Brain structure, chemistry and function investigations in aging using MRI/MRS

使用 MRI/MRS 研究衰老过程中的脑结构、化学和功能

• 批准号: 9549398
• 负责人: Dimitrios Kapogiannis
• 金额: $ 42.34万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9549398
• 关键词: Affective; Age; Aging; Agonist; Alzheimer' s Disease; Amyloid deposition; Anterior; Area; Atrophic; Biological Markers; Brain; CNR1 gene; Caloric Restriction; Cephalic; Chemistry; Clinical Research; Cognitive; Collaborations; Data; Desire for food; Disease; Enrollment; Food; Functional Magnetic Resonance Imaging; Glucose; Glutamates; Glutamine; Glycine; Goals; Hypothalamic structure; Individual; Insula of Reil; Insulin; Investigation; Knowledge; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Metabolic; Metabolic Control; Metabolism; Methodology; Neurotransmitters; Pathogenesis; Patients; Peripheral; Placebo Control; Play; Positron-Emission Tomography; Prefrontal Cortex; Process; Publishing; Randomized; Reporting; Research; Rest; Role; Structure; Ventral Tegmental Area; age group; aging brain; brain metabolism; cognitive performance; exenatide; fluorodeoxyglucose positron emission tomography; gamma-Aminobutyric Acid; insulin secretion; memory encoding; memory retrieval; neurochemistry; neuroimaging; neuroimaging marker; neurotransmission; novel; response; sex; visual stimulus

In collaboration with Drs. Chia and Egan, we completed the "RISE study", a multi-faceted randomized placebo-controlled cross-over clinical study of the effects of a CB1 receptor agonist and antagonist on peripheral metabolism, brain function and brain metabolic control. The study included a robust neuroimaging component including fMRI and MRS. We performed two activation-paradigm fMRI studies, one to discover brain correlates of cephalic insulin secretion and the effects of CB1 receptors, the second to assess the effects of CB1 receptors on food appetitiveness. The goal of the first study was to demonstrate a rise in insulin levels in response to food visual stimuli (cephalic insulin response) as a result of activation of certain brain areas (insula, anterior cingulate, hypothalamus, ventral tegmental area, etc). Moreover, given the presence of CB1 receptors in the candidate areas, we aimed to demonstrate a difference in their level of activation with CB1 agonists and antagonists. The goal of the second study was to demonstrate dissociable effects of CB1 receptor stimulation on food value (food choices) and salience (intensity of such choices). In addition, we performed a resting fMRI study to assess CB1 modulation of functional connectivity of the various brain networks. Finally, we performed MRS to assess CB1 modulation of brain metabolism (glucose, lactate) and neurotransmission (glutamate, GABA, glycine). We are currently in the process of analyzing and interpreting the data from these studies.

我们与Drs. Chia和埃根合作完成了“RISE研究”，这是一项多方面的随机、安慰剂对照、交叉临床研究，研究了CB1受体激动剂和拮抗剂对外周代谢、脑功能和脑代谢控制的影响。这项研究包括一个强大的神经影像学组件，包括功能磁共振成像和磁共振成像。我们进行了两个激活范式功能磁共振成像研究，一个是发现大脑相关的头部胰岛素分泌和CB1受体的影响，第二个是评估CB1受体对食物食欲的影响。第一项研究的目的是证明胰岛素水平响应食物视觉刺激（头部胰岛素反应）的升高，这是由于某些脑区（小脑、前扣带回、下丘脑、腹侧被盖区等）的激活。此外，鉴于候选区域中存在CB1受体，我们旨在证明CB1激动剂和拮抗剂的激活水平存在差异。第二项研究的目的是证明CB1受体刺激对食物价值（食物选择）和显着性（这种选择的强度）的可分离影响。此外，我们进行了静息功能磁共振成像研究，以评估CB1调制的各种大脑网络的功能连接。最后，我们进行了MRS评估CB1对脑代谢（葡萄糖，乳酸）和神经传递（谷氨酸，GABA，甘氨酸）的调节。我们目前正在分析和解释这些研究的数据。