用于神经功能修复的电、近红外激光及其组合刺激方法的研究
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摘要
神经功能性疾病因很难通过药物等手段治愈，成为医学界的重大难题之一。从根本上讲，人体各种感觉和运动功能，都是与之对应的神经细胞或肌肉接受各种刺激产生动作电位的结果。当功能发生异常时，可以通过建立神经接口施加外界刺激而治愈。目前用于神经修复的刺激方式有电、光、化学、机械等。其中功能性电刺激是研究的热点，已进入临床阶段，并有很多产品问世。然而现有电刺激方法空间分辨率低，电极使用寿命短，且在供能、数据传输效率和安全方面都有待提高。新出现的红外激光神经刺激疗法采用低能量脉冲激光照射神经，具有空间分辨率高、安全性高等优点。但红外激光刺激疗法目前尚处于实验初步阶段，所研究的应用领域较窄，很多问题有待进一步研究解决。
针对上述研究背景，本学位论文围绕神经功能修复这一目的，在总结分析功能性神经电刺激、近红外激光神经刺激及其组合刺激的原理和应用的基础上，首先提出了实现多通道刺激信号体内外无线传输的新设计方案并最终通过动物实验进行了可行性验证，其次提出了短波长近红外激光应用到视皮层修复的方案并通过实验进行了初步验证，最后将两种刺激方法结合，借助阈下电刺激，降低光刺激阈值，避免了热消融现象，实现了对不同神经纤维的选择性激活与抑制以及动作电位的单向传导。本论文的研究内容主要总结如下：
1．基于微线圈阵列的多通道植入式神经电刺激系统的研制及实验研究
针对植入式神经电刺激器的能量供应和数据传输需求，提出了一种基于微线圈阵列的多通道神经电刺激信号透皮传输方案。该方案通过设计多组信号传输通道实现了多路电刺激信号的真正意义上的并行传输，且各通道信号有自己单独的控制电路和信号产生电路，能够根据需求灵活的发送各自的刺激信号。并且采用AM调制方式，对应的体内接收模块全部采用无源元件，电路简单且无需设计能量传输通道对其供电。在此基础上首先建立了该方案的数学模型，计算多通道系统的信号和噪声耦合系数，从理论上验证了基于微线圈阵列的多道神经电刺激信号透皮传输方案的可行性，并求得了系统的优化方法。然后基于此方案设计了一种多通道植入式神经电刺激系统，进一步对该系统的电路性能进行了测试，并开展了基于本系统的猫硬脑膜外电刺激视皮层的动物实验，验证了本系统的可靠性和实际可用性。
2．电刺激青蛙坐骨神经——神经纤维的选择性刺激
针对神经纤维的选择性刺激要求，本研究以青蛙坐骨神经为研究对象，建立了基于三电极模式多触点卡夫电极的电刺激青蛙坐骨神经的理论模型和实验模型。理论模型基于COMSOL、NEURON、SIMULINK三大软件实现，分析了电极的设计、刺激电流模式的选择、以及电极—电解液接口等因素对产生动作电位的影响，提出了改进电极使用寿命的方法，并实现了神经纤维的选择性刺激。在理论模型基础上开展了电刺激离体青蛙坐骨神经的实验，成功实现了电刺激对神经纤维的选择性激活和抑制。该方法可用于外周神经刺激器，有望解决电刺激在修复神经功能时带来的肌肉疲劳、疼痛等负面影响。
3．近红外激光刺激LE鼠视皮层——激光对中枢神经的兴奋和抑制
选择短波长脉冲式近红外激光为刺激光源，建立了近红外激光刺激老鼠视皮层实验平台。本研究从三方面验证近红外激光刺激对视皮层电位的影响：图形刺激眼球，记录诱发的视觉动作电位（VEP）；图形刺激眼球，同时近红外激光刺激视皮层，研究近红外激光刺激对正常VEP的影响；近红外激光刺激视皮层，研究是否诱发视皮层动作电位。同时建立了激光照射生物组织热效应理论模型，计算激光照射后组织的温度变化情况，并用红外测温成像仪对实际温度变化进行了初步试验验证。通过研究发现了短波长近红外激光对视皮层神经电活动的调制作用，该发现为建立一种无创伤、无感染、高空间分辨率的视皮层假体提供了实验基础。
4．光电组合刺激青蛙坐骨神经——局部瞬间热阻断
基于近红外激光对视皮层电活动的抑制性发现，以及激光高空间分辨率的优点，在电刺激青蛙坐骨神经的基础上搭建了光电组合刺激青蛙坐骨神经的理论模型和实验模型。研究两种方法共同作用下，青蛙坐骨神经动作电位的变化规律。通过理论和实验成功实现了激光对坐骨神经动作电位的局部瞬间热阻断，并成功抑制了动作电位的产生或传导，特别地实现了对动作电位的单边抑制。光电组合的刺激方法降低了抑制所需的激光能量阈值，有效地避免了单独近红外激光神经刺激时热消融的发生。
本论文从功能性电刺激、近红外神经刺激及其组合刺激三种刺激模式在神经修复中的关键技术进行了深入的研究，一方面改进了植入式神经电刺激系统，另一方面开拓了光刺激的可应用范围，最后实现了对不同神经的选择性刺激。本文取得的创新性研究结果总结如下：
