Intraneural ultramicroelectrode arrays for function-specific interfacing to the vagus nerve.

Selective interfacing to small multifunctional nerves such as the vagus nerve (VN) which is the main multimodal autonomic nerve that provides a major communication pathway from vital peripheral organs to the brain, can have significant potential in treating and diagnosing diseases as well as enhancing our understanding of peripheral nerve circuits. Here we describe the fabrication of a 16-channel intraneural electrode array with ultramicro-dimensioned electrodes to achieve improved functionally selective recording. We demonstrate that the amorphous silicon carbide ultramicroelectrode arrays (a-SiC UMEAs) provide selectivity in the detection of neural activity in the cVN related to changes in systemic oxygenation and blood pressure. We will also demonstrate spatially selective recording of micro-compound action potentials (µCAPs) by electrical stimulation of the subdiaphragmatic branches of the VN. Distinct neural activity was recorded on electrodes separated by less than about 100 µm. This is the first time that this level of spatially selectivity recording has been demonstrated in the cVN with an intraneural multielectrode array.

Electrochemical characterization of high frequency stimulation electrodes: role of electrode material and stimulation parameters on electrode polarization.

OBJECTIVE: With recent interest in kilohertz frequency electrical stimulation for nerve conduction block, understanding the electrochemistry and role of electrode material is important for assessing the safety of these stimulus protocols. Here we describe an approach to determining electrode polarization in response to continuous kilohertz frequency sinusoidal current waveforms. We have also investigated platinum, iridium oxide, and titanium nitride as coatings for high frequency electrodes. The current density distribution at 50 kHz at the electrode-electrolyte interface was also modeled to demonstrate the importance of the primary current distribution in supporting charge injection at high frequencies. APPROACH: We determined electrode polarization in response to sinusoidal currents with frequencies in the 1-50 kHz range and current amplitudes from 100 to 500 µA and 1-5 mA, depending on the electrode area. The current density distribution at the interface was modeled using the finite element method (FEM). MAIN RESULTS: At low frequencies, 1-5 kHz, polarization on the platinum electrode was significant, exceeding the water oxidation potential for high amplitude (5 mA) waveforms. At frequencies of 20 kHz or higher, the polarization was less than 300 mV from the electrode open circuit potential. The choice of electrode material did not play a significant role in electrode polarization at frequencies higher than 10 kHz. The current density distribution modeled at 50 kHz is non-uniform and this non-uniformity persists throughout charge delivery. SIGNIFICANCE: At high frequencies (>10 kHz) electrode double-layer charging is the principal mechanism of charge-injection and selection of the electrode material has little effect on polarization, with platinum, iridium oxide, and titanium nitride exhibiting similar behavior. High frequency stimulation is dominated by a highly nonuniform primary current distribution.

Thinking Small: Progress on Microscale Neurostimulation Technology.

OBJECTIVES: Neural stimulation is well-accepted as an effective therapy for a wide range of neurological disorders. While the scale of clinical devices is relatively large, translational, and pilot clinical applications are underway for microelectrode-based systems. Microelectrodes have the advantage of stimulating a relatively small tissue volume which may improve selectivity of therapeutic stimuli. Current microelectrode technology is associated with chronic tissue response which limits utility of these devices for neural recording and stimulation. One approach for addressing the tissue response problem may be to reduce physical dimensions of the device. "Thinking small" is a trend for the electronics industry, and for implantable neural interfaces, the result may be a device that can evade the foreign body response. MATERIALS AND METHODS: This review paper surveys our current understanding pertaining to the relationship between implant size and tissue response and the state-of-the-art in ultrasmall microelectrodes. A comprehensive literature search was performed using PubMed, Web of Science (Clarivate Analytics), and Google Scholar. RESULTS: The literature review shows recent efforts to create microelectrodes that are extremely thin appear to reduce or even eliminate the chronic tissue response. With high charge capacity coatings, ultramicroelectrodes fabricated from emerging polymers, and amorphous silicon carbide appear promising for neurostimulation applications. CONCLUSION: We envision the emergence of robust and manufacturable ultramicroelectrodes that leverage advanced materials where the small cross-sectional geometry enables compliance within tissue. Nevertheless, future testing under in vivo conditions is particularly important for assessing the stability of thin film devices under chronic stimulation.

Effect of planar microelectrode geometry on neuron stimulation: finite element modeling and experimental validation of the efficient electrode shape.

BACKGROUND: Microelectrode arrays have been used successfully for neuronal stimulation both in vivo and in vitro. However, in most instances currents required to activate the neurons have been in un-physiological ranges resulting in neuronal damage and cell death. There is a need to develop electrodes which require less stimulation current for neuronal activation with physiologically relevant efficacy and frequencies. NEW METHOD: The objective of the present study was to examine and compare the stimulation efficiency of different electrode geometries at the resolution of a single neuron. We hypothesized that increasing the electrode perimeter will increase the maximum current density at the edges and enhance stimulation efficiency. To test this postulate, the neuronal stimulation efficacy of common circular electrodes (smallest perimeter) was compared with star (medium perimeter), and spiral (largest perimeter with internal boundaries) electrodes. We explored and compared using both a finite element model and in vitro stimulation of neurons isolated from Lymnaea central ganglia. RESULTS: Interestingly, both the computational model and the live neuronal stimulation experiments demonstrated that the common circular microelectrode requires less stimulus to activate a cell compared to the other two electrode shapes with the same surface area. Our data further revealed that circular electrodes exhibit the largest sealing resistance, stimulus transfer, and average current density among the three types of electrodes tested. COMPARISON WITH EXISTING METHODS: Average current density and not the maximum current density at the edges plays an important role in determining the electrode stimulation efficiency. CONCLUSION: Circular shaped electrodes are more efficient in inducing a change in neuronal membrane potential.