Mapping Neurodevelopment Abnormality in Schizophrenia

脑结构异常已被证明是精神分裂症的一个关键生物学特征。在精神分裂症患者中发现组织体积损失和神经元密度变化，涉及颞叶和额叶中一组与功能相关的皮质结构。在精神分裂症患者的丘脑中也有神经元数量和体积的显著减少，这强调了评估该疾病中皮层-皮层下回路的重要性。该中心的中心目标是更详细地定义这些大脑结构异常的解剖模式，这些异常的原因（即遗传与非遗传），它们在动物模型中的潜在细胞基础，并建立这些异常与疾病的认知表现之间的联系。拟议的Conte神经科学研究可行性中心将有四个目标：1)在具有精神病学专业知识的科学家之间建立多机构合作；神经生物学;神经影像与生物医学工程；2)进一步开发一组计算机软件工具，这些工具将在定义神经精神疾病（包括但不限于精神分裂症）的神经生物学方面具有独特价值；3)检验特定假设，并提出与精神分裂症患者神经解剖学异常的原因和后果相关的新假设；4)进一步明确精神分裂症的发病机制。在由两个核心支持的三个相关项目的背景下，我们建议测试遗传因素导致神经发育异常级联的总体假设，这些神经发育异常后来表现为精神分裂症受试者的大脑结构、认知和精神病理异常。几个主题贯穿于为中心提出的各个项目。结合共享的技术和资源，这些主题代表了作为一个中心资助这项研究的有力理由，而不是一系列R01项目。在我们所有的项目中强调的第一个主题是在精确的神经解剖学框架内嵌入大脑功能的概念。我们用于高维大脑映射的新工具为每个项目提供了具体意义上的框架。所有项目共有的第二个主题是关注相同的大脑结构分布式网络。第三，我们在人类和非人类灵长类动物的研究中使用了共同的认知概念和范式。

Abnormalities of brain structure have been shown to be a key biologic characteristic of schizophrenia. Losses of tissue volume and changes in neuronal density have been found in subjects with schizophrenia, involving a group of functionally-related cortical structures in the temporal and frontal lobes. Substantial reductions in neuronal number and volume have also been described in the thalamus of schizophrenia subjects, underscoring the importance of assessing cortical-subcortical circuitry in the disease. The central goal of the proposed Center is to define in greater detail the anatomical pattern of these brain structure abnormalities, the cause of these abnormalities (i.e., genetic versus non-genetic), their potential cellular basis in an animal model, and to establish the linkages between these abnormalities and cognitive manifestations of the disease. The proposed Conte Feasibility Center for Neuroscience Research will have four objectives: 1) to establish a multi-institutional collaboration between scientists with special expertise is psychiatry; neurobiology; neuroimaging and biomedical engineering; 2) to further develop a group of computer software tools that will be of unique value in defining the neurobiology of neuropsychiatric disorders, including but not limited to schizophrenia; 3) to test specific hypotheses and to generate new hypotheses related to the causes and consequences of neuroanatomical abnormalities in subjects with schizophrenia; and 4) to further define the pathogenesis of schizophrenia. In the context of three related Projects supported by two Cores, we propose to test the overarching hypothesis that genetic factors lead to a cascade of neurodevelopment irregularities that are later manifested by abnormalities of brain structure, cognition, and psychopathology in subjects with schizophrenia. Several themes are carried across the individual Projects proposed for the Center. Taken together with shared technologies and resources, these themes represent a strong rationale for the funding of this research as a Center, rather that a series of R01 projects. The first theme stressed in all our projects is the embedding of concepts of brain function within a precise neuroanatomical framework. Our new tools for high dimensional brain mapping provide this framework in a concrete sense for each of the projects. A second theme shared by all projects is the focus on the same distributed network of brain structures. Thirdly, we have used common cognitive concepts and paradigms across studies of human and non- human primate subjects.