Department of Statistics, University of Connecticut, Storrs, CT 06269, United States.
Department of Biostatistics, Columbia University, New York, NY 10032, United States.
Biometrics. 2024 Oct 3;80(4). doi: 10.1093/biomtc/ujae130.
Mental disorders present challenges in diagnosis and treatment due to their complex and heterogeneous nature. Electroencephalogram (EEG) has shown promise as a source of potential biomarkers for these disorders. However, existing methods for analyzing EEG signals have limitations in addressing heterogeneity and capturing complex brain activity patterns between regions. This paper proposes a novel random effects state-space model (RESSM) for analyzing large-scale multi-channel resting-state EEG signals, accounting for the heterogeneity of brain connectivities between groups and individual subjects. We incorporate multi-level random effects for temporal dynamical and spatial mapping matrices and address non-stationarity so that the brain connectivity patterns can vary over time. The model is fitted under a Bayesian hierarchical model framework coupled with a Gibbs sampler. Compared to previous mixed-effects state-space models, we directly model high-dimensional random effects matrices of interest without structural constraints and tackle the challenge of identifiability. Through extensive simulation studies, we demonstrate that our approach yields valid estimation and inference. We apply RESSM to a multi-site clinical trial of major depressive disorder (MDD). Our analysis uncovers significant differences in resting-state brain temporal dynamics among MDD patients compared to healthy individuals. In addition, we show the subject-level EEG features derived from RESSM exhibit a superior predictive value for the heterogeneous treatment effect compared to the EEG frequency band power, suggesting the potential of EEG as a valuable biomarker for MDD.
精神障碍的诊断和治疗存在挑战,因为它们具有复杂和异质的性质。脑电图(EEG)已显示出作为这些障碍的潜在生物标志物的来源的潜力。然而,现有的分析脑电图信号的方法在解决异质性和捕捉区域之间的复杂大脑活动模式方面存在局限性。本文提出了一种用于分析大规模多通道静息态 EEG 信号的新的随机效应状态空间模型(RESSM),该模型考虑了组间和个体受试者之间大脑连通性的异质性。我们为时间动态和空间映射矩阵引入了多层次的随机效应,并解决了非平稳性问题,以便大脑连通模式可以随时间变化。该模型在与 Gibbs 抽样器耦合的贝叶斯层次模型框架下进行拟合。与以前的混合效应状态空间模型相比,我们直接对感兴趣的高维随机效应矩阵进行建模,而无需结构约束,并解决了可识别性的挑战。通过广泛的模拟研究,我们证明了我们的方法可以进行有效的估计和推断。我们将 RESSM 应用于一项重度抑郁症(MDD)的多中心临床试验。我们的分析揭示了 MDD 患者与健康个体之间静息态大脑时间动态的显著差异。此外,我们还表明,从 RESSM 中得出的个体水平 EEG 特征在预测异质治疗效果方面优于 EEG 频带功率,这表明 EEG 作为 MDD 有价值的生物标志物的潜力。