Physiological Basis of Functional MRI

描述（由申请人提供）： 功能性磁共振成像（fMRI）通过提供一种灵敏的、非侵入性的脑活动绘图工具，彻底改变了对人脑工作状态的研究。该方法利用MR信号对脱氧血红蛋白含量的局部变化的敏感性，称为血氧水平依赖（BOLD）效应。然而，尽管功能性磁共振成像被广泛使用，但对该方法的生理学基础--神经活动与血流和能量代谢的耦合--仍然知之甚少。BOLD效应背后的中枢生理现象是脑血流量（CBF）的增加远远超过脑氧代谢率（CMRO 2），因此在大脑活动增加期间，局部毛细血管和静脉血的含氧量更多。我们已经开发了一个模型来解释这种现象（氧限制模型），其中需要CBF的大变化来支持CMRO 2的小变化。所提出的模型基于两个想法：1）CBF大量增加的功能是将线粒体pO 2维持在恒定水平，因此氧气可用性不会限制CMRO 2，以及2）随着神经活动增加而产生CBF变化的机制是一个前馈过程，该过程在不反馈当前氧气可用性的情况下运行。该模型做出了两个预测：1）CBF/CMRO 2耦合在整个大脑中相当均匀，以及2）CBF随激活deltaF的变化独立于基线CBF。我们将使用MRI技术在人体研究中测试该模型，以测量CBF和CMRO 2。为了测试CBF/CMRO 2耦合的均匀性，我们将选择性地刺激初级视觉皮层中的富含细胞色素氧化酶的斑点或斑点间区域，并将CBF/CMRO 2耦合曲线彼此进行比较，并与手指敲击实验中在体感皮层中测量的耦合曲线进行比较。我们将通过用CO2和咖啡因改变基线CBF来测试激活的deltaF是否恒定。最后，我们将开发一个集成的数学模型，神经血管耦合，链接的想法提出了这里与其他几个提出的CBF控制机制。

DESCRIPTION (provided by applicant): Functional magnetic resonance imaging (fMRI) has revolutionized the study of the working human brain by providing a sensitive, non-invasive tool for mapping brain activity. The method exploits the sensitivity of the MR signal to local changes in the deoxy-hemoglobin content, called the Blood Oxygenation Level Dependent (BOLD) effect. Yet despite the widespread use of fMRI, the physiological basis of the method--the coupling of neural activity to blood flow and energy metabolismnis still poorly understood. The central physiological phenomenon underlying the BOLD effect is that cerebral blood flow (CBF) increases much more than the cerebral metabolic rate of oxygen (CMRO2), so that local capillary and venous blood are more oxygenated during increased brain activity. We have developed a model to explain this phenomenon (the Oxygen Limitation Model) in which a large change in CBF is required to support a small change in CMRO2. The proposed model is based on two ideas: 1) the function served by a large CBF increase is to maintain mitochondrial pO2 at a constant level, so that oxygen availability does not limit CMRO2, and 2) the mechanism that produces a CBF change with increased neural activity is a feed-forward process that operates without feedback on the current availability of oxygen. The model makes two predictions: 1) the CBF/CMRO2 coupling is reasonably uniform across the brain, and 2) the CBF change with activation deltaF is independent of the baseline CBF. We will test the model in human studies using MRI techniques to measure both CBF and CMRO2. To test the uniformity of CBF/CMRO2 coupling, we will selectively stimulate either the cytochrome oxidase-rich blobs in primary visual cortex or the inter-blob regions, and compare the CBF/CMRO2 coupling curves with each other and with the coupling curve measured in the somatosensory cortex in a finger-tapping experiment. We will test whether deltaF with activation is constant by altering baseline CBF with CO2 and caffeine. Finally we will develop an integrated mathematical model for neurovascular coupling that links the ideas proposed here with several other proposed mechanisms of CBF control.