用随机微分方程建模脑网络动态,精准预测阿尔茨海默病进展。
Spatio-Temporal Graph Deep Learning with Stochastic Differential Equations for Uncovering Alzheimer's Disease Progression
- 基于双随机微分方程建模不规则采样的脑功能影像数据
- 识别出海马旁皮层等关键脑区及注意与默认网络异常
- 可解释性强,发现性别特异性生物标志物,适合临床研究者
识别客观的神经影像生物标志物以预测阿尔茨海默病(AD)进展对及时干预至关重要。然而,由于潜在脑网络在时空特征上的复杂紊乱,现有方法常忽略这一问题。为此,我们提出一种可解释的时空图神经网络框架,利用双随机微分方程(SDEs)建模不规则采样纵向功能磁共振成像(fMRI)数据,以预测未来AD进展。我们在两个独立队列中验证方法,包括开放获取影像研究系列(OASIS-3)和阿尔茨海默病神经影像计划(ADNI)。该框架有效学习区域和连接重要性概率,揭示与疾病进展相关的脑环路异常。显著发现海马旁皮层、前额叶皮层和顶叶皮层异常,涉及腹侧注意、背侧注意及默认模式网络。这些异常与纵向临床症状强相关。此外,可解释策略揭示了既存及新发现的系统水平与性别特异性生物标志物,为理解AD神经生物学机制提供新视角。研究结果表明,基于时空图的学习在不规则纵向影像数据下仍具潜力,实现早期个体化预测。
原文摘要 · Abstract (English)
Identifying objective neuroimaging biomarkers to forecast Alzheimer's disease (AD) progression is crucial for timely intervention. However, this task remains challenging due to the complex dysfunctions in the spatio-temporal characteristics of underlying brain networks, which are often overlooked by existing methods. To address these limitations, we develop an interpretable spatio-temporal graph neural network framework to predict future AD progression, leveraging dual Stochastic Differential Equations (SDEs) to model the irregularly-sampled longitudinal functional magnetic resonance imaging (fMRI) data. We validate our approach on two independent cohorts, including the Open Access Series of Imaging Studies (OASIS-3) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our framework effectively learns sparse regional and connective importance probabilities, enabling the identification of key brain circuit abnormalities associated with disease progression. Notably, we detect the parahippocampal cortex, prefrontal cortex, and parietal lobule as salient regions, with significant disruptions in the ventral attention, dorsal attention, and default mode networks. These abnormalities correlate strongly with longitudinal AD-related clinical symptoms. Moreover, our interpretability strategy reveals both established and novel neural systems-level and sex-specific biomarkers, offering new insights into the neurobiological mechanisms underlying AD progression. Our findings highlight the potential of spatio-temporal graph-based learning for early, individualized prediction of AD progression, even in the context of irregularly-sampled longitudinal imaging data.
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