Data from: Maximizing negative correlations in resting-state functional connectivity MRI by time-lag

This paper aims to better understand the physiological meaning of negative correlations in resting state functional connectivity MRI (r-fcMRI). The correlations between anatomy-based brain regions of 18 healthy humans were calculated and analyzed with and without a correction for global signal and with and without spatial smoothing. In addition, correlations between anatomy-based brain regions of 18 naïve anesthetized rats were calculated and compared to the human data. T-statistics were used to differentiate between positive and negative connections. The application of spatial smoothing and global signal correction increased the number of significant positive connections but their effect on negative connections was complex. Positive connections were mainly observed between cortical structures while most negative connections were observed between cortical and non-cortical structures with almost no negative connections between non-cortical structures. In both human and rats, negative connections were never observed between bilateral homologous regions. The main difference between positive and negative connections in both the human and rat data was that positive connections became less significant with time-lags, while negative connections became more significant with time-lag. This effect was evident in all four types of analyses (with and without global signal correction and spatial smoothing) but was most significant in the analysis with no correction for the global signal. We hypothesize that the valence of r-fcMRI connectivity reflects the relative contributions of cerebral blood volume (CBV) and flow (CBF) to the BOLD signal and that these relative contributions are location-specific. If cerebral circulation is primarily regulated by CBF in one region and by CBV in another, a functional connection between these regions can manifest as an r-fcMRI negative and time-delayed correlation. Similarly, negative correlations could result from spatially inhomogeneous responses of rCBV or rCBF alone. Consequently, neuronal regulation of brain circulation may be deduced from the valence of r-fcMRI connectivity.

本研究旨在深入解析静息态功能连接磁共振成像（resting state functional connectivity MRI, r-fcMRI）中负相关的生理学意义。我们对18名健康成年人基于解剖学定义的脑区间相关性进行了计算与分析，分别设置全局信号校正、空间平滑两种操作的有无组合，形成四类分析场景。此外，我们还对18只未接触过相关实验的麻醉大鼠基于解剖学定义的脑区间相关性进行了计算，并将结果与人类数据集进行对比。本研究采用t统计量区分正、负功能连接。空间平滑与全局信号校正操作可提升显著正连接的数量，但二者对负连接的影响更为复杂。正连接主要出现于皮层结构之间，而多数负连接则存在于皮层与非皮层结构之间，非皮层结构之间几乎未观察到负连接。在人类与大鼠数据中，双侧同源脑区间均未发现负连接。人类与大鼠数据中，正、负连接的核心差异在于：正连接的显著性随时间延迟增加而降低，而负连接的显著性则随时间延迟增加而升高。该效应在四类分析场景（即有无全局信号校正、有无空间平滑）中均显著存在，但在未进行全局信号校正的分析中表现最为突出。我们提出如下假说：r-fcMRI连接的效价反映了脑血容量（cerebral blood volume, CBV）与脑血流量（cerebral blood flow, CBF）对血氧依赖水平（blood oxygen level dependent, BOLD）信号的相对贡献，且该相对贡献具有脑区特异性。若某一脑区的脑循环主要受脑血流量调控，而另一脑区主要受脑血容量调控，则二者之间的功能连接可表现为r-fcMRI负相关且存在时间延迟的相关性。类似地，仅相对脑血容量（relative cerebral blood volume, rCBV）或相对脑血流量（relative cerebral blood flow, rCBF）的空间非均匀响应，也可导致负相关的产生。因此，可通过r-fcMRI连接的效价推导脑循环的神经元调控机制。