling in brain resources when performing tasks of increasing complexity. When the ceiling is reached, performance suffers. The RFA also calls for proposals to ?Operationalize and harmonize imaging protocols and techniques for quantifying dynamic gait and motor functions?. In accordance with this call, our second aim is to characterize and harmonize high-density EEG during walking with fNIRS (during actual and imaged walking) and fMRI (during imagined walking). This will allow us to identify the most robust CRUNCH-related hallmarks of brain activity across neuroimaging modalities, which will strengthen our conclusions and allow for widespread application of our findings. Our third aim is to study the mechanisms related to CRUNCH during walking. Thus, our project will address a majority of the objectives in NIH RFA-AG-18-019 and will identify the neural correlates of walking in older adults, leading to unprecedented insight into mobility declines and dysfunction.

项目描述：老年人的行动障碍降低了生活质量，并伴随着高社会和经济负担。 NIH RFA-AG-18-019使用创新和尖端的方法征求应用程序来研究老年人的中枢神经控制。目前研究步行神经控制的方法受限于在行走期间无法测量人（功能磁共振成像，fMRI）或无法测量皮质下的活动（功能性近红外光谱，fNIRS）。我们断言，对老年人行走的神经控制的全面而准确的理解需要在实际行走期间对整个大脑中的活动区域进行实时测量。我们将通过使用具有高密度脑电图（EEG）的创新移动脑成像来实现这一目标。该方法依赖于创新的硬件和软件来在行走期间提供具有高空间和时间分辨率的活动皮质和皮层下脑区域的三维定位。结果是对行走神经控制的前所未有的洞察力。在这里，我们的首要目标是通过在行走期间收集脑电图并将这些发现与一系列不同的移动结果（基于诊所的步行，复杂步行和社区流动性测量）相关联来确定老年人的移动性的中枢神经控制。我们的第一个目标是评估实际行走期间大脑活动对移动性下降的影响程度。在横断面和纵向设计中，我们将确定较差的行走性能和较陡的下降轨迹是否与神经回路假设的补偿相关利用（CRUNCH）相关联。 CRUNCH是一种受到良好支持的大脑活动模式模型，当老年人执行日益复杂的任务时可以看到这种模式。 CRUNCH描述了老年人与年轻人相比，即使在低水平的任务复杂性下也会表现出过度招募的额顶脑网络。 CRUNCH还描述了老脑中可用的有限储备资源。这些因素导致老年人在执行日益复杂的任务时迅速达到大脑资源的上限。达到上限后，性能会受到影响。 RFA还要求提出建议：操作和协调成像协议和技术，以量化动态步态和运动功能？根据这一要求，我们的第二个目标是在使用fNIRS（在实际和成像行走期间）和fMRI（在想象的行走期间）行走期间表征和协调高密度脑电图。这将使我们能够识别出与神经成像模式相关的最强大的与CRUNCH相关的大脑活动标志，这将加强我们的结论，并允许广泛应用我们的研究结果。我们的第三个目标是研究行走过程中与CRUNCH相关的机制。因此，我们的项目将解决NIH RFA-AG-18-019中的大部分目标，并将确定老年人行走的神经相关性，从而对流动性下降和功能障碍有前所未有的洞察力。