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Human intracranial recordings reveal distinct cortical activity patterns during invasive and non-invasive vagus nerve stimulation.

ABSTRACT: Vagus nerve stimulation (VNS) is being used increasingly to treat a wide array of diseases and disorders. This growth is driven in part by the putative ability to stimulate the nerve non-invasively. Despite decades of use and a rapidly expanding application space, we lack a complete understanding of the acute effects of VNS on human cortical neurophysiology. Here, we investigated cortical responses to sub-perceptual threshold cervical implanted (iVNS) and transcutaneous auricular (taVNS) vagus nerve stimulation using intracranial neurophysiological recordings in human epilepsy patients. To understand the areas that are modulated by VNS and how they differ depending on invasiveness and stimulation parameters, we compared VNS-evoked neural activity across a range of stimulation modalities, frequencies, and amplitudes. Using comparable stimulation parameters, both iVNS and taVNS caused subtle changes in low-frequency power across broad cortical networks, which were not the same across modalities and were highly variable across participants. However, within at least some individuals, it may be possible to elicit similar responses across modalities using distinct sets of stimulation parameters. These results demonstrate that both invasive and non-invasive VNS cause evoked changes in activity across a set of highly distributed cortical networks that are relevant to a diverse array of clinical, rehabilitative, and enhancement applications.

SUBMITTER: Schuerman WL

PROVIDER: S-EPMC8611055 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAutonomic nerve stimulation is used as a treatment for a growing number of diseases. We have previously demonstrated that application of efferent vagus nerve stimulation (eVNS) has promising glucose lowering effects in a rat model of type 2 diabetes. This paradigm combines high frequency pulsatile stimulation to block nerve activation in the afferent direction with low frequency stimulation to activate the efferent nerve section. In this study we explored the effects of the parameters for nerve blocking on the ability to inhibit nerve activation in the afferent direction. The overarching aim is to establish a blocking stimulation strategy that could be applied using commercially available implantable pulse generators used in the clinic.MethodsMale rats (n = 20) had the anterior abdominal vagus nerve implanted with a multi-electrode cuff. Evoked compound action potentials (ECAP) were recorded at the proximal end of the electrode cuff. The efficacy of high frequency stimulation to block the afferent ECAP was assessed by changes in the threshold and saturation level of the response. Blocking frequency and duty cycle of the blocking pulses were varied while maintaining a constant 4 mA current amplitude.ResultsDuring application of blocking at lower frequencies (≤ 4 kHz), the ECAP threshold increased (ANOVA, p < 0.001) and saturation level decreased (p < 0.001). Application of higher duty cycles (> 70%) led to an increase in evoked neural response threshold (p < 0.001) and a decrease in saturation level (p < 0.001). During the application of a constant pulse width and frequency (1 or 1.6 kHz, > 70% duty cycle), the charge delivered per pulse had a significant influence on the magnitude of the block (ANOVA, p = 0.003), and was focal (< 2 mm range).ConclusionsThis study has determined the range of frequencies, duty cycles and currents of high frequency stimulation that generate an efficacious, focal axonal block of a predominantly C-fiber tract. These findings could have potential application for the treatment of type 2 diabetes.

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Human intracranial recordings reveal distinct cortical activity patterns during invasive and non-invasive vagus nerve stimulation.

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