1.提出一种基于微线圈阵列的多通道神经电刺激信号透皮传输方案。该方案实现了多通道信号的并行无线传输，各通道信号有自己单独的控制电路和信号产生电路，能够根据需求灵活的发送各自的刺激信号，并且所设计体内接收模块，电路简单，全部采用无源元件，无需设计能量传输通道对其供电。在此基础上建立了该多通道系统的数学模型，不仅可以计算任意位置的两线圈的耦合系数，并且可以求得各通道的信号和噪声，为系统的优化提供理论指导。该传输方案适用于如视皮层假体、视网膜假体等需要很多刺激电极且对各电极刺激信号的独立设计有较高要求的植入式神经电刺激器。
2.提出一种基于短波长近红外激光的视皮层神经假体的方案，并搭建了激光刺激LE鼠视皮层的动物实验平台，初步验证了短波长近红外激光对视皮层电活动的调控作用，为激光刺激视皮层神经假体的研究奠定了实验基础。短波长近红外激光穿透能力强，无需接触即可以刺激到深层的神经。并且激光方向性好，空间分辨率高，可以解决电刺激视皮层假体在多点刺激时由于电流扩散导致的作用范围重叠的问题。
3.建立了一种基于SIMULNK、COMSOL和NEURON三大软件结合实现对神经接受电刺激和激光照射的电活动的建模方法。该方法灵活性强，可以任意改变神经纤维的尺寸和位置，以及刺激电流或者激光的参数。在理论模型的基础上搭建了光电组合刺激青蛙坐骨神经的动物实验，并成功实现了对神经纤维的选择性激活和抑制，该方法即利用光刺激的高空间分辨率的优点，又借助阈下电刺激降低刺激所需激光的能量，避免了热消融对组织的损害，为神经功能修复提供了一个更安全有效的刺激模式。
Nerve functional disorder is a serious disease that affecting the quality of life formillions of patients worldwide today. Since it is often ineffective with conventionaldrug treatment and accompanying with harmful side effects, neuroprosthetics are thenext generation in an age-old practice of using assistive devices to improve our health.All the motor and sensory functions of the body are the process the muscle or nervecells change from a resting potential to an action potential after receiving a variety ofstimuli. Thus, nerve functional disorder can be repaired by applying an artifact neuralinterface with external stimuli. A number of methods have been proposed for nerverestoration typically based on electrical, optical, chemical and mechanical methods.Among them the most widely used and studied is the electrical method, which hasalready entered the clinical stage. However, the existing electrical techniques arechallenged by worse spatial resolution, short working life, low power and datatransmission efficiency, and the safety problem. The newly-minted optical stimulationmethod, applying pulse laser with low power to irradiate the nerve, has higher spatialresolution and security. However, the optical techniques are only at the experimentalstage now, with narrow application field and a lot of unsolved problems.
