# Modeling Activation and Block of Autonomic Nerves for Analysis and Design

> **NIH NIH OT2** · DUKE UNIVERSITY · 2020 · $1,758,863

## Abstract

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.

## Key facts

- **NIH application ID:** 10187336
- **Project number:** 3OT2OD025340-01S4
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Warren M. Grill
- **Activity code:** OT2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,758,863
- **Award type:** 3
- **Project period:** 2017-09-02 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187336

## Citation

> US National Institutes of Health, RePORTER application 10187336, Modeling Activation and Block of Autonomic Nerves for Analysis and Design (3OT2OD025340-01S4). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10187336. Licensed CC0.

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