【作者】 任力杰；

【导师】 陆兵勋；

【作者基本信息】 南方医科大学 ， 神经病学， 2010， 博士

【摘要】 几十年来,人们运用各种手段研究面部表情、情绪和大脑的关系,以期了解抑郁情绪产生和保持的脑功能机制。虽然各国学者对抑郁症病因进行了大量探讨,但具体机制仍不十分清楚,且存在不少相互矛盾的观点。抑郁患者的心理结构非常复杂,不仅仅有情绪的抑郁、沮丧,而且还有联想缓慢、焦虑及注意力不集中等,这对认知水平及其功能可能造成不同程度的影响。大量国内外研究表明,抑郁症有明显的认知功能障碍,抑郁症病人认知功能障碍表现有很多种,其中以执行控制[exeeutive control)功能、注意(attention)功能和记忆功能的减低最为显著,而额叶的执行功能障碍是抑郁症合并认知障碍的主要表现之一。近年来抑郁症患者的认知功能障碍已越来越受到国内外学者的关注,有研究表明,抑郁症患者的认知功能障碍可能独立于抑郁症状之外,这是抑郁症病人即使在缓解期仍不能恢复社会功能的主要原因之一。神经心理学测验是对脑障碍进行诊断和对精神活动进行量化评定的工具,可以反映人的认知功能。事件相关电位(Event related potentials,ERP)可以从不同时间进程上探讨情绪和认知加工过程脑活动变化,以其优越的时间分辨率(可达毫秒级)和相对较低的硬件要求而得到广泛应用。其中P300是比较稳定的指标,可以用来评价抑郁症认知功能尤其是执行功能损害的严重程度,具有潜在的临床应用价值。一系列研究表明抑郁症患者情绪及认知方面的异常可以在中枢神经系统解剖学层面反映出来,造成对应脑区结构、代谢及功能方面的异常。作为边缘系统的海马和杏仁核可能共同参与了情感行为的形成、自主活动和内分泌整合过程,在抑郁症的发病机理中起着非常重要的作用。MR扩散张量成像(Diffusion tensor imaging DTI)技术可以显示神经纤维的传导通路和纤维束的走行方向,无创跟踪脑内白质纤维,检测其解剖连通性,研究各脑区域之间的联系,是近年来应用于神经科学研究的一种新技术。而基于血氧水平依赖(BOLD)的功能性磁共振(FMRI)技术能够区分不同类型的情绪面部表情刺激,从而分离出不同的情绪,而且可以观察抑郁症病人在执行工作任务时相关功能脑区的激活情况,在抑郁症及其存在认知功能障碍的病理定位、抑郁状态的监视、抗抑郁药物治疗效果及预后等方面都具有很大潜力,尤其是其高时间、空间分辨率、无创性及易重复性特点使得FMRI在抑郁症研究中具有重要意义。本课题将分别从神经心理学测验、事件相关电位、海马杏仁核脑形态学、DTI技术、BOLD-FMRI技术系统研究抑郁症患者的情绪及认知功能,从全脑的灰质及白质细微结构,分析比较抑郁症患者与健康对照的差异,以探讨抑郁症的发病机制及其存在认知功能障碍的脑功能基础,并探讨MRI是否可以作为抑郁症诊断的客观的生物学指标,为临床预测、治疗抑郁症,改善抑郁症患者症状及预后提供新的证据、方法和思路。本课题包括五部分内容：第一部分、抑郁症的认知功能及事件相关电位P300的研究；第二部分、抑郁症的海马杏仁核形态学研究；第三部分、抑郁症的扩散张量成像MRI研究；第四部分、抑郁症情绪加工过程的功能性磁共振成像研究；第五部分、抑郁症认知功能的脑功能磁共振研究。第一部分、抑郁症的认知功能及事件相关电位的研究；目的：探讨抑郁症患者认知功能的损害特点。方法：使用汉密尔顿抑郁量表、威斯康星卡片分类测验(WCST)、N-BACK任务、P300等工具对24例抑郁症患者进行评定,以WCST中的完成分类数(cc)、错误应答数(Re)、完成第一个分类所需应答数(Rlst)、持续性错误数(Rpe)、不能维持完整分类数(Fm)以及P300潜伏期、波幅和N-back任务反应时(mRT)作为测量指标,并以24名正常人为对照组进行统计分析。结果：1)抑郁症组的神经心理学测验成绩WCST(包括错误应答数,持续性错误数,完成第一个分类所需应答数)、N-back任务反应时(mRT)以及P300潜伏期、P300波幅与对照组相比均有显著性差异。2)抑郁症组抑郁严重程度和神经心理学测验的得分无显著相关性,但病程和持续性错误数和反应时(mRT)呈正相关。3)P300潜伏期与错误应答数,反应时(mRT)呈正相关,P300波幅与完成分类数呈负相关。结论：1)抑郁症患者存在认知功能障碍,且表现为以执行功能为主的认知损害。2)病程而不是抑郁严重程度与认知损害的严重程度有相关关系,即病程越长,认知损害越重。3)WCST、N-back、P300三种方法可以从不同角度反应抑郁症的认知功能障碍,其中P300潜伏期、反应时(mRT)及持续性错误数(Rpe)是反映额叶执行功能的敏感指标。第二部分、抑郁症的海马杏仁核形态学研究；目的通过测量抑郁组、对照组两组受试者的双侧海马及杏仁核大小以探讨抑郁症的脑形态学基础,并分析抑郁症双侧海马及杏仁核大小与抑郁症的关系及其合并认知损害的神经病理基础。方法研究24例抑郁症患者及24例对照组,运用容积分析软件测量两侧海马及杏仁核体积,分析双侧海马及杏仁核大小与患者认知障碍(P300潜伏期、反应时及持续性错误数三个指标)之间的关系。结果1)抑郁症组中两侧海马体积均小于对照组,且差异有统计学意义,但两侧杏仁核体积两组间无显著性差异。2)抑郁症患者双侧海马与HAMD抑郁量表及抑郁症病程无相关关系。3)抑郁症患者海马体积与P300波幅呈正相关,未发现与rpe、mRT及潜伏期有相关性。结论1)抑郁症患者会出现海马体积的缩小,但与抑郁的病程及抑郁严重程度无关,海马体积异常可能是抑郁症的神经生物学基础,但尚不明确脑结构和功能的改变是抑郁症的病因还是结果2)海马在参与了情感过程中,主要参与了记忆的功能。3)海马与反应额叶功能指标的执行功能无明显关系。第三部分、抑郁症的扩散张量成像MRI研究；目的采用磁共振扩散张量成像(DTI)技术研究抑郁症的脑白质FA值改变及其意义,并探讨抑郁症患者认知损害与DTI各向异性的相关性,分析其合并认知损害的神经病理基础。方法采用DTI感兴趣区(ROI)法对抑郁症患者、对照者进行各部位脑白质FA值测量并进行比较,并对两组认知障碍和FA值进行统计学分析,统计分析由SPSS 13.0统计软件包完成,两组间比较采用独立样本t检验,以P<0.05为差异有统计学意义,相关性分析采用偏相关分析。结果1.抑郁组与对照组不同解剖部位FA值对比有显著性差异的部位有：双侧额叶、扣带回前部、胼胝体膝部。2.抑郁症患者双侧额叶、扣带回前部、胼胝体膝部FA值与HAMD抑郁量表无关,左侧额叶FA值与病程呈中度负相关(r=-0.566,P<0.01)。3.抑郁症P300潜伏期及Rpe与双侧额叶白质、扣带回前部、胼胝体膝部呈显著负相关(P<0.05),mRT与左额叶白质、扣带回前部、胼胝体膝部与成中度相关(P<0.05)。结论1.抑郁症组与对照组FA值有显著性差异的部位主要有双侧额叶、扣带回前部、胼胝体膝部,证实上述部位白质纤维束遭到了破坏。2抑郁症患者额叶FA值与病程呈负相关,提示FA值改变与抑郁症的强度无关,而与病程有关,说明FA值改变可能与抑郁本身有关,长期的抑郁可能导致了髓鞘的慢性损害。3.抑郁症组双侧额叶白质、扣带回前部FA值与持续性错误百分数(Rpe)呈负相关关系。这证实额叶白质纤维损害可能是抑郁症认知功能障碍的病理基础之一,同时证实这些部位完整性的损害主要导致的是执行功能的异常。4、这些白质纤维损害可能是抑郁症情绪和认知功能障碍的共同的病理基础,白质的完整性尤其是额叶白质的完整性是维持人正常情感和记忆的的重要解剖结构,从神经影像学上进一步解释了抑郁症患者常常合并认知功能障碍这一临床上常见现象。第四部分抑郁症情绪加工过程的功能性磁共振成像研究；目的采用功能性磁共振方法研究抑郁症患者对不同性质情绪图片的差异脑激活反应,以探讨抑郁症患者的脑活动特征。方法对15例抑郁症患者、15例对照组进行国际情绪图片系统图片刺激的脑功能磁共振成像(fMRI)扫描,任务为组块设计,用神经功能影像分析(AFNI)软件处理影像数据。结果1、对照组识别中性图像、正性图像、负性图像的激活脑区有双侧额上、中、下回、中央前回、角回、缘上回、扣带回前部及压部、海马、杏仁核、枕叶视皮质区、脑桥及小脑半球。2、与中性图片对比,正性、负性图片激活区主要在激活双侧顶下小叶、颞上回及基底节区和额中回处重叠,而正性图片、负性图片的激活不同。负性—正性有著差异的正性激活脑区有双侧额上、中、下回、放射冠区、扣带回前部及压部、颞中回、岛叶及小脑蚓部,右侧丘脑、脑桥。