Background

Disentangling physiological noise and signal of interest is a major issue when evaluating BOLD-signal changes in response to breath holding. Currently-adopted approaches for retrospective noise correction are general-purpose, and have non-negligible effects in studies on hypercapnic challenges.

New method

We provide a novel approach to the analysis of specific and non-specific BOLD-signal changes related to end-tidal CO₂ (P_ETCO₂) in breath-hold fMRI studies. Multiple-order nonlinear predictors for P_ETCO₂ model a region-dependent nonlinear input-output relationship hypothesized in literature and possibly playing a crucial role in disentangling noise. We explore Retrospective Image-based Correction (RETROICOR) effects on the estimated BOLD response, applying our analysis both with and without RETROICOR and analyzing the linear and non-linear correlation between P_ETCO₂ and RETROICOR regressors.

Results

The RETROICOR model of noise related to respiratory activity correlated with P_ETCO₂ both linearly and non-linearly. The correction affected the shape of the estimated BOLD response to hypercapnia but allowed to discard spurious activity in ventricles and white matter. Activation clusters were best detected using non-linear components in the BOLD response model.

Comparison with existing method

We evaluated the side-effects of standard physiological noise correction procedure, tailoring our analysis on challenging understudied brainstem and subcortical regions. Our novel approach allowed to characterize delays and non-linearities in BOLD response.

Conclusions

RETROICOR successfully avoided false positives, still broadly affecting the estimated non-linear BOLD responses. Non-linearities in the model better explained CO₂-related BOLD signal fluctuations. The necessity to modify the standard procedure for physiological-noise correction in breath-hold studies was addressed, stating its crucial importance.

中文翻译：

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BOLD 信号变化对呼气末 CO2 的映射依赖性：线性和非线性建模，以及生理噪声校正的影响

背景

在评估响应屏气的 BOLD 信号变化时，解开生理噪声和感兴趣的信号是一个主要问题。目前采用的回顾性噪声校正方法是通用的，在高碳酸血症挑战的研究中具有不可忽视的影响。

新方法

我们提供了一种新方法来分析屏气 fMRI 研究中与呼气末 CO ₂ (P _ET CO ₂ )相关的特定和非特定 BOLD 信号变化。P _ET CO _{2 的}多阶非线性预测器模拟了文献中假设的区域相关非线性输入-输出关系，并且可能在解开噪声中起关键作用。我们探索了基于回顾性图像的校正 (RETROICOR) 对估计的 BOLD 响应的影响，在使用和不使用 RETROICOR 的情况下应用我们的分析，并分析 P _ET CO ₂和 RETROICOR 回归量之间的线性和非线性相关性。

结果

与呼吸活动相关的噪声的 RETROICOR 模型与 P _ET CO ₂线性和非线性相关。校正影响了对高碳酸血症的估计 BOLD 反应的形状，但允许丢弃心室和白质中的虚假活动。使用 BOLD 响应模型中的非线性组件可以最好地检测激活簇。

与现有方法的比较

我们评估了标准生理噪声校正程序的副作用，调整我们对具有挑战性的未研究脑干和皮层下区域的分析。我们的新方法允许表征 BOLD 响应中的延迟和非线性。

结论

RETROICOR 成功避免了误报，仍然广泛影响估计的非线性 BOLD 响应。模型中的非线性更好地解释了与 CO ₂相关的 BOLD 信号波动。讨论了修改屏气研究中生理噪声校正标准程序的必要性，指出其至关重要。