Doubovikov Evan D, Aksenov Daniil P
Department of Radiology, Endeavor Health, 2650 Ridge Ave, Evanston, IL 60201, USA.
Department of Radiology, Endeavor Health, 2650 Ridge Ave, Evanston, IL 60201, USA; Department of Anesthesiology, Endeavor Health, 2650 Ridge Ave, Evanston, IL 60201, USA; University of Chicago, Pritzker School of Medicine, 5841 S Maryland Ave, Chicago, IL 60637, USA; Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, E310, Evanston, IL 60208, USA.
Neuroimage. 2025 Aug 15;317:121334. doi: 10.1016/j.neuroimage.2025.121334. Epub 2025 Jun 17.
Blood oxygen level-dependent functional magnetic resonance imaging (fMRI) is a widely used, non-invasive method to assess brain hemodynamics. Resting-state fMRI (rsfMRI) estimates functional connectivity (FC) by measuring correlations between the time courses of different brain regions. However, the reliability of rsfMRI FC is fundamentally compromised by statistical artifacts arising from signal cyclicity, autocorrelation, and preprocessing-induced distortions. We discuss how standard rsfMRI preprocessing -particularly the widely used band-pass filters such as 0.009-0.08 Hz and 0.01-0.10 Hz- introduce biases that increase correlation estimates between independent time series. Additionally, filtering without appropriate downsampling further distorts correlation coefficients, inflating statistical significance and increasing the risk of false positives. Under these conditions, commonly used multiple comparison corrections fail to fully control Type I errors, with up to 50-60 % of detected correlations in white noise signals remaining significant after correction depending on the sampling rate, filter and duration. To mitigate these biases, we recommend adjusting sampling rates to align with the analyzed frequency band and employing surrogate data methods that better account for the statistical properties of rsfMRI signals and reduce autocorrelation-driven false positives. Additionally, we show that structured brain states-such as epilepsy and anesthesia-induced burst suppression-impose low-frequency neural activity that further amplifies these biases, distorting FC estimates. These findings indicate that accepted rsfMRI preprocessing pipelines systematically amplify spurious correlations and call for an improved statistical framework. This framework must explicitly account for autocorrelation, cyclicity, and multiple comparison biases, while excluding or correcting for structured neural activity that further distorts connectivity estimates.
血氧水平依赖性功能磁共振成像(fMRI)是一种广泛应用的非侵入性方法,用于评估脑血流动力学。静息态fMRI(rsfMRI)通过测量不同脑区时间序列之间的相关性来估计功能连接(FC)。然而,rsfMRI功能连接的可靠性从根本上受到信号周期性、自相关性和预处理引起的失真所产生的统计伪影的影响。我们讨论了标准的rsfMRI预处理——特别是广泛使用的带通滤波器,如0.009 - 0.08Hz和0.01 - 0.10Hz——如何引入偏差,增加独立时间序列之间的相关性估计。此外,在没有适当下采样的情况下进行滤波会进一步扭曲相关系数,夸大统计显著性并增加假阳性风险。在这些条件下,常用的多重比较校正无法完全控制I型错误,根据采样率、滤波器和持续时间的不同,在白噪声信号中检测到的相关性在校正后仍有高达50 - 60%保持显著。为了减轻这些偏差,我们建议调整采样率以与分析的频段对齐,并采用替代数据方法,该方法能更好地考虑rsfMRI信号的统计特性并减少自相关驱动的假阳性。此外,我们表明结构化脑状态——如癫痫和麻醉诱导的爆发抑制——会施加低频神经活动,进一步放大这些偏差,扭曲功能连接估计。这些发现表明,公认的rsfMRI预处理流程会系统性地放大虚假相关性,并呼吁改进统计框架。这个框架必须明确考虑自相关性、周期性和多重比较偏差,同时排除或校正进一步扭曲连接估计的结构化神经活动。
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