负性激活脑区有右侧中脑。3、两组受试者识别中性、正性、负性图片存在组间差异1)、识别中性图像(抑郁症组减对照组)有显著差异的负性激活脑区有双侧顶上小叶、扣带回及胼胝体压部,左额中回、右海马旁回、海马、丘脑、右缘上回。正性激活脑区有右楔叶、枕叶视皮质区,左侧小脑半球。2)、识别正性图像(抑郁症组减对照组)：有显著差异的负性激活脑区有右侧额中、下回、双侧海马旁回、海马、背侧丘脑以及顶上小叶、楔前叶、颞中、下回、中脑及小脑半球,岛叶。正性激活脑区有双侧小脑半球、枕叶视皮质区及右侧顶叶。3)、识别负性图像(抑郁症组减对照组)：有显著差异的负性激活脑区有小脑半球和顶上小叶,左顶下小叶。正性激活脑区有左侧额中、下回、双侧海马旁回、丘脑、楔叶、枕叶视皮质区及小脑半球,右侧海马、杏仁核、颞中、下回及顶叶。结论1、3种图片的激活脑区均主要包括额顶叶皮层-皮层下网状系统、下丘脑和边缘系统(杏仁核、海马—小脑中部)的脑区,这些脑区共同参与了情绪的加工机制。它们整合加工情绪信息,产生情绪行为。高兴、中性和悲伤情绪图片诱发的情绪反应存在共同的神经基础,同时大脑对不同效价的情感的加工并不是完全一致的,它们具有独立的脑加工机制。2、抑郁患者正性刺激注意减弱而对负性刺激注意增强,存在异常情绪加工的神经基础,抑郁症脑功能激活减弱的病理基础考虑和相关区域的神经元受到破坏有关。3、抑郁症与额叶、扣带回及边缘系统(海马、海马旁回、杏仁核)的损害涉等有密切关系,可能涉及以边缘系统-皮层-纹状体-苍白球-丘脑神经环路为主的多条神经环路的结构和功能异常。第五部分、抑郁症认知功能的脑功能磁共振研究目的通过脑功能磁共振研究抑郁症患者合并认知障碍的脑激活特点。方法对10例抑郁症患者和10名年龄及文化程度相当的对照组,同时进行数字工作记忆任务的功能磁共振成像(fMRI)。以AFNI软件对fMR I数据进行定位与定量分析。结果1.抑郁组比对照组的执行正确率低,反应时间长,有显著性差异。2.两组工作记忆激活脑区：(1)正常组数字工作记忆激活脑区有双侧额上、中、下回、颞下回顶上小叶、顶下小叶、楔前叶、中央前回、岛叶、扣带回前部、枕叶视皮质区、背侧丘脑。患者组数字记忆激活脑区与对照组相同。(2)抑郁组与对照组相比激活减弱的脑区有：双侧额上回、左额中回,额下回,顶上小叶。未发现抑郁组较对照组激活增强的脑区。结论1、前额叶和扣带回是工作记忆的脑功能基础,双侧顶叶等是后注意系统的重要部分。2、抑郁症患者存在工作记忆障碍,前额皮质激活减弱是其病理机制之一小结1.本文国内外首次采用前瞻性研究联合应用事件相关电位从时间上和应用磁共振技术从空间上(包括脑海马杏仁核体积、脑白质形态、脑灰质功能)研究了抑郁症及其合并认知功能障碍的时空模式：抑郁症的病理基础一般有其原因和诱因,先天性原因可能是髓鞘和神经元本身发育不良,或者对外界刺激较为敏感,容易受到损害,后天一般与应激有关,应激导致体内生化改变,主要是谷氨酸系统导致了前额叶及海马等部位的神经元的持续损害；这种损害使得这些部位的神经元在静息状态下发放神经冲动减少,从而使情绪和认知的神经环路受损,当在外界情绪图片的刺激下,或者表现为代偿性过度激活(早期),或者表现为激活减弱(晚期),在进行高级神经活动如工作记忆时早期表现出前额皮质、边缘系统活动代偿性增加,晚期表现出前额皮质、边缘系统活动减少,同样因为发放冲动减少导致了执行功能的下降,这些都可以在功能磁共振上得以体现；神经元的损害由于神经冲动发放减少,本身可以造成神经纤维的髓鞘的营养发生改变,从而导致神经纤维的损害；同时由于神经元的发放神经冲动减少,可能会导致髓鞘数量的减少和神经突触的减少(这些神经纤维的变化可以在DTI上得以显示,表现为FA值下降),而神经纤维的变化,会影响神经通路(几个重要通路)之间的联系(导致了潜伏期和N-back任务反应时的延长),这种联系的减少同样会影响额叶及海马神经元神经环路的完整性,完整性的损害导致了功能神经元缺乏刺激,从而使神经元进一步的损害,并可能出现结构上的改变,如海马的萎缩,神经元和神经纤维脑结构形态这些空间上的异常会在时间上表现出来,电生理事件相关电位P300上会出现潜伏期的延长,N-BACK会出现反应时间的延长和错误率的增加,同时WCST会出现执行功能的下降,如持续性错误数的增加,在患者表现出情绪和认知等异常症状,如情绪低落(额叶、、颞叶)注意障碍(顶叶)、记忆障碍(颞叶)、计划能力下降和做事犹豫不决(额叶)、做事效率下降(联络皮质)等等,这些由于情绪和认知的神经元和神经传导通路存在交叉,因此会出现抑郁和认知功能的共同损害,在行为学上表现为抑郁、认知功能下降等各种症状。2本文国内外首次从解剖学角度提出抑郁症合并认知功能障碍的发病机制是状态性和特质性都存在本研究结果显示在行使执行任务时,正激活脑区均表现为患者组低于正常对照组,以双侧额上回、左额中回有显著意义,而同时我们发现额叶在抑郁症情绪加工中也起着重要作用,且对比正性图像,在观察中性、负性图片时双侧额叶均以负性激活为主,结合既往的研究神经影像学研究,说明抑郁病人前额皮质的神经生理异常与情绪、语言、注意选择、视觉空间记忆有关,抑郁发作时背侧前额皮质生理活性减弱,抑郁状态时这些脑区功能的钝化,反映了认知和情绪的共同障碍,说明了情绪和认知加工之间的神经生理联系。此外我们还发现抑郁症情绪和认知动用了不同的脑区,它们存在不同的脑功能基础,这也从解剖学上证实了抑郁症郁症认知功能障碍特质性和状态性均存在。有研究发现,抑郁症患者在治疗后抑郁症状得到明显缓解,但认知功能与对照组相比,均存在显著性统计学差异。这提示了抑郁症认知功能障碍的特质性,这说明抑郁症情绪和认知功能障碍的脑功能基础存在不同的脑区,这已经在我们的研究中得到了证实；但该研究还发现,治疗后,随着病情的缓解,患者的认知功能也有明显的改善；WCST成绩的改善与抑郁好转有显著的相关性,这提示了抑郁症认知障碍状态性均存在,抑郁症患者存在认知功能损害与抑郁的严重程度有相关性。分析原因,我们在DTI研究中发现抑郁症患者的双侧额叶白质、扣带回前部、胼胝体膝部的完整性下降,并与抑郁症病程呈正相关关系,而和持续性错误百分数(Rpe)呈负相关关系,这证实这些白质纤维损害可能是抑郁症情绪和认知功能障碍的共同的病理基础,这些白质纤维的损害同样在抑郁症情绪及认知功能的发生发展中起重要作用,结合抑郁症情绪和认知障碍有共同的脑区,比如额叶,因此积极控制抑郁症状,可促进了患者认知功能的恢复。3.抑郁症情绪障碍和认知障碍存在类似的病理基础,白质和灰质的共同损害导致抑郁症及其认知障碍的发生。4.抑郁症患者的认知功能和症状的严重程度无关,和病程呈正相关.抑郁症患者左侧额中回的白质FA值与病程呈负相关,提示病程迁延将可能加重抑郁症患者的脑白质损伤。更多还原

【Abstract】 For decades, people had been researching the relationship between the acial expressions、emotions and the brain by various means in order to understand the mechanisms of brain that. generates and maintains depression. Although the etiology of depression States have been done a lot of by scholars, but the exact mechanism is still unclear, and there are many conflicting views. Depression in patients have very complex psychological structure,including emotional depression, frustration, and the slow association, anxiety and inattention, which result in cognitive function in different degrees. A lot of research has shown that depression exists significant cognitive impairment and the implementation of