Modeling Activation and Block of Autonomic Nerves for Analysis and Design

自主神经激活和阻滞建模用于分析和设计

• 批准号: 10461325
• 负责人: Warren M. Grill
• 金额: $ 178.26万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-02 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10461325
• 关键词: Modeling; Activation; Block; Autonomic; Nerves

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.

绘制自主神经生理功能的实验和生物电子学的持续进步 治疗受到不充分的激活或目标神经纤维的阻断以及不需要的共激活或 非目标神经纤维块。更根本的是，施加的刺激与神经之间的关系 激活或阻断的纤维，这种关系在个体和物种之间如何变化，以及这些纤维如何 关系能否被控制仍然很大程度上未知。我们将开发、实施和验证有效的 用于模拟电激活和阻滞内不同神经纤维类型的计算管道 自主神经。该管道将​​包括固定神经样本的显微解剖分割、三- 位于神经上的电极的维度有限元模型，以及不同神经元的非线性电缆模型 神经纤维类型，能够计算特定神经激活和阻断的定量输入输出图 纤维。作为管道开发以及拟议分析和设计工作的关键基准，我们将 在 SPARC 鉴定的动物中建立大鼠颈迷走神经 (VNc) 和腹迷走神经 (VNa) 模型 模型，以及人类。 VNc 是一个出色的测试台，因为它包含广泛的神经纤维类型， 有实验数据方便模型验证，VNc刺激有多种应用 缺乏纤维选择性限制了治疗窗口。 VNa 是对颈椎的绝佳补充 VNc，作为一种典型的自主神经，其大小与许多目标小自主神经相当 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 解决被确定为 SPARC 优先事项的关键差距。具体来说，我们将量化物种内的影响 通过为每个样本建立单独的样本特定模型来观察激活和阻断时神经形态的差异 神经和物种。这些模型还将用于量化神经纤维激活的物种间差异 和块并确定产生同等程度的电极设计和刺激参数 跨物种的激活和阻断。我们将把所得模型与工程优化相结合 设计方法来提高不同神经纤维类型的激活和阻断的选择性和效率。 结果将是用于模拟自主神经、电极几何形状和刺激的管道 参数以及解决神经刺激选择性和效率限制的工具 生理图谱研究的不断进步和生物电子疗法的发展。

项目成果

Sources of off-target effects of vagus nerve stimulation using the helical clinical lead in domestic pigs.

使用螺旋临床引导在家猪中进行迷走神经刺激的脱靶效应的来源。

• 发表时间: 2020
• 作者: Nicolai, Evan N;Settell, Megan L;Knudsen, Bruce E;McConico, Andrea L;Gosink, Brian A;Trevathan, James K;Baumgart, Ian W;Ross, Erika K;Pelot, Nicole A;Grill, Warren M;Gustafson, Kenneth J;Shoffstall, Andrew J;Williams, Justin C;Ludwig, Kip A
• 通讯作者: Ludwig, Kip A

Validated computational models predict vagus nerve stimulation thresholds in preclinical animals and humans.

经过验证的计算模型可以预测临床前动物和人类的迷走神经刺激阈值。

• 发表时间: 2023-06-15
• 作者: Musselman, Eric D;Pelot, Nicole A;Grill, Warren M
• 通讯作者: Grill, Warren M

Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance.

非单调千赫兹频率神经块阈值是由振幅和频率相关的电荷不平衡引起的。

• 发表时间: 2021
• 影响因子: 4.6
• 作者: Peña, Edgar;Pelot, Nicole A;Grill, Warren M
• 通讯作者: Grill, Warren M

Functional vagotopy in the cervical vagus nerve of the domestic pig: implications for the study of vagus nerve stimulation.

家猪颈部迷走神经的功能性迷走神经：对迷走神经刺激研究的影响。

• 发表时间: 2020
• 作者: Settell, Megan L;Pelot, Nicole A;Knudsen, Bruce E;Dingle, Aaron M;McConico, Andrea L;Nicolai, Evan N;Trevathan, James K;Ezzell, J Ashley;Ross, Erika K;Gustafson, Kenneth J;Shoffstall, Andrew J;Williams, Justin C;Zeng, Weifeng;Poore, Samuel O
• 通讯作者: Poore, Samuel O

Effects of vagal neuromodulation on feeding behavior.

迷走神经调节对进食行为的影响。

• 发表时间: 2018-08-15
• 影响因子: 2.9
• 作者: Pelot, Nicole A;Grill, Warren M
• 通讯作者: Grill, Warren M