Chow Winn W, Seghouane Abd-Krim, Seghier Mohamed L
School of Computing and Information Systems, The University of Melbourne, Melbourne, Australia.
School of Mathematics and Statistics, The University of Melbourne, Melbourne, Australia.
Hum Brain Mapp. 2025 Feb 1;46(2):e70145. doi: 10.1002/hbm.70145.
This study examined the statistical underpinnings of dynamic functional connectivity in mental disorders, using resting-state fMRI signals. Notably, there has been an absence of research demonstrating the non-stationarity of the empirical probability distribution of functional connectivity. This gap has prompted debate on the existence of dynamic functional connectivity, leading skeptics to question its relevance and the reliability of research findings. Our aim was to fill this gap by conducting a comprehensive empirical distribution analysis of functional connectivity, using Pearson's correlation as a measure. We conducted our analysis on a set of preprocessed resting-state fMRI samples obtained from 186 subjects selected from the UCLA Consortium for Neuropsychiatric Phenomics dataset. Departing from conventional methods that aggregated signals over voxels within a region of interest, our approach leveraged individual voxel signals. Specifically, our approach offered a precise characterization of the empirical probability distribution of resting-state fMRI signals by evaluating the temporal variations and non-stationarity in dynamic functional connectivity, as measured by Pearson's correlation. Our study investigated functional connectivity patterns across 49 regions of interest, comparing healthy control subjects with patients diagnosed with ADHD, bipolar disorder, and schizophrenia. Our analysis revealed that (1) the empirical distribution of the correlation coefficient exhibited non-stationarity, (2) the beta distribution was an accurate approximation of the exact correlation coefficient distribution, and (3) the empirical distribution of means derived from the fitted beta distributions, unraveled distinctive dynamic functional connectivity patterns with potential as biomarkers associated with different mental disorders. A key contribution of our study was the presentation of the first comprehensive empirical distribution analysis of dynamic functional connectivity, thus providing compelling evidence for its existence. Overall, our study presented an innovative statistical approach that advances our understanding of the dynamic nature of functional connectivity patterns derived from resting-state fMRI. Our examination of the empirical distribution of dynamic functional connectivity provided solid evidence supporting its existence. The distinctive dynamic functional connectivity patterns we identified across various mental disorders hold promise as potential biomarkers for further development.
本研究使用静息态功能磁共振成像(fMRI)信号,探讨了精神障碍中动态功能连接的统计学基础。值得注意的是,目前尚无研究证明功能连接的经验概率分布具有非平稳性。这一空白引发了关于动态功能连接是否存在的争论,怀疑者质疑其相关性以及研究结果的可靠性。我们的目标是通过使用皮尔逊相关性作为度量方法,对功能连接进行全面的经验分布分析来填补这一空白。我们对从加州大学洛杉矶分校神经精神疾病基因组学联盟数据集中选取的186名受试者获得的一组预处理静息态fMRI样本进行了分析。与传统方法在感兴趣区域内的体素上聚合信号不同,我们的方法利用了单个体素信号。具体而言,我们的方法通过评估动态功能连接中的时间变化和非平稳性(以皮尔逊相关性衡量),对静息态fMRI信号的经验概率分布进行了精确表征。我们的研究调查了49个感兴趣区域的功能连接模式,将健康对照受试者与被诊断患有注意力缺陷多动障碍(ADHD)、双相情感障碍和精神分裂症的患者进行了比较。我们的分析表明:(1)相关系数的经验分布呈现非平稳性;(2)贝塔分布是精确相关系数分布的准确近似;(3)从拟合的贝塔分布导出的均值经验分布揭示了独特的动态功能连接模式,这些模式有可能作为与不同精神障碍相关的生物标志物。我们研究的一个关键贡献是首次对动态功能连接进行了全面的经验分布分析,从而为其存在提供了令人信服的证据。总体而言,我们的研究提出了一种创新的统计方法,推进了我们对源自静息态fMRI的功能连接模式动态性质的理解。我们对动态功能连接经验分布的研究提供了支持其存在的坚实证据。我们在各种精神障碍中识别出的独特动态功能连接模式有望作为潜在生物标志物用于进一步开发。
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