Department of Bioengineering, Imperial College London, South Kensington, London, SW7 2AZ, UK.
Department of Mathematics, Imperial College London, South Kensington, London, SW7 2AZ, UK.
Neuroinformatics. 2019 Jan;17(1):63-81. doi: 10.1007/s12021-018-9383-z.
Bioelectronic Medicines that modulate the activity patterns on peripheral nerves have promise as a new way of treating diverse medical conditions from epilepsy to rheumatism. Progress in the field builds upon time consuming and expensive experiments in living organisms. To reduce experimentation load and allow for a faster, more detailed analysis of peripheral nerve stimulation and recording, computational models incorporating experimental insights will be of great help. We present a peripheral nerve simulator that combines biophysical axon models and numerically solved and idealised extracellular space models in one environment. We modelled the extracellular space as a three-dimensional resistive continuum governed by the electro-quasistatic approximation of the Maxwell equations. Potential distributions were precomputed in finite element models for different media (homogeneous, nerve in saline, nerve in cuff) and imported into our simulator. Axons, on the other hand, were modelled more abstractly as one-dimensional chains of compartments. Unmyelinated fibres were based on the Hodgkin-Huxley model; for myelinated fibres, we adapted the model proposed by McIntyre et al. in 2002 to smaller diameters. To obtain realistic axon shapes, an iterative algorithm positioned fibres along the nerve with a variable tortuosity fit to imaged trajectories. We validated our model with data from the stimulated rat vagus nerve. Simulation results predicted that tortuosity alters recorded signal shapes and increases stimulation thresholds. The model we developed can easily be adapted to different nerves, and may be of use for Bioelectronic Medicine research in the future.
生物电子药物可以调节周围神经的活动模式,有望成为一种治疗从癫痫到风湿等多种疾病的新方法。该领域的进展建立在对活体进行耗时且昂贵的实验的基础上。为了减少实验负荷并允许更快、更详细地分析周围神经刺激和记录,结合实验见解的计算模型将非常有帮助。我们提出了一种外周神经模拟器,它将生物物理轴突模型和数值求解的理想化细胞外空间模型结合在一个环境中。我们将细胞外空间建模为一个三维电阻连续体,由麦克斯韦方程组的电准静态近似来控制。不同介质(均质、盐水中的神经、套管中的神经)的有限元模型中预先计算了电势分布,并将其导入我们的模拟器中。另一方面,轴突被更抽象地建模为一维的隔室链。无髓纤维基于 Hodgkin-Huxley 模型;对于有髓纤维,我们根据 McIntyre 等人在 2002 年提出的模型进行了改编,以适应较小的直径。为了获得现实的轴突形状,一个迭代算法沿着神经放置纤维,其不规则性与成像轨迹拟合。我们使用刺激大鼠迷走神经的数据验证了我们的模型。模拟结果表明,不规则性改变了记录的信号形状并增加了刺激阈值。我们开发的模型可以很容易地适应不同的神经,并且可能对未来的生物电子医学研究有用。