frontal lobe dysfunction is.one of the main performance in depression and its cognitive impairment. In recent years, cognitive dysfunction in depression patients was more and more be concerned by scholars home and abroad, Some studies show that depression may be independent of cognitive impairment in depression symptoms, which is one of the main reason that depression patients in remission still can not even restore.Neuropsychological testing is a brain disorder diagnosis and assessment of mental activities, the tools to quantify, can reflect the person’s cognitive function. Event-related potentials (Event related potentials, ERP) from different time course of the processing of emotional and cognitive changes in brain activity, with its superior temporal resolution (up to milliseconds) and relatively low hardware requirements are widely used. Which is relatively stable indicators of P300 can be used to evaluate depression, cognitive dysfunction, particularly the implementation of the extent of potential clinical value.Many studies show that abnormal emotional and cognitive aspects in patients with depression result in the abnormality metabolism of corresponding brain structure and could be reflected by anatomy in the central nervous system, the hippocampus and amygdala of the limbic system might be involved in the formation of emotional behavior, locomotor activity and endocrine integration and plays a very important role in the pathogenesis of depression. MR diffusion tensor imaging (Diffusion tensor imaging DTI) technology can show nerve fiber pathways and fiber bundles traveling direction, track non-invasively brain white matter fiber, detect anatomical connectivity among every brain region, so it is a new technique for neuroscience research in recent years。Based on blood oxygen level dependent (BOLD) functional magnetic resonance imaging (FMRI) technology can distinguish among different types of emotional facial stimuli, separate from different emotions, and observe the stimuli of functional areas of brain related to the implementation of tasks .so that it have great potential in the pathological positioning,in depression and its cognitive impairment, in the monitoring of depression, in the antidepressant treatment and prognosis, and it is very important to study depression.because of its characteristics of high time, spatial resolution, non-invasive and easily repeatableWe will study the brain structure and function of depression patients by the morphology, DTI technique, BOLD-FMRI technology system, and explore the pathogenesis of depression and cognitive impairment based on brain function by fine structure analysis gray matter and white matter of the whole brain and comparison between patients and healthy controls, so that we can explore whether MRI can be used as an objective biological indicators for clinical diagnosis and provide new evidence, methods and ideas that improve prognosis and prediction, treatment of patients. of depression.This topic includes five parts:the first part, the study of cognitive function and event related potentialsof patients with depression; the second part; the study of the hippocampal and amygdala morphology of depression; the third part the study of diffusion tensor imaging MRI of depression; the fourth section, the study of emotional processing of depression by functional magnetic resonance imaging; the fifth section, the study of cognitive function of depression by functional magnetic resonance imagingThe first part, the study of cognitive function and event