Vascular Dynamics in Functional MRI

描述(申请人提供)：自十多年前引入以来，功能磁共振成像(FMRI)已迅速成为研究工作中人类大脑不可或缺的工具。绝大多数fMRI研究利用血氧水平依赖(BOLD)信号，该信号反映了血液动力学对神经活动的反应。在这些研究中，粗体信号的差异通常被解释为神经活动的差异。然而，越来越多的证据表明，药物、年龄和疾病等因素引起的基线血管状态的变化可以显著改变BOLD信号的幅度和形状。这些因素可能会增加不同受试者和实验条件下BOLD信号的可变性，并使fMRI实验的解释复杂化。这项应用的目标是确定基线血管状态的非侵入性测量是否可以解释由血管活性物质和衰老过程引起的BOLD信号的变异性。这一建议的中心假设得到了强有力的初步数据的支持，即对BOLD信号低频分量功率的归一化测量，称为0.1赫兹频谱指数，可用于探测基线血管状态，并可解释BOLD反应的很大一部分变异性。这项建议的目的是(1)评估0.1赫兹频谱指数和其他基线血管状态的指标对血管活性物质引起的BOLD反应的变异性的解释能力，以及(2)评估这些指标对BOLD反应中与年龄相关的变异性的解释能力。这些目标将通过(1)评估咖啡因和高碳酸血症对基线血管状态和大胆反应的影响的研究和(2)表征年轻(20至45岁)和老年(65至95岁)受试者的基线血管状态和大胆反应的研究来实现。与公共卫生的相关性：预计拟议的研究将提供必要的知识，以便将0.1赫兹频谱指数应用于改进功能磁共振研究的解释。例如，一旦0.1赫兹频谱指数的预测能力被证明，它就可以应用于评估各种药物治疗精神疾病的疗效的研究。通过使研究人员能够评估大胆反应中与药物相关的变化是否反映了神经活动的变化，还是主要反映了药物对血管的影响，0.1赫兹频谱指数将使研究人员能够更有效地确定哪些药物可能具有临床价值。

DESCRIPTION (provided by applicant): Since its introduction just over a decade ago, functional magnetic resonance imaging (fMRI) has rapidly become an indispensable tool for studies of the working human brain. The vast majority of fMRI studies utilize the blood oxygenation level dependent (BOLD) signal, which reflects the hemodynamic response to neural activity. In these studies, differences in the BOLD signal are typically interpreted as differences in neural activity. However, there is growing evidence that shifts in the baseline vascular state due to factors such as medication, age, and disease can significantly alter the amplitude and shape of the BOLD signal. These factors can increase the variability of the BOLD signal across subjects and experimental conditions and complicate the interpretation of fMRI experiments. The goal of this application is to determine whether non-invasive measures of the baseline vascular state can account for the variability in the BOLD signal that is caused by vasoactive agents and the aging process. The central hypothesis of this proposal, which is supported by strong preliminary data, is that a normalized measure of the power in low frequency components of the BOLD signal, referred to as the 0.1 Hz spectral index, can be used to probe the baseline vascular state and can account for a significant fraction of the variability in the BOLD response. The aims of this proposal are to (1) evaluate the ability of the 0.1 Hz spectral index and other measures of the baseline vascular state to account for the variability in the BOLD response caused by vasoactive agents, and (2) evaluate the ability of these measures to account for age-related variability in the BOLD response. These aims will be achieved using (1) studies that assess the impact of caffeine and hypercapnia on the baseline vascular state and the BOLD response and (2) studies that characterize the baseline vascular state and the BOLD response in young (20 to 45 years old) and old (65 to 95 years old) subjects. Relevance to Public Health The proposed studies are expected to provide the knowledge necessary for the application of the 0.1 Hz spectral index to the improved interpretation of fMRI studies. For example, once the predictive capability of the 0.1 Hz spectral index is demonstrated, it could be applied to studies evaluating the efficacy of various medications for mental illness. By enabling investigators to assess whether medication-related changes in the BOLD response reflect changes in neural activity or are primarily a reflection of the vascular effects of the medication, the 0.1 Hz spectral index would allow investigators to more effectively determine which medications are likely to be of clinical value.