本文關(guān)鍵詞： 自發(fā)低頻振蕩 血液動(dòng)力學(xué) 神經(jīng)活躍性 微電極陣列 激光多普勒血流儀 內(nèi)源光學(xué)功能成像 格蘭杰因果模型 負(fù)信號(hào)　出處：《國(guó)防科學(xué)技術(shù)大學(xué)》2015年博士論文　論文類(lèi)型：學(xué)位論文

【摘要】：本文以微電極陣列、激光多普勒血流儀和內(nèi)源光學(xué)功能成像為觀測(cè)手段,研究了大鼠皮層自發(fā)低頻振蕩(low-frequency oscillation,LFO)的神經(jīng)代謝機(jī)制,并觀測(cè)了視覺(jué)刺激對(duì)自發(fā)LFO的時(shí)空調(diào)制現(xiàn)象。另外,對(duì)短時(shí)后肢電刺激引起的負(fù)信號(hào)的神經(jīng)代謝機(jī)制進(jìn)行了探索。自發(fā)LFO和負(fù)信號(hào)的神經(jīng)代謝機(jī)制是神經(jīng)血管耦合研究范疇的重要主題。這些研究工作對(duì)深入厘清大腦功能信號(hào)成分、理解大腦內(nèi)在運(yùn)作機(jī)制具有重要意義。本文主要研究工作及其貢獻(xiàn)概括如下:自發(fā)LFO的多模態(tài)觀測(cè)。以往,研究者對(duì)自發(fā)LFO的觀測(cè)多集中于血液動(dòng)力學(xué)層面。本文使用三種技術(shù)手段包括微電極陣列、激光多普勒血流儀和內(nèi)源光學(xué)功能成像對(duì)麻醉大鼠體感和視覺(jué)皮層的自發(fā)LFO進(jìn)行了觀測(cè)和記錄,既獲得了血容量、脫氧血紅蛋白和血流速度等血液代謝信號(hào),也得到了局部場(chǎng)電位和神經(jīng)元放電序列等神經(jīng)活躍性電信號(hào)。通過(guò)多窗口譜估計(jì)方法,發(fā)現(xiàn)在這些信號(hào)中均存在廣泛的自發(fā)LFO。在神經(jīng)活躍性信號(hào)中記錄到的自發(fā)LFO豐富和擴(kuò)展了以往對(duì)自發(fā)LFO的觀測(cè)。另外,本文還實(shí)現(xiàn)了微電極陣列與激光多普勒血流儀的同時(shí)觀測(cè),這為研究自發(fā)LFO的神經(jīng)代謝機(jī)制提供了必要的條件。自發(fā)LFO的格蘭杰因果分析。本文使用格蘭杰因果模型分析了大鼠體感和視覺(jué)皮層血流速度、局部場(chǎng)電位和神經(jīng)元放電序列三者之間的因果關(guān)系。這三種信號(hào)由激光多普勒血流儀和微電極陣列同時(shí)記錄得到。結(jié)果發(fā)現(xiàn)在0.1Hz附近,三者有顯著的因果關(guān)系,局部場(chǎng)電位和神經(jīng)元放電序列是因,血流速度是果。而且,局部場(chǎng)電位與血流之間的因果關(guān)系強(qiáng)度要大于神經(jīng)元放電序列與血流之間的因果關(guān)系強(qiáng)度。這些結(jié)果說(shuō)明,自發(fā)LFO有可能來(lái)源于神經(jīng)活躍性特別是局部場(chǎng)電位。據(jù)我們所知,該研究第一次探求了血流、局部場(chǎng)電位和神經(jīng)元放電序列之間的格蘭杰因果關(guān)系,并發(fā)現(xiàn)在0.1Hz附近神經(jīng)活躍性與血液動(dòng)力學(xué)信號(hào)之間有顯著的格蘭杰因果關(guān)系,神經(jīng)活躍性特別是局部場(chǎng)電位是LFO生成的原因。該結(jié)果有可能為自發(fā)LFO來(lái)源于神經(jīng)活躍性這一觀點(diǎn)提供支持,從而進(jìn)一步為靜息態(tài)fMRI研究提供理論依據(jù)。視覺(jué)刺激對(duì)自發(fā)LFO的時(shí)空調(diào)制。研究刺激對(duì)自發(fā)LFO的時(shí)空調(diào)制現(xiàn)象,對(duì)于探索LFO的起源和揭示其與大腦功能的聯(lián)系有重要意義。本文利用單眼LED閃光作為視覺(jué)輸入,觀測(cè)了其對(duì)內(nèi)源光學(xué)功能成像信號(hào)中自發(fā)LFO的時(shí)空調(diào)制,發(fā)現(xiàn)兩個(gè)現(xiàn)象:一是刺激使自發(fā)LFO的振蕩節(jié)律加快,二是刺激使大范圍腦區(qū)的自發(fā)LFO相位收斂。另外,刺激對(duì)自發(fā)LFO的調(diào)制作用是參數(shù)依賴(lài)的,即調(diào)制作用只在一定范圍的刺激頻率或強(qiáng)度下出現(xiàn),而且頻率參數(shù)的調(diào)制作用比強(qiáng)度參數(shù)的調(diào)制作用更明顯。這些結(jié)果表明,自發(fā)LFO可以被參數(shù)依賴(lài)的閃光刺激所調(diào)制,視覺(jué)刺激范式在探索LFO的起源和功能方面可能具有潛在意義。負(fù)血液動(dòng)力學(xué)響應(yīng)信號(hào)的神經(jīng)代謝機(jī)制研究。目前,對(duì)負(fù)血液動(dòng)力學(xué)響應(yīng)信號(hào)(簡(jiǎn)稱(chēng)負(fù)信號(hào))神經(jīng)代謝機(jī)制的研究,報(bào)道還不多而且爭(zhēng)議很大。人們通常把負(fù)信號(hào)解釋為神經(jīng)活躍性的減小即神經(jīng)去激活。本文使用內(nèi)源光學(xué)功能成像技術(shù)觀測(cè)短時(shí)后肢電刺激引發(fā)的正信號(hào)區(qū)域附近的負(fù)信號(hào),并使用微電極陣列記錄了負(fù)信號(hào)區(qū)域的神經(jīng)活躍性信號(hào)。結(jié)果發(fā)現(xiàn),刺激之后負(fù)信號(hào)區(qū)域的神經(jīng)活躍性不變或者增加,這說(shuō)明在該刺激范式下神經(jīng)去激活機(jī)制并不適用。通過(guò)對(duì)正負(fù)信號(hào)曲線的時(shí)間動(dòng)態(tài)進(jìn)行分析,推測(cè)血液轉(zhuǎn)移可能是潛在機(jī)制。另外,神經(jīng)活躍性的增加也是該刺激范式下負(fù)信號(hào)的可能機(jī)制。因此在將負(fù)信號(hào)解釋為神經(jīng)活躍性減小時(shí)要更加謹(jǐn)慎,特別是當(dāng)負(fù)信號(hào)位于正信號(hào)區(qū)域附近時(shí)。該研究可能提供了一個(gè)神經(jīng)去激活機(jī)制的反例并且利于加深我們對(duì)大腦皮層負(fù)信號(hào)神經(jīng)代謝機(jī)制的理解。
