Optimization Of Electrical Stimulation Pulse And Waveform For Epiretinal Prostheses

ObjectiveVisual prosthesis is an artificial organ for the blinds to regain vision by electrical stimulation applied to the specific visual nerve cells on optic pathway for generating neural excitation. There are many different visual prostheses based on the placement of stimulus microelectrodes. Epiretinal prosthesis is one of visual prostheses whose microelectrodes are applied on the retinal ganglion cells(RGC). The extensive research and application of the epiretinal prostheses have been done, but the experimental and clinical effect is still not very satisfactory. One of the important factors that affect the application of epiretinal prostheses is stimulation waveform. The conventional waveform is the biphasic rectangular pulse, whose stimulus parameters are comprised of the stimulus amplitude of cathode, the cathodic duration, the amplitude ratio of cathode to anode and the interphase gap. Currently, stimulus parameters of rectangular pulse applied on epiretinal prostheses are not relatively unified. In addition to the bipolar rectangular pulse, there are actually a variety of electrical stimulation waveforms. It is still uncertain which stimulus waveform is more suitable for epiretinal prostheses. It is particularly important to find the appropriate parameters of pulse and the shape of stimulation waveform for epiretinal prostheses. MethodsThe extracellular simulation model was built to simulate the electrical stimulation of epiretinal prostheses, in which the RGC cell was represented by multi-compartmental model and the cell’s membrane kinetics properties was evaluated with the Fohlmeister-Colman-Miller(FCM) model, and the simulated extracellular electrode, placed over the soma, was treated as an ideal point electrode.The optimal parameters of rectangular pulse was found by the parametric sweep method. According to literatures, the parametric ranges of pulse were established as follows: the cathodic duration(0.1ms to 1ms), the amplitude ratio of cathode to anode(1 to 30), and the interphase gap(0ms to 5ms). Only varying the stimulus amplitude of cathode, whenever an action potential(AP) was successfully detected on RGC cell, the minimal amplitude for that rectangular pulse, called as stimulation threshold, was saved. The above-mentioned parametric space was swept to determine the rectangular pulse with the minimal threshold, the smallest energy or the minimal charge transferred by cathode at threshold. The best parameters of rectangular pulse that has the minimum threshold, threshold energy and charge was selected.Genetic algorithm(GA) was used to optimize the shape of electrical stimulation for epiretinal prostheses. The stimulation waveform used today in epiretinal prostheses consists of a first, cathodal, activating phase and a second, anodal, charge-balanced phase. In this paper, GA algorithm was used for optimizing the cathodal phase of stimulation waveform with a fixed duration. To keep the balance of charge, the anode was a rectangular pulse behind the cathode. The duration and charge quantity of anode were equal to those of cathode phase. With a different cost function of GA algorithm, different optimized shapes could be obtained. The energy and charge quantity of waveforms optimized by GA algorithm were compared with those of other stimulus waveforms, including rectangular pulse, exponent wave, step wave, linear wave, triangle wave, sine wave, Gaussian wave. ResultsThe entire electrical stimulation process of RGC cell could be simulated by the extracellular stimulation model. When the threshold of a pluse was arrived, an AP could be generated with the RGC cell’s stimulation model. With the membrane voltage varied, the changes of ionic current and state variables of ion channels during RGC cell’s AP could also be observed with the stimulation model.The duration of cathode was swept with the other parameters of rectangular pulse fixed. When the cathodic duration of pulse was 0.1ms, the lowest stimulation threshold was 15.4μA, and the lowest energy consumption was 474.4pJ. The minimal charge quantity was 11.49 nC at the 0.1ms cathodic duration. When the amplitude ratio of cathode to anode was 29 or 30 with keeping the other parameters constant, the lowest threshold of rectangular pulses was 28.7μA, the lowest energy consumption was 757.8pJ, and the smallest charge quantity was 13.21 nC. When the interphase gap of rectangular pulse ranged from 0.5ms to 1.1ms under the other parameters fixed, the minimum threshold was 26.3μA. Under the above-mentioned circumstances energy consumption and charge quantity were respectively the smallest, which were 636.4pJ and 12.10 nC.When the parameters of pulse were simultaneously optimized, the minimum stimulation threshold was 13.7μA. The stimulation pulse had the minimum threhold whose cathodic duration was 1ms, the amplitude ratio of cathode to anode was 30 and interphase gap was from 0.8ms to 5ms. When cathodic duration was 1ms, the amplitude ratio was 30 and gap was 5ms, energy consumption was as low as 188.5pJ. When charge quantity was the minimum(11.84nC), the cathodic duration was 0.1ms, the amplitude ratio was 30 and the interphase gap was 5ms.With the progress of GA algorithm, the stimulus waveform gradually converge to an optimal shape with the smallest energy consumption or charge quantity. The GA energy waveform was the shape optimized by GA algorithm with a cost function of energy consumption, whose shape was similar to the truncation skewness curve after optimization of ten thousand generations. The GA waveform, optimized by GA algorithm with a cost function that consisted of energy consumption and transferred charge quantity after optimization of ten thousand generations, was similar to GA energy waveform, but whose shape was smoother. The smalllest energy consumption of GA energy waveform whose cathodic duartion was 0.46 ms was 760.8pJ, and the transferred charge quantity reached 13.04 nC. The energy consumption and charge quantity of GA waveform with 0.46 ms cathodic duration were 766.8pJ and 12.55 nC, respectively.Compared to other stimulus waveforms, the GA energy waveform had the lowest energy, which was followed by two-step stimulation waveform. The increasing exponential waveform had the highest energy consumption and charge quantity when an AP was triggered. Under the condition of 0.46 ms cathodic duration, the energy of GA energy waveform was reduced by 673.3pJ and the transferred charge amount was reduced by 0.53 nC at most. The rate of relative reduction were up to 87.03% and 1.13%, respectively. The energy and charge of GA waveform reduce by 667.3pJ and 9.01 nC at most. ConclusionsThe stimulus threshold, energy consumption and charge quantity at threshold are affected by the parameters of rectangular pulse. The rectangular pulse satisfying the corresponding optimal conditions that are the mimimal threshold, energy or charge at threshold is found by sweeping the parametric space of pulse for epiretinal prostheses. The longer cathodic duration is, the lower threshold and energy consumption are, but the greater transferred charge amount is. When the amplitude ratio of cathode to anode is increased, the threshold, energy and delivered charge gradually reduced and rapidly rose. With the gap increased gradually, the threshold, energy and charge quantity slowly rose and rapidly fel. There are not the parameters of pulse that meet the minimum threshold, energy consumption and charge quantity at the same time.The stimulus waveform with a fixed duration optimized by GA algorithm progressively convert to a similar shape. The lower energy consumption and the smaller transmitted charge quantity of waveforms optimized by GA algorithm were obtained than those of others waveforms when an AP was triggered. The GA energy waveform has the lowest energy consumption. The GA waveform is an optimal shape when energy consumption and transmitted charge are considered at the same time.The optimized parameters of rectangular pulse or the optimized waveform presented in this paper have important implications for research and application of epiretinal prostheses, as well as other types of visual prostheses. If the optimized parameters or stimulus waveforms would be used, the life of epiretinal prostheses could be prolonged, thereby substantially reducing the cost of epiretinal prostheses. These suggest a possible means for more effective stimulation fitted with epiretinal prostheses.