Novelli Leonardo, Barnett Lionel, Seth Anil K, Razi Adeel
School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Melbourne, Victoria, Australia.
Sussex Centre for Consciousness Science, Department of Informatics, University of Sussex, Brighton, UK.
Hum Brain Mapp. 2025 Jul;46(10):e70285. doi: 10.1002/hbm.70285.
Granger causality (GC) is widely used in neuroimaging to estimate directed statistical dependence between brain regions using time series of brain activity. A known problem is that fMRI measures brain activity indirectly via the blood-oxygen-level-dependent (BOLD) signal, which can distort GC estimates by introducing different time-to-peak responses across brain regions. However, how these distortions affect the validity of inferred connections is not fully understood. Previous studies have shown that false positives are not introduced if the haemodynamic response function (HRF) is minimum-phase; but whether the HRF is actually minimum-phase has remained contentious. Here, we address this issue by studying the transfer functions of three realistic biophysical models. We find that the minimum-phase condition is met for a wide range of physiologically plausible parameter values. Therefore, statistical testing of GC can be viable even if the HRF varies across brain regions, with the following two limitations. First, the minimum-phase condition is violated for parameter combinations that generate an initial dip in the HRF. Second, slow sampling of the BOLD signal (seconds) compared to the timescales of neural signal propagation (milliseconds) may still introduce spurious GC inferences. Beyond GC analysis, the closed-form expressions for the transfer functions of these popular HRF models are valuable for modeling fMRI time series since they balance mathematical tractability with biological plausibility.
格兰杰因果关系(GC)在神经影像学中被广泛用于利用脑活动的时间序列来估计脑区之间的定向统计依赖性。一个已知的问题是,功能磁共振成像(fMRI)通过血氧水平依赖(BOLD)信号间接测量脑活动,这可能会通过在不同脑区引入不同的峰值时间响应来扭曲GC估计。然而,这些扭曲如何影响推断连接的有效性尚未完全了解。先前的研究表明,如果血液动力学响应函数(HRF)是最小相位的,则不会引入假阳性;但HRF实际上是否为最小相位仍存在争议。在这里,我们通过研究三种现实生物物理模型的传递函数来解决这个问题。我们发现,对于广泛的生理上合理的参数值,都满足最小相位条件。因此,即使HRF在不同脑区有所变化,GC的统计检验仍然可行,但有以下两个限制。首先,对于在HRF中产生初始下降的参数组合,最小相位条件会被违反。其次,与神经信号传播的时间尺度(毫秒)相比,BOLD信号的慢采样(秒)可能仍然会引入虚假的GC推断。除GC分析外,这些流行的HRF模型的传递函数的闭式表达式对于fMRI时间序列建模很有价值,因为它们在数学易处理性和生物学合理性之间取得了平衡。