颞叶癫痫患者伏隔核功能连接网络的静息态fmri研究

发布时间：2018-05-01 05:11

本文选题：伏隔核 + 颞叶癫痫　；参考：《南方医科大学》2014年硕士论文

【摘要】：目的伏隔核是额颞叶连接中一个重要结构,并且参与颞叶癫痫活动的传导。我院神经外科于2012年创新地将立体定向双侧伏隔核毁损术运用于治疗双侧颞叶起源的难治性癫痫,并开展20余例手术,对患者术后随访资料进行评估,证实毁损双侧伏隔核对于双侧颞叶癫痫控制有显著效果。然而伏隔核在癫痫发生及传导中的作用,尚未十分明确。目前脑功能研究中缺乏关于伏隔核对颞叶癫痫网络影响的报道。本研究试图通过静息态fmri的方法,以伴海马硬化的单侧内侧颞叶癫痫(mTLE)作为研究对象,探索内侧颞叶癫痫患者双侧伏隔核与全脑功能连接改变情况,验证其在颞叶癫痫致痫网络中的作用；并进一步研究这些改变的功能连接强度与颞叶癫痫患者的病程、发病年龄、精神症状之间有无相关性。材料与方法研究被试包括：24名内侧颞叶癫痫患者(其中右侧颞叶癫痫患者组13人,平均年龄25.36±8.23岁,男性10名,女性3名；左侧颞叶癫痫患者组11人,平均年龄22.24±6.38岁,男性8名,女性3名)及24名健康志愿者(17-35岁,平均年龄25.67±2.58岁,男性15名,女性9名)。内侧颞叶癫痫组入组标准为：1.癫痫的临床症状与发作类型符合2010年国际抗癫联盟的诊断标准与分类标准；2.连续两次长程视频脑电图结果提示异常脑电起源于单侧颞部,且异常脑电的偏侧和发作特点无矛盾；3.FDG-PET/CT提示的发作间期低代谢区与脑电图检查相符；4.高分辨率MR检查显示无明显异常,或存在与脑电图结果偏侧性一致的单侧海马硬化。5.满足颞叶癫痫手术治疗的适应症,拟行前颞叶切除术,且术后病理证实切除海马组织符合海马硬化；6.汉族中国人,右利手(中国人利手分类标准)。排除标准：1.MRI检查除海马硬化外,还存在其他脑部结构异常(如皮层发育不良、软化灶、肿瘤、寄生虫、血管畸形等)；2.合并其他神经、精神类疾病；3.有长期酗酒和药物滥用史；4.患者存在严重认知障碍或精神异常,合作不良者。正常对照组选取与颞叶癫痫组性别、年龄、教育程度相匹配的24例作为对照；所有正常被试：1.无任何系统性疾病及神经系统症状体征；2.无本人及家族性精神疾病病史；3.无药物(包括酒精)滥用史；4.头部MRI检查正常；5.汉族中国人,右利手。所有受试者均完成横断位T2WI扫描、静息状态下功能磁共振(fMRI)扫描及矢状位3D-T1WI扫描。使用Matlab2010、SPM8、DPARSFA V2.1等软件对数据进行预处理,包括：①将原始图像的DICOM格式转化为用于数据分析的NIFTI格式；②去除前十个时间点的扫描图像；③时间序列校正；④头动校正(realignment);⑤空间标准化(Normalization)处理；⑥进行去线性飘移(lineardetrends)与低频滤过(temporally filterd)处理；⑦协变量(covariates)的去除。预处理之后的时间序列信号用于进一步的功能连接分析。采用FSL软件提供的图集Harvard-Oxford cortical and subcortical structural atlases,分别选取双侧伏隔核作为感兴趣区(ROD。利用统计参数图谱(SPM8)进行数据处理。根据感兴趣区NAc MASK文件提供的坐标信息计算出每个被试感兴趣区(ROI)内的平均时间序列作为参照时间序列,对感兴趣区的平均信号变化和全脑逐体素时间序列进行相关分析。左、右侧颞叶癫痫组和健康对照组的双侧伏隔核功能连接采用基于体素的单样本t检验,左、右侧颞叶癫痫组与正常对照组之间伏隔核功能连接异常的比较利用两样本t检验,设显著水平为p=0.01,使用AlphaSim校正,设定连接准则rmm=5(边连接),高斯平滑核4mm,利用单样本t检验显著区所做MASK设定聚类的最小体素个数为15,最终获得组间功能连接差异图。用matlab自带的corr脚本,在癫痫组,将与伏隔核有差异的功能连接与其病程、起病年龄及SAS、SDS量表作Pearson相关分析(MASK为上一步两样本t检验所得显著差异的功能连接),计算线性相关系数r以及p值,统计阈值设置p=0.05,得出癫痫患者与病程、起病年龄及SAS、SDS量表评分呈线性相关的功能连接。结果 1.左、右侧癫痫患者组与健康对照组三组被试之间年龄(F=1.747,p=0.186),受教育程度(F=2.792,p=0.072),起病年龄(t=0.892,p=0.382)、病程(t=0.113,p=0.911)及性别构成(χ2=0.922,p=0.631)无明显统计学差异。 2.功能连接分析 ①左侧颞叶癫痫组与健康对照组基于左、右侧伏隔核功能连接的差异以左侧伏隔核(L-NAc)为感兴趣区,左侧颞叶癫痫组与健康对照组相比,与其功能连接减低的脑区主要有：双侧丘脑(左侧为著)、右侧壳核、楔前叶、后扣带回等；无明显功能连接增强的脑区。以右侧伏隔核(R-NAc)为感兴趣区,左侧颞叶癫痫组与健康对照组相比,与其功能连接减低的脑区主要有：小脑蚓部、楔前叶、扣带回、双侧角回、左侧额中回、左侧辅助运动区、中央旁小叶及中央前回等；无明显功能连接增强的脑区。 ②右侧颞叶癫痫组与健康对照组基于左、右侧伏隔核功能连接的差异以左侧伏隔核(L-NAc)为感兴趣区,右侧颞叶癫痫组与健康对照组相比,与其功能连接减低的脑区主要有：小脑蚓部、右侧小脑扁桃体、左侧小脑半球(齿状核)、右侧海马旁回、右侧额下回眶部、双侧丘脑(右侧为著)、左侧额中回等；无明显功能连接增强的脑区。以右侧伏隔核(R-NAc)为感兴趣区,右侧颞叶癫痫组与健康对照组相比,与其功能连接减低的脑区主要有：小脑蚓部、右侧小脑扁桃体、左侧小脑半球(齿状核)、左侧直回、脑干左侧、双侧角回、左侧额上回内侧及额内侧回等；无明显功能连接增强的脑区。 3.颞叶癫痫患者个体水平分析左、右侧颞叶癫痫患者组的左侧伏隔核的异常功能连接均未表现出与病程、发病年龄、SAS、SDS评分之间的相关性；右侧颞叶癫痫患者组：右侧伏隔核-脑干左侧功能连接与病程之间呈正性相关,相关系数R=0.6394,P=0.02517；左侧颞叶癫痫患者组右侧伏隔核-左侧额中回功能连接强度与SAS评分呈负性相关,相关系数R=-0.7953,P=0.0325。结论 1.本研究通过对伏隔核静息态功能连接分析发现左、右侧颞叶癫痫患者伏隔核全脑功能连接均全面减低,减低的区域涉及双侧丘脑、海马旁回、额下回等癫痫网络结构,楔前叶、扣带回等默认网络结构,以及辅助运动区、中央前回等运动网络结构,提示伏隔核可能是颞叶癫痫传导通路中的一个重要中继站,在颞叶癫痫网络中具有重要意义。 2.右侧颞叶癫痫患者右侧伏隔核-脑干左侧功能连接与病程之间呈正性相关,提示癫痫网络可能随发病时间延长而出现功能重塑； 3.左侧颞叶癫痫癫痫患者右侧伏隔核-左侧额中回功能连接强度与SAS评分呈负性相关,猜测该功能连接受损可能是颞叶癫痫患者焦虑症状的神经机制。
[Abstract]:Purpose

