BOLD and its discontents: age-differences in the neurophysiology of fMRI signal

描述（由申请人提供）：神经认知衰老理论是基于使用功能磁共振成像（fMRI）测量的血氧水平依赖信号（BOLD）的年龄差异。然而，越来越多的人认识到，BOLD的年龄变化是由许多生理、神经和认知因素引起的，这些因素仍然知之甚少，并且使BOLD作为与年龄相关的神经变化的直接指标的解释复杂化。一旦与年龄相关的BOLD变化背后的生理因素被解开并单独测量，就可以制定更精确的神经认知衰老假设。三个这样的因素是脑血流量的变化（ΔCBF），将氧气输送到活跃的神经元，脑氧代谢率的变化（ΔCMRO2），代谢神经活动的估计和事件相关电位（ERP），突触后神经活动的估计。这些因素并没有像我们在这里提出的那样在衰老中得到广泛的研究。使用双回波BOLD/ASL MRI脉冲序列，我们最近证明了这些重要的生理因素可以在脑衰老研究中测量，同时使用传统的BOLD信号。在本课题中，我们计划进行更系统的研究，以评估年龄与血流、血氧、脑代谢等任务诱发生理反应的关系，以及任务需求对这些因素的影响。我们提出了一个关于脑生理学中与年龄相关的变化的一般模型，可以调和神经认知衰老文献中的不同结果。我们在三个目标中测试该模型。目的1和2是测量视觉和运动皮层BOLD、ERP、cmor2和CBF对不同强度的感觉和运动任务需求的反应的年龄差异。在目标3中，我们将评估cbf - cmr2解耦在年龄相关的工作记忆和加工速度变化中的作用。实现我们的资助目标将产生以下方面的新知识：(1)神经功能年龄变化的基本机制，(2)与年龄相关的神经血管变化导致BOLD变化，以及(3)这些基本机制如何与表现联系在一起。

DESCRIPTION (provided by applicant): Neurocognitive aging theories are based on age differences in blood-oxygen-level-dependent signal (BOLD) as measured with functional magnetic resonance imaging (fMRI). However, there is a growing recognition that BOLD age-changes result from many physiologic, neural, and cognitive factors that remain poorly understood and complicate interpretation of BOLD as a straightforward index of age-related neural change. More precise neurocognitive aging hypotheses can be formulated once the physiologic factors underlying age-related BOLD change are disentangled and measured separately. Three such factors are changes in cerebral blood flow (ΔCBF), that deliver O2 to active neurons, change of the cerebral oxygen metabolism rate (ΔCMRO2), an estimate of metabolic neural activity, and event-related potential (ERP), an estimate of post-synaptic neural activity. These factors have not been studied as extensively in aging as we propose to here. Using a dual-echo BOLD/ASL MRI pulse sequence, we have recently demonstrated that these important physiologic factors can be measured in brain aging studies, simultaneously with conventional BOLD signal. In this proposal, we plan to conduct a more systematic study to assess the relationship between age and task-evoked physiologic responses in blood flow, blood oxygenation, brain metabolism, as well as the influence of task-demand on these factors. We propose a general model on age-related changes in brain physiology that can reconcile diverse results in neurocognitive aging literature. We test the model in three Aims. Aims 1 and 2 are to measure age differences in visual and motor cortex BOLD, ERP, CMRO2, and CBF response to sensory and motor task-demands of varying strength. In Aim 3 we will assess the role of CBF-CMRO2 uncoupling in age- related working memory and processing speed changes. Achieving our grant aims will yield new knowledge about (1) basic mechanisms of age-changes in neural function, (2) age-related neural-vascular changes that give rise to BOLD changes, and (3) how these basic mechanisms are tied to performance.