Objective.The electrode-tissue interface provides the critical path for charge transfer in neurostimulation therapies and exhibits well-established nonlinear properties at high applied currents or voltages. These nonlinear properties may influence the efficacy and safety of applied stimulation but are typically neglected in computational models. In this study, nonlinear behavior of the electrode-tissue interface impedance was incorporated in a computational model of deep brain stimulation (DBS) to simulate the impact on neural activation and safety considerations.Approach.Nonlinear electrode-tissue interface properties were incorporated in a finite element model of DBS electrodesin vitroandin vivo,in the rat subthalamic nucleus, using an iterative approach. The transition point from linear to nonlinear behavior was determined for voltage and current-controlled stimulation. Predicted levels of neural activation during DBS were examined and the region of linear operation of the electrode was compared with the Shannon safety limit.Main results.A clear transition of the electrode-tissue interface impedance to nonlinear behavior was observed for both current and voltage-controlled stimulation. The transition occurred at lower values of activation overpotential for simulatedin vivothanin vitroconditions (91 mV and 165 mV respectively for current-controlled stimulation; 110 mV and 275 mV for voltage-controlled stimulation), corresponding to an applied current of 30μA and 45μA, or voltage of 330 mV at 1 kHz. The onset of nonlinearity occurred at lower values of the overpotential as frequency was increased. Incorporation of nonlinear properties resulted in activation of a higher proportion of neurons under voltage-controlled stimulation. Under current-controlled stimulation, the predicted transition to nonlinear behavior and Faradaic charge transfer at stimulation amplitudes of 30μA, corresponds to a charge density of 2.29μC cm-2and charge of 1.8 nC, well-below the Shannon safety limit.Significance.The results indicate that DBS electrodes may operate within the nonlinear region at clinically relevant stimulation amplitudes. This affects the extent of neural activation under voltage-controlled stimulation and the transition to Faradaic charge transfer for both voltage- and current-controlled stimulation with important implications for targeting of neural populations and the design of safe stimulation protocols.
Keywords: computational model; deep brain stimulation; electrode-tissue interface; non-linear region; parkinson’s disease.
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