| ObjectiveEpiretinal Prosthesis(EP)is a nerve implantation device that implants microelectrode arrays on top of retina to stimulate surviving retinal ganglion cells(RGC)to restore the vision of the blind.EP is a widely studied and applied visual prosthesis,but its clinical effect is still not ideal.There are many factors affecting the clinical effect of the experiment,such as electrical stimulation waveforms or microelectrode arrays.Therefore,this paper establishes a multi-compartment model of optic nerve fibers using MATLAB as the experimental simulation platform to study the efficiency of different factors on the stimulation effect,so as to provide some guidance for the theoretical research and clinical application of epiretinal prosthesis.MethodsUsing MATLAB as an experimental simulation platform,a multi-compartment model of extracellular electrical stimulation of RGCs was established.The model took axons,dendrites and cell bodies into account and modeled.The membrane characteristics were described by Fohlmeister-Colman-Miller(FCM).The electrodes for extracellular electrical stimulation are point electrodes placed directly above the axons of the RGCs,and the electrodes are in a homogeneous medium with a conductivity of 57 W× cm.Frequency-current curve was used to identify the type of neurons,determine the type of ganglion cells and determine the criteria for judging the threshold.The characteristics of ion channels in cell membranes and the response of RGC multicompartment model to different extracellular electrical stimulations were analyzed.The dynamic process of action potential produced by RGC multi-compartment model was analyzed by phase diagram.The relationship between stimulus current and time in RGC multi-compartment model was analyzed by intensity-time curve under extracellular electrical stimulation.The changes of action potential and stimulation threshold were analyzed according to the different positions of ideal point electrodes from optic nerve fibers.Rectangular wave contained five parameters: polarity,amplitude,the ratio of cathode to anode,stimulation time and the interval between cathode and anode.The effects of changing these parameters on stimulation effect were analyzed,and the effects of other stimulation waveforms on stimulation effect are also analyzed.Results 1.The multi-compartment model of RGCs established in this paper reproduced the response of each part of neurons after extracellular electrical stimulation.Method for classifying cells according to Hodgkin,RGCs were identified as the first type of neurons,and the method to determine the threshold was obtained,that was,the current intensity determined the threshold.2.The FCM model contains five main ion currents.The simulation results of membrane dynamics showed that fast sodium ion current played a major role in the rise of action potential.The delayed potassium ion current and type A potassium ion current played a major role in the repolarization of action potential,while calcium ion current and calcium activated potassium ion current played a minor role in the process of action potential generation.3.According to the phase diagram analysis,the generation time of action potential was related to the intensity of stimulating current,and the action point potential had no attenuation in the process of transmission.From the strength-time curve,it can be seen that the threshold current decreases with the increase of stimulation time,and the basic intensity current was the minimum stimulation current under long-lasting stimulation.4.By changing the stimulation position of the electrode,analyzing the generation of action potential and the change of stimulation threshold,the point electrode was placed in the first boundary node atrium,the vertical distance from the optic nerve fibers was 30 um.At the beginning of stimulation,only the first atrioventricular node was activated and the action potential was generated.At 1 ms,the membrane potential reached its maximum value.The vertical distance from the point electrode to the optic nerve fibers increased from 30 um to 35 um,while the action potential of the first atrioventricular node reached its maximum at 1.3 ms.The point electrodes were placed in the atrioventricle of the central node of the optic nerve fibers with a vertical distance of 30 um,and the action potential reached its maximum at 0.9 ms.The vertical distance from the point electrode to the optic nerve fibers increased from 30 um to 35 um by keeping the position of the point electrode at the atrioventricular node unchanged.At 2.1 ms,the action potential of the central atrioventricular node reached its maximum.When the vertical distances between the point electrodes and the fibers were 20 um,25 um,30 um,35 um and 40 um respectively,the stimulation thresholds of the boundary atrioventricular nodes were 17.2 u A,22.3 u A,27.7 u A,33.5 u A and 39.8 u A,respectively.The stimulation thresholds of central atrioventricle were 22.9 u A,29.7 u A,37.2 u A,45.5 u A and 54.6 u A,respectively.5.When the vertical distance between the electrode and the fiber was 10 um,the stimulation threshold decreases from 36.1 u A to 8.5 u A when the stimulation pulse width increases from 0.1 ms to 1 ms.When the vertical distance between the electrode and the fiber was 40 um,the stimulation threshold decreases from 218.3 u A to 40.3 u A when the stimulation pulse width increased from 0.1 ms to 1 ms.When the stimulation threshold changed from 0.1 ms to 0.2 ms,the change degree was the greatest.6.When the anode phase was in front,the pulse duration was 1 ms and there was no interval between the anode and the cathode,the threshold of action potential stimulation was 36.5 u A.By changing the sequence of anode and cathode,the stimulation threshold of action potential will be increased,which was 26.5 u A.By changing the symmetry of the rectangular wave,the charge balance of the rectangular wave can be maintained by adding 1 ms interval between the anode and cathode phases.The stimulation threshold of the anode phase in front was 56 u A,and that of the cathode phase in front was 26 u A.At an interphase spacing of 0.35 ms or 0.4 ms,the biphasic rectangular pulse had the lowest stimulation threshold.When the amplitude ratio was the maximum of 35,the stimulation threshold was minimal.7.The stimulation thresholds for stimulating nerve fibers with different electrical stimulation waveforms and generating action potentials were compared.These waveforms were rect,sin,gaus,centri,decexp,and declin,inclin,twost,fivest,and the stimulus thresholds were 29.5 u A,28.13 u A,27.96 u A,26.35 u A,27.57 u A,29.74 u A,28 u A,29.5 u A,28.63 u A,28.04 u A.Conclusions 1.According to the classification method of Hodgkin cells,RGCs are identified as the first type of neurons,and the method to determine the threshold is obtained,that is,the current intensity determines the threshold.2.The simulation results of membrane dynamics of RGC multi-compartment model show that different ions play different roles in the generation of action potential.3.The results of phase plan study without stimulating current show that the action potential of RGC multi-compartment model varied with the time of discharge.4.The analysis of the stimulation positions of different point electrodes show that changing the position of point electrodes have no effect on the waveform,peak value and duration of action potential,and the peak value remains at +20 m V for about 1.5 ms.At the beginning of stimulation,the atrioventricular node closest to the point electrode is the first to excite,the transmembrane voltage will rise,and the transmembrane voltage of other atrioventricular nodes will first decrease.When the central atrioventricular node is first activated,the action potential will be transferred from the activated node to the atrioventricular node at both ends.When the boundary atrioventricle is activated preferentially,the action potential is transmitted in one direction.The longer the vertical distance between the point electrode and the fibers,the longer the peak time of action potential will be.The farther the point electrode is from the central atrioventricle of the fibers,the longer the action potential reaches its peak value.At the same vertical distance,the farther the distance between the point electrode and the central atrioventricle is,the smaller the stimulation threshold is.5.Different stimulus pulse widths have different stimulating effects.During the stimulation period,it is crucial to select the appropriate pulse polarity.The stimulation effect will be better if the cathode phase is in front of the stimulation.Increasing a certain width of rectangular wave pulse can reduce the threshold.The spacing and amplitude ratio between the cathode phase and the anode have a significant effect on the stimulation threshold and stimulation effect.6.In the 0.46 ms cathodic phase duration electrical stimulation waveform,the exponential rising waveform has the largest stimulation threshold,while the Gaussian waveform has the smallest stimulation threshold,and the rectangular wave has the same stimulation threshold as the linear rising waveform.The results obtained in this paper have a certain significance for the study of prosthesis on the retina. |
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