【作者】 刘军；

【导师】 耿道颖； 孟令平； 刘含秋； 沈天真；

【作者基本信息】 复旦大学 ， 影像医学与核医学， 2006， 博士

【摘要】 第一部分正常人的不同广度数字正反序工作记忆的fMRI研究目的：利用血氧水平依赖性功能磁共振成像技术(BOLD—fMRI)研究视觉呈现的不同广度数字正序和反序任务工作记忆的脑功能区分布特点及两种任务的神经机制；初步探讨该方法在临床上的应用价值。材料和方法：12名正常志愿者(男6，女6)分别参加数字正序(Forward 2、5、8位数字)和反序(Backward 2、5、8位数字)复述记忆的实验；实验采用参数设计，使用single—trial设计方法；功能磁共振扫描使用GE公司的3.0T Signa VH／i系统；结构像扫描为SE序列T1WI，功能成像程序(brain wave)采用GRE-EPI序列进行Bold—fMRI扫描，以FSPGR序列进行全脑三维扫描。数据分析应用linux操作系统下的AFNI软件，测量兴趣区的Talairach坐标并分析激活强度进行组间定量统计。统计处理使用Matlab6.5.1软件进行数据整理，spss10.0软件做统计运算，利用重复观测多因素方差分析(Repeated Measures ANOVA)方法，分别进行组内分析(双因素，任务类型(正背、反背)*负载(2位数字、5位数字、8位数字))，组内因素分析有交互作用的ROI，进行Post-hoc，t检验。结果：两种类型和三种负载任务刺激所取得感兴趣区激活强度分别进行比较(1)5位数字正倒背比较，倒背激活强度大于正背；正背8位和5位数字比较，8位大于5位；倒背5位和2位数字比较，5位大于2位，上述三组比较统计结果达到显著性(p＜0.05)的脑区范围较广，共同脑区包括辅助运动区SMA、左侧前运动区、左侧DLPFC、左侧顶叶、枕叶视觉皮层、双侧壳核、左侧broca区；5位数字正倒背比较组还有双侧的MTL，正背8位和5位数字比较组、倒背5位和2位数字比较组激活脑区还包括后语言区Wernick’s area；(2)8位数字倒背大于正背组和倒背8位大于5位数字组统计差别的脑区较少，除了相同脑区枕叶视觉皮层、后语言区Wernick’s area，还分别包括左侧顶叶和左侧DLPFC；(3)2位数字的正倒背、正背2位和5位数字之间比较无显著性差异；(4)前额叶内侧区和楔叶区表现出正背大于倒背(5、8)和负载反效应(2大于5，5大于8位数字)结论：数字正反序工作记忆激活脑区重叠性较多，主要反映词语工作记忆系统，并且部分脑区在正序任务时具有一定的强度线性相关性，其中数字反序记忆与额叶相关密切；数字正反序记忆任务可作为理想的fMRI刺激模型在临床上应用。第二部分额叶脑外伤后1月的数字工作记忆损害的fMRI研究目的：利用功能磁共振成像技术(fMRI)研究额叶外伤1月时执行数字工作记忆任务时脑激活功能区的改变与额叶脑结构损伤的关系，探讨功能区变化的神经机制及TBI临床fMRI研究的可操作性。材料和方法：对10例额叶外伤后1月的患者(伤后平均31天，其中男7，女3；平均年龄30.1y)和12例正常志愿者作为对照组(男7，女5；平均年龄26.9y)分别进行2位和4位数字的正反序工作记忆的实验，实验采用参数设计，使用single—trial设计方法；功能磁共振扫描使用GE公司的3.0T Signa VH／i系统，采用8通道线圈；SE序列采集横轴位T1WI结构像，功能成像程序(brain wave)，采用GRE-EPI序列进行BOLD—fMRI扫描，以FSPGR序列进行全脑三维扫描。数据分析应用linux操作系统下的AFNI软件，利用时间信号曲线确定感兴趣激活脑区，测量兴趣区的Talairach坐标并分析激活强度进行组间定量统计。统计处理使用Matlab6.5.1软件进行数据整理，spss10.0软件做统计运算。取BOLD信号时间曲线的积分面积作为指标，利用重复观测多因素方差分析(Repeated Measures ANOVA)方法，分别进行组内分析(双因素，任务类型(正背、反背)*负载(2位数字、4位数字))和组间分析(三因素，一个组间因素(病人、正常人)，两个组内因素(任务类型(正背、反背)*负载(2位数字、4位数字)))。分析有交互作用的ROI，进行Post-hoc，t检验。结果：(1)正常对照组任务类型和负载交互作用达到显著性的区域，进行Post-hoc,t检验后反序4位数字任务大于正序4位数字脑区有辅助运动区SMA，双侧背外侧前额叶，左侧顶叶，右侧角回；(2)患者组反序4位数字任务大于正序4位数字的脑区有左侧枕叶；(3)组间比较：正常对照组反序4位数字任务时激活强度显著大于患者组的部位有左侧DLPFC和右侧角回；正序4位数字大于患者组的部位有左侧枕叶和左侧角回。而患者组反序4位数字任务时激活强度显著大于对照组的部位有楔状回和右侧Broca区；正序4位数字大于对照组的部位有右侧初级运动区MA和右侧额极区。结论：额叶区是脑工作记忆网络中的重要节点，损伤后工作记忆功能区明显受损，大脑右侧半球在执行工作记忆任务时起到巨大代偿作用；fMRI研究可提供认知功能损伤的影像学依据及神经功能机制，临床上应用fMRI研究TBI有一定难度。第三部分额叶外伤恢复后期脑记忆功能重组的fMRI研究目的：利用功能磁共振成像技术(fMRI)显示额叶外伤患者恢复后期(病程＞6月)工作记忆脑功能区的激活特点，推断额叶损伤后脑功能可塑性变化以及功能重组的可能的机制，初步探讨fMRI对于外伤后工作记忆损伤康复期的阶段检测的价值。材料和方法：对8例额叶外伤恢复后期患者(病程＞6月，伤后平均17.8月，其中男5，女3；平均年龄28.75y)与12例正常志愿者作为对照组(男7，女5；平均年龄26.9y)分别进行2位和4位数字的正反序工作记忆的实验，实验采用参数设计，使用single—trial设计方法；功能磁共振扫描使用GE公司的3.0T Signa VH／i系统，采用8通道线圈；SE序列采集横轴位T1WI结构像，功能成像程序(brain wave)，采用GRE-EPI序列进行BOLD—fMRI扫描，以FSPGR序列进行全脑三维扫描。数据分析应用linux操作系统下的AFNI软件，利用时间信号曲线确定感兴趣激活脑区，测量兴趣区的Talairach坐标并分析激活强度进行组间定量统计。统计处理使用Matlab6.5.1软件进行数据整理，spss10.0软件做统计运算。取BOLD信号时间曲线的积分面积作为指标，利用重复观测多因素方差分析(Repeated Measures ANOVA)方法，分别进行组内分析(双因素，任务类型(正背、反背)*负载(2位数字、4位数字))和两两组间分析(三因素，一个组间因素(病人、正常人)，两个组内因素(任务类型(正背、反背)*负载(2位数字、4位数字)))。分析有交互作用的ROI，进行Post-hoc,t检验。结果：(1)正常对照组任务类型和负载交互作用达到显著性的区域，进行Post-hoc,t检验后反序4位数字任务大于正序4位数字脑区有辅助运动区SMA，双侧背外侧前额叶，左侧顶叶，右侧角回；(2)患者组右侧顶叶和左侧角回正序4位数字激活强度大于2位数字。(3)组间比较：患者组正序4位数字任务时激活强度显著大于对照组的部位有左侧运动区、双侧DLPFC、双侧顶叶、左侧基底区、左侧角回、右侧运动区、楔状回、右侧Broca和右侧额极等脑区；反序4位数字任务时激活强度显著大于对照组的部位有右侧DLPFC、楔状回和右侧Broca。结论：额叶损伤后在自然恢复状态下记忆功能受损严重，慢性期大脑侧化效应更明显；FMRI能够显示脑损伤后功能区的功能重组，临床上应用FMRI指导康复治疗有潜在的价值。更多还原

