Mapping the linkage between auricular vagus nerve receptors and cardiovagal modulation

Massachusetts General Hospital, Boston MA

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Abstract

The vagus nerve is regarded as the main parasympathetic conduit of the autonomic nervous system and is involved in the regulation of multiple visceral organs. Vagus nerve stimulation (VNS) has been suggested and/or used as a neuromodulatory therapy for multiple visceral organ disorders, from hypertension to functional dyspepsia and gastroparesis. However, given that VNS is an invasive procedure and has been associated with significant adverse events, the mapping of alternative non-invasive pathways for vagal modulation is of critical relevance. Interestingly, the auricular branch of the vagus (ABVN) is the only peripheral branch of this nerve that distributes to the skin. Previous animal studies have demonstrated that ABVN sensory fibers terminate in the nucleus tractus solitarius (NTS), and, similar to invasive VNS, ABVN stimulation has also been shown to modulate cardiac and gut function. While the anatomy of this nerve has been studied in detail, the functional mapping of the circuitry connecting ABVN stimulation with cardiovascular and gastrointestinal outcomes remains poorly understood. Moreover, as NTS activity and the dorsal medullary vagal system operates in tune with respiration, our group has previously suggested that the neuromodulatory effects of ABVN afference can be optimized by gating stimulation to the respiratory cycle. Hence, our overall goal is to functionally map the ABVN-brainstem-vagal outflow pathway in humans and assess its sensitivity to the modulatory effects of respiration. We will apply state-of-the-art ultrahigh-field functional MRI (7T fMRI), which will afford enhanced spatiotemporal resolution to evaluate the response of the dorsal medullary vagal system and hypothalamus to ABVN stimulation. Neuroimaging will incorporate simultaneous cardiophysiological assessment and dynamic high frequency heart rate variability (HF-HRV) assessment of cardiovagal modulation, using advanced point-process adaptive filtering algorithms developed by our group. Novel stomach MRI pulse sequences will be used to assess stomach accommodation and peristalsis in conjunction with brain fMRI during ABVN stimulation. In summary, the functional mapping of the ABVN pathway in humans is of pivotal importance given its accessibility and its potential neuromodulatory effects on cardiovascular and gastrointestinal physiology, and our proposal will significantly improve our understanding of the mapping from auricular vagus nerve receptors to visceral organs.