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.

该项目将通过检查精神分裂症与 NMDA 功能减退相关的假设来检验 通过结合使用质子磁共振波谱（MRS）获得的体内大脑数据 和 BOLD 功能磁共振成像 (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-乙酰天冬氨酰谷氨酸 (NAAG)，在时间和 精神分裂症患者和健康对照的前额皮质区域。 MRS数据将在4T上采集 采用新开发方法的扫描仪可提高峰值和信号分量的分辨率 在质子谱内，从而提高 NAA 测量的可解释性，并扩展 MRS 包括 NAAG 量化的能力。这些代谢物的定量与主要相关 中心资助的假设是我们小组的工作报告了颞叶皮质中 NAA 的减少 双边。此外，NAAG 与 NMDA 功能减退有关。目前体内测量 这些代谢物尚未在精神分裂症中同时得到表征。此外，还显示 海马体中的 NMDA 受体对于空间学习至关重要，并且药理学 NMDA 受体的阻断会损害空间导航。因此，作为探索性终点，我们建议 在完成空间导航任务的虚拟模拟过程中获取 3Tscanner 上的功能磁共振成像数据， 水迷宫，评估空间记忆表现。我们还将在传递过程中获取功能磁共振成像数据 评估关系记忆的推理任务，以及在面部回忆挑战期间，先前显示的任务 由海马体介导。最后，与 Don Goff 博士（临床试验部门）合作，我们将 招募 60 名精神分裂症患者参加 D-丝氨酸的安慰剂对照试验，D-丝氨酸是甘氨酸位点的激动剂 NMDA 受体。将使用上述 MRS/fMRI 方案对患者进行成像，以检查 D-丝氨酸治疗对空间和关系记忆表现、BOLD 激活和 NAA 的影响 NAAG 浓度。