Novel in vivo synaptic imaging in experienced meditators

项目摘要/摘要 尽管 研究 vbl.已 正念冥想对各种临床疾病的潜在好处以及对 近年来，关于冥想的基本机制尚不完全清楚。突触的变化 作为冥想潜在益处的可信假说提出，因为突触对 行为和认知功能。拟议的研究项目应用了新的分子神经成像技术。 方法用正电子发射技术直接研究有经验的冥想者(EM)的突触 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。这种示踪剂与 突触囊泡糖蛋白2A或SV2A是一种基本的囊泡膜蛋白，在几乎所有的 突触。这项提议首次研究了在活体内EM是否存在突触密度差异。 这项研究将对20名EM受试者和20名对照受试者进行为期两年的详细比较。 我们的主要目标是确定11C-UCB-J在经验者脑区的分布特征 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震级和 EM受试者中突触密度较高的区域模式涉及脑区，包括 脑岛、杏仁核、后扣带回、额中上沟和前额叶皮质。我们会 还要检查突触密度的潜在差异是否与结构和功能MRI数据有关，如 由基于体素的形态测量和主要脑区的静息状态功能连接性确定 对大脑的兴趣。 EM科目将从合作伙伴和顾问目前和过去的研究项目中招聘，以及 当地的口口相传和向冥想社区的广告。纳入/排除标准将是 两组相同，将包括体检和精神检查(包括心电图和实验室 研究)，以确定研究资格。有资格参与的受试者将接受解剖磁共振成像，以进行联合 配准(和部分体积校正)和高分辨率研究断层扫描(HRRT)PET扫描 放射性示踪剂11C-UCB-J。 这个项目将通过第一次允许在活体内估计突触密度来进一步加深我们的理解。 经验丰富的冥想者。这是冥想研究中的一项重要进展，原因有几个。会是 第一项直接检查冥想效果的可信机制的研究，突触差异 相关的大脑区域，这需要建立。其次，目前的结果将与 结构和功能磁共振成像，测试是否有突触差异的分子证据作为固体 其他成像工作的基础。最后，评估体内突触密度的能力将是非常有用的。 在未来的研究中，使用专注于临床人群的冥想技术。

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.