视神经和脉络膜上腔电刺激诱发视觉皮层响应的特性研究

发布时间：2018-06-16 15:45

本文选题：视觉假体 + 电刺激参数　；参考：《上海交通大学》2012年博士论文

【摘要】：人类认识外界世界的信息至少有70%是通过视觉系统提供，失明不但严重影响了患者的生活质量，而且给社会带来了很大负担。随着科学技术的不断发展，用人工视觉假体修复盲人视觉功能成为全世界研究的热点。中国的视觉假体研究小组提出了刺入式视神经视觉假体这一新型人工视觉修复方案，目前这一方案有待于系统的研究。本课题主要对视神经电刺激在视觉皮层诱发的响应特征进行了系统的分析，并对不同的刺激波形和刺激参数在视神经电刺激中的作用应用皮层诱发电位进行了评估。针对视网膜假体，我们小组自主研发了适合植入脉络膜上腔对视网膜进行电刺激的基于Micro-electro-mechanical System (MEMS)的聚酰亚胺薄膜多电极阵列。本课题对这一刺激电极阵列的可行性及其在视觉皮层诱发电位的时间和空间特性进行了初步的探索。具体内容如下：在视神经电刺激研究中，，我们采用自制铂铱合金丝电极阵列对视神经纤维进行微电流刺激，并在初级视觉皮层放置银球电极阵列记录诱发的视皮层响应信号，系统地研究了视神经电刺激波形和刺激参数对视觉皮层诱发的多波响应电位的时空特性影响，获得了视神经电刺激诱发的皮层响应中不同波形成分的阈值信息以及优化的刺激参数信息，为理解视觉信息的传递过程及进一步优化视神经视觉假体刺激参数提供了实验依据。主要结果包括：（1）通过微电流刺激视神经纤维，可以在视觉初级皮层诱发含有多个波形成分的场电位，最多时可记录到P0，N1，P1，P2和P3五个波形成分。不同的波形成分具有不同的阈值和时间特性。阈值越低的成分潜伏期和持续时间都越短。（2）在视神经颞背侧象限内电刺激视神经纤维，对皮层多电极记录的快波响应（P1）与皮层视野拓扑对应关系图比较，发现视皮层响应最大的区域与电刺激视神经部位对应的视野一致。证明靠近眼球部位的视神经保持了较好的视觉拓扑对应关系，适合植入视觉假体。（3）刺激的波形和参数对视神经电刺激诱发的视皮层响应具有重要的影响。与对称的电荷平衡刺激波形相比，具有窄高负相脉冲和宽矮正相脉冲的非对称波形可以降低电刺激的阈值。在同样刺激电荷密度下诱发较大响应的刺激波形其诱发响应的空间分布范围也较大。在刺激波形两脉冲相位之间加入时间间隔可以降低刺激阈值，时间间隔为0.2ms时达到饱和；对称的先负后正刺激波形加入时间间隔后能够诱发最大的响应。随着刺激频率的升高，皮层诱发响应的幅值呈下降趋势；不同波形成分随着刺激频率的升高变化规律不同。这些实验结果对于开发研制视神经视觉假体提供了实验依据。在脉络膜上腔电刺激研究中，我们将60刺激位点的MEMS薄膜电极植入到脉络膜上腔对视网膜进行电刺激，验证了刺激电极阵列的有效性，并通过记录分析初步探讨了皮层多通道诱发响应的时空特性。结果显示脉络膜上腔微电流刺激能够成功诱发视觉皮层响应，单个刺激电极的电流阈值为48.57±6.90μA，对应的电荷密度为25.24±3.59μC/cm2；整排电极（10个刺激位点）的电流阈值为25.55±5.43μA，对应的电荷密度为13.28±2.82μC/cm2。刺激电流与电荷密度阈值皆位于刺激电极和被刺激组织的安全刺激范围内。随着刺激电流强度的增强，皮层诱发响应的幅值增大，皮层响应范围不断增加，但最大响应位点保持不变，具有一致性和稳定性。不同的刺激电极（最小距离为750μm）可在视皮层不同位置诱发响应，证明脉络膜上腔电刺激具有一定的空间对应性。本项研究进一步验证了脉络膜上腔电刺激的可行性和有效性，量化了电刺激的一些参数，为脉络膜上腔视觉假体电刺激参数设计提供了参考。
[Abstract]:At least 70% of the human knowledge of the outside world is provided by the visual system. Blindness not only seriously affects the quality of life of the patients, but also brings a great burden to the society. With the continuous development of science and technology, the use of artificial visual prosthesis to repair the visual function of the blind has become a hot spot in the world. The research of visual prosthesis in China is small The group proposed a new artificial visual prosthesis of the spiny optic optic visual prosthesis. The present scheme needs to be studied systematically. This topic mainly analyzes the response characteristics of the optic nerve electrical stimulation in the visual cortex, and the effect of different stimulus waves and stimulation parameters on the optic nerve electrical stimulation. For the retinal prosthesis, we independently developed a polyimide polyimide array based on Micro-electro-mechanical System (MEMS), which is suitable for electrical stimulation of the retina in the upper choroidal cavity. The feasibility of this array of electrodes and the visual cortex induced by this topic. The temporal and spatial characteristics of the potential were preliminarily explored.
In the study of optic nerve electrical stimulation, we used a self-made platinum iridium alloy electrode array to stimulate the optic nerve fibers and recorded the evoked visual cortex response signals in the primary visual cortex. We systematically studied the waveform of the electrical stimulation of the optic nerve and the multiwave response induced by the prickling parameters to the visual cortex. The threshold information of different waveform components in the cortical response induced by optic nerve electrical stimulation and the optimized stimulus parameters are obtained, which provide experimental basis for understanding the transmission process of visual information and further optimizing the stimulus parameters of the optic vision prosthesis. The main results include: (1) through the micro current stimulation The optic nerve fibers can induce a field potential containing multiple waveform components in the