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Data from: Application of kilohertz-frequency block to mitigate off-target motor effects of vagus nerve stimulation

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Jan 15, 2026 version files 152.99 GB

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Abstract

Bioelectronic medicines are a growing medical device sector with numerous applications spanning neurologic, rehabilitation, cardiopulmonary, and pain applications. In many cases, therapeutic efficacy is limited by off-target activation of motor fibers which can cause unwanted, and sometimes painful, muscle activation. Owing to their large diameter and myelinated nature, motor fibers have lower activation thresholds than the small diameter fibers that are typically targeted for therapeutic applications. To address this limitation, achieving net selective activation of small diameter fibers has been an active area of neuromodulation research with numerous techniques developed to overcome the threshold differences between off-target and on-target fiber types. One such technique is the usage of high-frequency (HF) waveforms which has been previously demonstrated to block neural fibers in a fiber-size dependent manner in rodent models. Here, we investigated HF block during vagus nerve stimulation (VNS) in a large (pig) animal model while recording the neural (evoked compound action potential), muscle (electromyogram), and heart rate (electrocardiogram) responses to standard, low-frequency (LF) VNS when varying amplitudes of HF stimulation are applied. We found that HF was able to selectively block fibers, and their resultant physiologic effect, in an amplitude and fiber-size dependent manner in a large diameter mixed nerve, comparable in size and complexity to the human vagus. We characterize the block/activation thresholds needed to achieve block of the large diameter motor fibers responsible for off-target activation and demonstrate that they can be reliably blocked without significant effects on small diameter fiber conduction or physiologic outcomes. This potentially allows for much higher stimulation amplitudes to be applied in bioelectronic medicines by mitigating the issue of off-target motor activation during the application of treatment.