Using neural biomarkers to personalize dosing of vagus nerve stimulation

Berthon, A.; Wernisch, L.; Stoukidi, M.; Thornton, M.; Tessier-Lariviere, O.; Fortier-Poisson, P.; Mamen, J.; Pinkney, M.; Lee, S.; Sarkans, E.; Annecchino, L.; Appleton, B.; Garsed, P.; Patterson, B.; Gonshaw, S.; Jakopec, M.; Shunmugam, S.; Edwards, T.; Tukiainen, A.; Jennings, J.; Lajoie, G.; Hewage, E.; Armitage, O.

doi:10.1101/2023.08.30.555487

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bioRxiv · 10.1101/2023.08.30.555487

Using neural biomarkers to personalize dosing of vagus nerve stimulation

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Abstract

BackgroundVagus nerve stimulation (VNS) is an established therapy for treating a variety of chronic diseases, such as epilepsy, depression, obesity, and for stroke rehabilitation. However, lack of precision and side-effects have hindered its efficacy and extension to new conditions. ObjectiveTo achieve a better understanding of the relationship between VNS parameters and neural and physiological responses to enable the design of personalized dosing procedures to improve precision and efficacy of VNS therapies. MethodsWe used biomarkers from recorded evoked neural activity and short-term physiological responses (throat muscle, cardiac and respiratory activity) to understand the response to a wide range of VNS parameters in anaesthetised pigs. Using signal processing, Gaussian processes (GP) and parametric regression models we analyse the relationship between VNS parameters and neural and physiological responses. ResultsFirstly, we observe inter-subject variability for both neural and physiological responses. Secondly, we illustrate how considering multiple stimulation parameters in VNS dosing can improve the efficacy and precision of VNS therapies. Thirdly, we describe the relationship between different VNS parameters and the evoked neural activity and show how spatially selective electrodes can be used to improve fibre recruitment. Fourthly, we provide a detailed exploration of the relationship between the activations of neural fibre types and different physiological effects, and show that recordings of evoked neural activity are powerful biomarkers for predicting the short-term physiological effects of VNS. Finally, based on these results, we discuss how recordings of evoked neural activity can help design VNS dosing procedures that optimize short-term physiological effects safely and efficiently. ConclusionUnderstanding of evoked neural activity during VNS provide powerful biomarkers that could improve the precision, safety and efficacy of VNS therapies.

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Berthon, A., Wernisch, L., Stoukidi, M., Thornton, M., Tessier-Lariviere, O., Fortier-Poisson, P., Mamen, J., Pinkney, M., Lee, S., Sarkans, E., Annecchino, L., Appleton, B., Garsed, P., Patterson, B., Gonshaw, S., Jakopec, M., Shunmugam, S., Edwards, T., Tukiainen, A., Jennings, J., Lajoie, G., Hewage, E., Armitage, O.. 2023-09-01. Using neural biomarkers to personalize dosing of vagus nerve stimulation. https://doi.org/10.1101/2023.08.30.555487

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