基于ELP4基因多态性的BECTS的多模态影像学研究

发布时间：2018-03-02 12:29

本文选题：基于体素的形态学分析　切入点：灰质　出处：《南方医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：第一部分ELP4基因多态性对BECTS的灰质结构影响的形态学研究[目的]采用基于体素的形态学分析(VBM)观察ELP4 rs964112不同基因型的患儿和正常儿童灰质结构的差异,通过评估灰质结构、脑电、视听整合连续测试(IVA+CPT)和瑞文标准推理测验的结果差异,探讨风险基因型在伴中央颞区棘波的儿童良性癫痫(BECTS)中的作用机制及其对认知功能的影响。[材料和方法]本研究纳入68例BECTS和89例正常儿童志愿者,使用MRI采集高分辨率T1结构像(3DT1),并对部分BECTS采集1000s同步EEG-fMRI数据。采用VBM8软件对3DT1像进行配准、切割和预处理后得到每个被试的灰质图像,同时处理并读取脑电数据。对部分被试行IVA+CPT和瑞文标准推理测验。采用SPM8软件统计分析基因和疾病交互作用脑区、基因主效应脑区和疾病主效应脑区,并用SPSS22.0分析临床信息和量表在病例对照中的差异,及其与影像结果的相关性。[结果]ELP4rs964112的基因型分布在BECTS和正常儿童中有显著差异,GG为高风险型,T携带为低风险型,BECTS(GG)较BECTS(Tcar)的中央颞区棘波(CTS)平均发放次数增加,HC(GG)较HC(Tcar)注意力、智商减弱,基因和BECTS交互作用灰质结构改变脑区为右侧丘脑和左侧Rolandic区。基因主效应脑区为双侧丘脑和双侧Rolandic区,疾病的主效应脑区为双侧丘脑和右侧Rolandic区。[结论]ELP4rs964112是BECTS的潜在遗传风险因素,高风险型BECTS的CTS发放显著增加,ELP4rs964112的多态性影响丘脑-Rolandic区皮质结构发育,这可能是BECTS患儿癫痫易感性增加的结构基础。第二部分基于ELP4rs964112基因多态性对BECTS的脑功能连接和脑网络拓扑学性质的研究[目的]基于ELP4rs964112不同基因型的灰质结构差异,进一步分析其脑功能连接(FC)的异常和脑网络拓扑学的改变,评价ELP4rs964112对BECTS脑网络改变的潜在影响和机制。[材料和方法]本研究纳入68例BECTS和89例正常儿童志愿者,采集BOLD和3DT1像。预处理后的数据以第一部分VBM的基因和疾病交互作用的脑区为感兴趣区(ROI),用rest软件行ROI与全脑的功能连接分析,并比较各组差异,同时用GRETNA软件分析各组被试全脑网络的全局参数和局域参数。[结果]与BECTS(Tcar)相比,BECTS(GG)的基因和疾病交互作用的灰质结构改变脑区丘脑与双侧Rolandic区、壳核/尾状核的FC减弱,Rolandic区与双侧壳核/尾状核的FC增强;与HC(Tcar)相比,HC(GG)的丘脑与双侧Rolandic区、壳核/尾状核的FC增强。与BECTS(Tcar)相比,BECTS(GG)的左侧丘脑的节点中介中间性、双侧丘脑的加权的连接强度的加权连接强度和节点效率减低。与HC(GG)组相比,HC(Tcar)组的左侧中央沟盖节点中介中间性减低。各组被试均具有小世界属性,脑网络全局参数无统计学差异。[结论]ELP4rs964112的多态性与以Rolandic区、丘脑和纹状体之间功能连接异常为主的脑功能网络改变有关。不同基因型被试组仍具有小世界属性,部分节点局部参数显示高风险基因型组较低风险组丘脑和Rolandic区处理信息的能力和效率减弱。
[Abstract]:The first part of the gray matter structure of ELP4 gene polymorphism on the impact of BECTS morphological research [Objective] using voxel based morphometry (VBM) to observe the differences of different genotypes of ELP4 rs964112 children and normal children's gray matter structure, through the assessment of gray matter structure, EEG, audiovisual integration continuous test (IVA+CPT) and raven standard reasoning test the difference on risk genotypes with centrotemporal spikes in children with benign epilepsy (BECTS) mechanism and its effect on cognitive function. Materials and methods: This study included 68 cases of BECTS and 89 cases of normal children volunteers, the use of MRI to acquire high resolution T1 (3DT1), and the like on the part of the BECTS acquisition 1000s synchronous EEG-fMRI data. The 3DT1 image registration using VBM8 software, cutting and pretreatment after gray images of each subject, at the same time and read EEG data. On the part of the trial IVA+CPT and raven standard reasoning test. The SPM8 software was used for statistical analysis of gene and disease interactions between brain regions, the main genetic effect of brain areas and the main effect of brain diseases, and SPSS22.0 analysis of clinical information and scale differences in case-control, genotype and its correlation with imaging results. Results the distribution of]ELP4rs964112 has significant difference in BECTS and normal children, GG is high risk, low risk for carrying T, BECTS (GG) BECTS (Tcar) central temporal spikes (CTS) the average firing frequency increasing, HC (GG) HC (Tcar) concentration, the intelligence quotient decreased, and BECTS gene interaction in gray matter change the structure of brain regions for the right thalamus and left Rolandic area. The main genetic effect brain regions of bilateral thalamus and bilateral Rolandic, brain diseases as the main effect of the bilateral thalamus and right Rolandic area. Conclusion]ELP4rs964112 is a potential genetic risk factors for BECTS, high risk BECTS CTS release increased significantly, the polymorphisms affect cortical structure of thalamic -Rolandic Development Zone ELP4rs964112, which may be the structural basis of increased susceptibility to BECTS in children with epilepsy. The second part of ELP4rs964112 gene polymorphism on brain function of the connection of BECTS and network topological properties of brain [Objective] Based on the differences of gray matter structure of different ELP4rs964112 genotype based on the further analysis of the brain functional connectivity (FC) and the abnormal brain network topology changes, ELP4rs964112 evaluation of potential effects and mechanisms of BECTS brain network changes. Materials and methods: This study included 68 cases of BECTS and 89 normal children volunteers, BOLD and 3DT1. As a collection of data after pretreatment with brain in the first part of VBM gene and disease interactions for region of interest (ROI), using rest software for ROI is connected with the whole brain function analysis, and compare the differences between each group, at the same time by GRE TNA software to analyze the subjects of whole brain network global parameters and local parameters. Compared with BECTS (Tcar), BECTS (GG) changes in gray matter structure and disease gene interaction of brain regions in the thalamus and bilateral caudate putamen / Rolandic area, FC area and Rolandic decreased, bilateral caudate / putamen enhanced FC and HC; (Tcar), HC (GG) of the thalamus and bilateral caudate putamen / Rolandic, enhanced FC and BECTS. (Tcar) compared to BECTS (GG) of the intermediate node intermediary left thalamus, weighted connection strength weighted bilateral thalamus connection strength and node efficiency reduced. And HC (GG) group, HC (Tcar) group of the central sulcus of the left side cover decreased. Middle node intermediary subjects had small world properties, and polymorphism in Rolandic region showed no significant difference. Conclusion]ELP4rs964112 global brain network parameters, abnormal function between the thalamus and striatum connections The changes of brain function network were mainly related. Different genotype subjects still had small world attributes. Partial node local parameters showed that the high-risk group and low risk group had less information and ability to deal with information in hypothalamic and Rolandic regions.

【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742.1;R445.2

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