感知觉-运动系统在药物相关线索反应中的作用及神经机制

药物相关线索反应是成瘾行为的重要标志,它直接导致心理渴求和强迫性的刺激-反应式自动化用药行为。其神经机制是包含了经典和操作条件反射的联结学习。在联结过程中,除奖赏系统外,感觉-动作系统在相关线索反应中也起到了重要作用。其机理可能是与感觉运动脑区部分重合的镜像神经的理解、分析和推测动作意图目的以及内隐模仿的功能有关。另外,动作记忆的形成及功能也可能在这种自动化动作图式的形成中起到了重要的作用。其确切的机制需要进一步研究证据。     

镜像神经系统—研究药物依赖行为的新靶点

镜像神经是近年来认知与大脑神经科学研究中崭新的课题,大量实验证实了镜像神经元(系统)参与到了多种心理能力的发展与进化之中。目前有研究发现,吸烟相关线索会激活尼古丁成瘾者大脑相应的动作脑区,而该区域也正是人类镜像神经区域,这意味着镜像神经在相关线索激发的心理渴求中可能扮演了重要角色。该实验结果有重要的意义,动作计划脑区的神经线索反应为发展可靠的依赖行为的生物学标记提供了另一个新目标,不仅开发了一个新型的依赖行为的理论模型,还为把神经科学的研究发现运用到实践应用打下了良好的基础。     

用药动作线索诱发海洛因戒断者的镜像神经活动:一项fMRI研究

相关线索能够诱发药物依赖者的心理渴求,而健康人不会对相关线索产生心理渴求。15名海洛因成瘾者和12名没有任何物质滥用的健康被试参与实验,收集了他们在观看相关线索与对照线索时的脑神经活动。结果发现,药物线索能够诱发戒断者更多脑区的活动,包括扣带回和楔前叶。两组被试在对照动作线索刺激诱发作用下,其颞叶、顶叶均出现了较为一致的活动。在用药动作线索诱发作用下,戒断组双侧颞中回、双侧顶下小叶、左侧顶上小叶和右侧额下回显示出显著活动,并且与对照动作线索激活脑区一致;健康组被试除枕叶-颞叶联合区外,没有出现显著的脑区活动。以上结果表明,用药动作线索诱发了海洛因戒断者颞中回、顶下小叶、额下回等镜像神经系统的活动,这些脑区对不同类型的相关线索十分敏感,它们可能通过对用药动作的心理模拟,参与了用药动作线索的快速自动化加工。     

网络相关文字刺激和压力对网络成瘾者线索诱发渴求的影响

渴求感特别是线索诱发渴求是成瘾行为维持和戒断失败的主要原因。本研究通过两个实验分别探讨了网络相关文字刺激和压力对网络成瘾者线索诱发渴求的影响。研究一以25名网络成瘾大学生为被试,以网络相关和中性词语为实验材料,采用线索暴露范式（Cue-reactivity Paradigm）的研究发现,只有网络相关文字刺激能显著诱发网络成瘾者的渴求感。在此基础上,研究二以40名网络成瘾大学生为被试,以公开演讲范式为压力诱发情境,以网络相关词语和中性词语为实验材料,采用线索暴露范式（Cue-reactivity Paradigm）的研究发现,在压力条件下,网络相关文字能诱发网络成瘾者更为强烈的渴求感。本研究深化了对网络成瘾形成维持心理机制的研究,也为网络成瘾的干预矫正提供了思路。     

