Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA.
Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
Neuroimage Clin. 2020;28:102443. doi: 10.1016/j.nicl.2020.102443. Epub 2020 Sep 20.
Previous studies examining the resting-state functional connectivity of the periaqueductal gray (PAG) in chronic visceral pain have localized PAG coordinates derived from BOLD responses to provoked acute pain. These coordinates appear to be several millimeters anterior of the anatomical location of the PAG. Therefore, we aimed to determine whether measures of PAG functional connectivity are sensitive to the localization technique, and if the localization approach has an impact on detecting disease-related differences in chronic visceral pain patients. We examined structural and resting-state functional MRI (rs-fMRI) images from 209 participants in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. We applied three different localization techniques to define a region-of-interest (ROI) for the PAG: 1) a ROI previously-published as a Montreal Neurological Institute (MNI) coordinate surrounded by a 3 mm radius sphere (MNI-sphere), 2) a ROI that was hand-traced over the PAG in a MNI template brain (MNI-trace), and 3) a ROI that was hand-drawn over the PAG in structural images from 30 individual participants (participant-trace). We compared the correlation among the rs-fMRI signals from these PAG ROIs, as well as the functional connectivity of these ROIs with the whole brain. First, we found important non-uniformities in brainstem rs-fMRI signals, as rs-fMRI signals from the MNI-trace ROI were significantly more similar to the participant-trace ROI than to the MNI-sphere ROI. We then found that choice of ROI also impacts whole-brain functional connectivity, as measures of PAG functional connectivity throughout the brain were more similar between MNI-trace and participant-trace compared to MNI-sphere and participant-trace. Finally, we found that ROI choice impacts detection of disease-related differences, as functional connectivity differences between pelvic pain patients and healthy controls were much more apparent using the MNI-trace ROI compared to the MNI-sphere ROI. These results indicate that the ROI used to localize the PAG is critical, especially when examining brain functional connectivity changes in chronic visceral pain patients.
先前研究考察了慢性内脏疼痛患者的脑桥导水管周围灰质（periaqueductal gray，PAG）静息态功能连接，这些研究使用 BOLD 响应诱发急性疼痛来定位 PAG 坐标。这些坐标似乎位于 PAG 的解剖位置前几毫米处。因此，我们旨在确定 PAG 功能连接的测量值是否对定位技术敏感，以及定位方法是否会影响检测慢性内脏疼痛患者的疾病相关差异。我们检查了多学科慢性盆腔疼痛研究网络（MAPP Research Network）研究中的 209 名参与者的结构和静息态功能磁共振成像（rs-fMRI）图像。我们应用了三种不同的定位技术来定义 PAG 的感兴趣区域（region-of-interest，ROI）：1）以前发表的以蒙特利尔神经学研究所（Montreal Neurological Institute，MNI）坐标为中心，周围 3 毫米半径球的 ROI（MNI-sphere）；2）在 MNI 模板脑上手动追踪的 PAG ROI（MNI-trace）；3）在 30 名个体参与者的结构图像上手动绘制的 PAG ROI（participant-trace）。我们比较了这些 PAG ROI 的 rs-fMRI 信号之间的相关性，以及这些 ROI 与整个大脑的功能连接。首先，我们发现脑干 rs-fMRI 信号存在重要的非均匀性，因为 MNI-trace ROI 的 rs-fMRI 信号与 participant-trace ROI 比与 MNI-sphere ROI 更为相似。然后，我们发现 ROI 的选择也会影响全脑功能连接，因为大脑中 PAG 功能连接的测量值在 MNI-trace 和 participant-trace 之间更为相似，而在 MNI-sphere 和 participant-trace 之间则不相似。最后，我们发现 ROI 的选择会影响疾病相关差异的检测，因为与 MNI-sphere ROI 相比，使用 MNI-trace ROI 更能明显检测到盆腔疼痛患者和健康对照组之间的功能连接差异。这些结果表明，用于定位 PAG 的 ROI 非常关键，尤其是在检查慢性内脏疼痛患者的大脑功能连接变化时。
