基于MRI新技术的精神分裂症及其核心症状的神经机制研究

发布时间：2018-05-15 00:17

本文选题：精神分裂症 + 磁共振成像　；参考：《天津医科大学》2017年博士论文

【摘要】：第一部分:精神分裂症静息态脑血流及血流连接的改变【目的】样本量小和个体差异大是导致精神分裂症静息态脑血流(CBF)研究结果不一致的主要原因。精神分裂症的CBF连接改变亦不是十分清楚。在本研究中,我们试图阐明以下问题:(1)精神分裂症患者的CBF改变模式;(2)CBF改变与临床指标的关系;(3)精神分裂症患者存在CBF改变的脑区是否也有CBF连接的改变。【方法】利用三维伪连续动脉自旋标记(3D-pcASL)成像技术测量100例精神分裂症患者和94例正常对照的静息态CBF,并使用标准化CBF减小个体变异。我们比较两组受试者CBF的差异,并在患者中评估CBF改变和临床指标的相关性。并且,我们还比较了存在局部CBF改变脑区的CBF连接的组间差异。【结果】和正常对照相比,精神分裂症患者双侧颞下回、双侧丘脑、双侧壳核CBF增高,左侧岛叶、左侧额中回、双侧前扣带皮层、双侧枕中回CBF减低。校正灰质体积以后,精神分裂症患者CBF的改变仍然显著。在精神分裂症患者中,CBF改变和临床指标存在显著的相关性。更重要的是,我们发现精神分裂症患者左侧丘脑和右侧额上回内侧部、左侧岛叶和左侧中央前回的CBF连接减低。【结论】我们的发现提示精神分裂症患者不仅存在局部CBF的异常,还存在CBF连接的改变,这些改变可能是精神分裂症临床症状的神经机制。第二部分:基于扩散峰度成像的精神分裂症脑白质损害研究【目的】扩散峰度成像(DKI)技术是传统扩散张量成像(DTI)技术的延伸,该技术在探索神经组织发育性或病理性改变时具有更高的敏感度和特异度。在本研究中,我们试图评估DKI和DTI技术在探索精神分裂症脑白质异常中的能力及差异。【方法】首先对94例精神分裂症患者和91例正常对照行DKI和DTI图像数据采集。评估脑白质完整性的指标包括:DKI数据解算得到部分各项异性(FA)、平均扩散率(MD)、轴向扩散率(AD)、径向扩散率(RD)、平均峰度值(MK)、轴向峰度值(AK)、径向峰度值(RK);DTI数据解算得到FA、MD、AD、RD。利用基于纤维束的空间统计(TBSS)方法比较11个指标的组间差异。【结果】DKI指标发现精神分裂症白质损害的敏感性(异常体素数/全脑白质骨架体素总数)分别为:RD(37%)MK(34%)FA(24%)MD(21%)AK(20%)RK(3%);DTI指标发现精神分裂症白质损害的敏感性分别为:RD(43%)FA(30%)MD(21%)。DKI扩散指标(RD、FA和MD)可以更敏感地探测到纤维排布一致的白质区(胼胝体和内囊前肢)异常,而DKI峰度指标(MK和AK)可以更敏感地探测到纤维排布复杂的白质区(皮层下白质和放射冠)异常。并且,精神分裂症MK的减低主要是由AK的减低引起,提示轴突受损,而FA的减低主要是由RD的增高引起,提示髓鞘损害。【结论】这些发现提示DKI扩散指标及峰度指标在探测精神分裂症脑白质损害时可以提供互补的信息,因而联合应用多指标更易于揭示精神分裂症的脑白质病理损害机制。第三部分:家族型和散发型精神分裂症静息态脑功能网络研究【目的】既往的研究发现家族型和散发型精神分裂症患者的临床症状和脑结构有明显差异,但是两种亚型患者的脑功能差异却不是十分清楚。在本研究中,我们试图探究家族型和散发型精神分裂症患者的静息态脑功能网络损害特征。【方法】我们采集26例家族型精神分裂症患者、26例散发型精神分裂症患者和26例正常对照的静息态功能磁功能成像(fMRI)数据。然后用图论的方法构建全脑功能网络,并比较三组被试脑功能网络拓扑属性(包括全局指标、节点指标和边指标)的差异。【结果】我们发现三组被试的脑功能网络都满足典型的小世界网络拓扑属性。在全局水平,只有家族性精神分裂症患者的聚类系数、小世界性、局部效率下降,提示该亚型患者的脑功能网络向随机化转变。在局部水平,家族型和散发型精神分裂症患者有不同特异性神经环路的损害,包括全脑广泛分布的节点中心性增高或减低及功能连接强度减低。并且,有些网络指标的改变与精神症状的严重程度有显著的相关性。【结论】这些发现提示家族型和散发型精神分裂症患者的脑功能网络拓扑结构损害存在不同的模式,而这可能是由于病因的不同所致。第四部分:精神分裂症妄想症状的神经机制研究【目的】妄想是精神分裂症的主要阳性症状之一,但妄想的神经机制仍然不是十分清楚。在本研究中,我们试图用多模态MRI技术探究精神分裂症妄想症状的神经机制。【方法】我们采集了19例妄想型精神分裂症患者、30例无妄想型患者和30例正常对照的扩散、结构和灌注MRI数据。然后,用基于体素的分析方法比较部分各向异性(FA)、灰质体积(GMV)和CBF的组间差异。【结果】和正常对照相比,无妄想型精神分裂症患者存在广泛白质区FA和灰质区GMV的减低;而妄想型精神分裂症患者的FA和GMV相比于正常对照无显著差异。相比于正常对照,两种亚型精神分裂症患者在前扣带皮层和杏仁核表现出一致性的GMV减低,在额中回和岛叶表现出一致性的CBF减低,在右侧楔前叶表现出一致性的CBF增高。更重要的是,我们发现妄想型精神分裂症患者前扣带皮层的CBF相比于无妄想型患者进一步减低。【结论】这些发现提示妄想型精神分裂症患者可能具有相对正常的脑结构。此外,精神分裂症患者前扣带皮层血流灌注的过度减低可能与妄想症状的产生密切相关。第五部分:精神分裂症言语性幻听的特异性脑血流改变【目的】既往研究发现言语性幻听(AVH)的产生与听觉/语言相关网络的异常密切相关。但是,精神分裂症言语性幻听的特异性CBF改变却不是十分清楚。在本研究中,我们试图在精神分裂症患者中探究与言语性幻听症状相关的CBF改变。【方法】我们采集了35例言语性幻听型精神分裂症患者、41例无幻听型患者和50例正常对照的ASL-MRI数据。然后使用基于体素的分析方法比较三组受试者CBF的差异。【结果】和正常对照相比,两种亚型精神分裂症患者在双侧枕叶皮层、左外侧前额叶皮层、左侧岛叶以及右侧前扣带皮层有一致性的CBF减低,在双侧外侧颞叶皮层、双侧壳核、左侧中扣带皮层以及右侧丘脑有一致性的CBF增高,这些一致性的CBF改变被定义为精神分裂症共同的CBF改变。和无幻听型患者以及正常对照相比,言语性幻听型患者双侧枕叶皮层和左侧顶叶皮层CBF减低,右侧颞上回和右侧尾状核CBF增高,这些CBF的改变被定义为言语性幻听特异性CBF改变。【结论】言语性幻听存在特异性CBF改变,即听觉区和纹状体区CBF增高,视觉区和顶叶皮层CBF减低,该发现提示CBF的再分布与精神分裂症言语性幻听症状密切相关。
[Abstract]:The first part: the changes in the resting state of the cerebral blood flow and blood flow connection in schizophrenia [Objective] the small sample size and the large individual difference are the main reasons for the disagreement of the resting state cerebral blood flow (CBF) results in schizophrenia. The CBF connection change of schizophrenia is not ten distinct. In this study, we try to clarify the following questions: ( 1) CBF changes in schizophrenic patients; (2) the relationship between CBF changes and clinical indicators; (3) whether there is a change in the CBF connection in the brain region of the schizophrenic patients as well as in the CBF changes. [Methods] the resting state CBF of 100 schizophrenics and 94 normal controls was measured by the three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL) imaging technique. We compared the individual variation with standardized CBF. We compared the differences in CBF in the two subjects and assessed the correlation between the CBF changes and the clinical indicators in the patients. Furthermore, we also compared the differences in the group of CBF connections in the brain region of the local CBF. [results] the contrast to the normal