Modeling the impact of neurovascular coupling impairments on BOLD-based functional connectivity at rest
Modeling the impact of neurovascular coupling impairments on BOLD-based functional connectivity at rest
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DOI：
10.1016/j.neuroimage.2020.116871
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发表时间：
2020-09-01
期刊：
影响因子：
5.7
通讯作者：
Preibisch, Christine
中科院分区：
文献类型：
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作者：
Archila-Melendez, Mario E.;Sorg, Christian;Preibisch, Christine
血氧水平依赖（BOLD）信号在静息状态下的功能磁共振成像（fMRI）被广泛用于研究患有和不患有脑疾病的人的缓慢波动持续脑活动（BOLD-FC）的功能连接（FC）。虽然生理损伤，例如异常灌注或血管反应性，在神经和精神疾病中很常见，但其对BOLD-FC的影响广泛未知并被忽视。因此，我们的模拟研究的目的是研究受损的神经血管耦合对静息态BOLD-FC的影响。模拟的BOLD信号包括血管内和血管外的贡献，来自调整后的气球模型，该模型允许脑血流量（CBF）和脑氧代谢率（CMRO 2）反应的独立定义，由具有低频（0.05Hz）幅度调制的合成振荡输入信号引起。然后通过生理参考BOLD时间曲线（基于种子的BOLD-FC的种子）和测试BOLD时间曲线（BOLD-FC的目标）之间的相关性来定义BOLD-FC，所述测试BOLD时间曲线以改变的生理变量（CMRO 2、CBF、脑血容量（CBV））为特征。在三种不同的情况下研究了受损的神经血管耦合对BOLD-FC的影响，其中（1）CBF和CMRO 2振幅，（2）CBF和CMRO 2延迟，以及（3）CBF和CBV之间的耦合独立变化。对于场景1，我们发现CMRO 2和CBF振幅对BOLD-FC的“线性”影响：对于给定的CMRO 2幅度，BOLD-FC随着CBF幅度的增加而从负FC变为正FC，并且增加CMRO 2幅度只是线性地移动这种依赖性。对于场景2，CMRO 2和CBF延迟对BOLD-FC有复杂的“非线性”影响：对于小CMRO 2延迟，我们发现BOLD-FC随着CBF延迟的增加从正BOLD-FC变为负BOLD-FC，但是对于大CMRO 2延迟，正BOLD-FC仅仅随着CBF延迟的增加而减小。对于场景3，CBF-CBV耦合的变化对BOLD-FC几乎没有影响。所有这些变化并没有受到信噪比和时间分辨率modulations.Our研究结果的重要性，在异常静息态BOLD-FC的神经血管耦合的改变。根据我们的数据，我们建议补充BOLD-FC研究，至少在高危患者人群中，灌注和氧合敏感的MRI。在无法获得这些结果的情况下，我们建议仔细解释BOLD-FC结果，并考虑先前有关血流动力学-代谢变化的发现。在未来，准确建模的血流动力学-代谢的背景下，可能会提高我们的理解血管-血流动力学-神经元成分的内在BOLD-FC和异常BOLD-FC的脑血管血流动力学损伤的疾病的评估之间的关键相互作用。
Functional magnetic resonance imaging (fMRI) of blood oxygenation level dependent (BOLD) signals during the resting-state is widely used to study functional connectivity (FC) of slowly fluctuating ongoing brain activity (BOLD-FC) in humans with and without brain diseases. While physiological impairments, e.g. aberrant perfusion or vascular reactivity, are common in neurological and psychiatric disorders, their impact on BOLD-FC is widely unknown and ignored. The aim of our simulation study, therefore, was to investigate the influence of impaired neurovascular coupling on resting-state BOLD-FC.Simulated BOLD signals comprising intra- and extravascular contributions were derived from an adjusted balloon model, which allows for independent definitions of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) responses, being elicited by a synthetic oscillatory input signal with low frequency (0.05 Hz) amplitude modulations. BOLD-FC was then defined by correlations between physiological reference BOLD time curves (seeds of seed-based BOLD-FC) and the test BOLD time curves (targets of BOLD-FC) featuring altered physiological variables (CMRO2, CBF, cerebral blood volume (CBV)). Impact of impaired neurovascular coupling on BOLD-FC was investigated for three different scenarios with independent changes in (1) CBF and CMRO2 amplitudes, (2) CBF and CMRO2 delays, and (3) coupling between CBF and CBV.For scenario 1, we found `linear' influences of CMRO2 and CBF amplitudes on BOLD-FC: for a given CMRO2 amplitude, BOLD-FC changes from negative to positive FC with increasing CBF amplitude, and increasing CMRO2 amplitude simply shifts this dependence linearly. For scenario 2, CMRO2 and CBF delays had a complex 'non-linear' effect on BOLD-FC: for small CMRO2 delays, we found that BOLD-FC changes from positive to negative BOLD-FC with increasing CBF delays, but for large CMRO2 delays positive BOLD-FC simply diminishes with increasing CBF delay. For scenario 3, changes in CBF-CBV coupling have almost no effect on BOLD-FC. All these changes were not critically influenced by both signal-to-noise-ratio and temporal resolution modulations.Our results demonstrate the importance of alterations in neurovascular coupling for aberrant resting-state BOLD-FC. Based on our data, we suggest to complement BOLD-FC studies, at least of at-risk patient populations, with perfusion and oxygenation sensitive MRI. In cases where this is not available, we recommend careful interpretation of BOLD-FC results considering previous findings about hemodynamic-metabolic changes. In the future, accurate modeling of the hemodynamic-metabolic context might improve both our understanding of the crucial interplay between vascular-hemodynamic-neuronal components of intrinsic BOLD-FC and the evaluation of aberrant BOLD-FC in brain diseases with vascular-hemodynamic impairments.