related potentialsof patients with depressionObjective:To investigate cognitive damage characteristics in patients with depression.Methods:24 cases of depression were assessed by the Hamilton Depression Rating Scale, Wisconsin Card Sorting Test (WCST), N-BACK task, P3OO tools. Complete the categories number (cc), the error response number (Re), the number of respondents that complete of the first category (Rlst), persistent errors (Rpe), no maintain the integrity of the number of categories (Fm) of wcst, latency and amplitude of P300 and reaction time (mRT) of N-back task are the measures,the patient were statistically analyzed to 24 normal controls.Results:1) Neuropsychological test scores WCST (including error responses, continuity errors, complete the first category the number of required responses), reaction time(mRT) of N-back task and latency,and amplitude of P300 of depression group had significant statistical difference compared with the control group.2) There are no significant correlation between Severity of depression and neuropsychological test scores, but there are positively correlated between the duration and continuity errors and reaction time (mRT).3) There are positively correlated,between latency of P300 and error responses, there are negatively correlated.between eaction time (mRT) P300 amplitude and completed categories. Conclusion:1) Depressed patients have cognitive dysfunction, and show cognitive impairment based perform functions.2) The course of disease rather than the severity of depression was correlated to the severity of cognitive impairment, that is, the longer duration, more severe cognitive impairment.3) WCST, N-back, P300 are three ways to respond from a different perspective of cognitive impairment of depression, which P3OO latency, reaction time (mRT) and continuity errors (Rpe) are indicators reflecting the sensitivity of frontal executive function.The second part; the study of the hippocampal and amygdala morphology of depression;Objective 1To measure the bilateral hippocampus and amygdala size of depression group and control group, explore the basis of depression in brain morphology, and analysis the relationship.between depression and bilateral hippocampus and amygdala size,2 To explore the correlation between the cognitive impairment in patients with depression and bilateral hippocampus and amygdala size, and analysis the neuropathological basis of memory impairment of depression. Methods To measuret on volumes of both sides of the hippocampus and amygdala. of 24 patients with depression and 24 control patients, by volume analysis software and analysis the relationship between the. size of bilateral hippocampus and amygdala and cognitive impairment (three indicators:latency of P300, reaction time and persistent error.Results 1) Volume of both sides of the depression group in the hippocampal was significantly Less than control group, but the volume on both sides in the amygdala was no significant difference between the two groups.2), bilateral hippocampus in patients with was no correlation between duration and depression HAMD depression scale and depression.3) Hippocampal volume in patients with depression was positively correlated with P300 amplitude, but no correlated with rpe, mRT and latency.Conclusion 1) Hippocampal volume of depression appears reduced, but with depression course and severity of depression independent of hippocampal volume abnormalities, it may be the basis of the neurobiology of depression, but not yet clear changes in brain structure and