Optimization Of Rectangular Pulse Parameters And Waveforms For Electrically Stimulating RGCs With Genetic Algorithm

ObjectiveThe epiretinal prosthesis?EP?is a kind of neuroimplantation prosthesis,which restores blind patients'vision through electrically stimulating the survival retinal ganglion cells?RGCs?to elicit excitation and processing the externally acquired image information by implanting microelectrode arrays on the retina surface.The EP has been widely used in experimental and clinical studies.However,there are still many performance defects that need to be improved,such as low image resolution,low biocompatibility,high energy consumption,and short device life.At present,there are many methods for improving the function of prosthesis,such as improving the microelectrode array or electrical stimulation waveform.The electrical stimulation waveform for EP is currently a charge-balanced rectangular waveform consisting of a stimulating phase and a balance phase.However,the parameters combination of rectangular stimulation waveform applied to the prosthesis is not uniform,and whether the rectangular waveform is the best is still debatable.This study aims to find the best electrical stimulation waveform shapes.MethodsA multi-compartmental simulation model for extracellular electrical stimulation of RGCs was established.The model includes axons,soma,dendrites and an electrode;Fohlmeister-Colman-Miller?FCM?model was used to characterize the membrane properties of RGCs.The stimulating electrode is a unipolar ideal point electrode that acts on the soma of RGCs,and the medium between them is a homogeneous vitreous medium with a conductivity of 0.057 k??cm.The effect of parameter changes in rectangular waveform on the stimulating effect was studied.The parameters of the traditional rectangular waveform includes five parts:the stimulation polarity,the amplitude?A?,the stimulation duration?pd1?,the amplitude ratio of the stimulating phase and the balance phase?PDR?,and the interval gap?ipi?.The frequency-current curve was used to identify the type of RGCs and threshold criteria was determined according to the RCGs'type.Action potentials were generated as the membrane potential that exceeded+20 mV.The energy and charge were calculated with the varied parameters.The minimum current amplitude of the stimulation required to generate an action potential in a rectangular waveform was described by a strength-duration curve.The genetic algorithm?GA?was used to optimize the parameters of rectangular waveform and the stimulating waveform shape.Three cost functions were designed for GA optimization.The cost function only containing the energy consumption would obtain the energy optimal results;when only the safety was considered,the charge optimal results were obtained;when both the energy consumption and the safety were taken into account,the GA optimal results were obtained.Once the difference of cost values between two successive generations was less than 0.001%,the one optimization is terminated.Rectangular waveform parameters were optimized with GA.According to the experimental results from literatures,the parameter space of the duration,amplitude,amplitude ratio and gap were determined.The polarity was always cathodic-first.The rectangular waveforms composed of optimized parameters were compared with traditional symmetrical rectangular waveform in energy and charge.Electrical stimulation waveform shape was optimized with GA.Only the stimulating phase in the waveform was optimized,and a rectangular waveform with the same width and charge as stimulating phase was used as the balance phase.According to the experimental results from literatures,the ranges of initial generation stimulus amplitude and pulse width of GA were determined.The optimized results were compared with the traditional rectangular waveform in the energy and charge.ResultsThe RGCs extracellular electrical stimulation models can effectively simulate the response of various parts of RCGs.The RGCs belong to the first type neuron according to Hodgkin classification method and the current intensity can be used to determine the threshold.The stimulation threshold amplitude was defined by the lowest amplitude of a pulse that causes RGCs to initiate an AP,and energy and charge at the threshold level were obtained.When the polarity in the rectangular waveform was changed,the threshold amplitude with anodic-first pulse was 33.109?A,while the amplitude with cathodic-first pulse was 25.004?A,the energy consumption was reduced by 42.96%,and the charge was lower than the former of 24.47%.The duration of the waveform?range of0.1-3ms?was changed using a cathodic-first symmetric rectangular waveform without an interval.When the maximum duration was 3ms,the minimum threshold current was17.9?A,called rheobase current.The chronaxie was close to 0.5ms,and the minimum energy was 1204.09pJ.For the duration of 0.1ms,the minimum charge was 10.47nC,which was lower than the charge at chronaxie of 6.88nC.The effect of other parameters was observed when the stimulus duration was fixed at chronaxie.When the amplitude ratio?range of 1-35?was 35,the minimum energy was 764.38pJ,which is reduced by439.71pJ than the symmetric pulse.When the gap?range of 0-1ms?was 0.35ms or0.4ms,the lowest energy was 759.51pJ,which was lower than the rectangular waveform without an interval of 444.58pJ.The adjustment of parameters can reduce the energy or charge of stimulation,GA was used to optimize the parameters of cathodic-first rectangular waveform.The energy and charge of the traditional symmetric rectangular waveform at threshold level were 795.21pJ and 13.52nC,respectively.Only considering the energy consumption,the energy optimal parameter combinations were₁A?28?25.181?A,pd₁?28?0.603ms,PDR?28?29.99,ipi?28?4.91ms and the energy was 389.9560pJ,which was 50.96%lower than the threshold energy.The charge optimal parameters wereA₁?28?55.10?A,pd₁?28?0.22ms,PDR?28?9.33,ipi?28?3.95ms,and the charge was 12.26nC,which was nearly 10%lower than the threshold charge.The GA optimal parameters were ₁A?28?15.625?A,pd₁?28?0.86ms,PDR?28?29.88,ipi?28?4.99ms.The charge and energy were13.11nC and 211.15533pJ,respectively,which were reduced by 3.06%and 73.45%.When GA was used to optimize the stimulation waveform,the stimulating phase width was 1ms according to the actual prosthesis application data from literatures,the energy and charge of the rectangular waveform at this time were 489.5272pJ and15.409nC.And waveforms were converged into waveforms with similar shapes.Both the energy optimal waveform and the GA optimal waveform were similar to a truncated Gaussian waveform,and the charge optimal waveform was similar to a T-type waveform.The energy of the energy optimal waveform was 465.2082pJ,which was24.319pJ lower than that of rectangular waveform.The charge of the charge optimal waveform was 14.0528nC,which was 1335pC lower than that of rectangular waveform.The energy and charge of the GA optimal waveform were reduced by 24.0295pJ and854pC from the rectangular waveform.After the pulse width was extended,the charge of all the optimized waveforms were lower than that of the rectangular waveform,and the energy decreased with time.ConclusionsThe results have shown that the change in the stimulation parameters of the rectangular waveform affects RGCs response to the electrical stimulation.The polarity of the pulse plays a role in the stimulating effect,and the cathodic-first pulse can stimulate RCGs to generate APs with a lower amplitude.Increasing the pulse width can reduce the stimulus amplitude and energy of rectangular waveform,while the shortest pulse width consumes the smallest charge.Changes in the gap between phases have a more obvious effect on energy.Optimizing both the parameters in rectangular waveform and the waveform shape can generate lower energy and charge than that of the traditional rectangular waveform.The GA optimized waveform shapes resemble a truncated Gaussian waveform or a T-type waveform.Longer pulse widths consume less energy than shorter ones,but the change of charge is opposite.The energy and charge of GA waveforms with the same pulse width are both lower than these of the rectangular waveform.Therefore,the traditional rectangular waveform has been proven not to be optimal waveforms in terms of the energy and charge.Multiple factors should be taken into account in the application of the retinal prosthesis.Optimizing the waveform and parameters of the electrical stimulation can reduce energy consumption and/or charge.The optimized results have a certain significance for improving the performance of the retinal prosthesis.