Intraoperative Laryngeal Muscle and Heart Rate Responses to Implanted Vagus Nerve Stimulation.

OBJECTIVES: Implanted cervical vagus nerve stimulation (VNS) is used to treat refractory epilepsy, depression, stroke sequelae, and rheumatoid arthritis. It is necessary to understand the recruitment of different neural elements in response to VNS to uncover the therapeutic mechanisms for these therapies. We quantified VNS-evoked physiologic responses in participants who underwent VNS implant surgery: laryngeal muscle activation (electromyogram [EMG]; indicating side effects; mediated by activation of large-diameter myelinated A-fibers) and changes in heart rate (HR; mediated by activation of small-diameter myelinated B-fibers). Moreover, it is necessary to validate noninvasive measurements of laryngeal EMG. MATERIALS AND METHODS: We recruited adult participants (seven females, three males) with treatment-resistant epilepsy who were receiving a new VNS implant ("acute") or replacement of an implanted VNS pulse generator ("chronic"). During these procedures, we delivered VNS across pulse widths (50, 250, and 1000 μs per phase) and stimulation amplitudes (0.05-28 mA) while recording laryngeal EMG and HR. RESULTS: The median stimulation amplitudes to evoke 50% of maximal laryngeal EMG response were 1.32, 0.49, and 0.34 mA for pulse widths of 50, 250, and 1000 μs per phase, respectively; thresholds were comparable between EMG electrodes placed endotracheally and subcutaneously. The median stimulation amplitudes to cause a 10% decrease in HR were 13.39 and 3.53 mA at 50 and 250 μs per phase, respectively-that is, approximately six to 63 times higher than the 50% EMG thresholds. We did not observe a qualitative difference in EMG or HR responses between sexes, acute/chronic, or stimulation polarities. For each subject in the chronic implant group, clinician-selected stimulation amplitudes were higher than the 50% EMG thresholds and lower than the 10% HR thresholds. CONCLUSIONS: Thresholds to evoke bradycardia were two times higher than clinician-selected stimulation amplitudes. This suggests that target fibers may not be activated by VNS (given low responder rates and confounds in clinical trials), target fibers of VNS for epilepsy may have a larger diameter than those projecting to the heart, and/or the therapeutic effect in refractory epilepsy may be evoked with less fiber activation than is required to produce bradycardia. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT05395026.

Duke Scholars

Author Nikki Pelot  

Author Warren M. Grill Biomedical Engineering

Author Derek Southwell Neurosurgery