基于fMRI的弱視視覺神經損傷機理研究
本文關鍵詞: 弱視 fMRI 視網膜拓撲 靜息態(tài) 多焦點閃爍 雙眼偏差系數(shù) 功能連接 出處:《中國科學技術大學》2017年博士論文 論文類型:學位論文
【摘要】:弱視是最常見的眼部疾病之一,指眼部沒有明顯的器質性病變,但其矯正視力低于正常人,發(fā)病與早期異常視覺經驗有關。弱視在普通人群中發(fā)病率在3%左右,存在視力低下、對比敏感度及立體視功能受損等視覺障礙,嚴重影響弱視患者的正常生活。弱視因其神經機制復雜,雖然關于其發(fā)病原因,功能損傷機制研究和討論很多,但是目前還沒有一致性的結論。主流觀點包括投射連接紊亂、空間標度的低頻偏移和采樣率降低等。對于弱視的神經損傷機制深入研究,不僅對臨床治療具有重要幫助,有助于指導新的弱視治療方法的探索,并且對進一步理解視覺神經系統(tǒng)的可塑性和信息處理機制有重要意義。動物模型在弱視神經理論建立上起到關鍵作用,由于弱視致病機理的復雜性,動物模型較難準確模擬弱視模型。心理物理實驗研究對了解弱視也起到重要作用,但是間接的測量方法引發(fā)很多爭議,主要因其較難從復雜的弱視機理中直接提取神經損傷的信息。功能磁共振成像(fMRI)因其較高的時間空間分辨率、無創(chuàng)和低危害等優(yōu)良特性,成為探索人類和動物腦科學的重要手段。采用磁共振方法來研究弱視的損傷機制,可以直觀的了解弱視大腦皮層的響應,得到視皮層損傷的直接證據。因此本文利用fMRI技術對屈光參差性弱視視覺神經損傷機理進行研究,主要包括視網膜拓撲、多焦點閃爍實驗、靜息態(tài)磁共振實驗,具體內容如下:1視網膜拓撲:是精細描繪個體自身視野位置和其對應視覺腦區(qū)的經典模型。采用VFS(Visual field sign)算法進行分析,得到個體基于視網膜拓撲分析的視覺精細分區(qū)數(shù)據(V1-V4等),這些分析有利于深入了解視覺神經系統(tǒng)的拓撲機制,為后續(xù)精細處理不同視覺分區(qū)相關功能提供了可能,也避免了數(shù)據因標準化造成的非線性形變誤差。2多焦點閃爍實驗:通過棋盤格刺激,研究弱視視皮層對于不同視野位置的閾上刺激的損傷機制。通過計算雙眼偏差系數(shù),我們發(fā)現(xiàn)弱視組結果比正常組在紋狀皮層和紋外皮層都有顯著性增大,在中央區(qū)刺激得到的雙眼偏差系數(shù)與視力損傷程度有顯著的相關性,而在旁中央的刺激則沒有顯著相關性。因為實驗中使用與實驗無關的中央刺激反饋(正確率大于90%)來保證被試中央注視,所以我們可以推測正常組與弱視組雙眼偏差系數(shù)的顯著性差異可能是由拓撲紊亂引起的。通過計算%BOLD信號變化的平均激活強度,顯著性激活的體素數(shù)目和最大激活點的激活強度指標,弱視結果比正常組存在顯著性降低,弱視的相對健眼的結果比弱視眼存在顯著性增加,可以推測即使在閾上刺激,視皮層中有較少的神經元參與刺激信息的處理,更多的神經元具有較低的信噪比。在不同皮層內部和之間的信息傳遞過程中存在采樣率降低的現(xiàn)象。3腦部蘊含的大量信息,目前對腦部信息表征的研究還處于初級階段。對靜息狀態(tài)下的腦部活動,特別是對病理狀態(tài)下靜息態(tài)信號的分析,可以幫助我們更好的研究神經系統(tǒng)疾病,特別是像弱視這種沒有明顯器質性病變的神經系統(tǒng)疾病。通過對功能連接、局部一致性和低頻振幅等信息的研究,可以定量分析弱視在非任務態(tài)下視覺皮層甚至全腦皮層與正常被試的差異,進一步挖掘出弱視神經系統(tǒng)損傷的機理信息。在功能連接實驗中,我們選取Brodmann17(V1),Brodmann18(V2)和Brodmann19(V3,V4和V5)三個經典視覺分區(qū)作為種子點,在對視覺分區(qū)功能連接分析過程中,發(fā)現(xiàn)弱視V1與V2和更高級皮層功能連接要弱于正常組,說明弱視的V1區(qū)存在損傷,其在向高級視皮層信息處理和傳遞過程中存在功能連接損傷。弱視的V2區(qū)與V1和V3等更高級皮層功能連接要強與正常組,可能原因是弱視傳遞相同的信息需要更多的神經元連接,也可能V2對初級視皮層損傷進行了功能代償,進而表現(xiàn)出與其他視皮層的連接增強。在局部一致性(regional homogeneity,ReHo)和低頻振幅(amplitude of low frequency fluctuations,ALFF)研究中發(fā)現(xiàn)弱視在認知、控制和注意等相關腦區(qū)的一致性與正常對照組有顯著差異,并且首次發(fā)現(xiàn)視力損傷程度與這些腦區(qū)有顯著相關性。綜上所述,弱視功能損傷機制是多樣性的,屈光參差性弱視可能同時存在拓撲連接紊亂和采樣率降低等功能損傷。在靜息態(tài)磁共振數(shù)據分析中,視覺區(qū)功能連接顯示,弱視初級視皮層存在損傷,V1區(qū)向更高級視皮層的功能連接弱于正常組。局部一致性和低頻振幅的結果顯示,弱視在認知、控制和注意相關腦區(qū)的一致性低于正常對照組,這提示了弱視在視覺區(qū)以外的高級皮層信息處理也可能存在缺陷。
[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.
【學位授予單位】:中國科學技術大學
【學位級別】:博士
【學位授予年份】:2017
【分類號】:R445.2;R777.44
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