Modeling Activation and Block of Autonomic Nerves for Analysis and Design

自主神经生理功能图谱的实验和生物电子学的持续进展 治疗受到靶向神经纤维的不充分激活或阻断以及不必要的共同激活或 阻断非靶向神经纤维。更根本的是，施加的刺激和神经之间的关系 被激活或被阻止的纤维，这种关系如何在个体和物种中变化，以及这些 可以控制的关系在很大程度上仍是未知的。我们将开发、实施和验证一个高效的 用于模拟不同类型神经纤维内部电激活和阻断的计算流水线 自主神经。这条管道将包括从固定的神经样本中分割显微解剖结构，三个- 神经上电极的空间有限元模型和不同类型的非线性电缆模型 神经纤维类型，能够计算特定神经的激活和阻断的定量输入-输出图 纤维。作为管道发展和拟议分析和设计工作的主要基准，我们将 用SPARC鉴定的动物建立大鼠颈部(VNC)和腹部(VNA)迷走神经模型 模特，在人类身上。VNC是一个很好的试验台，因为它包含了广泛的神经纤维类型， 有有助于模型验证的实验数据，以及VNC刺激的多种应用 其中缺乏纤维选择性限制了治疗窗口。VNA是对宫颈的极好补充 VNC作为一种典型的自主神经，其大小与许多目标小型自主神经相当 由SPARC项目提供。我们将使用管道中出现的模型来实现分析和设计目标 以解决被确定为SPARC优先事项的关键差距。具体地说，我们将量化物种内的影响 通过建立单独的样本特异性模型对激活和阻断的神经形态的差异 神经和金币。这些模型也将被用于量化神经纤维激活的物种间差异。 并确定产生等效度的电极设计和刺激参数 跨物种激活和阻止。我们将把得到的模型与工程优化相结合，以 增加不同类型神经纤维激活和阻断的选择性和效率的设计方法。 结果将是一条模拟自主神经、电极几何形状和刺激的管道 参数，以及解决阻碍神经刺激选择性和效率限制的工具 生理标测研究的持续进展和生物电子疗法的发展。

Experiments to map physiological functions of autonomic nerves and the continued advance of bioelectronic therapies are limited by inadequate activation or block of targeted nerve fibers and unwanted co-activation or block of non-targeted nerve fibers. More fundamentally, the relationship between applied stimuli and the nerve fibers that are activated or blocked, how this relationship varies across individuals and species, and how these relationships can be controlled remain largely unknown. We will develop, implement and validate an efficient computational pipeline for simulation of electrical activation and block of different nerve fiber types within autonomic nerves. The pipeline will include segmentation of microanatomy from fixed nerve samples, three- dimensional finite-element models of electrodes positioned on nerves, and non-linear cable models of different nerve fiber types, enabling calculation of quantitative input-output maps of activation and block of specific nerve fibers. As key benchmarks of pipeline development and for the proposed analysis and design efforts, we will implement models of the cervical (VNc) and abdominal (VNa) vagus nerves in rat, in a SPARC-identified animal model, and in human. The VNc is an excellent test bed as it contains a broad spectrum of nerve fiber types, there are experimental data to facilitate model validation, and there are multiple applications of VNc stimulation where a lack of fiber selectivity limits the therapeutic window. The VNa is an excellent complement to the cervical VNc, as a prototypical autonomic nerve of a size comparable to many of the small autonomic nerves targeted by SPARC projects. We will use the models that emerge from the pipeline to achieve analysis and design goals to address critical gaps identified as SPARC priorities. Specifically, we will quantify of the effects of intra-species differences in nerve morphology on activation and block by building individual sample-specific models for each nerve and specie. These models will also be used to quantify inter-species differences in nerve fiber activation and block and to identify electrode designs and stimulation parameters that produce equivalent degrees of activation and block across species. We will combine the resulting models with engineering optimization to design approaches to increase the selectivity and efficiency of activation and block of different nerve fiber types. The outcomes will be a pipeline for modeling autonomic nerves, electrode geometries, and stimulation parameters, as well as tools that address the limitations of nerve stimulation selectivity and efficiency that hinder the continued advance of physiological mapping studies and the development of bioelectronic therapies.