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

Study Purpose: To implement, simulate, and validate computational models of VNS across rats, pigs, and humans for a range of fiber types and stimulation pulse widths.

Data Collection: We used ASCENT v1.1.1 to build a 3D model of nine human (acute and chronic; LivaNova), 20 pig (acute; LivaNova), and 1 rat (acute; Micro-Leads Neuro) vagus nerves and cuff electrodes. We simulated thresholds for myelinated and unmyelinated fibers for biphasic rectangular pulses to match stimulation-evoked physiological and neural responses from in vivo and clinical studies.

Primary Conclusion: Modeled activation thresholds quantitatively matched stimulation-evoked responses from preclinical and clinical studies for a large range of nerve morphologies, fiber types, and stimulation pulse widths.

Curator's Notes

Experimental Design: Computational models of vagus nerve stimulation in rats, pigs, and humans.

Completeness: This dataset is complete.

Subjects & Samples: Only virtual subjects were used in this study, which are based on previously published histology from perfused rats, fresh pigs, and embalmed human cadavers.

Primary vs derivative data: Not applicable. This is a computational study. The files in primary/sub-*/sam-*-sub-*/samples/*/ are ASCENT input configuration files (i.e., sample.json, models/*/model.json) and outputs (i.e., individual fiber activation thresholds models/*/sims/*/n_sims/*/data/outputs/thresh_inner*_fiber*.dat). Additionally, the files in primary/sub-*/sam-*-sub-*/samples/*/ contain key intermediate files created by ASCENT, including the extracellular potentials applied to the fiber models (models/*/sims/*/n_sims/*/data/inputs/inner*_fiber*.dat) and the stimulation waveform (models/*/sims/*/n_sims/*/data/inputs/waveform.dat).

Code Availability: The code used to parameterize, implement, and simulate the computational models is available in ASCENT v1.1.1 (repository; documentation). To analyze and visualize the data, plotting scripts are located in files/code/, as further detailed in the README.