Fascicles split or merge every ∼560 microns within the human cervical vagus nerve

Objective. Vagus nerve stimulation (VNS) is Food and Drug Administration-approved for epilepsy, depression, and obesity, and stroke rehabilitation; however, the morphological anatomy of the vagus nerve targeted by stimulatation is poorly understood. Here, we used microCT to quantify the fascicular structure and neuroanatomy of human cervical vagus nerves (cVNs). Approach. We collected eight mid-cVN specimens from five fixed cadavers (three left nerves, five right nerves). Analysis focused on the 'surgical window': 5 cm of length, centered around the VNS implant location. Tissue was stained with osmium tetroxide, embedded in paraffin, and imaged on a microCT scanner. We visualized and quantified the merging and splitting of fascicles, and report a morphometric analysis of fascicles: count, diameter, and area. Main results. In our sample of human cVNs, a fascicle split or merge event was observed every similar to 560 mu m (17.8 +/- 6.1 events cm(-1)). Mean morphological outcomes included: fascicle count (6.6 +/- 2.8 fascicles; range 1-15), fascicle diameter (514 +/- 142 mu m; range 147-1360 mu m), and total cross-sectional fascicular area (1.32 +/- 0.41 mm(2); range 0.58-2.27 mm). Significance. The high degree of fascicular splitting and merging, along with wide range in key fascicular morphological parameters across humans may help to explain the clinical heterogeneity in patient responses to VNS. These data will enable modeling and experimental efforts to determine the clinical effect size of such variation. These data will also enable efforts to design improved VNS electrodes.

Automated summary

The study used microCT to quantify the fascicular structure and neuroanatomy of human cervical vagus nerves, finding a high degree of fascicular splitting and merging, as well as wide range in key fascicular morphological parameters across humans. These findings may help explain clinical heterogeneity in patient responses to VNS and could be useful for designing improved VNS electrodes.