In order to solve the existing problems, this thesis firstly analysed the theoreticalbasis and applications of Functional Electrical Stimulation, Near-infrared NeuralStimulation, and their combination application in neural prosthesis. Then this thesisproposed a new method on multichannel signals’ wireless transmission with microcoilarray and verified its feasibility through animal experiments. Thirdly, the thesis appliedshort-wavelength near-infrared laser to stimulate the visual cortex in the preliminaryanimal experiments. Finally, the dissertation combined the two stimulation methods toachieve selective activation or inhibition of different nerve fibers and unidirectionalconduction of action potentials. The research context of this paper is mainly:
1. Design and experimental study of the microcoil-array based multichannel
neural electrical stimulation implantable system
This paper has developed a multichannel electrical stimulation implantable systembased on the multigroup of electromagnetic induction coils. This system can realize thereal parallel transmission of signal in different channels. And each channel has its ownindependent control circuit and signal generating circuit. Moreover, AM modulation is used in the system and the receiving part is group of passive elements which reduceenergy consumption. An analytical model for inductively coupled multichannelimplantable system with micro-coil array was built to check up the feasibility of theenergy and data transmission on microcoil-arry and find the optimization method for thesystem. Then the electrical performance and the the reliability of the system was test,and the system was implanted on the duramater and successfully activated the visualcortex of cat.
2. Electrical stimulation of the frog’s sciatic nerve——selective stimulation of thenerve fibers
In order to achieve selective stimulation of different nerve fibers, this paperchooses the frog sciatic nerve as the object and establishes the tripolar multi-contactcuff electrode electrical stimulation experimental platform. Theoretical model andexperimental model are established to analyze the effect of various factors on thegeneration of action potential, including the electrode, the waveform of the stimuluscurrent and the electrode-electrolyte interface. Finally, we realize selective activationand blocking the given nerve fiber and find the method to improve the electrode withlonger service life. This method can be used for peripheral nerve stimulator, which isexpected to solve the musle fatigue, pain and other negative effects from electricalstimulation.
3. Near-infrared neural stimulation of LE rat visual cortex——the activation andinhibition of the laser on central nervous system
Choose the pulsed short-wavelength near-infrared laser as light source and set upthe near-infrared neural stimulation experimental platform for LE rat visual cortex.Effect of the near-infrared stimulus on the visual cortex from three aspects was test:stimulating the eyes with image to record the induced visual evoked potential (VEP);stimulating the eyes with image while stimulating the visual cortex with near infraredlaser to inspect the effect of the laser irradiation on the normal VEP; only stimulatingthe visual cortex with near infrared laser to record the electrical behavior of the visualcortex. Meanwhile, a model of biological tissue thermal effects under laser irradiation isbuilt to calculate the temperature variation and an infrared temperature imaging camerais used to test the real temperature during the irradiation of the laser. This studydiscovered that short-wavelength near-infrared laser can modulate the electrical activityof visual cortex. This finding establishs the experimental basis for a new visual cortexprosthesis with high resolution and no trauma and infection.
4. Combined near-infrared and electrical stimulation of the frog sciaticnerve——the localized transient heat block
Based on the experiment of electrical stimulation of the frog sciatic nerve, this partadded the near-infrared laser stimulation on the local nerve and tested the electricalbehavior of the frog sciatic with two kinds of stimulation. The near-infrared stimulationsuccessfully blocked the generation and/or propagation of action potential withlocalized transient heat increase of the nerve fiber. Theoretical model was also built tosimulate the electrical behavior of the sciatic nerve, with finite element softwareCOMSOL calculating electric distribution, NEURON software simulating the neuralelectricity physiological characteristics of sciatic nerve. The combined stimulationmethod reduces the inhibition threshold of the laser energy, and effectively avoids theoccurrence of thermal ablation.
