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bioRxiv · 10.1101/2024.10.16.618681

Simulation Insights on the Compound Action Potential in Multifascicular Nerves

Tharayil, J. J.·Zinno, C.·Agnesi, F.·Lloyd, B.·Farcito, S.·Cassara, A.·Kuster, N.·Reimann, M. W.·Micera, S.·Neufeld, E.
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Abstract

ObjectiveDevelop an efficient method for simulating evoked compound action potential (eCAP) signals from complex nerves to help optimize and interpret eCAP recordings; validate it through comparison with measured vagus nerve eCAP recordings; elucidate the subtle interplay giving rise to specific eCAP signal shapes and magnitudes. ApproachWe developed an extended reciprocity theorem approach to model neuron signals in heterogeneous environments, and use it to study analytically the single fibre action potential. We then established a semi-analytic model that also uses hybrid electromagnetic-electrophysiological simulations to model eCAP signals from complex nerves populated with heterogeneous fiber populations of fibers. A cuff electrode was used to measure activity induced by vagus nerve stimulation in in vivo porcine experiments; these measurements were compared with signals produced by the model. Main ResultsThe semi-analytic model produces signals that approximate the shape and amplitude of in vivo measurements. Partially activated fascicles contribute substantially to the signal, as eCAP contributions from smoothly varying fiber calibers in fully activated ones partially cancel. As a result, eCAP magnitude does not depend monotonically on the stimulation current and recruitment level. Because the eCAP is sensitive to the degree of activation in individual fascicles, and to the location of the recording electrodes with respect to individual fascicles, the contributions of different fascicles to the recorded eCAP signals vary significantly with changes in the shape and placement of the stimulus and the recording electrodes. SignificanceOur method can be used to rapidly assess new stimulation and recording setups involving complex nerves and neurovascular bundles, e.g., to maximize signal information content, for closed-loop control in bioelectronic medicine applications, and potentially to non-destructively reconstruct structural and functional nerve topologies through inverse problem solving.

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Tharayil, J. J., Zinno, C., Agnesi, F., Lloyd, B., Farcito, S., Cassara, A., Kuster, N., Reimann, M. W., Micera, S., Neufeld, E.. 2024-10-18. Simulation Insights on the Compound Action Potential in Multifascicular Nerves. https://doi.org/10.1101/2024.10.16.618681

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