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 (CBF0) 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 CBF0 was documented in the mTBI subjects (P < 0.05, corrected), relative to the controls. A normalization method designed to account for differences in CBF0 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 CBF0. 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.

中文翻译：

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利用局部生理学对静息状态进行多模式标准化可减少 mTBI 患者中观察到的功能连接模式的变化。

血氧水平依赖（BOLD）静息态功能磁共振成像（rs-fMRI）可以作为敏感标记来识别轻度创伤性脑损伤（mTBI）后大规模网络架构可能发生的变化。然而，源自 BOLD rs-fMRI 的功能连接 (FC) 测量值的差异可能会因局部脑血管生理学和神经血管耦合机制的变化而混淆，而底层神经元驱动的网络连接不会发生变化。在这项研究中，收集了 23 名报告 mTBI 的受试者（术后 14.6±14.9 个月）的多模态神经影像数据，包括 BOLD rs-fMRI、基线脑血流量 (CBF0) 和脑血管反应性（CVR；通过高碳酸气体呼吸挑战获得） -损伤）和 27 名年龄匹配的健康对照。尽管感兴趣网络内的 CVR 没有组间差异（P > 0.05，已校正），但相对于对照组，mTBI 受试者的 CBF0 明显较高（P < 0.05，已校正）。引入了一种标准化方法，旨在解释 mTBI 后 CBF0 的差异，以评估这种方法对报告的网络连接组差异的影响。将区域灌注测量纳入大规模网络内部和跨大规模网络的相关系数的计算缩小了各组之间 FC 的差异，这表明这种方法可以阐明 mTBI 后连接性的独特变化，同时考虑与 CBF0 的共享方差。总而言之，我们的结果提供了一个强有力的范例，支持需要考虑 BOLD 生理调节剂的变化，以扩大我们对脑损伤对皮质网络大规模 FC 影响的理解。