In this thesis, the key technologies of the three stimulation patterns have beenstudied deeply. The electrical stimulation system was improved and the application ofinfrared neural stimulation was expanded, and finally the selective stimulation wasrealized in the experiments. Innovative research results of this thesis are summarized asfollows:
1. Proposed a new method on multichannel signals wireless transmission based onmicrocoil array. This method solves the problem of short supply of energy whilehundreds of stimulating electrodes are working at the same time. Also it realizes theparallel transmission of signal in different channels, and each channel has its ownseparate control circuit and signal generating circuit, which makes the stimulation moreclose to the real world. On this basis, a mathematical model of the multichannel systemwas established, which can calculate not only the coupling coefficient between any twocoils, but also the signal and noise in each channel. The mathematical model alsoprovides theoretical guidance for the optimization of the system. This transmissionmethod applies to the system such as visual cortex prosthesis and retinal prosthesis.
2. Proposed a new method to design visual cortex prosthesis based on theshort-wavelength near-infrared laser and built the animal experiment platform forinfrared stimulation of LE rat visual cortex. The preliminary experiment results validatethe regulatory role of the short-wavelength near-infrared on the electrical activity of thevisual cortex and lay the experiment foundation for the visual cortex prosthesis based oninfrared laser stimulation. Short-wavelength near-infrared is with deep penetration depth in biological tissue, contactless and high spatial resolution, which can solve thecurrent spreading effect of the electrical stimulation in multi-point stimulation.
3. Designed a new model based on SIMULINK, COMSOL and NEURONsoftware. This model can simulate the electrical activity of the nerve under extracellularstimulation by electrical or/and infrared stimulus. The main advantage of thisframework over the other proposed models is that spatial properties of the extracellularstimulus can be selected arbitrarily, so that one can simulate a variety of electrode-neurongeometries of practical interest. Based on the theoretical model, we implemented theanimal experiments and successfully achieved the selective activation or/and inhibitionof nerve fibers. The combined stimulation method reduces the inhibition threshold of thelaser energy, effectively avoids the occurrence of thermal ablation, and affords a moreeffective and safer stimulus pattern for nerve function repair.
针对上述研究背景，本学位论文围绕神经功能修复这一目的，在总结分析功能性神经电刺激、近红外激光神经刺激及其组合刺激的原理和应用的基础上，首先提出了实现多通道刺激信号体内外无线传输的新设计方案并最终通过动物实验进行了可行性验证，其次提出了短波长近红外激光应用到视皮层修复的方案并通过实验进行了初步验证，最后将两种刺激方法结合，借助阈下电刺激，降低光刺激阈值，避免了热消融现象，实现了对不同神经纤维的选择性激活与抑制以及动作电位的单向传导。本论文的研究内容主要总结如下：
1．基于微线圈阵列的多通道植入式神经电刺激系统的研制及实验研究
