Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Department of Radiology, Mayo Clinic, Rochester, MN, United States.
Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; NYU Langone Eye Center, Department of Ophthalmology, NYU School of Medicine, NYU Langone Medical Center, New York University, New York, NY, United States; Department of Radiology, NYU School of Medicine, NYU Langone Medical Center, New York University, New York, NY, United States.
Neuroimage. 2018 Apr 1;169:352-362. doi: 10.1016/j.neuroimage.2017.12.070. Epub 2017 Dec 22.
Functional imaging of spontaneous activity continues to play an important role in the field of connectomics. The most common imaging signal used for these experiments is the blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal, but how this signal relates to spontaneous neuronal activity remains incompletely understood. Genetically encoded calcium indicators represent a promising tool to study this problem, as they can provide brain-wide measurements of neuronal activity compared to point measurements afforded by electrophysiological recordings. However, the relationship between the calcium signal and neurophysiological parameters at the mesoscopic scale requires further systematic characterization. Therefore, we collected simultaneous resting-state measurements of electrophysiology, along with calcium and hemodynamic imaging, in lightly anesthetized mice to investigate two aims. First, we examined the relationship between each imaging signal and the simultaneously recorded electrophysiological signal in a single brain region, finding that both signals are better correlated with multi-unit activity compared to local field potentials, with the calcium signal possessing greater signal-to-noise ratio and regional specificity. Second, we used the resting-state imaging data to model the relationship between the calcium and hemodynamic signals across the brain. We found that this relationship varied across brain regions in a way that is consistent across animals, with delays increasing by600 ms towards posterior cortical regions. Furthermore, while overall functional connectivity (FC) measured by the hemodynamic signal is significantly correlated with FC measured by calcium, the two estimates were found to be significantly different. We hypothesize that these differences arise at least in part from the observed regional variation in the hemodynamic response. In total, this work highlights some of the caveats needed in interpreting hemodynamic-based measurements of FC, as well as the need for improved modeling methods to reduce this potential source of bias.
自发性活动的功能成像在连接组学领域继续发挥着重要作用。这些实验中最常用的成像信号是血氧水平依赖（BOLD）功能磁共振成像（fMRI）信号，但该信号与自发性神经元活动的关系仍不完全清楚。遗传编码钙指示剂代表了研究这一问题的一种很有前途的工具，因为与电生理记录提供的点测量相比，它们可以提供大脑范围内的神经元活动测量。然而，钙信号与介观尺度上的神经生理参数之间的关系需要进一步系统地描述。因此，我们在轻度麻醉的小鼠中同时收集了静息状态下的电生理、钙和血液动力学成像测量数据，以研究两个目的。首先，我们检查了单个脑区的每个成像信号与同时记录的电生理信号之间的关系，发现两种信号与多单位活动的相关性都优于局部场电位，钙信号具有更高的信噪比和区域特异性。其次，我们使用静息状态成像数据来模拟大脑中钙和血液动力学信号之间的关系。我们发现，这种关系在不同脑区之间存在差异，在动物之间是一致的，向后皮质区域的延迟增加了 600 毫秒。此外，尽管通过血液动力学信号测量的整体功能连接（FC）与通过钙测量的 FC 显著相关，但发现这两个估计值存在显著差异。我们假设这些差异至少部分是由于观察到的血液动力学反应的区域变化引起的。总的来说，这项工作强调了在解释基于血液动力学的 FC 测量时需要注意的一些问题，以及需要改进建模方法来减少这种潜在的偏差源。
