Novel in vivo synaptic imaging in experienced meditators

经验丰富的冥想者体内的新型突触成像

• 批准号: 10470833
• 负责人: DAVID A MATUSKEY
• 金额: $ 20.94万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-17 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10470833
• 关键词: Adult; Advertisements; Amygdaloid structure; Anatomy; Animal Model; Anisotropy; Area; Attention; Awareness; Behavioral; Binding; Biological; Biological Markers; Blood Vessels; Blood capillaries; Blood flow; Brain; Brain region; Brain scan; Breathing; Cardiovascular system; Clinical; Communities; Data; Development; Disease; Effectiveness; Electrocardiogram; Eligibility Determination; Exclusion Criteria; Frequencies; Functional Magnetic Resonance Imaging; Future; Glycoproteins; Hour; Image; Insula of Reil; Investigation; Laboratory Study; Lead; Link; Literature; Magnetic Resonance Imaging; Measurement; Measures; Medical; Meditation; Membrane Proteins; Mental disorders; Methods; Molecular; Morphologic artifacts; Motion; Neuroglia; Neurons; Neuropil; Outcome; Pattern; Persons; Population; Positron-Emission Tomography; Prefrontal Cortex; Proteins; Psychiatric therapeutic procedure; Research; Research Project Grants; Resolution; Rest; Solid; Stress and Coping; Structure; Synapses; Synaptic Vesicles; Techniques; Testing; Thick; Time; Tracer; Validation; Vesicle; Work; base; cingulate cortex; cognitive function; comparative; density; experience; functional MRI scan; gray matter; imaging approach; imaging study; in vivo; interest; mindfulness; mindfulness meditation; molecular imaging; morphometry; neuroimaging; neuromechanism; novel; radioligand; recruit; superior frontal sulcus; virtual

Project Abstract/Summary Despite research been potential benefits of mindfulness meditation to various clinical disorders and an increase in interest in in recent years, the basic mechanisms of meditation are stil l not fully known. Synaptic changes have proposed as a plausible hypothesis for the potential benefits of meditationas synapses are important for behavioral and cognitive functioning. The proposed research project applies novel molecular neuroimaging methods to directly investigate synapses in experienced meditators (EM) by using positron emission tomography (PET) imaging with our newly developed synaptic density tracer, 11C-UCB-J. This tracer binds to the synaptic vesicle glycoprotein 2A or SV2A, an essential vesicle membrane protein expressed in virtually all synapses. This proposal examines, for the first time, whether synaptic density differences occurs in EM in vivo. The study will perform a detailed comparison between 20 EM subjects and 20 control subjects over 2 years. Our primary objective is to characterize the distribution of 11C-UCB-J in brain areas implicated in experienced meditators compared to non-meditative controls (Aim 1). We hypothesize that there will be a magnitude and regional pattern of higher synaptic density in EM subjects involving brain areas including the including the insula, amygdala, posterior cingulate cortex, middle and superior frontal sulci and the prefrontal cortex. We will also examine if potential differences in synaptic density relates to structural and functional MRI data as determined by voxel based morphometry and resting-state functional connectivity in the primary regions-of- interest in the brain. EM subjects will be recruited from current and past research projects of the Co-I and consultant as well as local word of mouth and advertisements to the meditation communities. Inclusion/exclusion criteria will be the same for both groups and will include medical and psychiatric examination (including ECG and laboratory studies) to determine study eligibility. Subjects eligible to participate will receive an anatomical MRI for co- registration (and partial volume corrections) and a High Resolution Research Tomography (HRRT) PET scan with the radiotracer11C-UCB-J. This project will further our understanding by allowing, for the first time, in-vivo estimation of synaptic density of experienced meditators. This is an important development in meditation research for several reasons. It will be the first study to directly examine a plausible mechanism of meditation's effects, synaptic differences in associated brain regions, which needs to be established. Secondly, the current results will be compared to structural and functional MRIs, testing whether there is molecular evidence of synaptic differences as a solid underpinning of other imaging work. Lastly, the ability to assess synaptic density in vivo would be of high utility in future studies using meditative techniques that are focused on clinical populations.

项目摘要/总结 尽管 研究 到过 正念冥想对各种临床疾病的潜在好处以及增加对这些疾病的兴趣 近年来，冥想的基本机制仍不完全清楚。突触变化有 提出了冥想潜在益处的合理假设，因为突触对于冥想很重要 行为和认知功能。拟议的研究项目应用新型分子神经影像学 使用正电子发射直接研究经验丰富的冥想者（EM）突触的方法 使用我们新开发的突触密度示踪剂 11C-UCB-J 进行断层扫描 (PET) 成像。该示踪剂绑定到 突触小泡糖蛋白 2A 或 SV2A，一种基本的小泡膜蛋白，几乎在所有细胞中表达 突触。该提案首次研究了体内 EM 中是否存在突触密度差异。 该研究将对 20 名 EM 受试者和 20 名对照受试者进行为期 2 年的详细比较。 我们的主要目标是表征 11C-UCB-J 在与经验丰富的人有关的大脑区域中的分布。 冥想者与非冥想对照组的比较（目标 1）。我们假设将会有一个规模和 EM 受试者中较高突触密度的区域模式涉及大脑区域，包括 岛叶、杏仁核、后扣带皮层、中、上额沟和前额叶皮层。我们将 还检查突触密度的潜在差异是否与结构和功能 MRI 数据相关 由基于体素的形态测量和主要区域的静息态功能连接确定 对大脑的兴趣。 EM 受试者将从 Co-I 和顾问以及过去的研究项目中招募 当地的口碑和冥想社区的广告。纳入/排除标准将是 两组的情况相同，包括医学和精神检查（包括心电图和实验室检查） 研究）以确定研究资格。有资格参加的受试者将接受解剖 MRI 检查 配准（和部分体积校正）和高分辨率研究性断层扫描 (HRRT) PET 扫描 使用放射性示踪剂 11C-UCB-J。 该项目将首次允许体内估计突触密度，从而进一步加深我们的理解。 经验丰富的冥想者。出于多种原因，这是冥想研究的重要进展。这将是 第一项直接检验冥想效果的合理机制的研究，即突触差异 相关的大脑区域，需要建立。其次，将当前结果与 结构和功能 MRI，测试是否存在突触差异的分子证据 为其他影像工作奠定基础。最后，评估体内突触密度的能力将具有很高的实用性 在未来的研究中使用专注于临床人群的冥想技术。