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

BOLD 及其不满：fMRI 信号神经生理学的年龄差异

• 批准号: 8979195
• 负责人: Hanzhang Lu
• 金额: $ 34.02万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8979195
• 关键词: Adult; Age; Aging; Base of the Brain; Bilateral; Blood; Blood Vessels; Blood flow; Brain; Brain region; Cerebrovascular Circulation; Cerebrum; Cognitive; Core-Binding Factor; Coupling; Dependence; Event-Related Potentials; Fingers; Frequencies; Functional Magnetic Resonance Imaging; Grant; Health; Imaging Techniques; Imaging technology; Individual; Knowledge; Literature; Longevity; Magnetic Resonance Imaging; Measures; Mediating; Mediator of activation protein; Memory; Metabolic; Metabolism; Methods; Modeling; Motor; Motor Cortex; Nature; Neurocognitive; Neurons; Neurophysiology - biologic function; Oxygen; Pattern; Perception; Performance; Physiologic pulse; Physiological; Physiology; Prefrontal Cortex; Psyche structure; Psychometrics; Role; Sensory; Short-Term Memory; Signal Transduction; Synapses; Testing; Thumb structure; Time; Variant; Visual Cortex; age difference; age group; age related; aging brain; base; blood oxygen level dependent; brain metabolism; cognitive function; cognitive task; indexing; insight; memory process; neurophysiology; processing speed; relating to nervous system; response; theories; vascular contributions; visual motor; young adult

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.

描述（由申请人提供）：神经认知老化理论基于功能性磁共振成像（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，并使BOLD作为与年龄相关的神经变化的直接指标的解释变得复杂。一旦年龄相关的BOLD变化的生理因素被解开并分别测量，就可以制定更精确的神经认知老化假说。三个这样的因素是脑血流量（ΔCBF）的变化，将O2传递到活跃的神经元，脑氧代谢率（Δ CMRO 2）的变化，代谢神经活动的估计值，以及事件相关电位（ERP），突触后神经活动的估计值。这些因素在衰老过程中还没有像我们在这里提出的那样得到广泛的研究。使用双回波BOLD/ASL MRI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测量，同时与传统的BOLD信号。在本研究中，我们计划进行一个更系统的研究，以评估年龄和任务诱发的血流，血氧，脑代谢的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变化的一般模型，可以调和神经认知老化文献中的不同结果。我们在三个目标中测试模型。目的1和2是测量年龄差异的视觉和运动皮层BOLD，ERP，CMRO 2，和CBF响应不同强度的感觉和运动任务的要求。在目标3中，我们将评估CBF-CMRO 2解偶联在年龄相关的工作记忆和处理速度变化中的作用。实现我们的资助目标将产生关于以下方面的新知识：（1）神经功能年龄变化的基本机制，（2）引起BOLD变化的与年龄相关的神经血管变化，以及（3）这些基本机制如何与表现联系在一起。