Towards enhanced functionality of vagus neuroprostheses through in silico optimized stimulation

• Published in: Nature communications 2024-07, Vol.15 (1), p.6119-20, Article 6119
• Main Authors: Ciotti, Federico, John, Robert, Katic Secerovic, Natalija, Gozzi, Noemi, Cimolato, Andrea, Jayaprakash, Naveen, Song, Weiguo, Toth, Viktor, Zanos, Theodoros, Zanos, Stavros, Raspopovic, Stanisa
• Format: Article
• Language: English
• Subjects: 13/51; 14/63; 631/114/2398; 631/114/794; 631/378/1959/1315; 639/166/985; 639/705/1042; 64; 9/10; 9/25; 9/97; Algorithms; Animal models; Animal research; Animals; Bioelectricity; Cardiac muscle; Clinical trials; Computer Simulation; Effectiveness; Experiments; Heart rate; Heart Rate - physiology; Humanities and Social Sciences; Mental disorders; multidisciplinary; Muscles; Nerves; Neural prostheses; Neuromodulation; Physiology; Prosthetics; Science; Science (multidisciplinary); Side effects; Stimulation; Swine; Vagus nerve; Vagus Nerve - physiology; Vagus Nerve Stimulation - methods
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-50523-6

Bioelectronic therapies modulating the vagus nerve are promising for cardiovascular, inflammatory, and mental disorders. Clinical applications are however limited by side-effects such as breathing obstruction and headache caused by non-specific stimulation. To design selective and functional stimulation, we engineered VaStim, a realistic and efficient in-silico model. We developed a protocol to personalize VaStim in-vivo using simple muscle responses, successfully reproducing experimental observations, by combining models with trials conducted on five pigs. Through optimized algorithms, VaStim simulated the complete fiber population in minutes, including often omitted unmyelinated fibers which constitute 80% of the nerve. The model suggested that all Aα-fibers across the nerve affect laryngeal muscle, while heart rate changes were caused by B-efferents in specific fascicles. It predicted that tripolar paradigms could reduce laryngeal activity by 70% compared to typically used protocols. VaStim may serve as a model for developing neuromodulation therapies by maximizing efficacy and specificity, reducing animal experimentation. Advancements in bioelectronic therapies offer new hope for treating various disorders. Here, the authors present an accurate, subject-specific model of vagus nerve stimulation for enhancing efficacy and reducing side effects.