Fig 1.
Analysis of fiber recruitment.
a) To assess sciatic nerve recruitment, we measured force of hindlimb muscle contraction in response to a range of stimulation intensities. Shaded region represents stimulation at 30Hz for 0.5 seconds. b) To measure vagus nerve recruitment, we measured reductions in SpO2. Shaded region represents stimulation at 30Hz for 5 seconds. c) An example recruitment curve with a fitted sigmoid function and all outcome measures identified.
Fig 2.
Modeling the effect of various cuff electrode parameters on recruitment of rat sciatic nerve.
Recruitment curves were generated with different values for several design parameters. a) Increasing the inner diameter of the cuff (1 mm contact separation, 1 mm cuff overhang, 270°) drastically reduces recruitment. b) Increasing the distance between the two stimulating contacts (1 mm cuff inner diameter, 1 mm cuff overhang, 270°) increases recruitment. c) Increasing the amount of cuff overhang (1 mm cuff inner diameter, 1 mm contact separation, 270°) increases recruitment. d) Reducing the angle of coverage (1 mm cuff inner diameter, 1 mm contact separation, 1 mm cuff overhang) has minimal effect on recruitment.
Fig 3.
Approximately flat electrode does not reduce fiber recruitment in rat sciatic nerve.
a) Schematic diagram of the experimental setup. b) Schematic diagram of the three cuff electrode designs tested on the rat sciatic nerve. c) Force generated as a function of stimulation intensity for each electrode design. All geometries result in similar recruitment. Shaded regions represent SEM. d-g) Thresholds, saturation currents, dynamic ranges, and slopes are similar for each electrode design. Data indicate mean ± SEM, and circles represent individual data.
Fig 4.
Reducing angle of coverage increases fiber recruitment in a model of the rat vagus nerve.
a) Recruitment curves generated using a cuff with a 1 mm inner diameter, but with the nerve positioned at next to the contacts. Reducing the angle increases recruitment. b) Recruitment curves generated using a cuff with a 1 mm inner diameter, but with the nerve positioned in the middle of the cuff lumen. Reducing the angle has no effect. c) Recruitment curves generated using a cuff with a 1 mm inner diameter, but with the nerve on the opposite side of the cuff lumen from the contacts. Reducing the angle decreases recruitment. d) Recruitment curves generated by modeling cuff electrodes with various angles of completion around the rat vagus. Instead of a 1 mm inner diameter, the cuff diameter was set to 0.44 mm to keep the ratio of the cuff diameter to nerve the same as in the sciatic model. When the cuff is sized to fit the nerve, reducing the angle has little effect on fiber recruitment.
Fig 5.
Reducing angle of coverage to approximate a flat electrode increases fiber recruitment in rat vagus nerve.
a) Schematic diagram of the experimental setup. b) Schematic diagram of the two cuff electrode designs tested on the rat vagus nerve. c) Decreases in SpO2, a biomarker of vagal activation, as a function of stimulation intensity for each electrode design (y-axis is percent of maximum reduction). Similar to modeling results, the decreased angle of coverage generates more efficient nerve recruitment. d-g) Thresholds are similar for each design. The 60° electrodes displayed reduced saturation current, dynamic range, and increased slope compared to the 270° electrodes. Data indicate mean ± SEM, and circles represent individual data.
Fig 6.
Flat and circumferential electrodes provide similar recruitment in a model of the rabbit sciatic nerve.
Recruitment curves generated by modeling cuff electrodes around the rabbit sciatic nerve with either flat or circumferential contacts. Note the similarity in fiber recruitment.
Fig 7.
Models of flat and circumferential electrodes in various extracellular media and on various nerve sizes.
a) Recruitment curves generated by modeling flat and circumferential electrodes in various ambient mediums. The conductivity of the ambient medium was varied from saline to fat. As expected, the extracellular medium influences recruitment efficiency, but recruitment is similar between the two electrode designs in all cases. b) Recruitment curves generated by modeling flat and circumferential electrodes on various diameter nerves. All features of the cuff electrode were kept proportional and scaled to match the nerve. In all cases, recruitment is similar between the two designs.
Fig 8.
Flat electrodes result in greater threshold variability for individual fascicles, but similar recruitment of the whole nerve.
a) Whole nerve recruitment curves for the four combinations modeled. b-e) Recruitment curves for each fascicle (line color corresponds to fascicle of same color) and whole nerve recruitment (thick black line).
Fig 9.
Flat and circumferential electrodes provide similar recruitment of rabbit sciatic nerve.
a) Schematic diagram of the experimental setup. b) Schematic diagram of the two cuff electrode designs tested on the rabbit sciatic nerve. c) Force generated as a function of stimulation intensity for flat and circumferential electrodes. Both designs achieve efficient recruitment of the sciatic nerve, consistent with modeling predictions. d-f) Thresholds, saturation current, and dynamic range are similar for each electrode design. Data indicate mean ± SEM, and circles represent individual data.
Fig 10.
Recruitment of vagus nerve is similar in humans and rats due to cuff electrode design.
Larger nerves require more current to recruit, but the therapeutic range of vagus nerve stimulation is similar in rats and humans (Fig 7B). This phenomenon can be explained by the use of tight-fitting stimulating electrodes for human studies and poorly fitting, oversized cuff electrodes for rat studies. Cuff electrodes used in rats are significantly larger than the nerve which leads to inefficient recruitment and brings the two curves into alignment. If rat cuff electrodes were reduced in size, recruitment would be greatly increased. This is consistent with the importance of the ratio of cuff inner diameter to nerve diameter (Fig 2A).