Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality and its pathophysiological mechanisms remain unknown. Goal: We set to record and analyze for the first time concurrent electroencephalographic (EEG), electrocardiographic (ECG), and unrestrained whole-body plethysmographic (Pleth) signals from control (WT - wild type) and SUDEP-prone mice (KO- knockout Kcna1 animal model). Methods: Employing multivariate autoregressive models (MVAR) we measured all tri-organ effective directional interactions by the generalized partial directed coherence (GPDC) in the frequency domain over time (hours). Results: When compared to the control (WT) animals, the SUDEP-prone (KO) animals exhibited (p < 0.001) reduced afferent and efferent interactions between the heart and the brain over the full frequency spectrum (0-200Hz), enhanced efferent interactions from the brain to the lungs and from the heart to the lungs at high (>90 Hz) frequencies (especially during periods with seizure activity), and decreased feedback from the lungs to the brain at low (<40 Hz) frequencies. Conclusions: These results show that impairment in the afferent and efferent pathways in the holistic neuro-cardio-respiratory network could lead to SUDEP, and effective connectivity measures and their dynamics could serve as novel biomarkers of susceptibility to SUDEP and seizures respectively.

中文翻译：

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神经-心脏和呼吸系统的定向连接分析揭示了对 SUDEP 易感性的新生物标志物

癫痫猝死（SUDEP）是癫痫相关死亡的主要原因，其病理生理机制尚不清楚。目标：我们开始记录和分析来自对照（WT-野生型）和 SUDEP 倾向小鼠（KO-敲除 Kcna1 动物模型）。方法：使用多元自回归模型 (MVAR)，我们通过频域中的广义部分定向相干 (GPDC) 随着时间 (小时) 测量所有三器官有效方向相互作用。结果：与对照 (WT) 动物相比，SUDEP 倾向 (KO) 动物表现出 (p < 0.001) 在整个频谱 (0-200Hz) 上心脏和大脑之间的传入和传出相互作用减少，增强的传出相互作用来自在高频率（>90 Hz）下（特别是在癫痫发作期间），大脑到肺部和从心脏到肺部，而在低频率（<40 Hz）下从肺部到大脑的反馈减少。结论：这些结果表明，整体神经 - 心 - 呼吸网络中传入和传出通路的损伤可能导致 SUDEP，有效的连通性测量及其动力学可以分别作为对 SUDEP 和癫痫发作易感性的新生物标志物。