[Abstract]:In this paper, microelectrode array, laser Doppler flowmetry and intrinsic optical imaging observation means of rat cortical spontaneous oscillation (low-frequency oscillation LFO) the neural metabolic mechanism, and observing the visual stimuli on the spatiotemporal modulation phenomenon of spontaneous LFO. In addition, the neural metabolic mechanism of negative signals caused by electrical stimulation of the hind legs for a short time is studied. The nerve metabolism mechanism of spontaneous LFO and negative signals is an important research subject category. These nerve vascular coupling research to clarify the brain signals components of depth, has important significance in understanding the operation mechanism of the brain. The main research work and contributions are summarized as follows: multimodal observation of spontaneous LFO. Previous researchers. The observation of spontaneous LFO focused on hemodynamic level. This paper uses three kinds of techniques including microelectrode array, laser Doppler flow Spontaneous LFO instrument and intrinsic optical imaging of somatosensory and visual cortex of anesthetized rats were observed and recorded, not only to obtain the blood volume, deoxygenated hemoglobin and blood flow rate of blood metabolic signals, also obtained the local field potential and neuronal firing sequences of neural activity signal spectrum estimation method. Through the window, found in these signals are widely active spontaneous LFO. signaling in neural recordings of spontaneous LFO to enrich and extend previous observations of spontaneous LFO. In addition, this paper also realized the microelectrode array with laser Doppler flow meter and the observation, which provides the necessary conditions for the study of the spontaneous neural metabolism mechanism of LFO Grainger. Analysis of causal spontaneous LFO. In this paper, using the Grainger causal model analysis of the rat somatosensory and visual cortex blood flow velocity, local field potentials and neuronal discharge sequence three The causal relationship between the three. This kind of signal by laser Doppler flowmetry and microelectrode array. Results also recorded in the vicinity of 0.1Hz, a significant causal relationship among the three, the local field potential and neuronal firing sequence is due, flow velocity is the result. Moreover, the causal relationship between the strength of the local field potential and the blood flow is greater than the causal the relationship between the intensity of firing sequence and blood flow. These results suggest that LFO may have come from spontaneous neural activity especially in the local field potential. To our knowledge, this is the first study to explore the blood flow between local field potentials and firing sequence of the Grainger causality, and found in the vicinity of 0.1Hz neural activity significantly the