针对植入式神经电刺激器的能量供应和数据传输需求，提出了一种基于微线圈阵列的多通道神经电刺激信号透皮传输方案。该方案通过设计多组信号传输通道实现了多路电刺激信号的真正意义上的并行传输，且各通道信号有自己单独的控制电路和信号产生电路，能够根据需求灵活的发送各自的刺激信号。并且采用AM调制方式，对应的体内接收模块全部采用无源元件，电路简单且无需设计能量传输通道对其供电。在此基础上首先建立了该方案的数学模型，计算多通道系统的信号和噪声耦合系数，从理论上验证了基于微线圈阵列的多道神经电刺激信号透皮传输方案的可行性，并求得了系统的优化方法。然后基于此方案设计了一种多通道植入式神经电刺激系统，进一步对该系统的电路性能进行了测试，并开展了基于本系统的猫硬脑膜外电刺激视皮层的动物实验，验证了本系统的可靠性和实际可用性。
2．电刺激青蛙坐骨神经——神经纤维的选择性刺激
针对神经纤维的选择性刺激要求，本研究以青蛙坐骨神经为研究对象，建立了基于三电极模式多触点卡夫电极的电刺激青蛙坐骨神经的理论模型和实验模型。理论模型基于COMSOL、NEURON、SIMULINK三大软件实现，分析了电极的设计、刺激电流模式的选择、以及电极—电解液接口等因素对产生动作电位的影响，提出了改进电极使用寿命的方法，并实现了神经纤维的选择性刺激。在理论模型基础上开展了电刺激离体青蛙坐骨神经的实验，成功实现了电刺激对神经纤维的选择性激活和抑制。该方法可用于外周神经刺激器，有望解决电刺激在修复神经功能时带来的肌肉疲劳、疼痛等负面影响。
3．近红外激光刺激LE鼠视皮层——激光对中枢神经的兴奋和抑制
选择短波长脉冲式近红外激光为刺激光源，建立了近红外激光刺激老鼠视皮层实验平台。本研究从三方面验证近红外激光刺激对视皮层电位的影响：图形刺激眼球，记录诱发的视觉动作电位（VEP）；图形刺激眼球，同时近红外激光刺激视皮层，研究近红外激光刺激对正常VEP的影响；近红外激光刺激视皮层，研究是否诱发视皮层动作电位。同时建立了激光照射生物组织热效应理论模型，计算激光照射后组织的温度变化情况，并用红外测温成像仪对实际温度变化进行了初步试验验证。通过研究发现了短波长近红外激光对视皮层神经电活动的调制作用，该发现为建立一种无创伤、无感染、高空间分辨率的视皮层假体提供了实验基础。
4．光电组合刺激青蛙坐骨神经——局部瞬间热阻断
基于近红外激光对视皮层电活动的抑制性发现，以及激光高空间分辨率的优点，在电刺激青蛙坐骨神经的基础上搭建了光电组合刺激青蛙坐骨神经的理论模型和实验模型。研究两种方法共同作用下，青蛙坐骨神经动作电位的变化规律。通过理论和实验成功实现了激光对坐骨神经动作电位的局部瞬间热阻断，并成功抑制了动作电位的产生或传导，特别地实现了对动作电位的单边抑制。光电组合的刺激方法降低了抑制所需的激光能量阈值，有效地避免了单独近红外激光神经刺激时热消融的发生。
本论文从功能性电刺激、近红外神经刺激及其组合刺激三种刺激模式在神经修复中的关键技术进行了深入的研究，一方面改进了植入式神经电刺激系统，另一方面开拓了光刺激的可应用范围，最后实现了对不同神经的选择性刺激。本文取得的创新性研究结果总结如下：
1.提出一种基于微线圈阵列的多通道神经电刺激信号透皮传输方案。该方案实现了多通道信号的并行无线传输，各通道信号有自己单独的控制电路和信号产生电路，能够根据需求灵活的发送各自的刺激信号，并且所设计体内接收模块，电路简单，全部采用无源元件，无需设计能量传输通道对其供电。在此基础上建立了该多通道系统的数学模型，不仅可以计算任意位置的两线圈的耦合系数，并且可以求得各通道的信号和噪声，为系统的优化提供理论指导。该传输方案适用于如视皮层假体、视网膜假体等需要很多刺激电极且对各电极刺激信号的独立设计有较高要求的植入式神经电刺激器。
2.提出一种基于短波长近红外激光的视皮层神经假体的方案，并搭建了激光刺激LE鼠视皮层的动物实验平台，初步验证了短波长近红外激光对视皮层电活动的调控作用，为激光刺激视皮层神经假体的研究奠定了实验基础。短波长近红外激光穿透能力强，无需接触即可以刺激到深层的神经。并且激光方向性好，空间分辨率高，可以解决电刺激视皮层假体在多点刺激时由于电流扩散导致的作用范围重叠的问题。
3.建立了一种基于SIMULNK、COMSOL和NEURON三大软件结合实现对神经接受电刺激和激光照射的电活动的建模方法。该方法灵活性强，可以任意改变神经纤维的尺寸和位置，以及刺激电流或者激光的参数。在理论模型的基础上搭建了光电组合刺激青蛙坐骨神经的动物实验，并成功实现了对神经纤维的选择性激活和抑制，该方法即利用光刺激的高空间分辨率的优点，又借助阈下电刺激降低刺激所需激光的能量，避免了热消融对组织的损害，为神经功能修复提供了一个更安全有效的刺激模式。
Nerve functional disorder is a serious disease that affecting the quality of life formillions of patients worldwide today. Since it is often ineffective with conventionaldrug treatment and accompanying with harmful side effects, neuroprosthetics are thenext generation in an age-old practice of using assistive devices to improve our health.All the motor and sensory functions of the body are the process the muscle or nervecells change from a resting potential to an action potential after receiving a variety ofstimuli. Thus, nerve functional disorder can be repaired by applying an artifact neuralinterface with external stimuli. A number of methods have been proposed for nerverestoration typically based on electrical, optical, chemical and mechanical methods.Among them the most widely used and studied is the electrical method, which hasalready entered the clinical stage. However, the existing electrical techniques arechallenged by worse spatial resolution, short working life, low power and datatransmission efficiency, and the safety problem. The newly-minted optical stimulationmethod, applying pulse laser with low power to irradiate the nerve, has higher spatialresolution and security. However, the optical techniques are only at the experimentalstage now, with narrow application field and a lot of unsolved problems.
