P4-Structure and function of white mater in schizophrenia

额叶、基底前脑、边缘等脑区连通性的改变 系统被认为是精神分裂症的网络缺陷。世界银行的多区域问题 假设的连通性问题意味着白质可能存在缺陷，这可能导致 改变路线或中断一些特定的大脑回路。精神分裂症患者的全球髓鞘缺失可能 也产生了一种分布的多地区赤字的模式，与复杂的、不明确的本地化的、 精神分裂症患者的行为和认知障碍。数量、分布和数量的变化 少突胶质细胞的超微结构完整性是白质的关键成分，最近在 精神分裂症患者的前额叶皮质，与我们最初发现的弥散张量减少一致 额叶白质的各向异性和我们在这个项目的第一个资助期复制的结果。 为了扩大我们在精神分裂症中发现的白质异常，我们计划了四个项目：1)我们将 完成一项纵向样本研究，并对一组精神分裂症患者进行3年的随访扫描 并控制我们已经从已经获得的扩散张量和结构图像的位置 3T纵向样本的获得性样本(240名受试者-125名精神分裂症患者和115名匹配患者 对照)；2)我们还将在32个队列中获得绝对葡萄糖定量的FDG-PET 未服用药物的精神分裂症患者和32名年龄和性别匹配的对照组进一步发展我们最初的 发现精神分裂症患者脑白质相对代谢率增高，我们将开展探索性体素- 各向异性与葡萄糖代谢率之间的体素相关性；3)我们将利用我们最近的 开发了轨迹追踪程序以评估扣带的特定轨迹方向和终止点， 前额叶皮质中的丘脑、纹状体和胼胝体纤维；4)我们将分享白质各向异性和 关于项目1、2、3和5以及核心B的体积措施，以促进和告知其潜力 选择要检查的大脑区域。综合起来，这些目标将使我们能够获得最可靠的、 有效的、功能不同的和信息量丰富的白质评估，以确定特定的丘脑-兄弟， 精神分裂症患者额纹状体和扣带回通路异常。

Alterations in connectivity among brain regions such as the frontal lobe, basal forebrain and limbic system have been proposed as network deficits in schizophrenia. The multiregional aspects of the hypothesized problems in connectivity implicate a possible deficit in white matter that could lead to the rerouting or interruption of a number of specific brain circuits. A global deficit in myelin in schizophrenia may also produce a pattern of distributed multiregional deficits compatible with the complex, not clearly localizing, behavioral and cognitive disorganization in schizophrenia. Alteration in numbers, distribution, and ultrastructural integrity of oligodendrocytes, key white matter components, has recently been reported in the prefrontal cortex in schizophrenia, consistent with our original diffusion tensor findings of diminished anisotropy in frontal white matter and our replication of this in the first funding period of this project. To extend our findings of white matter abnormalities in schizophrenia we plan four projects: 1) we will complete a longitudinal sample study with follow-up scans 3 yrs in a cohort of patients with schizophrenia and controls where we have already acquired diffusion tensor and structural images from the already acquired sample of 3T longitudinal sample (240 subjects - 125 patients with schizophrenia and 115 matched controls); 2) We will also acquire FDG-PET with absolute glucose quantification on a cohort of 32 unmedicated patients with schizophrenia and 32 age- and sex-matched controls to further develop our initial finding of increased white matter relative metabolic rate in schizophrenia, we will develop exploratory voxelby- voxel correlations between anisotropy and glucose metabolic rate; 3) We will exploit our recently developed tract tracing programs to assess the specific tract directions and termination points for cingulate, thalamic, striatal, and callosal fibers in the prefrontal cortex; 4) We will share white matter anisotropy and volumetric measures with Projects 1, 2, 3 and 5 and Core B in order to facilitate and inform their potential choice of brain areas to be examined. Taken together, these aims will allow us to obtain the most reliable, valid, functionally different, and informative white matter assessments to confirm specific thalamo-frental, fronto-striatal and cingulate pathway abnormalities in schizophrenia.