【Abstract】 Purpose: To study the characteristic brain activation associated with different fordward and backward digital span by BOLD-fMRI and the difference between the mechanism involved in the two tasks at the neural level , and to explore the application value of the task in clinic. Matreial and Method: Functional magnetic resonance imaging (fMRI) on fordward and backward digits tasks of the different span (forward 2, 5, 8 digit and backword 2, 5, 8 digit respectively) in 12 in healthy voluntary, single-trial software was adopted. Images were acquired by GE 3.0T magnet including T1W image with SE sequence, Bold-fMRI images with GRE-EPI and 3D images with FSPGR. The signal changing amplitude in region of interest(ROI) were counted using AFNI. Repeated Measures ANOVA was applied to analyze the interaction between the task category and load in the group, and further to analyze the data involved in task category (forword and backword) and load (2,5 and 8digit). Results: (l)There are many areas showed more activation in the tasks backward 5 vs forward 5 digit group, forward 8 vs 5 digit group and backward 5 vs 2 digit group including SMA, left BA 6, left DLPFC, left parietal lobe, occipital visual lobe, both dorsal caudate putamen, left Broca, and additional both MTL in backward 5 vs forward 5 digit group, Wernick’ s area in forward 8 vs 5 digit group and backward 5 vs 2 digit group. (2) The activation increased in the occipital visual lobe, left parietal lobe and Wernick’s area in task of backward 8 vs forward 8 digit, and more activation in the occipital visual lobe, left DLPFC and Wernick’ s area in task of backward 8 vs 5 digit group. (3)No significant different activation in the backward 2 vs forward 2 digit , forward 2 vs 5 digit groups. (4) The medial PFC and precuneate lobe showed contrary effect in the task of forward-backward and digit load. Conclusion: Both digital forward and digital backward rely on a largely overlapping functional neural system associated with language working memory and the degree of activation in some regions increased linearly with increasing forward task diffi culty. The digits backward memory wasclosely correlated with the frontal lobe and the task of digits memory can be better model by fMRI in the clinical application. Part II A fMRI Study of damaged Digital Working Memory 1 month after traumaticfrontal lobe injuryPurpose: To examine the brain activation while performing a digital working memory in persons with traumatic frontal lobe injury after 1 month by fMRI . To study the correlation between the activated changes and focal lesion in frontal lobe and to investigate the neural mechanism behind it and the feasibility in TBI research. Matreial and Method: FMRI was used to assess brain activation during a forword and backword digital span working memory task in 10 patients with TBI and 12 healthy controls, single-trial software was adopted. Images were acquired by GE 3.0T magnet including T1W image with SE sequence, Bold-fMRI images with GRE-EPI and 3D images with FSPGR. The signal changing amplitude in region of interest(ROI) were counted using AFNI. Repeated Measures ANOVA was applied to analyze the interaction between the task category and