Novel in vivo synaptic imaging in experienced meditators

项目摘要/摘要 尽管 研究 被 正念冥想对各种临床疾病的潜在益处，以及对 近年来，人们对冥想的基本机制仍不完全了解。突触的变化 提出了一个合理的假设，认为冥想的潜在好处是因为突触对于 行为和认知功能。拟议的研究项目应用新的分子神经成像 使用正电子发射直接研究经验冥想者（EM）突触的方法 使用我们新开发的突触密度示踪剂11 C-UCB-J进行断层扫描（PET）成像。 突触囊泡糖蛋白2A或SV 2A，一种基本的囊泡膜蛋白，在几乎所有的细胞中表达， 突触这项建议检查，第一次，是否突触密度差异发生在EM在体内。 本研究将在2年内对20例EM受试者和20例对照受试者进行详细比较。 我们的主要目的是描述11 C-UCB-J在与经历过的脑损伤有关的脑区的分布特征。 冥想者与非冥想对照组（目标1）。我们假设会有一个量级， EM受试者中涉及脑区的较高突触密度的区域模式，包括 杏仁核、后扣带皮层、额中沟和上级沟以及前额叶皮层。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， 通过基于体素的形态测量和主要区域中的静息状态功能连接来确定， 对大脑的兴趣。 研究对象将从首席研究员和顾问目前和过去的研究项目中招募， 当地的口碑和广告到冥想社区。入选/排除标准为 两组相同，将包括医学和精神病学检查（包括ECG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（和部分容积校正）和高分辨率研究断层扫描（HRRT）PET扫描 放射性示踪剂11 C-UCB-J 该项目将通过首次允许在体内估计突触密度来加深我们的理解。 经验丰富的冥想者这是冥想研究的一个重要进展，原因有几个。将 这是第一项直接研究冥想效果的合理机制的研究， 相关的大脑区域，这需要建立。其次，将目前的结果与 结构和功能MRI，测试是否有突触差异的分子证据作为一个坚实的 支持其他成像工作。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冥想技术，重点是临床人群。

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.