In order to solve the existing problems, this thesis firstly analysed the theoreticalbasis and applications of Functional Electrical Stimulation, Near-infrared NeuralStimulation, and their combination application in neural prosthesis. Then this thesisproposed a new method on multichannel signals’ wireless transmission with microcoilarray and verified its feasibility through animal experiments. Thirdly, the thesis appliedshort-wavelength near-infrared laser to stimulate the visual cortex in the preliminaryanimal experiments. Finally, the dissertation combined the two stimulation methods toachieve selective activation or inhibition of different nerve fibers and unidirectionalconduction of action potentials. The research context of this paper is mainly:
1. Design and experimental study of the microcoil-array based multichannel
neural electrical stimulation implantable system
This paper has developed a multichannel electrical stimulation implantable systembased on the multigroup of electromagnetic induction coils. This system can realize thereal parallel transmission of signal in different channels. And each channel has its ownindependent control circuit and signal generating circuit. Moreover, AM modulation is used in the system and the receiving part is group of passive elements which reduceenergy consumption. An analytical model for inductively coupled multichannelimplantable system with micro-coil array was built to check up the feasibility of theenergy and data transmission on microcoil-arry and find the optimization method for thesystem. Then the electrical performance and the the reliability of the system was test,and the system was implanted on the duramater and successfully activated the visualcortex of cat.
2. Electrical stimulation of the frog’s sciatic nerve——selective stimulation of thenerve fibers
In order to achieve selective stimulation of different nerve fibers, this paperchooses the frog sciatic nerve as the object and establishes the tripolar multi-contactcuff electrode electrical stimulation experimental platform. Theoretical model andexperimental model are established to analyze the effect of various factors on thegeneration of action potential, including the electrode, the waveform of the stimuluscurrent and the electrode-electrolyte interface. Finally, we realize selective activationand blocking the given nerve fiber and find the method to improve the electrode withlonger service life. This method can be used for peripheral nerve stimulator, which isexpected to solve the musle fatigue, pain and other negative effects from electricalstimulation.
