基于fMRI的弱视视觉神经损伤机理研究

发布时间：2018-02-27 09:31

本文关键词： 弱视 fMRI 视网膜拓扑静息态多焦点闪烁双眼偏差系数功能连接　出处：《中国科学技术大学》2017年博士论文　论文类型：学位论文

【摘要】：弱视是最常见的眼部疾病之一,指眼部没有明显的器质性病变,但其矫正视力低于正常人,发病与早期异常视觉经验有关。弱视在普通人群中发病率在3%左右,存在视力低下、对比敏感度及立体视功能受损等视觉障碍,严重影响弱视患者的正常生活。弱视因其神经机制复杂,虽然关于其发病原因,功能损伤机制研究和讨论很多,但是目前还没有一致性的结论。主流观点包括投射连接紊乱、空间标度的低频偏移和采样率降低等。对于弱视的神经损伤机制深入研究,不仅对临床治疗具有重要帮助,有助于指导新的弱视治疗方法的探索,并且对进一步理解视觉神经系统的可塑性和信息处理机制有重要意义。动物模型在弱视神经理论建立上起到关键作用,由于弱视致病机理的复杂性,动物模型较难准确模拟弱视模型。心理物理实验研究对了解弱视也起到重要作用,但是间接的测量方法引发很多争议,主要因其较难从复杂的弱视机理中直接提取神经损伤的信息。功能磁共振成像(fMRI)因其较高的时间空间分辨率、无创和低危害等优良特性,成为探索人类和动物脑科学的重要手段。采用磁共振方法来研究弱视的损伤机制,可以直观的了解弱视大脑皮层的响应,得到视皮层损伤的直接证据。因此本文利用fMRI技术对屈光参差性弱视视觉神经损伤机理进行研究,主要包括视网膜拓扑、多焦点闪烁实验、静息态磁共振实验,具体内容如下:1视网膜拓扑:是精细描绘个体自身视野位置和其对应视觉脑区的经典模型。采用VFS(Visual field sign)算法进行分析,得到个体基于视网膜拓扑分析的视觉精细分区数据(V1-V4等),这些分析有利于深入了解视觉神经系统的拓扑机制,为后续精细处理不同视觉分区相关功能提供了可能,也避免了数据因标准化造成的非线性形变误差。2多焦点闪烁实验:通过棋盘格刺激,研究弱视视皮层对于不同视野位置的阈上刺激的损伤机制。通过计算双眼偏差系数,我们发现弱视组结果比正常组在纹状皮层和纹外皮层都有显著性增大,在中央区刺激得到的双眼偏差系数与视力损伤程度有显著的相关性,而在旁中央的刺激则没有显著相关性。因为实验中使用与实验无关的中央刺激反馈(正确率大于90%)来保证被试中央注视,所以我们可以推测正常组与弱视组双眼偏差系数的显著性差异可能是由拓扑紊乱引起的。通过计算%BOLD信号变化的平均激活强度,显著性激活的体素数目和最大激活点的激活强度指标,弱视结果比正常组存在显著性降低,弱视的相对健眼的结果比弱视眼存在显著性增加,可以推测即使在阈上刺激,视皮层中有较少的神经元参与刺激信息的处理,更多的神经元具有较低的信噪比。在不同皮层内部和之间的信息传递过程中存在采样率降低的现象。3脑部蕴含的大量信息,目前对脑部信息表征的研究还处于初级阶段。对静息状态下的脑部活动,特别是对病理状态下静息态信号的分析,可以帮助我们更好的研究神经系统疾病,特别是像弱视这种没有明显器质性病变的神经系统疾病。通过对功能连接、局部一致性和低频振幅等信息的研究,可以定量分析弱视在非任务态下视觉皮层甚至全脑皮层与正常被试的差异,进一步挖掘出弱视神经系统损伤的机理信息。在功能连接实验中,我们选取Brodmann17(V1),Brodmann18(V2)和Brodmann19(V3,V4和V5)三个经典视觉分区作为种子点,在对视觉分区功能连接分析过程中,发现弱视V1与V2和更高级皮层功能连接要弱于正常组,说明弱视的V1区存在损伤,其在向高级视皮层信息处理和传递过程中存在功能连接损伤。弱视的V2区与V1和V3等更高级皮层功能连接要强与正常组,可能原因是弱视传递相同的信息需要更多的神经元连接,也可能V2对初级视皮层损伤进行了功能代偿,进而表现出与其他视皮层的连接增强。在局部一致性(regional homogeneity,ReHo)和低频振幅(amplitude of low frequency fluctuations,ALFF)研究中发现弱视在认知、控制和注意等相关脑区的一致性与正常对照组有显著差异,并且首次发现视力损伤程度与这些脑区有显著相关性。综上所述,弱视功能损伤机制是多样性的,屈光参差性弱视可能同时存在拓扑连接紊乱和采样率降低等功能损伤。在静息态磁共振数据分析中,视觉区功能连接显示,弱视初级视皮层存在损伤,V1区向更高级视皮层的功能连接弱于正常组。局部一致性和低频振幅的结果显示,弱视在认知、控制和注意相关脑区的一致性低于正常对照组,这提示了弱视在视觉区以外的高级皮层信息处理也可能存在缺陷。
[Abstract]:Amblyopia is one of the most common diseases of the eye, the eye that no significant qualitative changes, but the visual acuity lower than normal people, is associated with early abnormal visual experience. Amblyopia in the general population incidence of about 3%, have low vision, contrast sensitivity and stereoscopic function impaired visual impairment, serious influence the normal life of amblyopia patients. Amblyopia due to its complex mechanisms, although about its causes, and discuss the mechanism of injury, but there is no consistent conclusion. The mainstream view including projection connection disorder, low frequency offset space scale and reduce the sampling rate. For the further studies on the mechanism of nerve injury in amblyopia. Not only is of great help for clinical treatment, explore help guide new method for the treatment of amblyopia, and to further understanding of visual system plasticity and information processing mechanism Is of great significance. In theory to establish the animal model of amblyopia nerve play a key role, because of the complexity of the pathogenic mechanism of amblyopia, amblyopia animal model is difficult to accurately simulate the model. Research on psychophysical experiments to understand the amblyopia also play an important role, but the indirect measurement method caused a lot of controversy, mainly because it is difficult from the mechanism of amblyopia the complex direct extraction of nerve injury. Functional magnetic resonance imaging (fMRI) because of its high spatial resolution, non-invasive and low damage and other excellent properties, has become an important means of exploring human and animal brain science. To study the damage mechanism of amblyopia by magnetic resonance method, intuitive understanding of the cerebral cortex in response to amblyopia the direct evidence of cortical injury. So we use fMRI technology to research the anisometropic amblyopia visual nerve injury mechanism, including retinal topology, Multifocal flicker experiments, resting state fMRI experiment, the specific contents are as follows: 1 retinal topology: is a classic model depicting fine individual vision position and its corresponding visual areas of the brain. The VFS (Visual field sign) algorithm based on visual analysis, get individual fine partition data topology analysis of the retina (V1-V4, etc.) the analysis is conducive to understanding the topology mechanism of visual system, provides the possibility for subsequent fine