Functional MR of the Effects of D-Serine

D-丝氨酸作用的功能 MR

• 批准号: 8074009
• 负责人: JOSEPH T. COYLE
• 金额: $ 24.85万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8074009
• 关键词: Agonist; Brain; Clinical Trials; Collaborations; Data; Enrollment; Face; Functional Magnetic Resonance Imaging; Glycine; Grant; Hippocampus (Brain); Image; Learning; Magnetic Resonance Spectroscopy; Measurement; Measures; Mediating; Memory; Methods; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; N-acetylaspartate; N-acetylaspartylglutamate; Neurobehavioral Manifestations; Occipital lobe; Patients; Performance; Protocols documentation; Protons; Relative (related person); Reporting; Resolution; Schizophrenia; Serine; Signal Transduction; Site; Spectrum Analysis; Task Performances; Temporal Lobe; Testing; Water; Work; analog; blood oxygenation level dependent response; improved; in vivo; placebo controlled study; relational memory; virtual; way finding

This project will test the hypothesis that schizophrenia is associated with NMDA hypofunction by examining in-vivo brain data acquired through the combined use of proton magnetic resonance spectroscopy (MRS) and BOLD functional magnetic resonance imaging (fMRI). We propose to measure proton metabolite concentrations, including N-acetyl-aspartate (NAA) and N-acetyl-aspartyl-glutamate (NAAG), in temporal and prefrontal cortical regions in schizophrenic patients and healthy controls. MRS data will be acquired on a 4T scanner with newly developed methods that provide improved resolution of peaks and signal components within the proton spectrum, thus improving interpretability of NAA measurements, as well as extending MRS capabilities to include quantification of NAAG. The quantification of these metabolites is relevant for the main hypothesis of the center grant as work from our group has reported reduced NAA in temporal cortex bilaterally. Further, NAAG has been implicated in NMDA hypofunction. At present in-vivo measurements of these metabolites, have not been concurrently characterized in schizophrenia. Moreover, it has been shown that NMDA receptors in the hippocampus are essential for spatial learning and that pharmacological blockade of NMDA receptors impairs spatial navigation. Therefore, as an exploratory endpoint, we propose to acquire fMRI data on a 3Tscanner during the completion of a virtual analogue of a spatial navigation task, the water maze, to assess spatial memory performance. We will also acquire fMRI data during a transitive inference task to assess relational memory, and during a facial recall challenge, tasks previously shown to be mediated by the hippocampus. Finally, in collaboration with Dr. Don Goff (Clinical Trials Section), we will enroll 60 schizophrenic patients into a placebo-controlled trial of D-serine, an agonist at the glycine site on the NMDA receptor. Patients will be imaged with the MRS/fMRI protocols described above to examine the effects of D-serine treatment on spatial and relational memory performance, BOLD activation and NAA and NAAG concentrations.

本项目将通过检查精神分裂症与NMDA功能低下相关的假设， 通过结合使用质子磁共振波谱（MRS）获得的体内脑数据 和BOLD功能性磁共振成像（fMRI）。我们建议测量质子代谢物 浓度，包括N-乙酰-天冬氨酸（NAA）和N-乙酰-天门冬氨酸-谷氨酸（NAAG），在时间和 精神分裂症患者和健康对照者的前额叶皮质区域。将在4 T上采集MRS数据 具有新开发方法的扫描仪，可提供峰和信号分量的改进分辨率 在质子谱内，从而提高NAA测量的可解释性，以及扩展MRS 能力包括NAAG的量化。这些代谢物的定量与主要代谢物相关。 中心补助金的假设，因为我们小组的工作报告了颞叶皮层中NAA的减少 双边。此外，NAAG与NMDA功能减退有关。目前， 这些代谢物尚未在精神分裂症中同时得到表征。此外，它已被证明 海马中的NMDA受体对于空间学习是必不可少的， NMDA受体的阻断损害空间导航。因此，作为探索性终点，我们建议 为了在完成空间导航任务的虚拟模拟期间在3 T扫描仪上获取fMRI数据， 水迷宫来评估空间记忆能力。我们还将在一个过渡期间获得fMRI数据， 推理任务，以评估关系记忆，并在面部回忆挑战，任务先前显示， 由海马体介导。最后，与Don Goff博士（临床试验科）合作，我们将 招募60名精神分裂症患者参加安慰剂对照试验D-丝氨酸，一种甘氨酸位点的激动剂， NMDA受体。患者将使用上述MRS/fMRI方案进行成像，以检查 D-丝氨酸处理对空间和关系记忆表现、BOLD激活和NAA的影响， NAAG浓度。