contrast, the bilateral temporal gyrus, and the bilateral mound in schizophrenic patients Brain, bilateral putamen CBF increased, left insula, left middle frontal gyrus, bilateral anterior cingulate cortex, bilateral occipital gyrus, CBF decreased. After correction of gray matter volume, the changes of CBF in schizophrenic patients were still significant. In schizophrenia patients, there was a significant correlation between CBF changes and clinical indicators. More importantly, we found schizophrenia patients. CBF connections in the left thalamus and right medial frontal gyrus, left Island leaf and left precentral gyrus were reduced. [Conclusion] our findings suggest that schizophrenia patients not only have abnormalities in local CBF, but also the changes in CBF connections. These changes may be the neural mechanisms of the clinical symptoms of schizophrenia. The second part: Based on the proliferation peak Degree imaging of schizophrenia brain white matter damage study [Objective] diffusion kurtosis imaging (DKI) technology is the extension of traditional diffusion tensor imaging (DTI) technology. This technique has a higher sensitivity and specificity in exploring the developmental or pathological changes of nerve tissue. In this study, we try to evaluate the spirit of DKI and DTI in exploring the spirit. The ability and difference in the abnormal white matter of schizophrenia. [Methods] first of all, 94 patients with schizophrenia and 91 normal controls were collected for DKI and DTI images. The indicators for assessing the integrity of the white matter included: the DKI data were calculated to obtain partial heterosexual (FA), average diffusion rate (MD), axial diffusivity (AD), radial diffusivity (RD), and average peak Degree value (MK), axial kurtosis (AK) and radial kurtosis (RK); DTI data were calculated to obtain FA, MD, AD, and RD. using the spatial statistics (TBSS) method based on fiber bundles to compare the differences between the 11 indexes. [results] DKI indicators found that the sensitivity of white matter damage in schizophrenia (the number of abnormal voxels / total brain white matter cytoskeleton) was RD (37%) MK ( 34%) FA (24%) MD (21%) AK (20%) RK (3%); DTI index found that the sensitivity of RD (43%) FA (30%) MD (21%).DKI diffusion index (RD, FA and MD) can be more sensitive to detect the abnormal white matter area (corpus callosum and inner capsule forelimb) in fiber arrangement, and the index of kurtosis index can be more sensitive to detect the fiber row. The complex white matter area (subcortical white matter and radiant crown) is abnormal. And the decrease of MK in schizophrenia is mainly caused by the decrease of AK, indicating that the axon is damaged, and the decrease of FA is mainly caused by the increase of RD, suggesting the myelin damage. [Conclusion] these findings suggest that the DKI diffusion index and kurtosis index are in the detection of white matter loss in the brain of schizophrenia. The third part: the resting state brain functional network of familial and sporadic schizophrenics [Objective] to find out the clinical symptoms and brain of patients with familial and sporadic schizophrenia. There are significant differences in the structure, but the difference in brain function of the two subtypes is not very clear. In this study, we tried to explore the resting state brain function network damage characteristics of familial and sporadic schizophrenics. [Methods] We collected 26 familial schizophrenia patients and 26 schizophrenic patients. And 26 normal controls, resting functional magnetic functional imaging (fMRI) data. Then the whole brain functional network was constructed with graph theory, and the differences in the topological properties of the three groups were compared. [results] we found that the brain functional networks of the three groups were satisfied with the typical small world. Network topology properties. At the global level, only familial schizophrenia has a clustering coefficient, small cosmopolitan and