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

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.