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功能障碍相关的假设 通过质子磁共振光谱（MRS）共同使用获得的体内脑数据 和大胆的功能磁共振成像（fMRI）。我们建议测量质子代谢物 在时间和 精神分裂症患者和健康对照的前额叶皮质区域。 MRS数据将在4T上获取 扫描仪具有新开发的方法，可改善峰值和信号成分的分辨率 在质子光谱中，从而提高了NAA测量的可解释性，并扩展了MRS 包括NAAG定量的功能。这些代谢物的定量与主要 作为我们小组的工作，中心授予的假设报告了颞皮质中的NAA 双侧。此外，NAAG已与NMDA功能障碍有关。目前的体内测量 这些代谢物在精神分裂症中尚未同时表征。而且，它已显示 海马中的NMDA受体对于空间学习至关重要，并且药理 NMDA受体的封锁会损害空间导航。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类似过程中，以获取3TSCANNER的fMRI数据， 水迷宫，以评估空间记忆性能。我们还将在及时及时获得fMRI数据 评估关系记忆的推理任务，以及在面部召回挑战期间，先前显示的任务 由海马介导。最后，与Don Goff博士合作（临床试验部分），我们将 将60名精神分裂症患者招募参加D-Serine的安慰剂对照试验，D-Serine是甘氨酸部位的激动剂 NMDA受体。将使用上述MRS/FMRI方案对患者进行成像，以检查 D-丝氨酸处理对空间和关系记忆性能，大胆激活和NAA的影响 NAAG浓度。