脑自发低频振荡的神经代谢机制研究

发布时间：2018-02-20 17:34

本文关键词： 自发低频振荡血液动力学神经活跃性微电极阵列激光多普勒血流仪内源光学功能成像格兰杰因果模型负信号　出处：《国防科学技术大学》2015年博士论文　论文类型：学位论文

【摘要】：本文以微电极阵列、激光多普勒血流仪和内源光学功能成像为观测手段,研究了大鼠皮层自发低频振荡(low-frequency oscillation,LFO)的神经代谢机制,并观测了视觉刺激对自发LFO的时空调制现象。另外,对短时后肢电刺激引起的负信号的神经代谢机制进行了探索。自发LFO和负信号的神经代谢机制是神经血管耦合研究范畴的重要主题。这些研究工作对深入厘清大脑功能信号成分、理解大脑内在运作机制具有重要意义。本文主要研究工作及其贡献概括如下:自发LFO的多模态观测。以往,研究者对自发LFO的观测多集中于血液动力学层面。本文使用三种技术手段包括微电极阵列、激光多普勒血流仪和内源光学功能成像对麻醉大鼠体感和视觉皮层的自发LFO进行了观测和记录,既获得了血容量、脱氧血红蛋白和血流速度等血液代谢信号,也得到了局部场电位和神经元放电序列等神经活跃性电信号。通过多窗口谱估计方法,发现在这些信号中均存在广泛的自发LFO。在神经活跃性信号中记录到的自发LFO丰富和扩展了以往对自发LFO的观测。另外,本文还实现了微电极阵列与激光多普勒血流仪的同时观测,这为研究自发LFO的神经代谢机制提供了必要的条件。自发LFO的格兰杰因果分析。本文使用格兰杰因果模型分析了大鼠体感和视觉皮层血流速度、局部场电位和神经元放电序列三者之间的因果关系。这三种信号由激光多普勒血流仪和微电极阵列同时记录得到。结果发现在0.1Hz附近,三者有显著的因果关系,局部场电位和神经元放电序列是因,血流速度是果。而且,局部场电位与血流之间的因果关系强度要大于神经元放电序列与血流之间的因果关系强度。这些结果说明,自发LFO有可能来源于神经活跃性特别是局部场电位。据我们所知,该研究第一次探求了血流、局部场电位和神经元放电序列之间的格兰杰因果关系,并发现在0.1Hz附近神经活跃性与血液动力学信号之间有显著的格兰杰因果关系,神经活跃性特别是局部场电位是LFO生成的原因。该结果有可能为自发LFO来源于神经活跃性这一观点提供支持,从而进一步为静息态fMRI研究提供理论依据。视觉刺激对自发LFO的时空调制。研究刺激对自发LFO的时空调制现象,对于探索LFO的起源和揭示其与大脑功能的联系有重要意义。本文利用单眼LED闪光作为视觉输入,观测了其对内源光学功能成像信号中自发LFO的时空调制,发现两个现象:一是刺激使自发LFO的振荡节律加快,二是刺激使大范围脑区的自发LFO相位收敛。另外,刺激对自发LFO的调制作用是参数依赖的,即调制作用只在一定范围的刺激频率或强度下出现,而且频率参数的调制作用比强度参数的调制作用更明显。这些结果表明,自发LFO可以被参数依赖的闪光刺激所调制,视觉刺激范式在探索LFO的起源和功能方面可能具有潜在意义。负血液动力学响应信号的神经代谢机制研究。目前,对负血液动力学响应信号(简称负信号)神经代谢机制的研究,报道还不多而且争议很大。人们通常把负信号解释为神经活跃性的减小即神经去激活。本文使用内源光学功能成像技术观测短时后肢电刺激引发的正信号区域附近的负信号,并使用微电极阵列记录了负信号区域的神经活跃性信号。结果发现,刺激之后负信号区域的神经活跃性不变或者增加,这说明在该刺激范式下神经去激活机制并不适用。通过对正负信号曲线的时间动态进行分析,推测血液转移可能是潜在机制。另外,神经活跃性的增加也是该刺激范式下负信号的可能机制。因此在将负信号解释为神经活跃性减小时要更加谨慎,特别是当负信号位于正信号区域附近时。该研究可能提供了一个神经去激活机制的反例并且利于加深我们对大脑皮层负信号神经代谢机制的理解。
[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.

【学位授予单位】：国防科学技术大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R338

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