Fractal Microelectrodes for More Energy-Efficient Cervical Vagus Nerve Stimulation

Abstract

Vagus nerve stimulation (VNS) has the potential to treat various peripheral dysfunctions, but the traditional cuff electrodes for VNS are susceptible to off-target effects. Microelectrodes may enable highly selective VNS that can mitigate off-target effects, but they suffer from the increased impedance. Recent studies on microelectrodes with non-Euclidean geometries have reported higher energy efficiency in neural stimulation applications. These previous studies use electrodes with mm/cm-scale dimensions, mostly targeted for myelinated fibers. This study evaluates fractal microelectrodes for VNS in a rodent model (N = 3). A thin-film device with fractal and circle microelectrodes is fabricated to compare their neural stimulation performance on the same radial coordinate of the nerve. The results show that fractal microelectrodes can activate C-fibers with up to 52% less energy (p = 0.012) compared to circle microelectrodes. To the best of the knowledge, this work is the first to demonstrate a geometric advantage of fractal microelectrodes for VNS in vivo.

Keywords: fractal; microelectrodes; vagus nerve stimulation.

Figure 1

Overview of the study and the device for the evaluation of the microelectrodes. a) The conceptual illustration of using microelectrodes for a spatially selective VNS in comparison with the circumferential cuff electrode, which is conventionally used for VNS. b) The concept of using the Vicsek fractal microelectrode toward energy‐efficient selective VNS. c) Schematic illustration of the design to compare the circle and the fractal microelectrodes in one nerve. d) Optical microscopic images of the devices as fabricated. Scale bar: 500 µm e,f) Optical microscopic images of the fractal (e) and the circle (f) microelectrodes after Pt‐black coating. Scale bar: 50 µm.

Figure 2

Electrochemical characterization of the bare Pt and Pt‐black electrode‐electrolyte interface. a) Cyclic voltammogram of each electrode type in PBS solution. b) Cathodic charge storage capacity of the circle/fractal microelectrode with bare Pt surface (* p = 0.0024, N = 4); and Pt‐black coated surface (** p = 0.00021, N = 4). c) Bode plots from the impedance response of each type of electrode. d) Bode plots from the phase angle responses of each type of electrode.

Figure 3

Voltage transient measurements of the microelectrodes. a) A representative plot of the voltage transient response of each type of microelectrode and monitored current pulse. b) E _mc profile for each type of microelectrode in PBS at 0.5 ms of pulse duration. The green dashed line indicates the cathodic limit of water electrolysis (−0.6 V vs Ag/AgCl). c) Load energy profile for each type of microelectrode at 0.5 ms of pulse duration. N = 4 electrodes each.

Figure 4

In vivo experiment of VNS with different electrodes and ECAP recordings. a) Schematic illustration of in vivo experiment setting. b,c) Photographic images of the surgical cavity with the implantation of the circumferential cuff electrode (b) or the thin‐film device with microelectrodes (c) for stimulation. Scale bar: 2 mm. d–f) Comparison of the mean ECAPs from the right cervical vagus nerve stimulated with different types of electrodes at different pulse current amplitudes in one animal (pulse duration = 1 ms). Diphasic volleys appear at a latency between 5 and 15 ms (shaded green). g–i) Diphasic volleys for different types of electrodes plotted with respect to conduction velocity. N1: Negative peak, P1: Positive peak.

Figure 5

Comparison of C‐fiber recruitment profiles from circle and fractal microelectrodes. a–c) Recruitment profiles of |V _pp| from three animals at 1 ms of pulse duration. d) Recruitment profile of normalized |V _pp| from all three animals. Shaded regions are 95% confidence intervals for circle (red) and fractal (gray). e) Profiles of load energy with respect to pulse current amplitude. f) Activation profile (normalized peak‐to‐peak amplitude of nerve response) with respect to load energy. The intersection of each line plot to the blue line (at 0.5 of normalized |V _pp|) shows the load energy level to recruit 50% of maximum recruitable axons from each microelectrode. Fractal microelectrodes consumed 51.99 ± 33% (p = 0.012) less energy (424.3 ± 53 nJ) than circle microelectrodes (883.8 ± 250 nJ). Pulse duration = 1 ms.

Figure 6

Thresholds of simulated Tigerholm C‐fiber model axons. a,b) Contour plots of threshold distribution for C‐fiber model axons for a circle (a) and a fractal (b) microelectrode. Red and grey rectangle annotations show the footprint extent of the circle and fractal microelectrodes, respectively. c) Scatter plot comparing the threshold of each C‐fiber axon stimulated with circle and fractal microelectrodes. d) Modeled recruitment profile of C‐fiber efferents and afferents for circle and fractal. Vertical lines indicate the threshold at 50% recruitment.