(58) Quantifying the Influence of Non-Linear Electrode-Tissue Interface Dynamics on Intracortical Microstimulation using Computational Modeling

Introduction: Intracortical microstimulation (ICMS) is used in preclinical and clinical studies to map neuronal circuitry in the brain, restore lost sensory functions, and establish a causal link between a brain region and its function. Existing models of ICMS neglect the effects of electrode-tissue interface (ETI) impedance. Since stimulus delivery in clinical and preclinical studies is current-controlled, the variations in ETI impedance are expected to have a negligible effect on neuronal activation as the potential distribution in the surrounding tissue remains unchanged. However, the ETI may exhibit nonlinear behavior at higher stimulus currents, particularly due to increased charge transfer through Faradaic processes, which can increase the risk for electrode and tissue damage [1, 2]. Hence, updating ICMS models to represent ETI impedance accurately is essential for determining non-damaging charge limits for stimulating microelectrodes.

Methods: We developed finite element models of a simplified electrode geometry immersed in saline, followed by an ultramicroelectrode array (developed by NeuroNexus, Inc) implanted in a cortical column. The electrical double-layer interface was approximated as a thin layer surrounding the electrode contact and represented using an electrical model comprising a constant phase element and a charge transfer resistance connected in parallel [1, 3]. We conducted simulations in the frequency domain across various frequencies and stimulation amplitudes, quantifying the variation of interface overpotentials with stimulation amplitude for both current- and voltage-controlled stimulation. Further, we computed time-dependent solutions using inverse Fourier Transform and compared the tissue voltage waveform evoked by biphasic stimulus pulse with and without the ETI impedance model.

Results: Interface overpotentials exhibited a linear relationship with stimulation amplitude up to a certain intensity for both current- and voltage-controlled stimulation, beyond which non-linearity emerged. This transition to non-linearity occurred at lower stimulation amplitudes for higher frequencies. In the case of voltage-controlled stimulation, time-domain analyses revealed substantial differences in the voltage waveform in the tissue between models with and without ETI impedance. In contrast, the impact of ETI impedance was minimal for current-controlled stimulation at the tissue. However, the tissue capacitance influenced the tissue voltage waveform for current-controlled stimulation.

Conclusion: The results underscore the importance of ETI impedance in ICMS models. Although current-controlled stimulation showed minimal impact of ETI impedance on tissue potential distribution, quantifying the stimulation intensity at which the ETI transitions to the non-linear regime is essential to establish the non-damage limits to prevent electrode or tissue damage.