Oozeer视神经纤维模型的特性分析及其胞外电刺激下的响应

发布时间：2018-04-09 10:38

本文选题：视神经假体　切入点：Oozeer视神经纤维模型　出处：《天津医科大学》2012年硕士论文

【摘要】：研究目的：电极刺激视神经是用于恢复盲人视觉的一种实现方式。利用这种方式形成的视觉假体称为视神经假体。为了了解电极刺激视神经的作用机制,设计视神经假体和指导视神经假体临床应用,Oozeer等人根据文献中视神经生理参数提出了一种视神经模型来模拟哺乳动物视神经动作电位变化,称为Oozeer视神经纤维模型。本文以MATLAB为平台,研究了Oozeer视神经纤维模型在不同刺激下视神经纤维离子通道特性和膜特性,和在圆柱形视神经容积导体模型内刺激参数对Oozeer视神经纤维模型响应的影响,为视神经假体的设计和临床应用提供一种计算支持。研究方法： 1.基于Oozeer视神经纤维模型的离子通道特性分析 (1)膜离子通道特性分析。分析模型在外加刺激下的动作电位响应,分析模型被激活时膜离子通道随时间响应。 (2)相平面分析。使用相图法探讨视神经纤维动作电位变化规律,观察整个动作电位阶段的动态变化。 (3)强度—时间曲线的研究。分析整个模型在胞外电刺激下的电流-时间关系。 2.胞外电刺激下视神经纤维模型的响应的仿真 (1)建立一个视神经导体模型,计算出在刺入式电极刺激下,视神经内各处电势分布,利用建立的视神经纤维模型计算不同深度纤维的刺激阈值,分析Oozeer视神经纤维模型在视神经导体内的响应。 (2)用激活函数和组织激活区来表征外加刺激的作用于视神经的效果。 (3)分析纤维的直径对刺激效果的影响。 (4)分析刺激脉冲参数对刺激效果的影响。研究结果： 1.刺激下视神经纤离子通道特性 (1)四种离子通道：速钠离子(INa)、快速钾离子(IK)、慢钾离子(Is)和持续钠离子(Ip)在动作电位的形成过程中作用阶段和大小各不相同,对动作电位的形成所起作用不也同。 (2)相图法分析动作电位的动态变化可知,不同强度阈上刺激,视神经纤维上产生的动作电位发放时间不同,动作电位能沿轴突无衰减传播,单个动作电位持续时间无明显变化。 (3)由模型强度-时间曲线可知,当时间t足够大时,激活纤维所需电流强度不再改变,脉冲持续时间短于时值时斜率渐渐接近1/τ,与动物实验中所测量得到强度-时间关系一致。Oozeer视神经纤维模型稳定,能够正确反映胞外电刺激视神经纤维的电流-时间关系。 2.胞外电刺激对视神经纤维作用效应 (1)激活距离电极0.2mm处纤维,刺入式电极刺激阈值为14gA,比袖套电极激活同一距离纤维阈值要小得多。处于容积导体内部视的神经纤维,电极-纤维距离由0.2mm逐步增加到1.5mm过程中,纤维刺激阈值由14μA增加至0260μA。 (2)纤维直径由1μm逐步增加到6μm,深度为0.5mm处纤维刺激阈值由36μA减小至24μA,；深度为1mm纤维刺激阈值由104gA减小至52μA。直径由1μm增加到2μm时,刺激阈值减小程度最大。 (3)将单相矩形波脉宽从0.1ms逐步增加到1.0ms,深度为0.5mm纤维刺激阈值由45gA减小至34gA；深度为1.0mm纤维刺激阈值由166gA减小至104A。0.1ms增加到0.2ms时,刺激阈值的减小程度最大结论： 1.仿真结果表明,所建立的视神经纤维模型能正确反映视神经纤维被胞外刺激激活的动作电位特性,在动作电位的过程中各个离子通道作用时间不同,对动作电位形成的影响也不同。 2.相平面分析表明,阈上不同强度的刺激电流刺激下,Oozeer视神经纤维模型放电时间不同,动作电位在各个阶段的变化速度不同。 3.Oozeer视神经纤维模型的强度-时间曲线表明,胞外刺激下模型的强度-时间曲线与胞内刺激不同,Oozeer视神经纤维模型的电流-时间关系与实验所得的结论一致。 4.容积导体内纤维能被刺入式电极施加的电流刺激成功激活,并比袖套电极有更小的激活阈值。容积导体内不同位置上的视神经纤维具有不同的刺激阈值,距离电极越远的电极刺激阈值越大。 5.不同直径的纤维具有不同的刺激阈值,纤维直径越大,视神经纤维刺激阈值越小 6.改变刺激脉冲的脉宽和强度能产生不同的激活效应。纤维的位置、直径、刺激脉冲的宽度和强度等,可以成为实现视神经选择性激活重要参考量。所得结论对以后视神经选择性刺激实验以及基于视神经刺激的视觉假体的研究具有一定的指导意义。
[Abstract]:The purpose of the study is:
Electrical stimulation of the optic nerve is a method for restoring the vision of the blind. Visual prosthesis by this way is called optic nerve prosthesis. In order to understand the mechanism of stimulation of the optic nerve, optic nerve prosthesis design and clinical application of optic nerve prosthesis guidance, Oozeer et al. According to the literature in neural physiological parameters, proposes a simulation the mammalian optic nerve in the optic nerve action potential model was called Oozeer optic nerve fiber model. Using MATLAB as a platform to study Oozeer optic nerve fiber model of optic nerve fiber ion channel characteristics and membrane characteristics under different stimulation, and in a cylindrical volume conductor model of optic nerve stimulation parameters on Oozeer nerve fiber model response the calculation provides a support for the design and clinical application of optic nerve prosthesis.
Research methods:
1. analysis of ion channel characteristics based on Oozeer optic nerve fiber model
(1) analysis of membrane ion channel characteristics. The action potential response of the model under external stimulation is analyzed. The response of the membrane ion channel to time is analyzed when the model is activated.
(2) phase plane analysis. The changes in the action potential of optic nerve fibers were studied by phase diagram method, and the dynamic changes of the whole action potential stage were observed.
(3) the study of the intensity time curve and the analysis of the current time relation of the whole model under the exo electric stimulation.
Simulation of the response of the optic nerve fiber model under 2. extracellular electrical stimulation
(1) establish a model of optic nerve conductors, calculate the potential distribution in the optic nerve under the stimulation of puncture electrodes, calculate the threshold of different depths of fiber using the established optic nerve fiber model, and analyze the echo of Oozeer optic nerve fiber in the optic nerve conductor.
(2) use the activation function and the tissue activation area to characterize the effect of external stimulation on the optic nerve.
