Imaging Hippocampal Function in Psychosis

摘要(项目摘要) 我们建议研究精神病早期(ESOP)海马区功能障碍的演变。 海马体体积变小是脑部结构异常最严重的表现之一。 精神分裂症。此外，现在有令人信服的证据表明， 精神分裂症。然而，目前尚不清楚在疾病过程中，海马体的结构和功能何时会变成 异常以及海马体的哪些区域受到影响。澄清这些问题将改善我们的 了解疾病机制和我们干预疾病过程的能力。 我们将招募出现精神障碍的早期患者来研究海马区。 高场7T磁共振成像的结构和3T磁共振的海马活动 脑血容量(CBV)和BOLD信号的标测。我们将在关系测试中测量性能 记忆，一种依赖于海马体的记忆，在精神分裂症中受损。我们会跟踪观察病人 连续2年，测量精神障碍患者海马区体积的变化。 我们预测，在疾病开始时，海马体活动已经异常，并且不会改变。 在疾病的整个过程中有显著的影响。作为异常活动的结果，记忆功能已经 发病时中度受损。在患病的头两年里， 海马体的活动会导致海马体的结构变化。这一结构性变化是 与记忆缺陷的进一步发展有关。 为了验证我们的假设，我们将开发两种类型的高分辨率海马区地图。第一，解剖学 地图将在整个前后方范围内区分四个扇区和两个区域的体积 海马体的。利用这张高分辨率的海马体切片，我们将检验假设 前部CA1主要受累于精神障碍患者。其次，功能图将评估 在海马区的四个扇区和两个区域有CBV和BOLD信号。我们将用这些地图来测试 精神病患者海马区抑制减弱的假说。我们将关联以下措施 海马体的结构和活动与关系记忆测试的表现，海马体的一种形式- 精神分裂症中受损的依赖记忆。 拟议的纵向研究设计将使我们能够研究海马区功能障碍的时间 精神错乱。本研究的目标是确定早期海马区的标志物。 精神病的诊断。

Abstract (Project Summary) We propose to study the evolution of hippocampal dysfunction in the early stage of psychosis (ESOP). Smaller hippocampal volume is one of the most robust structural brain abnormalities in patients with schizophrenia. In addition, there is now compelling evidence for an abnormality of hippocampal activity in schizophrenia. However, it is unclear when in the disease process hippocampal structure and function become abnormal and which regions of the hippocampus are affected. Clarifying these questions will improve our understanding of the disease mechanism and our ability to intervene in the disease process. We will recruit patients at an early stage of their emerging psychotic disorder to study hippocampal structure with high-field 7T magnetic resonance imaging and hippocampal activity with 3T magnetic resonance mapping of cerebral blood volume (CBV) and BOLD signal. We will measure performance on tests of relational memory, a form of hippocampus-dependent memory that is impaired in schizophrenia. We will follow patients for 2 years and measure the change of hippocampal volume in psychotic disorders. We predict that hippocampal activity is abnormal already at the onset of the illness and does not change significantly over the course of the illness. As a consequence of abnormal activity, memory function is already moderately impaired at illness onset. Over the course of the first 2 years of illness, the abnormally increased activity of the hippocampus leads to structural changes in the hippocampus. This structural change is associated with a further progression of memory deficits. To test our hypotheses, we will develop two types of high-resolution hippocampal maps. First, anatomical maps will distinguish the volume of four sectors and two regions throughout the entire anterior-posterior extent of the hippocampus. Using this high-resolution parcellation of the hippocampus, we will test the hypothesis that the anterior sector CA1 is primarily affected in psychotic disorder patients. Second, functional maps will assess CBV and BOLD signal in the four sectors and two regions of the hippocampus. With these maps we will test the hypothesis of decreased hippocampal inhibition in psychotic disorders. We will correlate the measures of hippocampal structure and activity with the performance on tests of relational memory, a form of hippocampus- dependent memory that is impaired in schizophrenia. The proposed longitudinal study design will allow us to study the timing of hippocampal dysfunction in psychotic disorders. The goal of this research project is the identification of hippocampal markers for the early diagnosis of psychotic disorders.