Functional MRI of Aging: Biophysical Characterization

描述（由申请人提供）：近年来，许多使用功能性磁共振成像（fMRI）的研究表明，在执行许多不同的感觉运动和认知任务时，老年受试者（50 - 50岁）和年轻受试者（21-40岁）的激活模式存在实质性差异。已经得出结论，观察到的对比是由于老年受试者的神经元活动的差异。然而，早期关于正常衰老涉及广泛的神经元损失的假设已经被修正，因为越来越多的证据表明，在大脑的大多数区域，神经元的数量在成年和衰老期间是稳定的。除了对神经元功能的直接影响外，已知在老年人中导致脑血管反应性的因素也会发生改变，从而导致血液动力学反应的改变。由于fMRI观察到的信号可以通过血流动力学和神经元变化引起的氧合变化来调节，因此必须将这两个因素分开，以便更好地了解fMRI获得的激活模式中与年龄相关的变化。目前提出的项目旨在结合基础科学、工程和计算问题，具体阐明导致老年受试者与年轻受试者相比大脑激活改变的机制（神经元vs血管）。通过无创技术（fMRI）获得的结果将为测量许多相关生理因素并对其进行生物物理表征提供方法，从而了解人类大脑随年龄增长的功能。所开发的方法和技术也可用于两个或更多不同群体之间的研究。

DESCRIPTION (provided by applicant): In the recent years, a number of studies using functional MRI (fMRI) have shown substantial differences between the activation pattern of older subjects (> 50 years of age) and younger subjects (21-40 years) while performing a number of different sensorimotor and cognitive tasks. It has been concluded that the contrast observed is due to differences in neuronal activity in the older subjects. However, early hypothesis that normal aging involves widespread loss of neurons have been revised in light of accumulating evidence that in most regions of the brain, the number of neurons is stable throughout adulthood and senescence. In addition to direct effects on neuronal function, factors contributing to cerebrovascular reactivity is known to be altered in older people that could give rise to altered hemodynamic responses. Since the signal observed using fMRI could be modulated both by hemodynamics and oxygenation changes resulting from neuronal changes, these two factors must be separated to gain a better understanding about age related changes in the activation pattern obtained using fMRI. The present project proposed intends to combine basic science, engineering, and computational issues to specifically elucidate mechanisms (neuronal vs vascular) that results in older subjects having altered brain activation in comparison to young subjects. Results obtained from the noninvasive technique (fMRI) would provide ways to measure a number of relevant physiological factors and characterize them biophysically to understand human brain function with aging. Methods and techniques developed can also be used to study between two or more different groups. PUBLIC HEALTH RELEVANCE: The present project will help determine biophysical aspects of aging using non-invasive functional Magnetic Resonance Imaging (fMRI). As longitudinal studies are very important to follow individuals through different stages of their life span, fMRI techniques would become crucial in obtaining valuable biomarkers in studies of aging. FMRI presents many caveats in determining the actual physiological indicators that influence signal response in young and old subjects. This project is designed to address certain caveats by effectively testing and quantifying the neural and hemodynamic components that may modulate signal response in young and old subjects. This study will significantly gain information regarding the underlying nature and necessary corrections in fMRI signals. Such a correction is necessary to accurately determine the progression and determinants of change across all segments of the life span that affect cognitive effects and brain function.