(3) the influence of the diameter of the fiber on the stimulation effect is analyzed.
(4) the effect of stimulation pulse parameters on the stimulation effect is analyzed.
The results of the study:
Properties of optic fiber ion channel under 1. stimulation
(1) four kinds of ion channels: fast sodium ion (INa), fast potassium ion (IK), slow potassium ion (Is) and continuous sodium ion (Ip), which act differently in the formation of action potential, and play a similar role in the formation of action potential.
(2) the dynamic change of action potential is analyzed by phase diagram method. We can see that different intensity suprathreshold stimulation can produce different action potential time on optic nerve fiber, action potential can propagate along axons, and there is no significant change in duration of single action potential.
(3) by the time intensity curve model shows that when t is large enough, the activation of fiber required current intensity does not change, the pulse duration is shorter than the slope gradually close to 1/ and tau, the measured intensity in animal experiment time consistent.Oozeer optic nerve fiber model is stable, it can correctly reflect the cell stimulation of optic nerve fiber current time relationship.
Effect of 2. extracellular electrical stimulation on optic nerve fiber
(1) the activation of 0.2mm fiber electrode distance, penetrating electrode stimulation threshold is 14gA, the same distance is much smaller than the threshold fiber cuff electrode activation. In optic nerve fibers of the inner conductor and the electrode fiber distance by 0.2mm gradually increased to 1.5mm in the process of fiber stimulation threshold by 14. A increased to 0260 A.
(2) the fiber diameter increased gradually from 1 m to 6 m, at a depth of 0.5mm fiber stimulation threshold by 36. A reduced to 24 A, depth of 1mm; fiber stimulation threshold is reduced from 104gA to 52 A. diameter increased from 1 m to 2 m, the largest decrease of stimulus threshold.
(3) the single phase square wave pulse width increased from 0.1ms to 1.0ms, and the depth of 0.5mm fiber decreased from 45gA to 34gA. When the depth of 1.0mm fiber was reduced from 166gA to 104A.0.1ms to 0.2ms, the threshold of stimulation decreased to a maximum.
Conclusion:
1. simulation results show that the established optic nerve fiber model can correctly reflect the action potential characteristics of optic nerve fiber stimulated by extracellular stimuli, and the action time of each ion channel is different during action potential, and the effect on action potential is also different.
The 2. phase plane analysis showed that when the threshold intensity was stimulated by different stimuli, the Oozeer optic nerve fiber model had different discharge time and the action potential varied at different stages.
The intensity time curve of 3.Oozeer optic nerve fiber model shows that the intensity time curve of extracellular stimulus is different from that of intracellular stimulation. The current time relationship of Oozeer optic nerve fiber model is consistent with the experimental conclusion.
The 4. volume conductor fiber current stimulation electrode piercing applied successfully activated, and cuff electrodes have smaller activation threshold. The volume conductor in different positions on the optic nerve fibers with different stimulation threshold, electrode electrode distance farther stimulation threshold more.
5. the fibers with different diameters have different stimulation thresholds. The greater the diameter of the fibers, the smaller the threshold of the optic nerve fibers is.
The pulse width and intensity change of 6. stimulus pulse can produce different activation effects. The position of the fiber, diameter, pulse width and intensity, can become the optic nerve selective activation of an important reference. The conclusion of the optic nerve after selective stimulation experiment and has guiding significance to the study of visual prosthesis based on optic nerve stimulation.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.0

【参考文献】