不同药物相关线索反应下感觉-运动脑区的激活及作用

药物相关线索反应不仅表现在心理渴求, 也表现在强迫性用药行为上。相关线索下, 除包括奖赏环路在内的边缘系统被激活外, 感觉-运动脑区也被激活, 引发自动化动作图式的表达, 这对相关线索反应及复吸行为具有特殊的意义。是否所有相关线索都会激活感觉-运动脑区, 目前, 还不清楚, 而这对临床治疗具有重要意义。本研究采用磁共振扫描, 生理测试等方法探索了不同类型相关线索下, 海洛因成瘾戒断者的大脑激活状况, 试图了解他们在不同线索刺激下的大脑反应。采用组内实验设计, 测量29名海洛因成瘾者相关线索反应下的血氧水平。结果发现, 相比对照线索, 所有药物相关线索, 包括药物、用药工具、用药动作线索都更多激活扣带回、海马、舌回、梭回等与奖赏机制相关的脑区; 而不同类型的药物相关线索之间的比较则显示, 用药工具和用药动作线索更多激活了双侧颞中回、双侧顶下小叶、左侧顶上小叶和右侧额下回等感觉-运动脑区。用药动作线索比单纯药物和用药工具线索, 激活了更为广泛的动作脑区。由此, 我们认为药物相关线索导致成瘾者大脑中奖赏和感觉-动作两套系统被激活, 包含用药工具、用药动作在内的相关线索会激活更多的感觉-运动脑区。     

镜像神经元是认知科学的“圣杯”吗?

镜像神经元作为近二十年来神经科学领域内最重要的发现之一,相关的一系列研究掀起了一场"理解社会行为的革命"。然而,通过系统考察镜像神经元最初的操作性定义、基本功能及其实验证据,发现许多研究者对于镜像神经元的定义存在误解,人类脑中是否存在镜像神经元及其功能依然是当前学术界的争议焦点。迄今仍然缺乏令人信服的证据表明镜像神经元(或系统)就是动作理解、动作模仿、共情以及读心的直接神经机制。因此,将镜像神经元视为"认知科学的圣杯"的主张是一种落后的模块论意识形态,只能催生新的"神经神话"。     

基于“相关线索-自动化用药行为”联结的成瘾记忆消退

成瘾记忆消退致力于消除成瘾者相关线索与药物奖赏效应的联结,以达到消除心理渴求、戒断成瘾行为的目的,但其效果还十分有限。最近,大量的动物和人类实验研究发现:在相关线索下,成瘾者的激活脑区不仅包括中脑边缘皮层-背内侧纹状体,还延伸到感觉运动脑区-背外侧纹状体。这意味着成瘾记忆中存在相关线索与自动化(习惯性)用药行为的联结。所以,与成瘾相关的记忆可能包含两种不同的成分:一是与药物奖赏效应相关的情绪记忆,另一种是与用药动作、技能有关的动作记忆(程序记忆)。由于在成瘾阶段,药物奖赏效应对药物使用和复发的作用已经相对减少,因此,针对成瘾记忆的消退训练,以相关线索与自动化用药行为的联结为标靶,可能可以取得更好的效果,值得做进一步的深入探索。     

镜像神经元系统的研究回顾及展望

镜像神经元系统的发现使得研究者从一个较为统一的神经机制层面了解人类多个层次的社会认知活动。在猕猴大脑F5区发现的镜像神经元可以在抽象的层面上帮助猕猴理解他人行为的意图。利用脑成像技术,研究发现人类的镜像神经元系统能够匹配外界的知觉表征和内在的动作表征从而通过“居身模仿”这一过程来进行模仿、语言理解、理解他人的意图及情绪这些重要的社会认知活动。另外,镜像神经元系统在社会交往中也起着重要作用,最后,就镜像神经元系统在心理理论中的作用、了解自我-他人问题和镜像神经元系统的关系、动机、经验等因素对镜像神经元系统活动的调控等问题对未来的研究方向进行了展望     

视觉线索诱发的香烟渴求感研究

本研究考察了90名男性青年志愿者(30名不吸烟者,60名香烟成瘾者被随机分成两组:被剥夺组和即时满足组,每组30名)在不同视觉线索刺激下诱发的心理渴求程度,以及喜欢和厌恶两种情绪的感受程度.视觉线索刺激为90张彩色图片,分为吸烟线索刺激图片(60张,包括与吸烟高度相关的图片和中度相关的图片,每类30张,和控制线索图片(30张,亦称与吸烟低度相关的图片),用计算机随机呈现给被试,每张图片呈现4秒钟,每呈现完一张图片,就让被试对该图片所诱发的香烟渴求程度,以及喜欢和厌恶感受进行评价.结果发现:(1)视觉线索能诱发香烟成瘾者对吸烟的渴求,并且诱发的渴求程度和剥夺状态有关,表现为被剥夺的香烟成瘾者的渴求程度高于即时满足的香烟成瘾者;(2)视觉线索与吸烟行为的相关程度越高,所诱发香烟成瘾者的心理渴求程度越强;(3)对香烟成瘾者来说,刺激图片对香烟渴求的诱发程度越高,引发的喜欢情绪越强,厌恶情绪越弱.     