local efficiency, suggesting that the brain function network of the subtype is changed to randomization. At the local level, the patients with familial and sporadic schizophrenia have different specific nerve loop damage, including the wide distribution of the whole brain. There is a significant correlation between the changes in some network indicators and the severity of mental symptoms. [conclusions] these findings suggest that there are different patterns of damage to the topological structure of the brain function network in patients with familial and sporadic schizophrenia, which may be due to The fourth part: the neurologic mechanism of paranoid symptoms of schizophrenia [Objective] delusion is one of the main positive symptoms of schizophrenia, but the nervous mechanism of delusion is still not very clear. In this study, we try to explore the neural mechanism of paranoid symptoms of schizophrenia with multimodal MRI technique. Methods: We collected 19 paranoid schizophrenic patients, 30 non paranoid patients and 30 normal controls with diffusion, structure and perfusion MRI data. Then, we compared partial anisotropy (FA), gray matter volume (GMV) and CBF between groups by voxel based analysis. There was a wide reduction in the white matter FA and the gray matter GMV in the patients with cleft disease, while the FA and GMV in paranoid schizophrenics had no significant differences compared to the normal controls. Compared to the normal controls, the two subtypes of schizophrenia showed a consistent GMV reduction in the anterior cingulate cortex and amygdala, and the middle frontal gyrus was consistent with the island leaf. CBF decreased and showed a consistent increase of CBF in the right anterior wedge. More importantly, we found that the CBF of the anterior cingulate cortex in paranoid schizophrenic patients was further lower than that of the undelusional patients. [Conclusion] these findings suggest that paranoid schizophrenics may have relatively normal brain structures. The excessive reduction of blood flow in the anterior cingulate cortex may be closely related to the occurrence of paranoid symptoms. Fifth part: specific cerebral blood flow changes in schizophrenic speech auditory hallucinations [Objective] previous studies have found that verbal auditory hallucinations (AVH) are associated with abnormal auditory / language related networks. The specific CBF changes in verbal auditory hallucinations were not very clear. In this study, we tried to explore CBF changes associated with verbal hallucinations in schizophrenic patients. [Methods] We collected 35 cases of auditory hallucinations, 41 cases without auditory hallucinations and 50 normal controls, and then ASL-MRI data. Using a voxel based analysis, the differences in CBF were compared between the three groups of subjects. [results] two subtypes of schizophrenic patients had a consistent CBF reduction in bilateral occipital cortex, left lateral prefrontal cortex, left insula, and right anterior cingulate cortex, in bilateral lateral temporal cortex, bilateral putamen, left middle buckle. The concordance of CBF increased in the cortex and the right thalamus, and these consistent CBF changes were defined as a common CBF change in schizophrenia. Compared with the non auditory and normal controls, the CBF decreased in the occipital and left parietal cortex of the speech auditory hallucinations, and the CBF in the right lateral temporal and right caudate nuclei increased, and these CBF The changes were defined as verbal hallucinations specific CBF changes. [Conclusion] there is a specific CBF change in speech auditory hallucinations, that is, the CBF of the auditory region and striatum is increased, and the visual area and the parietal cortex are reduced in CBF. This discovery suggests that the redistribution of CBF is closely related to the speech auditory hallucination of schizophrenia.

【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R445.2;R749.3

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