单胺类受体PET显像在恐怖情绪中的临床应用研究
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摘要
恐怖音乐可以快速引起听者类似真实的威胁生命经历的情绪变化,程度严重的可产生类似创伤后应激障碍的症状,然而通过音乐研究相关情绪变化发生机制的报道非常有限,目前的研究证据主要局限于脑区结构或单一神经物质的作用,这些神经化学物质之间及其在各相关脑区的相互作用机制尚未完全清楚,发生发展的最后神经通路尚未明确,其主要原因之一是由于无法在活体状态下直接观察相关关键神经传递信息在脑内的时空动态变化过程。本研究选择与单胺类受体有稳固结合力的显像剂11C-甲基哌啶螺环酮(11C-N-methylspiperone,11C-NMSP)在活体内无创地进行正电子发射断层扫描技术(Positron Emission Tomography, PET)显像,观察志愿者在恐怖状态下的大脑内多巴胺D2受体和5-羟色胺2A受体的变化情况,进一步从受体水平研究恐怖状态导致的脑功能改变的的机制。
第一部分：单胺类神经受体PET显像剂及模板建立
为了客观统计分析神经受体PET显像的结果,我们采用国际上通用的脑功能影像分析软件统计参数图(Statistical Parametric Mapping, SPM)来进行图像处理。由于SPM软件分析PET图像数据时需要相应显像剂的特定模板,现有的是脑血流灌注和葡萄糖代谢的模板,所以我们首先选择20名性别和年龄匹配的志愿者进行1小时的脑动态PET扫描,用ROI技术对特异性脑区和非特异性脑区放射性计数的比值,根据比值结果选取最佳显像时间。根据我们的比值曲线结果,图像在30分钟到40分钟采集的比值最理想。用此时间的20个11C-NMSP图像在SPM软件进行平均化得到单胺类受体的分析模板。
第二部分：恐惧音乐引起脑内单胺类受体变化：PET临床研究结果
通过11C-NMSP单胺类受体显像剂PET脑图像观察脑内单胺类受体在恐怖音乐刺激下的改变情况,用SPM软件进行统计分析其特异性受体活性增高和降低的脑区。10名年龄匹配的正常男性志愿者纳入此项研究,分别在听恐怖音乐前后进行11C-NMSP单胺类受体PET显像,同时我们记录下来听音乐同时志愿者的心理生理改变情况。研究结果发现志愿者在听音乐和基础状态相比,11C-NMSP在双侧尾状核、右侧边缘和旁边缘脑区,尤其在右侧前扣带回皮质明显减低；同时11C-NMSP在右侧额叶、枕叶、左侧颞叶明显增加。
我们的研究结果表明恐怖音乐引起的短暂的恐怖情绪可以引发脑内单胺类受体的迅速改变。这个研究结果从多巴胺和5-羟色胺受体分子水平帮助我们明确大脑恐怖的机制。
Frightening music can rapidly arouse emotions in listeners that mimic those from real life-threatening experiences. However, the study on the underlying mechanism for perceiving danger created by music is very limited. Present studies are mainly limited to the structures of brain regions or the simple neurochemical material. The mechanism of related brain regions and the relation of these neurochemical materials are still unknown, and one of the principal reasons is we cannot directly observe the changes of neurochemical messages in the living body. So we select the strong bond monoamine receptor imaging agent (11C-NMSP) to perform Positron Emission Tomography (PET) imaging. Then we can understand the pathological mechanism of PTSD (post trauma stress disorder) from the receptor molecular level through observing the changes of brain receptor of dopamine D2and5-HT2A in the volunteers under fear condition.
Part1:Monoamine Receptor PET Imaging Agent and Construction of its Template
We selected SPM (Statistical Parametric Mapping) software to analyze the monoamine receptor changes in volunteers. The present templates are only brain blood flow and glucose metabolism, so we have to construct the receptor imaging agent first.20age-matched male volunteers accepted the dynamic PET imaging of one hour. We chose the best imaging time of30min to40min after intravenous injection of agent after compare the ratio of specific region and nonspecific region. Then we acquire the11C-NMSP imaging template from realigning the20images at best time.
