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了组织体积的损失和神经元密度的变化，涉及到颞叶和额叶的一组与功能相关的皮质结构。精神分裂症受试者丘脑中神经元数量和体积的大幅减少也被描述为，强调了评估皮质-皮质下回路在疾病中的重要性。拟议中心的中心目标是更详细地确定这些大脑结构异常的解剖模式、这些异常的原因(即遗传性和非遗传性)、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认知表现之间的联系。拟建的Conte可行性神经科学研究中心将有四个目标：1)在精神病学、神经生物学、神经成像和生物医学工程等领域拥有专门知识的科学家之间建立多机构合作；2)进一步开发一组计算机软件工具，这些工具将在定义包括但不限于精神分裂症的神经精神疾病的神经生物学方面具有独特价值；3)测试特定假说，并产生与精神分裂症受试者神经解剖异常的原因和后果有关的新假说；以及4)进一步确定精神分裂症的发病机制。在两个核心支持的三个相关项目的背景下，我们建议测试最重要的假设，即遗传因素导致一系列神经发育异常，这些异常后来在精神分裂症受试者中表现为大脑结构、认知和精神病理学的异常。为该中心提出的各个项目都涉及几个主题。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强大理由，而不是一系列R01项目。我们所有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。我们用于高维大脑图的新工具为每个项目提供了具体意义上的这个框架。所有项目共有的第二个主题是对相同的分布式大脑结构网络的关注。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.