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刺入式视神经电刺激诱发皮层响应的时空特性及其视觉拓扑投射关系研究

发布时间:2018-11-25 10:43
【摘要】:视觉是人类用来认识客观世界的重要途径,因各种视网膜的病变引起的视觉功能丧失会对人的生活质量造成极大的负面影响。视觉假体是一种新兴的视觉功能修复方法,它是在采集外部图像信息后进行处理、编码,然后使用植入体内的微刺激器和电极阵列对视觉神经系统进行电刺激,最终在视觉中枢形成人工视觉的感知。基于刺入式电极阵列对视神经施加电刺激来帮助盲人实现视觉功能的修复是视觉假体的一种新方案,但这种视觉假体仍存在有待研究的基本问题,例如探索适合于视神经电刺激的模式和刺激策略、在眼球后植入怎样的电极阵列才能实现具有良好拓扑投射结构的电刺激,以及最终视神经假体能实现的空间分辨率和局部化刺激特性如何等方面。本课题使用刺入式电极对视神经进行电刺激并记录视皮层诱发响应的电生理信号,通过研究这一电生理响应的时间和空间特性,为视觉假体的基本理论、参数设计以及最终效果提供理论支持和实验依据。 在视觉假体的研究过程中,所有涉及到电刺激与电生理记录的实验中都发现皮层生理响应信号通常会受到由于电流在组织中传导而产生的物理性电伪迹的干扰,且无法使用传统方法去除。这种电刺激伪迹会对神经响应信号的处理与分析造成巨大的妨害,尤其是当在使用高强度、长间隔、高频率或复杂模式电刺激的情况下。本文使用了独立成分分析方法去除在各种视神经电刺激强度、波形、模式下多通道皮层响应中叠加的伪迹,并结合利多卡因阻断视神经的方法获取不含响应的纯伪迹,通过相关性分析来评估伪迹去除的效果和对信号的影响。实验结果表明:在改变电刺激强度、脉冲间隔,脉冲波形、刺激频率,甚至在进行复杂的多电极同步或异步刺激模式下,这种方法都可以有效地去除诱发皮层响应中叠加的电伪迹,,并且不会引起响应的失真;同时也发现去除伪迹的效果会随着皮层记录通道的减少而降低。本研究将为后续视神经视觉假体相关的电生理实验研究奠定数据分析基础。 在刺入式视神经电刺激的研究中,首先以白兔为实验动物模型,使用铂铱合金电极阵列对视神经进行电刺激,在视觉皮层使用银球电极阵列记录诱发的皮层响应信号,探索了适合于视神经视觉假体,具有低阈值和局部化特性的电刺激模式、脉冲波形、电极尺寸、间距和排列的方式。本实验的主要结果包括:系统研究电刺激视神经诱发的皮层响应多波成分的阈值和潜伏期,结合组织学方法发现较低阈值和潜伏期的P1波具有电刺激和皮层响应之间的拓扑对应性,是响应中最主要的成分;单极刺激模式下的负相在先脉冲具有更小的刺激阈值并能诱发更局部的皮层响应;比较了不同尺寸的电极对实现局部化电刺激的影响;证明了垂直视神经走向排列的间距150μm的两根电极可以诱发具有不同空间分布和位置的皮层响应,是适合于视神经假体的电极排列方式。本研究将为刺入式视神经视觉假体实现低阈值、局部化且可分辨的电刺激所需的刺激参数、模式、电极尺寸、间距和排列方式提供实验依据和支持。 然后以猫为动物模型,建立了在体定位刺入式视神经电极视野位置的方法,系统研究了刺入式视神经假体的视觉拓扑投射关系、空间分辨率和局部化等功能特性。本实验的主要结果包括:建立了使用稀疏噪声视觉刺激的方法用于对刺入式视神经电极的在体视野定位,并获取每只动物特异的视皮层和视野的视觉拓扑对应图;小尺寸的电极刺激具有较高的电荷密度阈值;证实了在眼球后的视神经内植入视神经假体能够实现具有良好视觉拓扑结构的电刺激,可以通过合理的电极排列与长度设计诱发具有拓扑规律的皮层响应;在电极间距150μm的情况下,刺入式视神经电刺激的空间分辨率为2 3°;通过计算皮层响应扩散范围,并和与视神经电极相同视野位置的视觉刺激诱发皮层响应进行对比,发现小尺寸电极下的视神经电刺激可以实现1 2°的局部化电刺激。本研究证明了视神经视觉假体是一种可行的视觉功能修复手段,并将为视觉假体的设计提供实验依据。
[Abstract]:Vision is an important way to recognize the objective world, and the loss of visual function caused by the pathological changes of the retina can have a great negative effect on the quality of human life. The vision prosthesis is an emerging visual function restoration method, which is used for processing and coding after the external image information is acquired, then the visual nervous system is electrically stimulated by using the microstimulator and the electrode array in the implanted body, and finally, the visual center forms the perception of the artificial vision. the repair of the visual function by the application of electrical stimulation to the optic nerve based on the puncture-type electrode array is a new solution to the visual prosthesis, but such a vision prosthesis still has a basic problem to be studied, such as the exploration of a pattern and a stimulation strategy suitable for electrical stimulation of the optic nerve, The electrode array implanted after the eyeball can realize the electrical stimulation with a good topological projection structure, and the spatial resolution and the local stimulation characteristic of the final optic nerve prosthesis can be realized. This subject uses the penetrating electrode to electrically stimulate the optic nerve and to record the electrical physiological signal of the visual cortex-induced response, and to provide the theoretical support and experimental basis for the basic theory, the parameter design and the final effect of the visual prosthesis by studying the time and space characteristics of the electrophysiological response. during the course of the study of the vision prosthesis, all of the experiments involved in electrical stimulation and electrophysiology recording found that the cortical physiological response signal would normally be disturbed by the physical electrical artifacts due to the conduction of the current in the tissue, and the conventional method could not be used Removal. This electrical stimulation artifact will cause great harm to the processing and analysis of the neural response signal, especially