Neurosurgery in our hospital , which is an important structure in frontal temporal lobe connection , is involved in the conduction of temporal lobe epilepsy . In 2012 , neurosurgeons in our hospital successfully applied stereotactic bilateral nuclear disrepair to the treatment of intractable epilepsy of bilateral temporal lobe origin , and carried out more than 20 procedures , which confirmed the remarkable effect on bilateral temporal lobe epilepsy control .

The purpose of this study was to investigate the changes of bilateral nuclear and whole brain function in patients with medial temporal lobe epilepsy and to verify its role in the epileptic network of temporal lobe epilepsy through the method of resting state fmri , with the unilateral medial temporal lobe epilepsy ( mTLE ) with hippocampus sclerosis as the subject .
The correlation between the functional connection intensity of these changes and the course , age and mental symptoms of patients with temporal lobe epilepsy was further studied .

Materials and Methods

The study was conducted in 24 patients with medial temporal lobe epilepsy ( 13 in the right temporal lobe epilepsy group , average age of 25.36 卤 8.23 years , male 10 , female 3 ) .
There were 11 patients in the left temporal lobe epilepsy group ( mean age : 22.24 卤 6.38 years , male 8 , female 3 ) and 24 healthy volunteers ( 17 - 35 years , mean age : 25.67 卤 2.58 years , male 15 , female 9 ) . The standard of seizure group of medial temporal lobe epilepsy group was 1 . The clinical symptoms and seizure types of epilepsy conformed to the diagnostic criteria and classification criteria of the 2010 international anti - epilepsy coalition ;
2 . The results suggested that abnormal EEG originated from unilateral temporal part , and the abnormal EEG was not in contradiction with the characteristic of attack .
3 . The low metabolic region of FDG - PET / CT was consistent with EEG examination .
4 . High - resolution MR examination showed no obvious abnormality , or there was unilateral hippocampus sclerosis which was consistent with the results of EEG .
6 . Han Chinese , right Lishi ( Chinese Lishi Classification Standard ) . Exclusion criteria : 1 . MRI examination besides the sclerosis of hippocampus , there are other abnormal brain structures ( such as cortical dysplasia , softening range , tumor , parasite , vascular malformation , etc . ) ;
2 . Concomitant other neurological and psychiatric disorders ;
3 . Long - term history of alcohol and drug abuse ;
4 . The patients had severe cognitive impairment or mental disorder and poor cooperation . The normal control group selected 24 cases with sex , age and education degree in temporal lobe epilepsy group as control ;
All normal subjects : 1 . No systemic disease and signs of neurological symptoms ;
2 . No personal and familial mental illness history ;
3 . Drug - free ( including alcohol ) abuse history ;
4 . MRI of the head was normal ;
5 . Han Chinese , right - hand .