function isthe cause or results of depression.2) the hippocampus involved in the emotional process, mainly involved in memory function3)The hippocampus hhas no relationship with the executive function response to.frontal lobe function..The third part the study of diffusion tensor imaging MRI of depressionObjective 1To study the white matter FA values and its significance of depression by magnetic resonance diffusion tensor imaging (DTI) Technology.2To explore the correlation between cognitive impairment and the DTI anisotropy in patients with depression and to analyze the neuropathological basis of cognitive impairment.Methods To measure and compare white matter FA values in different parts of patients with depression and controls by DTI regions of interest (ROI) method, and to analysis statistically by the SPSS 13.0 statistical package, and the measurement data was expresser byx±SD) and compared between the two groups by independent samples t test, P<0.05 for the difference was statistically significant. Cognitive impairment FA values by DTI imaging between depression patients and the control group, were statistically analyzed..Result.1. There was significant (P<0.05) between the depression group and the control group, FA value of different anatomical contrast of the site are:frontal, anterior cingulate gyrus, corpus callosum the knee.。2. FA values of bilateral frontal, anterior cingulate cortex, genu of corpus callosum has nothing to do with the HAMD depression scale, the left frontal FA values was moderate negative correlation with duration (r=-0.566, P<0.01).3.FA values of bilateral frontal white matter, cingulate gyrus, genu of corpus callosum were significantly negatively correlated with latency of P300 and Rpe (P<0.05), FA values of left frontal white matter, anterior cingulate cortex, genu of corpus callosum were moderate correlation with mRT (P<0.05).) Conclusion 1. The significantly different site in FA values between the depression and control groups mainly was frontal, anterior cingulate gyrus, genu of corpus callosum.。2. Long-term depression may have contributed to the injury site, resulting in important neural circuit or bilateral contact in the abnormal middle cerebral hemisphere, so affective disorder symptoms and some cognitive impairment increased. 3, DTI can reveal the damagement of the integrity of the myelin sheath of nerve fibers including of frontal, anterior cingulate cortex, genu of corpus callosum and other in patients with depression, It is to ensure that the basis of axonal conduction function if the myelin sheath is intact, which may affect the pathological basis of cognitive function.4, The damage of integrity of these areas is mainly due to abnormal executive function.The fourth section, the study of emotional processing of depression by functional magnetic resonance imagingObjective To study different brain activation response to different emotional pictures by functional magnetic resonance imaging in patients with depression and to explore the characteristics of brain activity in patients with depressionMethods 15 patients with depression and 15 cases of control group were stimulated by International Affective Picture System pictures to the brain functional magnetic resonance imaging (fMRI) scans, Task-block design, processing image data with neurological image analysis (AFNI) software.Result 1 The activated brain regions of identificating of the neutral control group, image, positive image, negative image is bilateral frontal, middle and next time, the central gyrus, angular