when using high intensity, long interval, high frequency or complex mode electrical stimulation In this paper, the method of independent component analysis is used to remove the pseudo-trace superimposed on the response of multi-channel cortex in various optic nerve electrical stimulation intensity, waveform and mode, and the method of blocking the optic nerve with lidocaine is used to obtain the non-response pure trace. The effect of the artifact removal and the signal to be evaluated by correlation analysis. The experimental results show that the electrical stimulation intensity, the pulse interval, the pulse waveform, the stimulation frequency, and even the complex multi-electrode synchronous or asynchronous stimulation mode can be used to effectively remove the electricity that is superimposed in the evoked cortex response. the artifact is false and does not cause distortion of the response; at the same time, it is also found that the effect of removing the artifact will follow the reduction of the cortical recording channel, This study will provide data analysis for the study of electrophysiological experiments related to the follow-up optic nerve visual prosthesis. Based on the study of the electro-stimulation of the penetrating optic nerve, the white rabbits were used as the experimental animal model, the optic nerve was electrically stimulated by using the electrode array of the platinum-based alloy, and the induced cortical response signal was recorded by using the silver-ball electrode array in the visual cortex. a visual prosthesis, an electrical stimulation mode with a low threshold and a localized characteristic, a pulse waveform, an electrode size, a pitch, The main results of this experiment include: the system studies the threshold and latency of the multi-wave component of the cortical response induced by the electro-stimulation of the optic nerve, and finds the topological correspondence between the electrical stimulation and the cortical response of the P1 wave with the lower threshold and the latency in combination with the histological method, which is the most responsive to the response the main components; the negative phase in the unipolar stimulation mode has a smaller stimulation threshold at the first pulse and can induce a more local cortical response; and the electrode pairs of different sizes are compared to realize the local electrical stimulation. The effect of the stimulation is that two electrodes with a spacing of 150. m u.m in the direction of the vertical optic nerve to be arranged can induce a cortical response with different spatial distribution and location, which is suitable for the electrical nerve prosthesis Pole arrangement. This study will provide an experiment for the stimulation parameters, patterns, electrode dimensions, spacing, and arrangement required to achieve a low threshold, localized, and resolvable electrical stimulation for the penetrating optic nerve visual prosthesis. In this paper, the visual topological projection relation, the spatial resolution and the spatial resolution of the penetrating optic nerve prosthesis were established by using the cat as an animal model. The main results of this experiment include the establishment of a method of visual stimulation using sparse noise, which is used to locate the penetrating optic nerve electrode in the field of view and to obtain the specific visual cortex and visual field of each animal. The results show that the optic nerve is implanted in the optic nerve, which can realize the electrical stimulation with a good visual topological structure, and can be induced to have a large scale by reasonable electrode arrangement and length design. 鎵戣寰嬬殑鐨眰鍝嶅簲锛涘湪鐢垫瀬闂磋窛150渭m鐨勬儏鍐典笅,鍒哄叆寮忚绁炵粡鐢靛埡婵

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