Brain Imaging in Major Psychoses: Examining Structural & Functional Connectivity

描述（由申请人提供）：确定精神分裂症的神经底物是开发更具针对性的治疗或确定分子机制的关键步骤。神经影像学的工具大大促进了这一研究。大约在过去的十年里，我们一直在探索精神分裂症患者患有“错误连接综合征”的假设：一种广泛分布的大脑区域网络的干扰。这种错误连接反过来导致整合信息的能力受损（“思维障碍”），这是精神分裂症的标志。拟议的项目检查结构连接（使用扩散张量成像，或DTI）和功能连接使用功能磁共振成像（fMR）检查随机情景沉默思维（“REST”）过程中的“默认网络”。我们将采用横截面和纵向设计，以检查结构和功能连接的损伤是否随着时间的推移而进展，基于我们的初步工作表明情况确实如此。我们将收集首次发作患者、慢性患者和健康正常志愿者的基线MR数据。首次发作患者的一个子集将在他们仍然未接受过抗精神病药物治疗时进行研究。将在两个时间点获得随访MR数据。迄今为止，只有少数研究检查了首次发作的患者。我们的研究将是第一个使用匹配的对照组来比较首发患者和慢性患者的研究。很少有研究检查DTI的进展或药物作用的问题。从未接受过抗精神病药物治疗的受试者从未接受过检查，也没有在纵向设计中应用DTI。DTI和fMR提供了关于大脑的不同和互补的数据;如果这些信息可以集成在一个单一的分析中，则可以提供额外的功能。我们将使用新的统计技术进行“数据融合”，将DTI测量的结构连接性与功能连接性的fMR测量的信息整合在一起。因此，拟议的工作具有很强的创新性。

DESCRIPTION (provided by applicant): Identifying the neural substrates of schizophrenia is a key step in developing more targeted treatments or identifying molecular mechanisms. The tools of neuroimaging have substantially facilitated this search. For approximately the past decade, we have been exploring the hypothesis that patients with schizophrenia suffer from a "misconnection syndrome": a disturbance in a widely distributed network of brain regions. This misconnection leads in turn to impairment in the ability to integrate information ("thought disorder") that is the hallmark of schizophrenia. The proposed project examines both structural connectivity (using diffusion tensor imaging, or DTI) and functional connectivity using functional magnetic resonance imaging (fMR) to examine the "default network" during random episodic silent thought ("REST"). We will employ both a cross-sectional and a longitudinal design in order to examine whether impairments in structural and functional connectivity progress over time, based on our preliminary work suggesting that this is the case. We will collect MR data at baseline in first episode patients, chronic patients, and healthy normal volunteers. A subset of the first episode patients will be studied when they are still neuroleptic naive. Follow-up MR data will be obtained at two time points. Only a few studies to date have examined first episode patients. Ours will be one of the first to compare first episode patients and chronic patients, using a matched control group. There are very few studies examining the issue of progression or of medication effects with DTI. Neuroleptic naive subjects have never been examined, nor has DTI been applied in a longitudinal design. DTI and fMR provide different and complementary data about the brain; additional power is provided if this information can be integrated in a single analysis. We will use novel statistical techniques for "data fusion" to integrate the information from DTI measures of structural connectivity with fMR measures of functional connectivity. Thus the proposed work with is highly innovative.