arXiv:2508.07032cs.LGq-bio.QM2025-08AAAI被引 4

提出分阶段专家混合模型,精准捕捉神经退行性疾病发展中的动态病理机制。

A Stage-Aware Mixture of Experts Framework for Neurodegenerative Disease Progression Modelling

  • 基于时间依赖的专家加权机制,区分不同疾病阶段的主导病理过程。
  • 利用不规则随访数据构建群体级进展轨迹,提升长时序建模精度。
  • 适合神经科学与医学人工智能研究者,可解释性强,助力临床洞察。

神经退行性疾病长期进展常被视作时空扩散过程,包含脑结构连接组上的图扩散与脑区内的局部反应过程。然而,由于纵向数据稀缺(受试者随访不规律且稀疏)以及病程中病理机制在脑区与阶段间的复杂交互,传统模型因假设机制恒定而面临挑战。为此,我们提出一种新型分阶段专家混合(Stage-aware MoE)框架,通过时变专家权重显式建模不同机制在各阶段的主导作用。数据层面,采用迭代双优化方法准确估计个体观测的时间位置,从零散快照构建群体级进展轨迹;模型层面,引入非齐次图神经扩散模型(IGND),允许扩散性随节点状态与时间变化,增强脑网络表征灵活性,并设计局部神经反应模块以捕捉超出标准过程的复杂动态。最终的IGND-MoE模型在不同时间状态动态整合多组件,提供理解阶段特异性病理机制贡献的理论依据。阶段权重揭示新临床洞见:早期以图相关过程为主导,后期则由未知物理过程占优,与文献高度一致。

原文摘要 · Abstract (English)

The long-term progression of neurodegenerative diseases is commonly conceptualized as a spatiotemporal diffusion process that consists of a graph diffusion process across the structural brain connectome and a localized reaction process within brain regions. However, modeling this progression remains challenging due to 1) the scarcity of longitudinal data obtained through irregular and infrequent subject visits and 2) the complex interplay of pathological mechanisms across brain regions and disease stages, where traditional models assume fixed mechanisms throughout disease progression. To address these limitations, we propose a novel stage-aware Mixture of Experts (MoE) framework that explicitly models how different contributing mechanisms dominate at different disease stages through time-dependent expert weighting.Data-wise, we utilize an iterative dual optimization method to properly estimate the temporal position of individual observations, constructing a co hort-level progression trajectory from irregular snapshots. Model-wise, we enhance the spatial component with an inhomogeneous graph neural diffusion model (IGND) that allows diffusivity to vary based on node states and time, providing more flexible representations of brain networks. We also introduce a localized neural reaction module to capture complex dynamics beyond standard processes.The resulting IGND-MoE model dynamically integrates these components across temporal states, offering a principled way to understand how stage-specific pathological mechanisms contribute to progression. The stage-wise weights yield novel clinical insights that align with literature, suggesting that graph-related processes are more influential at early stages, while other unknown physical processes become dominant later on.

神经退行动态建模专家混合脑网络

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