Part2:Frightening Music Triggers Rapid Changes in Brain Monoamine Receptors:A Pilot PET Study
We investigated monoamine receptor changes induced by frightening music using the11C-NMSP positron emission tomography (PET) study. Ten male, healthy volunteers were included, and their psychophysiological changes were evaluated. The radioactive accumulations of11C-NMSP were significantly decreased in the bilateral caudate, right limbic and paralimbic regions, especially in the right anterior cingulated cortex, but were increased in the cerebral cortex involving right frontal, occipital lobe and left temporal lobe when subjects had listened to frightening music, compared to a baseline condition.
Conclusion:Our results indicate that transient fear emotion in response to frightening music can trigger rapid change monoamine receptors. These findings help to understand the mechanism of brain response to fear emotion.
第一部分：单胺类神经受体PET显像剂及模板建立
为了客观统计分析神经受体PET显像的结果,我们采用国际上通用的脑功能影像分析软件统计参数图(Statistical Parametric Mapping, SPM)来进行图像处理。由于SPM软件分析PET图像数据时需要相应显像剂的特定模板,现有的是脑血流灌注和葡萄糖代谢的模板,所以我们首先选择20名性别和年龄匹配的志愿者进行1小时的脑动态PET扫描,用ROI技术对特异性脑区和非特异性脑区放射性计数的比值,根据比值结果选取最佳显像时间。根据我们的比值曲线结果,图像在30分钟到40分钟采集的比值最理想。用此时间的20个11C-NMSP图像在SPM软件进行平均化得到单胺类受体的分析模板。
第二部分：恐惧音乐引起脑内单胺类受体变化：PET临床研究结果
通过11C-NMSP单胺类受体显像剂PET脑图像观察脑内单胺类受体在恐怖音乐刺激下的改变情况,用SPM软件进行统计分析其特异性受体活性增高和降低的脑区。10名年龄匹配的正常男性志愿者纳入此项研究,分别在听恐怖音乐前后进行11C-NMSP单胺类受体PET显像,同时我们记录下来听音乐同时志愿者的心理生理改变情况。研究结果发现志愿者在听音乐和基础状态相比,11C-NMSP在双侧尾状核、右侧边缘和旁边缘脑区,尤其在右侧前扣带回皮质明显减低；同时11C-NMSP在右侧额叶、枕叶、左侧颞叶明显增加。
我们的研究结果表明恐怖音乐引起的短暂的恐怖情绪可以引发脑内单胺类受体的迅速改变。这个研究结果从多巴胺和5-羟色胺受体分子水平帮助我们明确大脑恐怖的机制。
Frightening music can rapidly arouse emotions in listeners that mimic those from real life-threatening experiences. However, the study on the underlying mechanism for perceiving danger created by music is very limited. Present studies are mainly limited to the structures of brain regions or the simple neurochemical material. The mechanism of related brain regions and the relation of these neurochemical materials are still unknown, and one of the principal reasons is we cannot directly observe the changes of neurochemical messages in the living body. So we select the strong bond monoamine receptor imaging agent (11C-NMSP) to perform Positron Emission Tomography (PET) imaging. Then we can understand the pathological mechanism of PTSD (post trauma stress disorder) from the receptor molecular level through observing the changes of brain receptor of dopamine D2and5-HT2A in the volunteers under fear condition.
Part1:Monoamine Receptor PET Imaging Agent and Construction of its Template
We selected SPM (Statistical Parametric Mapping) software to analyze the monoamine receptor changes in volunteers. The present templates are only brain blood flow and glucose metabolism, so we have to construct the receptor imaging agent first.20age-matched male volunteers accepted the dynamic PET imaging of one hour. We chose the best imaging time of30min to40min after intravenous injection of agent after compare the ratio of specific region and nonspecific region. Then we acquire the11C-NMSP imaging template from realigning the20images at best time.
Part2:Frightening Music Triggers Rapid Changes in Brain Monoamine Receptors:A Pilot PET Study
We investigated monoamine receptor changes induced by frightening music using the11C-NMSP positron emission tomography (PET) study. Ten male, healthy volunteers were included, and their psychophysiological changes were evaluated. The radioactive accumulations of11C-NMSP were significantly decreased in the bilateral caudate, right limbic and paralimbic regions, especially in the right anterior cingulated cortex, but were increased in the cerebral cortex involving right frontal, occipital lobe and left temporal lobe when subjects had listened to frightening music, compared to a baseline condition.
Conclusion:Our results indicate that transient fear emotion in response to frightening music can trigger rapid change monoamine receptors. These findings help to understand the mechanism of brain response to fear emotion.
引文
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