Mapping the MTL Memory System in Schizophrenia

描述（由申请人提供）：该职业发展计划将支持候选人的目标，即掌握新的成像方法来研究精神分裂症中特定大脑系统的多个方面。这种系统方法将使我们更深入地了解由内侧颞叶（MTL）记忆系统（海马体、海马旁区和大脑皮层）介导的陈述性记忆（DM）损伤的相关机制。来自有成就的调查人员的指导、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制度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大脑紊乱的病理生理基础。在精神分裂症中，糖尿病损伤和海马体积减少特别容易受到疾病过程的影响，并表明对该疾病的遗传易感性。然而，陈述性记忆（DM）的异常是否反映了区域大脑活动和/或功能连接的紊乱，以及这种损伤是否与该神经网络中的结构异常有关，目前尚不确定。为了解决这些问题，候选人将结合结构、功能和弥散张量成像来绘制精神分裂症患者、患者一级亲属和通过NIMH更大的研究“精神分裂症易感因素的传播”招募的健康对照受试者的MTL记忆系统的结构和功能异常。该研究计划包括先进的结构图像分析技术、功能磁共振成像（fMRI）和扩散张量成像（DTI）策略，这些策略将用于分离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，并确定遗传倾向效应的存在。

DESCRIPTION (provided by applicant): 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.