视网膜电刺激虚拟通道产生机理及其与视觉神经系统相互作用机制研究

Vision loss has become one of the severest disabilities affecting the quality of human life. Electrically stimulating part of the visual pathway from retina to visual cortex by implantable microelectrode array could restore some functional vision to the blind. It has become a hot topic in the field of neuroscience and neural engineering for past twenty years. Although research on restoration of vision has already made significant progress, the issue that how to fulfill the daily needs of visual information with the low-resolution percepts elicited from limited number of stimulating electrodes is still to be investigated, which has become a bottleneck for the development of visual prosthesis. We proposed an innovative method that improve the number of stimulating microelectrodes of retinal prosthesis by 'virtual stimulating channels', which is generated by vigilantly manipulating the electric-field interaction between adjacent electrodes. We would utilize multiple aspects of techniques, including computational simulation of electrical stimulation on the retina, fabrication of multi-electrode arrays, in vitro and in vivo studies of electrophysiological recording and optical imaging of intrinsic signals, to explore the rule of the electric-field effect for generating the virtual channel and the mechanism of neural information processing. Our research would also investigate the interactive mechanism between the virtual channel and the visual system, and assess the functionality and validity of the virtual channel by series of animal experiments. These studies will be critical for successful application of the virtual channel technology in visual prosthesis. The research is not only to provide an important theoretical basis for restoring the visual function, but also to further explore how the visual system processes the electrical stimulation-induced information and finally forms phosphene, i.e. visual perception elicited by electrical stimulation. This would ultimately promote the development of in cognitive science, neuroscience, neural engineering and information science.

视力丧失已成为影响人类生活质量最为严重的一种残疾。通过植入式神经微电极对盲人视觉系统中功能尚存的部分进行电刺激，从而实现视觉功能的修复已经成为神经科学与工程领域新的研究热点。视觉功能修复在取得重大进展的同时，也存在着输入信息需求大而刺激电极数量有限的瓶颈问题。本课题创新地提出在视网膜假体中通过调控相邻刺激电极电场的相互作用从而产生虚拟刺激通道的新思路。拟采用视网膜电刺激计算仿真模型、多通道微电极阵列，开展在体神经电生理和脑光学成像实验研究，探索虚拟通道产生的电场作用规律和神经信息处理机理，揭示虚拟通道与视觉神经系统的相互作用机制，并采用动物在体实验进行评估，从而为虚拟通道技术最终应用于人工视觉假体提供理论与实验依据。本课题不但为视觉功能修复提供重要的理论基础，而且能进一步探索大脑对电刺激视觉神经系统诱发视觉感知的信息处理机制，最终推动认知科学、神经科学及神经工程、信息科学领域的发展。

失明已成为影响人类生活质量最为严重的一种残疾。通过植入式神经微电极对盲人视觉系统中功能尚存的部分进行电刺激，从而实现视觉功能的修复已经成为神经科学与工程领域新的研究热点。视觉功能修复在取得重大进展的同时，也存在着输入信息需求大而刺激电极数量有限的瓶颈问题。本课题针对上述关键科学技术问题，创新地提出了在视网膜假体中通过调控相邻刺激电极电场的相互作用从而产生虚拟刺激通道的新思路。为了实现这一目标，本课题开展了一系列富有成效的研究工作，首先建立了视网膜神经节细胞电刺激仿真模型，基于该仿真模型探索了不同三维电极在视网膜上刺激的电场分布以及神经节细胞的响应规律，其次进一步提出了一种新颖的圆盘与圆环电极相结合的三维结构微电极阵列，通过建模仿真计算验证了该电极阵列能够通过刺激相邻电极产生虚拟通道，进而增加视网膜假体可产生的光幻视点数量，提高假体视觉分辨率；在此基础上，研制了高密度视网膜电刺激多通道柔性薄膜微电极阵列，通过调控相邻电极电流注入比例实现了刺激位点间神经节细胞的兴奋，为虚拟通道的动物在体实验研究提供了关键的技术手段；同时，开展了光声与OCT的血管-神经功能成像技术及其在动物在体实验系统中的应用研究，为后续的动物在体实验提供了一种新颖的技术手段；为了揭示虚拟通道与视觉神经系统的相互作用机制，通过动物在体实验，相继开展了基于内源性脑光学成像的电刺激视网膜诱发视皮层的时空响应机制研究、基于光学成像的电刺激视网膜诱发视觉通路响应特性研究，其研究成果不但能够为虚拟通道技术最终应用于人工视觉假体提供了良好的研究基础，而且为盲人视觉功能修复奠定了重要的理论基础及科学的实验依据，同时为未来高分辨率视网膜假体的研制提供了创新设计思路。