Objective. In nerve stimulation therapies, fibers in larger fascicles generally have higher activation thresholds, but the mechanisms are not well understood. We implemented and analyzed computational models to uncover the effects of morphological parameters on activation thresholds.Approach. We implemented finite element models of human vagus nerve stimulation to quantify the effects of morphological parameters on thresholds in realistic nerves. We also implemented simplified models to isolate effects of perineurium thickness, endoneurium diameter, fiber diameter, and fascicle location on current density, potential distributions (Ve), and activation thresholds across cuff geometries and stimulation waveforms. UsingVefrom each finite element model, we simulated activation thresholds in biophysical cable models of mammalian axons.Main results. Perineurium thickness increases with fascicle diameter, and both thicker perineurium and larger endoneurial diameter contributed to higher activation thresholds via lower peak and broader longitudinal potentials. Thicker perineurium caused less current to enter the fascicle transversely, decreasing peakVe. Thicker perineurium also inhibited current from leaving the fascicle, causing more constant longitudinal current density, broadeningVe. With increasing endoneurial diameter, intrafascicular volume increased faster than surface area, thereby decreasing intrafascicular current density and peakVe. Additionally, larger fascicles have greater cross-sectional area, thereby facilitating longitudinal intrafascicular current flow and broadeningVe. A large neighboring fascicle could increase activation thresholds, and for a given fascicle, fiber diameter had the greatest effect on thresholds, followed by fascicle diameter, and lastly, fascicle location within the epineurium. The circumneural cuff elicited robust activation across the nerve, whereas a bipolar transverse cuff with small contacts delivering a pseudo-monophasic waveform enabled more selective activation across fiber diameters and locations.Significance. Our computational studies provide mechanistic understanding of neural responses across relevant morphological parameters of peripheral nerves, thereby informing rational design of effective therapies.
Pubmed ID: 36917856 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
The SPARC data repository as of 2023 is an open data repository developed as part of the NIH SPARC initiative and has been used by SPARC funded investigator groups to curate and publish high quality datasets related to the autonomic nervous system. We are thrilled that as of August 2022, SPARC is accepting datasets from investigators that are not funded through the NIH SPARC program. The NIH's Common Fund Stimulating Peripheral Activity to Relieve Conditions (SPARC) program aims to transform our understanding of these nerve-organ interactions and ultimately advance neuromodulation field toward precise treatment of diseases and conditions for which conventional therapies fall short.
View all literature mentions