Champagne Allen A, Coverdale Nicole S, Ross Andrew, Chen Yining, Murray Christopher I, Dubowitz David, Cook Douglas J
Centre for Neuroscience Studies, Room 260, Queen's University, Kingston ON K7L 3N6 Canada.
Performance Phenomics, 180 John St., Toronto ON M5T 1 × 5 Canada.
Neuroimage Clin. 2020;26:102204. doi: 10.1016/j.nicl.2020.102204. Epub 2020 Feb 4.
Blood oxygenation level dependent (BOLD) resting-state functional magnetic resonance imaging (rs-fMRI) may serve as a sensitive marker to identify possible changes in the architecture of large-scale networks following mild traumatic brain injury (mTBI). Differences in functional connectivity (FC) measurements derived from BOLD rs-fMRI may however be confounded by changes in local cerebrovascular physiology and neurovascular coupling mechanisms, without changes in the underlying neuronally driven connectivity of networks. In this study, multi-modal neuroimaging data including BOLD rs-fMRI, baseline cerebral blood flow (CBF) and cerebrovascular reactivity (CVR; acquired using a hypercapnic gas breathing challenge) were collected in 23 subjects with reported mTBI (14.6±14.9 months post-injury) and 27 age-matched healthy controls. Despite no group differences in CVR within the networks of interest (P > 0.05, corrected), significantly higher CBF was documented in the mTBI subjects (P < 0.05, corrected), relative to the controls. A normalization method designed to account for differences in CBF post-mTBI was introduced to evaluate the effects of such an approach on reported group differences in network connectivity. Inclusion of regional perfusion measurements in the computation of correlation coefficients within and across large-scale networks narrowed the differences in FC between the groups, suggesting that this approach may elucidate unique changes in connectivity post-mTBI while accounting for shared variance with CBF. Altogether, our results provide a strong paradigm supporting the need to account for changes in physiological modulators of BOLD in order to expand our understanding of the effects of brain injury on large-scale FC of cortical networks.
血氧水平依赖（BOLD）静息态功能磁共振成像（rs-fMRI）可能是一种敏感的标志物，用于识别轻度创伤性脑损伤（mTBI）后大规模网络结构的可能变化。然而，源自BOLD rs-fMRI的功能连接（FC）测量差异可能会受到局部脑血管生理学和神经血管耦合机制变化的混淆，而网络潜在的神经元驱动连接并无变化。在本研究中，收集了23名报告有mTBI的受试者（受伤后14.6±14.9个月）和27名年龄匹配的健康对照者的多模态神经影像数据，包括BOLD rs-fMRI、基线脑血流量（CBF）和脑血管反应性（CVR；通过高碳酸血症气体呼吸激发获得）。尽管在感兴趣的网络内CVR无组间差异（P>0.05，校正后），但与对照组相比，mTBI受试者的CBF显著更高（P<0.05，校正后）。引入一种旨在考虑mTBI后CBF差异的归一化方法，以评估这种方法对报告的网络连接组间差异的影响。在大规模网络内部和之间的相关系数计算中纳入区域灌注测量，缩小了两组之间FC的差异，表明这种方法可能阐明mTBI后连接的独特变化，同时考虑到与CBF的共同方差。总之，我们的结果提供了一个强有力的范例，支持需要考虑BOLD生理调节因子的变化，以扩大我们对脑损伤对皮质网络大规模FC影响的理解。