visual primary cortex. At most, P0, N1, P1, P2 and P3 can be recorded. The different waveform components have different threshold and time characteristics. The lower the threshold and the duration of the component, the shorter the duration and duration of the component. (2) the electrical stimulation in the temporal dorsal quadrant of the optic nerve The optic nerve fibers, comparing the fast wave response recorded by the cortical multi electrode (P1) and the topological mapping of the cortical field, found that the region with the greatest response to the visual cortex was consistent with the visual field corresponding to the electrical stimulation of the optic nerve. It was proved that the optic nerve near the eyeball maintained a better visual topological correspondence and was suitable for implantation of visual prosthesis. (3) thorns. The excited waveforms and parameters have an important effect on the visual cortex response induced by the optic nerve electrical stimulation. Compared with the symmetrical charge balance stimulation waveform, the asymmetric waveform with the narrow negative phase pulse and the wide short positive phase pulse can reduce the threshold of the electrical stimulation. The stimulus wave induced by the same stimulus charge density is induced. The spatial distribution of the response is also larger. Adding time interval between the two pulse phase of the stimulus wave can reduce the threshold of stimulation, the time interval is 0.2ms, and the maximum response can be induced after the symmetrical first negative positive stimulus wave is added to the time interval. With the increase of the frequency of stimulation, the amplitude of cortical evoked response is lower. The variation of different waveform components with the increase of the frequency of stimulation is different. These experimental results provide an experimental basis for the development and development of optic nerve visual prosthesis.
In the study of the choroidal upper cavity electrical stimulation, we implanted the MEMS film electrode of the 60 stimulation site into the upper choroidal cavity to stimulate the retina. The effectiveness of the stimulus electrode array was verified. The temporal and spatial characteristics of the cortical multichannel induced response were preliminarily investigated by recording and analysis. The results showed that the microcurrent stimulation in the choroid cavity was able to be stimulated. The visual cortex response was successfully induced. The current threshold of the single stimulus electrode was 48.57 + 6.90 A, the corresponding charge density was 25.24 + 3.59 mu C/cm2, and the current threshold of the whole electrode (10 stimulation sites) was 25.55 + 5.43 mu A, and the corresponding charge density was 13.28 + 2.82 mu C/cm2. and the charge density threshold was both at the stimulation electrode and the stabbed electrode. The amplitude of cortical evoked response increased with the increase of stimulation current intensity, and the response range of cortex increased, but the maximum response site remained unchanged, with consistency and stability. Different stimulus electrodes (the minimum distance of 750 u m) could induce response in different positions of the visual cortex, and the choroid was proved to be on the choroid. This study further validates the feasibility and effectiveness of the electrical stimulation of the choroidal cavity, quantifies some parameters of the electrical stimulation, and provides a reference for the design of the electrical stimulation parameters for the visual prosthesis of the choroidal cavity.
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R774.6

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