causal relationship between Grainger and the hemodynamic signal, neural activity especially the local field potential is generated by LFO. The results may be as spontaneous LFO From the view of neural active support, so as to provide a theoretical basis for further study. Resting state fMRI visual stimulation on spatiotemporal modulation of spontaneous LFO. Research on stimulation of the spatiotemporal modulation phenomenon of spontaneous LFO, to explore the origin of LFO and reveal its relationship with brain function has important significance. This paper uses monocular flash as LED observation on the visual input, spatiotemporal modulation of spontaneous LFO intrinsic optical imaging signal, found two phenomena: one is to stimulate LFO to speed up the rhythm of spontaneous oscillation, two is to stimulate the spontaneous LFO wide range of brain regions of phase convergence. In addition, stimulation is parameter dependent on the modulation effect of spontaneous LFO. The modulation effect only in a certain range of stimulus frequency or intensity, and modulation frequency parameters than the modulation effect of strength parameters is more obvious. These results indicate that the LFO parameters can be spontaneous Modulation on flash stimulation, visual stimulation paradigm in the origin and function of exploring LFO may have potential significance. Study on the metabolic mechanism of neural signal hemodynamic response to negative. At present, the signal response to negative hemodynamic (the negative signal) of nerve metabolism, but few reports were controversial. People often put a negative signal in order to reduce the neural activity of the interpretation is to activate the nerve. The negative signal near the positive signal area using intrinsic optical imaging technology of electrical stimulation caused by short limb observations, and use the microelectrode array recorded negative signal region of the nerve activity signal. The results showed that after stimulation of negative signal region of the neural activity in the same or this shows that the increase in stimulation paradigm to neural activation mechanism is not suitable. Through the analysis of positive and negative time dynamic signal curve, push Measurement of the blood transfer may be a potential mechanism. In addition, the possible mechanism of negative signals of neural activity also increases as the stimulus paradigm. Therefore when the negative signal interpreted as neural activity is reduced to be more cautious, especially when the negative signal is located near the positive signal area. The study can provide a counterexample to a nerve to activate the mechanism and to deepen our understanding of the cerebral cortex nerve metabolic mechanism of negative signals.

【學(xué)位授予單位】：國(guó)防科學(xué)技術(shù)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R338

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