| Objective:Electrical stimulation of optic nerve is a method for restoring the vision of the blind. Visual prosthesis implemented by this method is called optic nerve prosthesis. To know the mechanism of the stimulation of optic nerve with electrical stimulus, and help to design the optic nerve prosthesis and guide its clinical application, Oozeer’s group developed a model of the mammalian optic nerve fiber based on experimental data, which was called Oozeer optic nerve fiber model. In this paper, the Oozeer model’s characteristics and its ionic channels were analyzed with computer software MATLAB. Then the response of the optic nerve fiber located in the cylindrical optic nerve conductor was analyzed, and the effects of different stimulus parameters on stimulation were also studied. The result offered a calculating support for the design and clinic application of the optic nerve prosthesis.Methods:1. Analysis of characteristics of Oozeer optic nerve fiber model(1) Analysis of characteristic of model’s ionic channels, the model’s action potential and the ionic channel response with time to extracellular stimulation were analyzed.(2) Phase plane method. The phase plane of the action potential was used to study the dynamic changes of the Oozeer optic nerve model.(3)Strength-duration curve. The strength-duration relationship of the model was used to help understanding the mechanisms and dynamic change of the model to extracellular stimulation.2. Response of Oozeer model to extracellular stimulation.(1) A volume conductor of optic nerve was developed, and the potential distribution of the stimulus applied by penetrating electrode was calculated, and the excitation thresholds of fibers at different depth were also calculated.(2)The activating function and activation region were used to characterize the influence of the externally applied electrical field on optic nerve activations.(3)The fiber diameter was changed to investigate its effect on stimulation.(4)The parameters of the stimulation pulses were changed to investigate their effect on stimulation.Result:1. Analysis of characteristics of Oozeer optic nerve fiber model(1)Oozeer optic nerve fiber model’s four ionic channels:fast sodium current(iNa), fast potassium current(IK), persist sodium current(Ip) and slow potassium current(Is) had different durations and values and played different roles in the formation of single action potential.(2) The phase plane curve of Oozeer optic nerve fiber model’s action potential showed its dynamic change:with different suprathreshold stimulus, the action potentials occured at different time, the acion potential can propagate along the axon without decay.(3) The model’s strength-duration curve showed:the current intensity changed little when the pulse duration was long enough, the slope asymptotically approached1/τ at pulse durations shorter than chronaxy. and this was consistent with animal experimental measurements result of the strength-duration relationship. The Oozeer model could accurately represent optic nerve fiber current-duration relationship to extracellular as the experiment results reported.2. Response of Oozeer model to extracellular stimulation(1) The activation thresholds of optic nerve with depth of0.2mm to the penetrating electrode was14μA which was much lower than that obtained from cuff electrodes. The activation thresholds of the optic nerve fibers increased as the electrode-fiber distance increased, and as the electrode-fiber distance increased from0.2mm to1.5mm gradually, the activation increased from14μA to260μA gradually.(2) As the diameter of the fiber increased from1um to6um step by step,the activation threshold of the fiber with depth of0.5mm decreased from36μA to24μA:the activation threshold of the fiber with depth of1.0mm decreased from104μA to52μA.The activation thresholds decreased most as the diameter increased from1μm to2μm. (3) he pulse width increased from0.1ms to1.0ms. the activation threshold of the fiber with depth of0.5mm decreased from45ua to34ua;the activation threshold of the fiber with depth of1.0mm decreased from166μA to104μA. The activation thresholds decreased most as the pulse width from0.1ms to0.2ms.The activation thresholds changed little for pulse durations greater than0.5ms.Conclusion:1. The simulation results indicated that the Oozeer optic nerve fiber model can accurately represent the real response characteristics of optic nerve fiber to extracellular stimulation, the four ionic channels of the model had different durations and played different roles in the formation of action potential.2. The analysis of the action potential with the phase plane method showed, with different intensity of the suprathreshold stimulations, action potentials which were induced had different latencies.3. The strength-duration curve of the model’s response to the extracellular stimulation was different to the one of intracellular stimulation, the curve was consistent with animal experimental measurements result of the strength-duration relationship.4. The fiber located in the cylindrical optic nerve conductor can be activated by the penetrating electrode and had lower excitation threshold compared to the cuff electrode, fibers located at different depth had different thresholds.5. Fibers with different diameters had different excitation thresholds, the greater the diameter was the smaller the activation thresholds was.6. Pulse with different width and intensities induced different optic nerve activation effect. The location, diameter of the fiber and the parameters of stimulation pulse could be treated as important parameters to realize selective activation of optic nerve. The present results provided some theoretical guidance for the design of experiments and the development of optic prosthesis based on optic nerve stimulation. |
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