gyrus, supramarginal gyrus, anterior cingulate gyrus and the pressure, the hippocampus, amygdala, occipital visual cortex, pons and cerebellum.2. Compared with neutral images, the activated area by positive and negative pictures was observed in overlap activation of bilateral inferior parietal lobule, superior temporal gyrus and basal ganglia area, while the positive image and the negative image of the activation is different. Significant activation of bilateral frontal brain regions of Negative-Positive differences are radiation crown area, anterior cingulate gyrus and press department, middle temporal gyrus, internal capsule, insula, and cerebellar vermis, right thalamus, pons. Negative brain activation in only the left brain.3.There are differences between the two groups to identify of neutral, positive and negative pictures。3.When recognizing of neutral images (depression group by control group), there had significantly negative activation of brain regions in bilateral superior parietal lobule, cingulate gyrus and corpus callosum, left middle frontal gyrus, hippocampus, right parahippocampal gyrus, Right supramarginal gyrus, thalamus and had significantly positive activation of brain regions in occipital visual cortex brain area, the right wedge leaf, the left cerebellar hemisphere.2 When recognizing of positive images (depression group by control group), there had significantly negative activation of brain regions in bilateral parahippocampal gyrus, hippocampus, dorsal thalamus and the superior parietal lobule, middle temporal, inferior gyrus, precuneus, in the cerebral and cerebellar hemispheres, putamen, the right amount, the next time, insula and had significantly positive activation of brain regions in bilateral cerebellar hemispheres, occipital visual cortex and right parietal lobe.3 When recognizing of negative images (depression group by control group), there had significantly positive activation of brain regions in Bilateral parahippocampal gyrus, wedge leaf, thalamus, occipital visual cortex and cerebellar hemisphere, amygdala, right hippocampus, middle temporal, inferior gyrus and parietal and had significantly negaitive activation of brain regions in Cerebellar hemisphere and left frontal, the next time, right inferior parietal lobule, superior parietal lobule。Conclusions Depression involved in such damage closely related to frontal lobe, cingulate gyrus and the limbic system (hippocampus, parahippocampal gyrus, amygdala, and may be involved in limbic system-the cortex-striatum-the globus pallidus-thalamus neural circuit-based multiple neural circuit structure and function abnormalities.The fifth section, the study of cognitive function of depression by functional magnetic resonance imaging Objective To study the characteristics of brain activation.function in patients with depression and cognitive impairmentMethods 10 patients with depression and 10 age and education level equivalent control group performanced the number of working memory tasks simultaneously by functional magnetic resonance imaging (fMRI). AFNI software analysis the data of FMR I locatedly and quantitatively。