3. Near-infrared neural stimulation of LE rat visual cortex——the activation andinhibition of the laser on central nervous system
Choose the pulsed short-wavelength near-infrared laser as light source and set upthe near-infrared neural stimulation experimental platform for LE rat visual cortex.Effect of the near-infrared stimulus on the visual cortex from three aspects was test:stimulating the eyes with image to record the induced visual evoked potential (VEP);stimulating the eyes with image while stimulating the visual cortex with near infraredlaser to inspect the effect of the laser irradiation on the normal VEP; only stimulatingthe visual cortex with near infrared laser to record the electrical behavior of the visualcortex. Meanwhile, a model of biological tissue thermal effects under laser irradiation isbuilt to calculate the temperature variation and an infrared temperature imaging camerais used to test the real temperature during the irradiation of the laser. This studydiscovered that short-wavelength near-infrared laser can modulate the electrical activityof visual cortex. This finding establishs the experimental basis for a new visual cortexprosthesis with high resolution and no trauma and infection.
4. Combined near-infrared and electrical stimulation of the frog sciaticnerve——the localized transient heat block
Based on the experiment of electrical stimulation of the frog sciatic nerve, this partadded the near-infrared laser stimulation on the local nerve and tested the electricalbehavior of the frog sciatic with two kinds of stimulation. The near-infrared stimulationsuccessfully blocked the generation and/or propagation of action potential withlocalized transient heat increase of the nerve fiber. Theoretical model was also built tosimulate the electrical behavior of the sciatic nerve, with finite element softwareCOMSOL calculating electric distribution, NEURON software simulating the neuralelectricity physiological characteristics of sciatic nerve. The combined stimulationmethod reduces the inhibition threshold of the laser energy, and effectively avoids theoccurrence of thermal ablation.
In this thesis, the key technologies of the three stimulation patterns have beenstudied deeply. The electrical stimulation system was improved and the application ofinfrared neural stimulation was expanded, and finally the selective stimulation wasrealized in the experiments. Innovative research results of this thesis are summarized asfollows:
1. Proposed a new method on multichannel signals wireless transmission based onmicrocoil array. This method solves the problem of short supply of energy whilehundreds of stimulating electrodes are working at the same time. Also it realizes theparallel transmission of signal in different channels, and each channel has its ownseparate control circuit and signal generating circuit, which makes the stimulation moreclose to the real world. On this basis, a mathematical model of the multichannel systemwas established, which can calculate not only the coupling coefficient between any twocoils, but also the signal and noise in each channel. The mathematical model alsoprovides theoretical guidance for the optimization of the system. This transmissionmethod applies to the system such as visual cortex prosthesis and retinal prosthesis.
2. Proposed a new method to design visual cortex prosthesis based on theshort-wavelength near-infrared laser and built the animal experiment platform forinfrared stimulation of LE rat visual cortex. The preliminary experiment results validatethe regulatory role of the short-wavelength near-infrared on the electrical activity of thevisual cortex and lay the experiment foundation for the visual cortex prosthesis based oninfrared laser stimulation. Short-wavelength near-infrared is with deep penetration depth in biological tissue, contactless and high spatial resolution, which can solve thecurrent spreading effect of the electrical stimulation in multi-point stimulation.
3. Designed a new model based on SIMULINK, COMSOL and NEURONsoftware. This model can simulate the electrical activity of the nerve under extracellularstimulation by electrical or/and infrared stimulus. The main advantage of thisframework over the other proposed models is that spatial properties of the extracellularstimulus can be selected arbitrarily, so that one can simulate a variety of electrode-neurongeometries of practical interest. Based on the theoretical model, we implemented theanimal experiments and successfully achieved the selective activation or/and inhibitionof nerve fibers. The combined stimulation method reduces the inhibition threshold of thelaser energy, effectively avoids the occurrence of thermal ablation, and affords a moreeffective and safer stimulus pattern for nerve function repair.
引文
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