MAPPING THE MTL MEMORY SYSTEM IN SCHIZOPHRENIA

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 这个职业发展计划将支持候选人掌握新的成像方法的目标，以调查精神分裂症特定大脑系统的多个方面。这种系统的方法将允许更深入地了解与陈述性记忆（DM）损伤相关的机制，这些机制由内侧颞叶（MTL）记忆系统（海马，海马旁区和大脑皮层）介导。来自有成就的研究者的指导，最先进的成像设备和教学培训提供了实现这些目标所需的基础设施。加州大学洛杉矶分校丰富的机构环境进一步支持候选人的长期计划，即利用成像方法开发一个富有成效和独立的研究项目，以更好地了解神经精神疾病中脑干扰的病理生理基础。DM损伤和海马体积减少被证明特别容易受到精神分裂症疾病过程的影响，并表明对疾病的遗传易感性。然而，它是不确定的陈述性记忆（DM）的异常是否反映在区域大脑活动和/或功能连接的干扰，以及是否这种损害涉及到这个神经网络内的结构异常。为了解决这些问题，候选人将结合联合收割机结构，功能和扩散张量成像，以映射精神分裂症患者，患者的一级亲属和健康对照受试者的MTL记忆系统的结构和功能异常，通过一个更大的NIMH研究，“精神分裂症脆弱因素的传播。“研究计划包括先进的结构图像分析技术和功能性磁共振成像（fMRI）和扩散张量成像（DTI）策略，将用于分离MTL紊乱的结构和功能相关性，包括精神分裂症的陈述性记忆缺陷，并建立遗传易感性效应的存在。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This career development plan will support the candidate's goals of mastering new imaging methodologies to investigate multiple aspects of a specific brain system in schizophrenia. This systems approach will allow a deeper understanding of the mechanisms associated with declarative memory (DM) impairments that are mediated by the medial temporal lobe (MTL) memory system (hippocampus, parahippocampal region and cerebral cortex). Guidance from accomplished investigators, state-of-the-art imaging facilities, and didactic training provide the infrastructure needed to achieve these goals. The rich institutional environment at UCLA further supports the candidate's long-term plan to develop a productive and independent program of research using imaging methods to better understand the pathophysiological underpinnings of brain disturbances in neuropsychiatric disorders. DM impairments and hippocampal volume reductions are shown particularly vulnerable to disease processes in schizophrenia and to indicate a genetic predisposition towards the illness. However, it is uncertain whether abnormalities of declarative memory (DM) reflect disturbances in regional brain activity and/or in functional connectivity and whether such impairments relate to structural abnormalities within this neural network. To address these questions, the candidate will combine structural, functional and diffusion tensor imaging to map structural and functional abnormalities of the MTL memory system in schizophrenia patients, first-degree relatives of patients and healthy comparison subjects recruited through a larger NIMH study, "Transmission of Vulnerability Factors for Schizophrenia." The research plan includes advanced structural image analysis techniques and functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) strategies that will be employed to dissociate the structural and functional correlates of MTL disturbances including declarative memory deficits in schizophrenia and to establish the presence of genetic liability effects.