processing of different visual partition function, but also to avoid the data for standard nonlinear distortion errors caused by.2 multifocal flicker experiments: by checkerboard stimulation of amblyopia visual cortex for injury mechanism of stimulation of different position on the threshold of vision by calculating the binocular deviation coefficient, we found the amblyopia group than the normal group in the striate cortex and extrastriate cortex has significantly increased, in the central stimulus There was a significant correlation between the eyes and vision deviation coefficient of damage degree, and in the central stimulus is no significant correlation. Because of the use of unrelated to experiment in the experiment of the central stimulus feedback (the correct rate is greater than 90%) to ensure the participants at the central, so we can speculate that the normal group significant difference and deviation coefficient of binocular amblyopia group may be caused by topological disorder. According to the average intensity of activation calculation of%BOLD signal changes, significant activation number of voxels and the maximal activation point activation intensity index, amblyopia results than normal group were significantly decreased, the relative results of ocular amblyopia than in amblyopia significantly increased, presumably stimulate even on the threshold, as there are fewer neurons in the cortex involved in stimulus information, more neurons with low SNR. In different cortex within and between information transfer A large number of sampling information phenomenon of.3 brain contains lower rates exist in the process of the current research on the brain information representation is still at the initial stage of the resting state brain activity, especially the analysis of resting state signal under pathological conditions, can help us study better by God system diseases, especially diseases like nervous system this kind of amblyopia no obvious pathological changes. Based on the study of local functional connectivity, consistency and amplitude of low-frequency information, quantitative analysis of amblyopia in non task state and the visual cortex in cerebral cortex of normal subjects and differences, to further explore the mechanism of amblyopia information of nervous system injury. In functional connectivity experiment we selected, Brodmann17 (V1), Brodmann18 (V2) and Brodmann19 (V3, V4 and V5) three classic visual partition as the seed point in the functional connectivity analysis on visual partition in the process of discovery V1 and V2 of amblyopia and higher cortical functional connectivity is weaker than the normal group, indicating the existence of damage of amblyopia in the District of V1, the existence of functional connectivity in the visual cortex damage to the advanced information processing and transmission process. The V2 and V1 of amblyopia and V3 higher cortical function stronger connection with the normal group, the possible causes of amblyopia the same information needs more neuronal connections, may also V2 the compensatory function of primary visual cortex injury, thus showing the connection with other visual cortex increased. In the local consistency (regional homogeneity, ReHo) and low frequency (amplitude of low frequency fluctuations amplitude, ALFF) amblyopia in cognitive research showed that consistent the brain regions related to control and attention have significant differences with the control group, and for the first time found that visual impairment degree have significant correlation with these brain regions. In summary, function mechanism of injury is amblyopia The diversity of anisometropic amblyopia may topological disorder and sampling function damage rate and reduce at the same time. In the analysis of resting state fMRI data, the visual function is connected with the display area, amblyopia in primary visual cortex damage, V1 to more advanced visual cortex functional connectivity is weaker than that of the normal group. The local consistency and low frequency the results show that the amplitude, amblyopia in cognitive control and pay attention to consistency of brain regions related to lower than the normal control group, suggesting that the amblyopia in the visual areas outside the senior cortical information processing may also exist defects.

【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R445.2;R777.44

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