Result 1. the implementation of the correct rate is less, the reaction time is longer in Depression group than in the control group, there are statistically significant 2 working memory brain activation of two groups:Digital working memory brain activation in normal include bilateral frontal, middle, next time, next time temporal parietal lobule, inferior parietal lobule, precuneus, medial frontal gyrus, insula, anterior cingulate gyrus, occipital visual cortex area, dorsal thalamus. Digital working memory activation in patients group and control group activate the same brain regions.Conclusion 1 prefrontal and cingulate are the basis of working memory of brain function. parietal is an important part of attention system 2 decreased activation of prefrontal cortex is one of the pathological mechanisms that patients with depression have working memory impairment.Summary1 This is the first time at home and abroad to study prospectively the spatial and temporal patterns of depression and its cognitive dysfunction in combination with event-related potentials from the time and magnetic resonance of technology from space (including the Hippocampus and Amygdala size, shape white matter, cerebral gray matter function).Pathological basis of depression generally have their reasons and incentives that may be due to congenital myelin and neurons themselves dysplasia, or more sensitive to external stimuli, are vulnerable to damage. Acquired generally related to stress, stress caused biochemical changes in vivo, mainly glutamate system has led to other parts of the prefrontal and hippocampal neurons sustained damage; Such damage makes these parts of the neurons release in resting state to reduce nerve impulses, so emotional and cognitive neural circuit damage. when the external stimulation of emotional pictures, or the performance of the compensatory over-activation (early), or showed less activation (late), such as higher nervous activity during working memory performance in the prefrontal cortex at an early stage, activities of compensatory increase in the limbic system, the late show prefrontal cortex, the limbic system activity decrease, the same impulse as payment reduction led to a decline in executive function, which can be reflected on the functional magnetic resonance; Neuronal damage reduction due issuing nerve impulses, nerve fibers themselves can cause nutritional changes of myelin, leading to nerve fiber damage; At the same time as the release of neurons to reduce nerve impulses may lead to reduction in the number of myelin and the nerve synapse reduction (changes in these nerve fibers can be displayed on the DTI, showed decreased FA value), and nerve fiber changes will affect the neural pathway (several important pathway) links between the (leading to the latent period and the N-back task reaction time extension), which links the reduction will affect the frontal and hippocampal neurons in the integrity of the loop, damage the integrity of neurons led to a lack of functional stimulation, so that further damage neurons, and possible structural changes such as shrinkage of the hippocampus, neurons and nerve fibers in brain morphology. The space in time exception will be shown, electrophysiological event-related potential P300 latency will appear on the extension, N-BACK reaction time occurs and the error rate of increase, while WCST decline in executive function occurs, such as sustained increase in the number of errors, the patient showed abnormal symptoms such as emotional and cognitive. Such as depression (frontal, temporal lobe) attention disorder (parietal lobe), and memory impairment (temporal lobe), reduced capacity and the work plan hesitation (frontal lobe), work efficiency decreased (association cortex), etc. These emotional and cognitive as neurons and neural pathways are crossed, and therefore depression and cognitive function in a common injury, manifested in behavioral depression, cognitive decline