Microstructural Characterization of White Matter in Schizophrenia

描述(由申请人提供)：精神分裂症是一种慢性、严重和致残的障碍，其特征是幻觉、妄想和运动障碍。此外，包括注意力、语言、记忆和执行功能问题在内的认知缺陷也与精神分裂症有关，并极大地影响了精神分裂症患者的正常日常功能。病理、功能和形态计量学研究表明，在精神分裂症患者中观察到的脑异常与连接不同脑区的白质通路的宏观和微观结构变化有关。已经提出了额叶-颞叶分离的模型来解释精神分裂症中观察到的一些缺陷。利用扩散张量成像(DTI)技术和基于体素的形态计量学技术或感兴趣区域方法，已经广泛地研究了脑白质的微结构完整性。然而，在不同的研究中，研究结果相当不一致。很少有研究探讨DTI所描绘的白质异常的行为相关性。该项目的目标是研究精神分裂症患者脑白质的微结构完整性，使用典型的DTI微结构完整性指标--平均扩散率和分数各向异性，以及一种新的指标--平均峰度，该指标已显示出更好地区分脑白质微结构改变的前景。平均峰度将使用扩散峰度成像技术来推导，这是DTI形式主义的推广。我们还将探索白质微结构与一套描述认知功能的指标之间的关系。将采取两种方法：1)将使用基于体素的形态测量技术来探索一组精神分裂症患者和一组健康受试者之间白色微结构的差异。2)白质束成像技术将被用来分割出上纵束的轨迹和范围，上纵束是连接前额叶、颞叶和顶叶的白质束。将对患者和对照组的全局和局部肠道微结构扩散措施进行调查。这项研究的结果可能揭示特定路径或大脑区域的连接性变化，从而有助于理解精神分裂症脑功能障碍的机制。对连接额叶和颞叶的白质通路的研究也将有助于理解精神分裂症患者普遍观察到的异常的额颞叶功能连接。公共卫生相关性：精神分裂症是一种严重的精神疾病，与严重的终身损伤和高患病率有关，在美国有200多万人受到影响。这项研究将调查连接负责认知控制的大脑功能区域的白质通路的完整性。对大脑连接受损的了解将为精神分裂症大脑功能障碍的机制提供新的见解，并有可能提高我们更好地诊断和评估这种疾病的治疗的能力。

DESCRIPTION (provided by applicant): Schizophrenia is a chronic, severe, and disabling disorder that is characterized by hallucinations, delusions, and motor deficits. In addition, cognitive deficits including problems with attention, language, memory, and the executive functions are also associated with the disorder and greatly affect normal day by day functioning of the schizophrenic patients. Pathological, functional, and morphometric studies have implied that the brain abnormalities that are observed in schizophrenia are associated with macro and microstructural alterations of the white matter pathways connecting different brain regions. Models of fronto-temporal disconnectivity have been proposed to explain some of the deficits observed in schizophrenia. Microstructural integrity of white matter has been extensively investigated using diffusion tensor imaging (DTI) techniques and either voxel based morphometry techniques or region of interest approaches. However, findings are rather inconsistent across different studies. Few studies have explored the behavioral correlations of the white matter abnormalities depicted by DTI. The goal of this project is to investigate the microstructure integrity of white matter mater in schizophrenia using both typical DTI measures of microstructural integrity - the mean diffusivity and fractional anisotropy and a new metric - the mean kurtosis, which has shown promise to better discriminate microstructural alterations of white matter. The mean kurtosis will be derived using the Diffusion Kurtosis Imaging technique, a generalization of the DTI formalism. We will also explore the relation between the white matter microstructure and a set of measures describing cognitive function. Two approaches will be undertaken: 1) Voxel based morphometry techniques will be used to explore differences in white microstructure between a group of patients with schizophrenia and a control group of healthy subjects. 2) White matter tractography techniques will be used to segment out the trajectory and extent of the superior longitudinal fasciculus, a white matter tract that connects the prefrontal, temporal, and parietal lobes. Both global and local tract microstructural diffusion measures will be investigated in patients versus the control group. The results of this study may reveal connectivity alterations in specific pathways or brain regions and thereby contribute to the understanding of the mechanisms underlying brain dysfunction in schizophrenia. The study of the white matter pathways connecting the frontal and temporal lobe will also contribute to the understanding of the abnormal fronto-temporal functional connectivity that is generally observed in schizophrenia. PUBLIC HEALTH RELEVANCE: Schizophrenia is a severe mental disorder associated with significant lifelong impairment and high prevalence, affecting more than two millions of people in the United States. This study will investigate the integrity of the white matter pathways that connect functional brain regions responsible for cognitive control. Knowledge of the impaired brain connectivity will provide new insights into the mechanisms that underlie brain dysfunction in schizophrenia and has the potential to improve our ability to better diagnose and assess treatment of this disorder.