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

描述(申请人提供)：神经认知老化理论是基于功能磁共振成像(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，大胆的年龄变化是由许多生理、神经和认知因素造成的，这些因素仍然知之甚少，并使对BOLD作为与年龄相关的神经变化的直接指标的解释复杂化。一旦与年龄相关的大胆变化背后的生理因素被分开并单独测量，就可以形成更精确的神经认知老化假说。三个这样的因素是脑血流量的变化(Δ脑血流量)，向活跃的神经元提供氧气的变化，脑氧代谢率的变化(ΔCMRO2)，代谢神经活动的估计，以及事件相关电位(事件相关电位)，突触后神经活动的估计。这些因素在衰老过程中的研究并不像我们在这里提出的那样广泛。使用双回波BOLD/ASL磁共振脉冲序列，我们最近已经证明，这些重要的生理因素可以在脑老化研究中与传统的BOLD信号同时进行测量。在这项建议中，我们计划进行一项更系统的研究，以评估年龄与任务诱发的血流、血氧、脑代谢生理反应之间的关系，以及任务需求对这些因素的影响。我们提出了一个与年龄相关的脑生理学变化的一般模型，该模型可以协调神经认知老化文献中的不同结果。我们从三个方面对该模型进行了测试。目标1和2是为了测量视觉和运动皮质BOLD、ERP、CMRO2和CBF对不同强度的感觉和运动任务的反应的年龄差异。在目标3中，我们将评估CBF-CMRO2解偶联在与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关于(1)年龄的基本机制-神经功能的变化，(2)引起大胆变化的与年龄相关的神经血管变化的新知识，以及(3)这些基本机制如何与成绩挂钩。

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.