and other symptoms 2. This is the first time at home and abroad to propose the pathogenesis of depression combined with cognitive dysfunction from the anatomy angle,that is state and trait there.The results show that in the exercise of duties, the activation of brain regions showed positive patients were lower than the control group as to bilateral superior frontal gyrus, left middle frontal gyrus was significant, while we found that frontal lobe in depressed mood also plays an important role in processing and contrast positive image, in the observation of neutral, negative picture of bilateral frontal activation are mainly negative, Combined with previous neuroimaging studies, indicating the prefrontal cortex of depressed patients neurophysiological abnormalities and emotional, language, attention selection, visual spatial memory, and depression onset dorsal prefrontal cortex decreased physical activity, depressive state function of these brain regions passivation, reflecting the common cognitive and emotional barriers, emotional and cognitive processing described neurophysiological link between. We also found that depressive mood and cognitive use of different brain regions, they are the basis of the existence of different brain functions, it also confirmed from the anatomy of depression depression and cognitive impairment in the state of nature are there. Some studies found that patients with depression symptoms in the treatment of depression were relieved, but cognitive function compared with the control group, there were a significant statistical difference. This suggests that depression, cognitive impairment trait, indicating that depressive mood and cognitive impairment in brain function based on the existence of different brain regions, which in our study had been confirmed; but the study also found that after treatment, with the condition of remission, the patient’s cognitive function has significantly improved; WCST performance improvement and depression improved significantly correlated, suggesting that the cognitive state of depression the presence of patients with recognized depression known function of the extent of damage and depression are related. Analyze the reasons that we found in the DTI study of depression in patients with bilateral frontal white matter, cingulate gyrus, corpus callosum, the integrity of the knee down, and with depression, a positive correlation between duration, and continuity errors and the percentage (Rpe) negative correlation, which confirmed the damage to white matter fibers may be depression, mood and cognitive impairment in the common pathological basis, such as damage to white matter fibers in the mood of depression and cognitive function plays an important role in the development, combined with depression have a common emotional and cognitive brain areas, such as frontal lobe, the positive control of depressive symptoms, cognitive function can promote the recovery of patients.3. Depression, emotional disorders and cognitive impairment based on a similar pathology, the joint damage of white matter and gray matter lead to depression and the occurrence of cognitive impairment.4.There is no relationship between the severity of Depression and cognitive function, but the duration of Depression were positively correlated to cognitive function. Depression on the left middle frontal gyrus white matter FA values were negatively correlated with the duration, suggesting that prolonged course may increase the injury of brain white matter in depression patients.更多还原