AU MRI Research Center, Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, USA.
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
Neuroimage Clin. 2017 Jul 25;16:409-417. doi: 10.1016/j.nicl.2017.07.016. eCollection 2017.
Functional MRI (fMRI) is an indirect measure of neural activity as a result of the convolution of the hemodynamic response function (HRF) and latent (unmeasured) neural activity. Recent studies have shown variability of HRF across brain regions (intra-subject spatial variability) and between subjects (inter-subject variability). Ignoring this HRF variability during data analysis could impair the reliability of such fMRI results. Using whole-brain resting-state fMRI (rs-fMRI), we employed hemodynamic deconvolution to estimate voxel-wise HRF. Studying the impact of mental disorders on HRF variability, we identified HRF aberrations in soldiers (N = 87) with posttraumatic stress disorder (PTSD) and mild-traumatic brain injury (mTBI) compared to combat controls. Certain subcortical and default-mode regions were found to have significant HRF aberrations in the clinical groups. These brain regions have been previously associated with neurochemical alterations in PTSD, which are known to impact the shape of the HRF. We followed-up these findings with seed-based functional connectivity (FC) analysis using regions-of-interest (ROIs) whose HRFs differed between the groups. We found that part of the connectivity group differences reported from traditional FC analysis (no deconvolution) were attributable to HRF variability. These findings raise the question of the degree of reliability of findings from conventional rs-fMRI studies (especially in psychiatric populations like PTSD and mTBI), which are corrupted by HRF variability. We also report and discus, for the first time, voxel-level HRF alterations in PTSD and mTBI. To the best of our knowledge, this is the first study to report evidence for the impact of HRF variability on connectivity group differences. Our work has implications for rs-fMRI connectivity studies. We encourage researchers to incorporate hemodynamic deconvolution during pre-processing to minimize the impact of HRF variability.
功能磁共振成像（fMRI）是一种间接测量神经活动的方法，其结果是由于血液动力学反应函数（HRF）和潜在（未测量）神经活动的卷积。最近的研究表明，HRF 在脑区之间存在变异性（个体内空间变异性）和个体之间的变异性（个体间变异性）。在数据分析过程中忽略这种 HRF 变异性可能会损害此类 fMRI 结果的可靠性。使用全脑静息态 fMRI（rs-fMRI），我们采用血液动力学去卷积来估计体素水平的 HRF。通过研究精神障碍对 HRF 变异性的影响，我们在患有创伤后应激障碍（PTSD）和轻度创伤性脑损伤（mTBI）的士兵（N=87）中发现了 HRF 异常，与战斗对照组相比。在临床组中，某些皮质下和默认模式区域被发现存在明显的 HRF 异常。这些脑区先前与 PTSD 中的神经化学改变有关，这些改变已知会影响 HRF 的形状。我们使用群体间 HRF 不同的感兴趣区域（ROI）进行基于种子的功能连接（FC）分析，对这些发现进行了跟进。我们发现，传统 FC 分析（无去卷积）报告的部分连接组差异归因于 HRF 变异性。这些发现提出了一个问题，即常规 rs-fMRI 研究（尤其是 PTSD 和 mTBI 等精神障碍人群）的发现的可靠性程度，这些研究受到 HRF 变异性的影响。我们还首次报告并讨论了 PTSD 和 mTBI 中的体素水平 HRF 改变。据我们所知，这是第一项报告 HRF 变异性对连接组差异影响的证据的研究。我们的工作对 rs-fMRI 连接研究具有启示意义。我们鼓励研究人员在预处理过程中纳入血液动力学去卷积，以最大程度地减少 HRF 变异性的影响。
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