發(fā)布時(shí)間：2018-11-25 10:43

【摘要】：視覺是人類用來認(rèn)識客觀世界的重要途徑，因各種視網(wǎng)膜的病變引起的視覺功能喪失會對人的生活質(zhì)量造成極大的負(fù)面影響。視覺假體是一種新興的視覺功能修復(fù)方法，它是在采集外部圖像信息后進(jìn)行處理、編碼，然后使用植入體內(nèi)的微刺激器和電極陣列對視覺神經(jīng)系統(tǒng)進(jìn)行電刺激，最終在視覺中樞形成人工視覺的感知�；诖倘胧诫姌O陣列對視神經(jīng)施加電刺激來幫助盲人實(shí)現(xiàn)視覺功能的修復(fù)是視覺假體的一種新方案，但這種視覺假體仍存在有待研究的基本問題，例如探索適合于視神經(jīng)電刺激的模式和刺激策略、在眼球后植入怎樣的電極陣列才能實(shí)現(xiàn)具有良好拓?fù)渫渡浣Y(jié)構(gòu)的電刺激，以及最終視神經(jīng)假體能實(shí)現(xiàn)的空間分辨率和局部化刺激特性如何等方面。本課題使用刺入式電極對視神經(jīng)進(jìn)行電刺激并記錄視皮層誘發(fā)響應(yīng)的電生理信號，通過研究這一電生理響應(yīng)的時(shí)間和空間特性，為視覺假體的基本理論、參數(shù)設(shè)計(jì)以及最終效果提供理論支持和實(shí)驗(yàn)依據(jù)。 在視覺假體的研究過程中，所有涉及到電刺激與電生理記錄的實(shí)驗(yàn)中都發(fā)現(xiàn)皮層生理響應(yīng)信號通常會受到由于電流在組織中傳導(dǎo)而產(chǎn)生的物理性電偽跡的干擾，且無法使用傳統(tǒng)方法去除。這種電刺激偽跡會對神經(jīng)響應(yīng)信號的處理與分析造成巨大的妨害，尤其是當(dāng)在使用高強(qiáng)度、長間隔、高頻率或復(fù)雜模式電刺激的情況下。本文使用了獨(dú)立成分分析方法去除在各種視神經(jīng)電刺激強(qiáng)度、波形、模式下多通道皮層響應(yīng)中疊加的偽跡，并結(jié)合利多卡因阻斷視神經(jīng)的方法獲取不含響應(yīng)的純偽跡，通過相關(guān)性分析來評估偽跡去除的效果和對信號的影響。實(shí)驗(yàn)結(jié)果表明：在改變電刺激強(qiáng)度、脈沖間隔，脈沖波形、刺激頻率，甚至在進(jìn)行復(fù)雜的多電極同步或異步刺激模式下，這種方法都可以有效地去除誘發(fā)皮層響應(yīng)中疊加的電偽跡，，并且不會引起響應(yīng)的失真；同時(shí)也發(fā)現(xiàn)去除偽跡的效果會隨著皮層記錄通道的減少而降低。本研究將為后續(xù)視神經(jīng)視覺假體相關(guān)的電生理實(shí)驗(yàn)研究奠定數(shù)據(jù)分析基礎(chǔ)。 在刺入式視神經(jīng)電刺激的研究中，首先以白兔為實(shí)驗(yàn)動物模型，使用鉑銥合金電極陣列對視神經(jīng)進(jìn)行電刺激，在視覺皮層使用銀球電極陣列記錄誘發(fā)的皮層響應(yīng)信號，探索了適合于視神經(jīng)視覺假體，具有低閾值和局部化特性的電刺激模式、脈沖波形、電極尺寸、間距和排列的方式。本實(shí)驗(yàn)的主要結(jié)果包括：系統(tǒng)研究電刺激視神經(jīng)誘發(fā)的皮層響應(yīng)多波成分的閾值和潛伏期，結(jié)合組織學(xué)方法發(fā)現(xiàn)較低閾值和潛伏期的P1波具有電刺激和皮層響應(yīng)之間的拓?fù)鋵?yīng)性，是響應(yīng)中最主要的成分；單極刺激模式下的負(fù)相在先脈沖具有更小的刺激閾值并能誘發(fā)更局部的皮層響應(yīng)；比較了不同尺寸的電極對實(shí)現(xiàn)局部化電刺激的影響；證明了垂直視神經(jīng)走向排列的間距150μm的兩根電極可以誘發(fā)具有不同空間分布和位置的皮層響應(yīng)，是適合于視神經(jīng)假體的電極排列方式。本研究將為刺入式視神經(jīng)視覺假體實(shí)現(xiàn)低閾值、局部化且可分辨的電刺激所需的刺激參數(shù)、模式、電極尺寸、間距和排列方式提供實(shí)驗(yàn)依據(jù)和支持。 然后以貓為動物模型，建立了在體定位刺入式視神經(jīng)電極視野位置的方法，系統(tǒng)研究了刺入式視神經(jīng)假體的視覺拓?fù)渫渡潢P(guān)系、空間分辨率和局部化等功能特性。本實(shí)驗(yàn)的主要結(jié)果包括：建立了使用稀疏噪聲視覺刺激的方法用于對刺入式視神經(jīng)電極的在體視野定位，并獲取每只動物特異的視皮層和視野的視覺拓?fù)鋵?yīng)圖；小尺寸的電極刺激具有較高的電荷密度閾值；證實(shí)了在眼球后的視神經(jīng)內(nèi)植入視神經(jīng)假體能夠?qū)崿F(xiàn)具有良好視覺拓?fù)浣Y(jié)構(gòu)的電刺激，可以通過合理的電極排列與長度設(shè)計(jì)誘發(fā)具有拓?fù)湟?guī)律的皮層響應(yīng)；在電極間距150μm的情況下，刺入式視神經(jīng)電刺激的空間分辨率為2 3°；通過計(jì)算皮層響應(yīng)擴(kuò)散范圍，并和與視神經(jīng)電極相同視野位置的視覺刺激誘發(fā)皮層響應(yīng)進(jìn)行對比，發(fā)現(xiàn)小尺寸電極下的視神經(jīng)電刺激可以實(shí)現(xiàn)1 2°的局部化電刺激。本研究證明了視神經(jīng)視覺假體是一種可行的視覺功能修復(fù)手段，并將為視覺假體的設(shè)計(jì)提供實(shí)驗(yàn)依據(jù)。
[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眰鍝嶅簲錛涘湪鐢墊瀬闂磋窛150渭m鐨勬儏鍐典笅,鍒哄叆寮忚紲炵粡鐢?shù)鍒簨?

本文編號：2355812