Zhang Nanyin, Zhu Xiao-Hong, Chen Wei
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
Neuroimage. 2008 Nov 1;43(2):204-12. doi: 10.1016/j.neuroimage.2008.06.033. Epub 2008 Jul 8.
Several studies have demonstrated significant nonlinearity in the blood-oxygenation-level-dependent (BOLD) signal. Completely understanding the nature of this nonlinear behavior is important in the interpretation of the BOLD signal. However, this task is hindered by the uncertainty of the source of BOLD nonlinearity which could come from neuronal and/or vascular origin. The obscurity of this issue not only impedes accurate modeling of BOLD nonlinearity, but also limits generalization of the conclusions regarding BOLD nonlinearity. To examine this issue, we eliminated nonlinear contributions from the neuronal response and selectively study BOLD nonlinearity under only the vascular effect by employing a paired-stimulus paradigm composed of two ultra-short visual stimuli separated by a variable inter-stimulus interval (ISI). ISIs chosen were long enough (> or = 1s) to ensure invariant neuronal activity to all stimuli. Under this circumstance, we still observed significant nonlinearity in the BOLD signal reflected by a progressive recovery of BOLD response to the second stimuli as ISI gets longer and delayed BOLD onset latency. These nonlinear behaviors identified in the BOLD signal originate entirely from the vascular responses as the neuronal responses to all stimuli are identical. More importantly, we found that BOLD nonlinearity became much less significant after we removed activated pixels from large vessels. These finds reveal that the dominant component, if not all, of the source of BOLD nonlinearity comes from large-vessel hemodynamic response. They also suggest a possible mechanism to improve the spatial specificity of gradient-echo BOLD signal for fMRI mapping based on the characteristics of vascular refractoriness.
多项研究已证明血氧水平依赖（BOLD）信号存在显著的非线性。全面理解这种非线性行为的本质对于解释BOLD信号至关重要。然而，这项任务受到BOLD非线性来源不确定性的阻碍，其可能源于神经元和/或血管。这个问题的模糊性不仅阻碍了对BOLD非线性的精确建模，也限制了关于BOLD非线性结论的推广。为了研究这个问题，我们消除了神经元反应的非线性贡献，并通过采用由两个超短视觉刺激组成的配对刺激范式，以可变的刺激间隔（ISI）分开，选择性地研究仅在血管效应下的BOLD非线性。选择的ISI足够长（≥1秒），以确保对所有刺激的神经元活动不变。在这种情况下，我们仍然观察到BOLD信号中存在显著的非线性，表现为随着ISI变长，对第二个刺激的BOLD反应逐渐恢复，以及BOLD起始潜伏期延迟。在BOLD信号中识别出的这些非线性行为完全源于血管反应，因为对所有刺激的神经元反应是相同的。更重要的是，我们发现从大血管中去除激活像素后，BOLD非线性变得不那么显著了。这些发现表明，BOLD非线性来源的主要成分（如果不是全部的话）来自大血管血流动力学反应。它们还基于血管不应性的特征，提出了一种可能的机制来提高用于功能磁共振成像（fMRI）映射的梯度回波BOLD信号的空间特异性。
