To establish and exploit novel biomarkers of demyelinating diseases requires a mechanistic understanding of axonal propagation. Here, we present a novel computational framework called the stochastic spike-diffuse-spike (SSDS) model for assessing the effects of demyelination on axonal transmission. It models transmission through nodal and internodal compartments with two types of operations: a stochastic integrate-and-fire operation captures nodal excitability and a linear filtering operation describes internodal propagation. The effects of demyelinated segments on the probability of transmission, transmission delay and spike time jitter are explored. We argue that demyelination-induced impedance mismatch prevents propagation mostly when the action potential leaves a demyelinated region, not when it enters a demyelinated region. In addition, we model sodium channel remodeling as a homeostatic control of nodal excitability. We find that the effects of mild demyelination on transmission probability and delay can be largely counterbalanced by an increase in excitability at the nodes surrounding the demyelination. The spike timing jitter, however, reflects the level of demyelination whether excitability is fixed or is allowed to change in compensation. This jitter can accumulate over long axons and leads to a broadening of the compound action potential, linking microscopic defects to a mesoscopic observable. Our findings articulate why action potential jitter and compound action potential dispersion can serve as potential markers of weak and sporadic demyelination.

中文翻译：

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通过峰-扩散-峰方法将脱髓鞘作用与复合作用电位分散联系起来。

建立和利用脱髓鞘疾病的新生物标记物需要对轴突传播的机械理解。在这里，我们提出了一种新颖的计算框架，称为随机峰扩散峰（SSDS）模型，用于评估脱髓鞘对轴突传递的影响。它通过两种类型的操作来模拟通过节点和节点间的传输：随机积分和发射操作捕获节点的兴奋性，而线性滤波操作描述节点间的传播。探索了脱髓鞘片段对传输概率，传输延迟和尖峰时间抖动的影响。我们认为脱髓鞘引起的阻抗失配主要是在动作电位离开脱髓鞘区域时阻止传播，而不是在进入脱髓鞘区域时阻止传播。此外，我们将钠通道重塑建模为节点兴奋性的稳态控制。我们发现，轻度脱髓鞘对传输概率和延迟的影响可以通过在脱髓鞘周围的节点处的兴奋性增加而大大抵消。但是，尖峰定时抖动反映了脱髓鞘水平，无论兴奋性是固定的还是允许补偿变化。这种抖动会在较长的轴突上积聚，并导致复合动作电位加宽，从而将微观缺陷与介观观察相联系。我们的发现阐明了为什么动作电位抖动和复合动作电位分散可以用作弱和偶发性脱髓鞘的潜在标志。我们发现，轻度脱髓鞘对传输概率和延迟的影响可以通过在脱髓鞘周围的节点处的兴奋性增加而大大抵消。但是，尖峰定时抖动反映了脱髓鞘水平，无论兴奋性是固定的还是允许补偿变化。这种抖动会在较长的轴突上积聚，并导致复合动作电位加宽，从而将微观缺陷与介观观察相联系。我们的发现阐明了为什么动作电位抖动和复合动作电位分散可以用作弱和偶发性脱髓鞘的潜在标志。我们发现，轻度脱髓鞘对传输概率和延迟的影响可以通过在脱髓鞘周围的节点处的兴奋性增加而大大抵消。但是，尖峰定时抖动反映了脱髓鞘水平，无论兴奋性是固定的还是允许补偿变化。这种抖动会在较长的轴突上积聚，并导致复合动作电位加宽，从而将微观缺陷与介观观察相联系。我们的发现阐明了为什么动作电位抖动和复合动作电位分散可以用作弱和偶发性脱髓鞘的潜在标志。反映了兴奋性是固定的还是允许改变补偿的脱髓鞘水平。这种抖动会在较长的轴突上积聚，并导致复合动作电位加宽，从而将微观缺陷与介观观察相联系。我们的发现阐明了为什么动作电位抖动和复合动作电位分散可以用作弱和偶发性脱髓鞘的潜在标志。反映了兴奋性是固定的还是允许改变补偿的脱髓鞘水平。这种抖动会在较长的轴突上累积，并导致复合动作电位变宽，从而将微观缺陷与介观观察相联系。我们的发现阐明了为什么动作电位抖动和复合动作电位分散可以用作弱和偶发性脱髓鞘的潜在标志。