load or interclass, and further to analyze the data about task category (forword and backword) and load (2 digital and 4digital ) within groups and interclass between the controls and patients. Results: The activation increased in both DLPFC and parietal lobe, left Broca and left angular gyrus in healthy controls comparing with backword 4 and forward 4 digital task, but only left occipital lobe showed more activation in patients with backword 4 comparing forward 4 task. The healthey controls showed stronger activation in left DLPFC, left angular gyrus(backward 4 task) and left occipital lobe , right angular gyrus (forward 4 task) than patients, and the patients showed more activation in right motor area, cuneate lobe(backward 4 task) and right Broca and frontal pole (forward 4 task) than healthy controls . Conclusion: Frontal lobe is the key point in the working memory net, and the memory function was damaged in the early periodafter the damaged frontal lobe. The right hemisphere can provide great compensation resource when needed in the net. FMRI can explore the neural mechanism after TBI, and supply cognitive impaired evidence in neuroimage information,there is some difficulty in TBI research. Part IE The Study of cortical reorganization with Working memoryDuring later TBI periodPurpose: To study the characteristic activation while performing a digital working memory in TBI persons during their later recovery period. To explore the underlying mechanism in the plascity changes after traumatic frontal lobe injury by fMRI and To investigate the value of fMRI to detect working memory injury rehabilitation. Matreial and Method: FMRI was used to assess brain activation during a forword and backword digital span working memory task in 8 patients with TBI during later recovery period and 12 healthy controls, single-trial software was adopted. Images were acquired by GE 3.0T magnet including T1W image with SE sequence, Bold-fMRI images with GRE-EPI and 3D images with FSPGR. The signal changing amplitude in region of interest(ROI) were counted using AFNI. Repeated Measures ANOVA was applied to analyze the interaction between the task category and load or interclass, and further to analyze the data about task category (forword and backword) and load (2 digits and 4digits) within groups and interclass between the controls and patients. Results: (1)The activation increased in both DLPFC and parietal lobe, left Broca and left angular gyrus in healthy controls comparing with backword 4 and forward 4 digital span. (2)Right parietal lobe and left angular gyrus showed more activation in patients with forward 4 digits vs 2 digits group. (3)The patients showed stronger activation in left MA, both DLPFC, both parietal lobe, left angular gyrus, left basal area, right MA, right Broca, right frontal pole and precuneate in forward 4 digits task and right DLPFC, right Broca and precuneate in backward 4 digits task than healthy controls . Conclusion: Working memory was damaged in nature recovery after frontallobe injury, the brain showed obvious side effect during later period. FMRI can discover the reorganization of the memory system and have the potential value in guiding the rehabilitation treatment.更多还原