慢性海洛因成瘾者的冲动性和行为抑制缺陷脑机制

PSYCH OpenIR > 中国科学院心理研究所回溯数据库(1956-2010)

	慢性海洛因成瘾者的冲动性和行为抑制缺陷脑机制
其他题名	The brain mechanism of the impulsivity and behavior inhibition deficits in chronic heroin addicts
	袁艺
	2008-05-30
摘要	近年来提出，抑制功能损伤是药物成瘾的一个重要原因，其中反应抑制缺陷是和冲动性的觅药行为紧密相关的，也是造成药物成瘾抑制缺陷的基础，但目前并没有充分的实验证据确定药物成瘾与行为抑制功能缺陷之间的关系，对相关神经基础研究的实验结果很不一致，而针对纯海洛因吸毒者的行为抑制脑成像研究报道极少。目前用来研究反应抑制缺陷的实验范式中，stop-signal范式是和冲动性的觅药行为最接近的，最能体现这一特征下的反应抑制能力，但是研究的最不清楚。因此我们采用stop-signal实验范式为主，对100多名慢性海洛因依赖者进行了较为系统的行为学和/或脑成像测量。行为学研究显示：(1)慢性海洛因成瘾者的简单反应时间长于控制组被试，对运动信号的反应时间似乎不受停止信号的影响；(2)在完成任务的策略上，海洛因依赖者倾向于更少的等待效应、更强的冲动性，同时对错误反应的监控和随时调整能力下降；(3)海洛因依赖组的停止信号反应时(SSRT)值显著长于控制组被试。这些结果确认了海洛因依赖者的行为抑制能力受损。进一步相关分析表明，海洛因依赖者的SSRT与其成瘾严重性指数(ASI)的四个分项指标呈正相关，其中和药物使用情况的相关最强，说明成瘾药物的使用可能是造成海洛因依赖者抑制功能损害的主要原因。 fMRI结果显示：(1)成瘾组和控制组在M1、SMA后部等运动执行区都没有显著差异；(2)但在要求对行为进行控制时，成瘾组在右侧背外侧前额叶、右侧腹侧前额叶、扣带回前部等脑区的激活强度都显著弱于控制组被试，而在双侧纹状体和杏仁核，成瘾组的激活强于控制组(显著或边缘显著)。右侧前额叶被认为是执行抑制功能的主要脑区，扣带回和错误监控等能力密切相关，而杏仁核一直被视为是冲动性、情绪控制的关键结构。这些脑区构成冲动与控制的神经环路，海洛因依赖者抑制功能损伤可能与这个环路的活动异常有关。脑结构测量显示，长期用药导致海洛因依赖患者前额叶广泛区域(包括双侧背外侧前额叶、额叶眶部、腹内侧额叶)和扣带回灰质密度下降，并且这种灰质密度下降随着患者药物依赖程度的加重而加剧。总之，本研究结果不但确认了纯海洛因依赖者抑制能力受损，而且证明其神经基础为冲动相关脑区活动增强和参与认知控制脑区活动减弱，而药物导致前额叶结构损伤可能是根本原因。
其他摘要	In recent years, the deficit of inhibition has become an important reason for explaining addiction. Response inhibition resembles the compulsive drug seeking behavior and it is the basement of addiction inhibition deficits. However, there were no enough evidence for the relationship between addiction and response inhibition deficits and the results of the neuro mechanisms studies remains unclear. Few studies has focused on the exploring the heroin users. Among those paradigms for study response inhibition deficits, stop signal is a very suitable model for the representation of compulsive drug seeking, but only a few researches has worked on this paradigm. In this study, we selected about 100 heroin abusers and had behaviour and neuro imaging scannings for investigating the response inhibition deficits. The behaviour researches found: first, the chronic heroin users had longer reaction time than control group and this reaction time were not affected by stop signals in heroin users. Second, heroin users had less waiting time than control group and they were more impulsive but less flexibility. Their erro monitoring and flexibale adjustment ability decreased. Third, the SSRT of heroin users was significantly longer than control group. These results suggested that the inhibition of heroin users were impaired. Further investigation showed that the SSRT of heroin users had positive correlation of four factor scores of ASI and the macro correlation coefficient was factor three of drug use. This correlation suggested that drug use was the main reason of inhibition deficits. fMRI results mainly focused on the ANOVA analysis for group difference. First, there was no intensity difference in M1 and SMA brain areas between the two groups. Second, heroin users had less activation in right dorsalateral prefrontal cortex, right inferior prefrontal cortex and anterior cingulated cortex, while in bilateral striatum and amygdala, heroin users had more activation than control group. The right prefrontal cortex was indentified as the main inhibition brain area. The anterior cingulated cortex has relationship with erro monitoring and amygdale was an important brain area for impulsivity and emotion control. The network of these brain areas was envovled in impulsivity and inhibition and it was suggested the mainly damaged network for heroin users’ disinhibition. We also investigated the gray matter changes of heroin users and found that chonic heroin use made their gray matter density decreased in prefrontal cortex (including bilateral dorsalateral prefrontal cortex, obital frontal cortex, inferior prefrontal cortex) and anterior cingulated cortex. The gray matter density in these brain regions had negative correlation with drug use duration. In conclusion, we indentified the disinhibition of heroin users and its neuro mechanism. Their compulsivity brain areas had more activation than control group and their inhibition brain areas had less activation than normal control. On the other side, the biological mechanism of this activation changes was the gray matter density decrease in these brain areas.
关键词	海洛因成瘾抑制冲动停止信号前额叶
学位类型	博士
语种	中文
学位授予单位	中国科学院心理研究所
学位授予地点	心理研究所
文献类型	学位论文
条目标识符	http://ir.psych.ac.cn/handle/311026/4650
专题	中国科学院心理研究所回溯数据库(1956-2010)
推荐引用方式 GB/T 7714	袁艺. 慢性海洛因成瘾者的冲动性和行为抑制缺陷脑机制[D]. 心理研究所. 中国科学院心理研究所,2008.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
10001_20051801250302（2215KB）			开放获取	--	浏览请求全文