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: 8931645
• 负责人: Dimitrios Kapogiannis
• 金额: $ 18.77万
• 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/8931645
• 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; Cognition; Cognitive; Collaborations; Data; Data Set; Databases; Disease; Disease Progression; Enrollment; Etiology; Financial compensation; Food; Functional Magnetic Resonance Imaging; Future; Generations; Genetic Crossing Over; Glucose; Glutamates; Glutamine; Glycine; Goals; Hippocampus (Brain); Hypothalamic structure; Image; Individual; Insula of Reil; Insulin; Insulin Resistance; Investigation; Journals; Knowledge; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Manuscripts; Measurement; Measures; Medial; Mentors; Metabolic; Metabolic Control; Metabolism; Methodology; Metric; Mind; Nerve Degeneration; Neurology; Neurotransmitters; Obesity; Participant; Pathogenesis; Pathway interactions; Patients; Pattern; Performance; Peripheral; Placebo Control; Play; Positron-Emission Tomography; Postdoctoral Fellow; Prefrontal Cortex; Process; Psychiatry; Publishing; Randomized; Religious Belief; Reporting; Research; Rest; Role; Staging; Structure; Techniques; Temporal Lobe; Ventral Tegmental Area; age group; aging brain; brain metabolism; brain volume; data reduction; disease diagnosis; exenatide; frontal lobe; gamma-Aminobutyric Acid; glucose metabolism; independent component analysis; insulin secretion; interest; memory encoding; memory retrieval; mild cognitive impairment; neurochemistry; neuroimaging; neurotransmission; novel; response; sex; systematic review; theories; trait; uptake; visual stimulus

Volumetric measures obtained with analysis of high-definition 3D structural MRI images capture neuroanatomical variability which may be associated with long-standing traits or may help explain why certain brain areas or individuals are vulnerable to neurodegenerative processes. This last year, I applied a data reduction technique called group-level independent component analysis (ICA) to structural MRI images to uncover patterns of structural covariance (Independent Components). We applied ICA to MRI data collected in the ADNI study and examined how they can discriminate between participants with normal cognition, mild cognitive impairment (MCI) and Alzheimer's disease (AD). We showed that ICs can be useful as classifiers and predictors of future AD diagnosis or conversion to AD from MCI (the manuscript is currently in press in "Psychiatry Research: Neuroimaging"). In addition, given the association between insulin resistance and Alzheimer's disease, we examined how volumetric and FDG-PET uptake measures for several key regions of interest for AD relate to peripheral insulin resistance. We found that insulin resistance promotes two abnormal and pathogenic compensations: it increases glucose metabolism in the hippocampus and medial temporal lobe at the stage of mild cognitive impairment and increases glucose metabolism in default mode network nodes at the stage of AD. Prior fMRI studies suggest that these compensatory increases in metabolism are associated with disease progression; therefore, insulin resistance seems to promote a maladaptive compensation. The manuscript is currently under review in the journal "Neurology". Together with a post-doctoral fellow I mentor, Dr. Auriel Willette, we conducted a systematic review of neuroimaging studies looking at associations of obesity and brain volume across the age-span. We found that increased obesity is associated with atrophy mainly in the frontal lobes. Our review was published by the journal "Aging Research Reviews". I conducted an fMRI study using a novel methodology for effective connectivity analysis to fMRI data based on the principles of Granger causality. This methodology allows us to uncover causal pathways between nodes of a brain network. I implemented this analysis in a dataset from a fMRI study on religious beliefs conducted in 2009. The findings support the theory that areas implicated in Theory of Mind are key to generation of religious beliefs. The study was published in the journal "Brain Connectivity". Finally, 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.

通过分析高清晰度3D结构MRI图像获得的体积测量值捕获了神经解剖学的变异性，这些变异性可能与长期存在的特征有关，或者可能有助于解释为什么某些大脑区域或个体容易受到神经退行性过程的影响。去年，我将一种称为组级独立分量分析（伊卡）的数据简化技术应用于结构性MRI图像，以揭示结构协方差（独立分量）的模式。我们将伊卡应用于ADNI研究中收集的MRI数据，并研究它们如何区分认知正常，轻度认知障碍（MCI）和阿尔茨海默病（AD）的参与者。我们表明，IC可以作为分类器和预测未来AD诊断或从MCI转换为AD（手稿目前正在出版的“精神病学研究：神经影像学”）。 此外，考虑到胰岛素抵抗和阿尔茨海默病之间的关联，我们研究了AD几个关键感兴趣区域的体积和FDG-PET摄取测量与外周胰岛素抵抗的关系。我们发现，胰岛素抵抗促进两种异常的和致病性的补偿：它增加在轻度认知障碍阶段的海马和内侧颞叶的葡萄糖代谢，并增加在AD阶段的默认模式网络节点的葡萄糖代谢。先前的fMRI研究表明，这些代谢的代偿性增加与疾病进展有关;因此，胰岛素抵抗似乎促进了适应不良的补偿。该手稿目前正在《神经病学》杂志上进行审查。 我们与我的博士后导师Auriel Willette博士一起，对神经影像学研究进行了系统的回顾，研究了肥胖与脑容量在不同年龄段的关系。我们发现肥胖的增加与额叶萎缩有关。我们的综述发表在《衰老研究综述》杂志上。 我进行了一项功能磁共振成像研究，使用一种新的方法，有效的连接分析功能磁共振成像数据的基础上的原则，格兰杰因果关系。这种方法使我们能够揭示大脑网络节点之间的因果路径。我在2009年进行的一项关于宗教信仰的fMRI研究的数据集中实现了这一分析。这些发现支持了心理理论中涉及的区域是产生宗教信仰的关键的理论。这项研究发表在《Brain Connectivity》杂志上。 最后，我们与Chia博士和埃根博士合作完成了“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CB 1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CB 1受体的影响，第二个是评估CB 1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CB 1受体，我们旨在证明CB 1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CB 1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CB 1调制的各种大脑网络的功能连接。最后，我们进行了MRS评估CB 1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。