Stimulation-induced changes at the electrode–tissue interface and their influence on deep brain stimulation

Abstract

Objective: During deep brain stimulation (DBS) the electrode-tissue interface forms a critical path between device and brain tissue. Although changes in the electrical double layer and glial scar can impact stimulation efficacy, the effects of chronic DBS on the electrode-tissue interface have not yet been established. Approach: In this study, we characterised the electrode-tissue interface surrounding chronically implanted DBS electrodes in rats and compared the impedance and histological properties at the electrode interface in animals that received daily stimulation and in those where no stimulation was applied, up to eight weeks post-surgery. A computational model was developed based on the experimental data, which allowed the dispersive electrical properties of the surrounding encapsulation tissue to be estimated. The model was then used to study the effect of stimulation-induced changes in the electrode-tissue interface on the electric field and neural activation during voltage- and current-controlled stimulation. Main results: Incorporating the observed changes in simulations in silico, we estimated the frequency-dependent dielectric properties of the electrical double layer and surrounding encapsulation tissue. Through simulations we show how stimulation-induced changes in the properties of the electrode-tissue interface influence the electric field and alter neural activation during voltage-controlled stimulation. A substantial increase in the number of stimulated collaterals, and their distance from the electrode, was observed during voltage-controlled stimulation with stimulated ETI properties. In vitro examination of stimulated electrodes confirmed that high frequency stimulation leads to desorption of proteins at the electrode interface, with a concomitant reduction in impedance. Significance: The demonstration of stimulation-induced changes in the electrode-tissue interface has important implications for future DBS systems including closed-loop systems where the applied stimulation may change over time. Understanding these changes is particularly important for systems incorporating simultaneous stimulation and sensing, which interact dynamically with brain networks.

Nonlinear effects at the electrode-tissue interface of deep brain stimulation electrodes

“…The electric field in the model of the rat brain was then coupled to a population of multicompartment neuron axon models representing branching axon collaterals within the STN to examine the effect of nonlinear electrode properties on the extent of neural activation [21,24]. The electric field surrounding the DBS electrode was simulated using a 3D piecewise heterogeneous model [4]. For both current and voltage-controlled stimulation, the electrode interface was incorporated into the finite element model using a thin layer approximation [16,17], with the constant phase element impedance and charge transfer resistance varying as a function of the activation overpotential in the nonlinear model.…”

“…The segmented masks of the different brain tissues were converted to a geometric model using the Simpleware ScanIP software (Synopsys, USA) as described in Evers et al [4]. The electrode was surrounded by 100 µm thick encapsulation tissue representing the glial scar formed during chronic electrode implantation [4].…”

“…Charge carried by electrons at the electrode is converted to charge carried by ions in the tissue either through capacitive coupling, with charging and discharging of the electrical double layer, or through Faradaic reactions involving oxidation and reduction, representing non-Faradaic and Faradaic charge transfer respectively [3]. During stimulation there may also be a reduction in electrode impedance due to stimulationinduced changes in the electrode-tissue interface, including desorption of protein ions at the electrode surface [4].…”

“…Changes in the impedance of the electrode-tissue interface directly affect the distribution of the electric field and extent of neural activation during voltagecontrolled stimulation. While electrode impedance would be expected to have a negligible effect on the activation of neurons under current-controlled stimulation, as the voltage distribution in the surrounding tissue remains unchanged [4,18], activation overpotentials generated at the electrode interface may alter the electrochemical behavior which can have an important influence in determining the safety of the applied stimulation.…”

“…To address these questions, in this paper we implemented a nonlinear model of the electrode interface in silico representing in vitro and in vivo conditions based on rat DBS electrodes for both current and voltage-controlled stimulation. The model incorporated experimentally obtained values for the electrode interface and encapsulation tissue electrical properties [4]. The unknown potentials at the electrode interface were solved using the time harmonic quasi-static formulation of Maxwell's equations with an iterative approach.…”