All subjects completed the scan of T _ T _ T _ T _ T _ T _ T _ T _ T _ T _ T _ T _ 1WI , functional magnetic resonance ( MRI ) scan and sagittal plane 3D - 1WI scan in resting state . The data were preprocessed by software such as Matlab2010 , SPM8 and DPARSFA V2.1 , including : ( 1 ) converting the DICOM format of the original image into NIFTI format for data analysis ;
( 2 ) removing the scanned image of the first ten time points ;
( 3 ) time series correction ;
( 4 ) head moveout correction ; ( 5 ) spatial standardization ;
( 6 ) carrying out linear detrends and low - frequency filtering ;
Based on the coordinate information provided by FSL software , the average time series in each region of interest ( ROI ) was used as reference time series , the average signal change of each region of interest ( ROI ) was calculated by using statistical parameter map ( SPM8 ) .

Results

1 . The age ( F = 1.747 , p = 0.186 ) , the degree of education ( F = 2.792 , p = 0.072 ) , the age of onset ( t = 0.892 , p = 0.382 ) , the course of disease ( t = 0.113 , p = 0.911 ) and sex ( 蠂 2 = 0.922 , p = 0.631 ) were not statistically significant .

2 . Functional connection analysis

In the left temporal lobe epilepsy group and the healthy control group , the left temporal lobe epilepsy group and the healthy control group were the regions of interest , and the left temporal lobe epilepsy group and the healthy control group were mainly composed of bilateral thalamus ( left side ) , right side shell nucleus , wedge anterior leaflet , posterior buckle and so on .
Compared with the healthy control group , the left temporal lobe epilepsy group and the healthy control group mainly include the cerebellar vermis part , the wedge anterior lobe , the buckle back , the bilateral angle gyrus , the left frontal gyrus , the left auxiliary motion area , the central parlobule and the central anterior gyrus , etc .
No obvious functional connection enhances the brain area .

In the right temporal lobe epilepsy group and the healthy control group , the difference of the function connection between the right temporal lobe epilepsy group and the healthy control group was mainly in the region of interest , the right temporal lobe epilepsy group , the left cerebellar hemisphere ( dentate nucleus ) , the right hippocampus side gyrus , the right frontal inferior orbital portion , the bilateral thalamus ( right side ) , the left frontal gyrus , and the like ;
Compared with the healthy control group , the brain regions of the right temporal lobe epilepsy group and the healthy control group mainly include the cerebellar vermis part , the right cerebellar tonsilic body , the left cerebellar hemisphere ( dentate nucleus ) , the left straight back , the left side of the brain stem , the bilateral angle gyrus , the left frontal gyrus and the medial frontal gyrus , etc . ;
No obvious functional connection enhances the brain area .

3 . Analysis of individual level in patients with temporal lobe epilepsy

The abnormal functional connections of left and right temporal lobe epilepsy patients showed no correlation with history , age , SAS and SDS scores .

Right temporal lobe epilepsy group : positive correlation between right - sided nucleus - brain stem left functional connection and course , correlation coefficient R = 0.6394 , P = 0.02517 ;
In the left temporal lobe epilepsy group , the left frontal septum nuclear - left frontal gyrus function connection strength was negatively correlated with the SAS score , the correlation coefficient R = - 0.7953 , P = 0.0325 .

Conclusion

1 . In this study , we found that all the functional connections in the left and right temporal lobe epilepsy patients were all decreased , and the decreased area involved the network structures such as bilateral thalamus , parahippocampal gyrus , frontal gyrus and the like , the default network structure such as wedge anterior and posterior gyrus , and the movement network structure of the auxiliary sports area and the central gyrus . It suggested that the nucleus accule nucleus may be an important relay station in the temporal lobe epilepsy conduction path , and it is of great significance in the temporal lobe epilepsy network .

2 . There was a positive correlation between the left functional connection and the course of left ventricular nucleus - brain stem in right temporal lobe epilepsy .

3 . In the left temporal lobe epilepsy , the connection strength of the right - sided nucleus - left frontal gyrus function was negatively correlated with the SAS score , and it was speculated that the impairment of the functional connection could be a neurological mechanism of anxiety symptoms in temporal lobe epilepsy .

【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.1;R445.2

【参考文献】