Publications

The NoVa-PVC trial was a 2-center, prospective, sham-controlled, single-blinded, crossover randomized clinical trial conducted in patients with symptomatic premature ventricular contractions (PVCs) with at least 5% daily PVC burden and who were refractory to medical therapy. Participants received two sequential, 10-day sessions of active low-level tragus stimulation (LLTS; 20 Hz, 1 mA below the discomfort threshold) and sham stimulation (earlobe stimulation). Each treatment was interrupted by an 8-day washout period. Of 36 randomized patients, 35 [19 (59.4%) male, mean age 58.0 (±17.1) years] were included in the analysis with median baseline PVC burden of 14.83±10.08. LLTS significantly reduced PVC burden compared to sham stimulation [12.8 ± 10.9% vs 9.9 ± 8.3%, p=0.021]. In patients with symptomatic PVCs refractory to medical therapy, non-invasive low-level tragus stimulation significantly reduced median PVC burden (median reduction ~13.4% vs ~8.6%; P = 0.021).

Objective: Sensory nerves of the peripheral nervous system (PNS) transmit afferent signals from the body to the brain. These peripheral nerves are composed of distinct subsets of fibers and associated cell bodies, which reside in peripheral ganglia distributed throughout the viscera and along the spinal cord. The vagus nerve (cranial nerve X) is a complex polymodal nerve that transmits a wide array of sensory information, including signals related to mechanical, chemical, and noxious stimuli. To understand how stimuli applied to the vagus nerve are encoded by vagal sensory neurons in the jugular-nodose ganglia, we developed a framework for micro-endoscopic calcium imaging and analysis. Approach: We developed novel methods for in vivo imaging of the intact jugular-nodose ganglion using a miniature microscope (Miniscope) in transgenic mice with the genetically-encoded calcium indicator GCaMP6f.

Vagus nerve stimulation (VNS) is a bioelectronic therapy where selective activation of afferent or efferent vagal fibers can maximize efficacy and minimize off-target effects. Evidence for directional VNS with anodal block (ABL) has been scarce and inconsistent. Through a series of vagotomies, physiological markers for afferent and efferent fiber activation by VNS were established: stimulus-elicited change in breathing rate (ΔBR) and heart rate (ΔHR), respectively. Cathode cephalad polarity caused an afferent pattern of responses (relatively stronger ΔBR) whereas cathode caudad caused an efferent pattern of responses. The study provides concrete physiological and neurophysiological evidence that anodal block is a viable mechanism for functionally demonstrable directional biasing in VNS, for a range of clinically relevant stimulation parameters.