背景性渴求与事件性渴求:区分心理渴求对尼古丁成瘾的不同作用路径

大量研究发现心理渴求机制的紊乱是尼古丁成瘾的核心机制之一。线索暴露是探索心理渴求与尼古丁成瘾关系的重要研究范式。但最近研究者提出该范式较难区分事件性渴求与背景性渴求,导致无法清楚定位渴求在尼古丁成瘾中扮演的角色。通过对以往文献的回顾,对不同成瘾概念、作用机制和生理基础进行对比分析,认为事件性渴求与背景性渴求两者在维持成瘾行为上的确存在不同的作用路径。未来研究应改进实验范式,分别探讨两种心理渴求与尼古丁成瘾的内在联系,完善心理渴求与尼古丁成瘾的关系模型,为尼古丁成瘾的治疗和干预等方法提供一定的理论依据。     

不同相关线索下海洛因成瘾者的反应差异及反应抑制特征：来自ERP的证据

采用ERP技术, 探究海洛因成瘾者在不同相关线索下的脑电反应及其与冲动性的关系。实验采用组间实验设计和双选择Oddball范式, 要求海洛因成瘾组和健康对照组被试对标准刺激与偏差刺激分别做不同的按键反应, 记录他们的EEG数据。结果发现：相比对照组被试, 海洛因成瘾者在观看药物相关线索时诱发的N2波幅更小, P3波幅更大; 在成瘾组内, 相比用药工具线索, 用药动作线索诱发了更小的N2波幅和更大的P3波幅。这表明海洛因成瘾者对药物相关线索存在反应抑制缺陷, 且不同的药物相关线索会激发海洛因成瘾者不同程度的反应抑制缺陷, 用药动作线索比用药工具线索更大程度地影响成瘾者的反应抑制能力, 反映出更高的动作冲动性。     

LISTENING TO SMOKING RESEARCHERS:

Abstract— The work of Baker and his colleagues indicates that a broadened view of withdrawal that recognizes its probable affective bases will suggest new treatment strategies for the treatment of smoking and, by extension, drug dependence. This commentary briefly reviews the current status of treating drug dependence by addressing negative affect and emphasizes that clinical research which allows for building more complex models, of individual change over time holds promise for clearer understanding of the role of negative affect among drug abusers and thus more effective treatments. Although clinical treatments for drug dependence have long recognized the significance of negative affect we are far from a thorough understanding of the role of negative affect in withdrawal, craving, and relapse to drug use.     

Conditioned craving cues elicit an automatic approach tendency

In two experiments, we used a Pavlovian differential conditioning procedure to induce craving for chocolate. As a result of repeated pairing with chocolate intake, initially neutral cues came to elicit an automatic approach tendency in a speeded stimulus-response compatibility reaction time task. This automatic approach tendency, moreover, seemed to be sensitive to manipulations of extinction and renewal in the Pavlovian conditioning procedure. These findings corroborate and extend previous reports of automatic approach tendencies elicited by substance-relevant cues in addiction, while controlling for alternative accounts for such observations. Moreover, our data lend support to and extend learning models of cue-induced craving and addiction. Finally, we argue that the procedure we present here provides an ecologically valid behavioural tool that allows studying processes involved in cue-induced craving, addiction and relapse without relying on verbal report.     

Incubation of food craving in rats: A review

Incubation of food craving is an abstinence-dependent increase in responding for reward-paired cues. Incubation of craving was first reported for rats responding for cocaine-paired cues, and later generalized to several drugs of abuse and for food. Incubation of drug and food craving has been reported in clinical studies as well. Incubation of food craving by rats has been reported for standard chow as well as for high fat and sucrose reinforcers. Parametric and other evaluations of the incubation of food craving reveal manipulations that reduce incubation, including environmental enrichment and pharmacological manipulation of dopamine, glutamate, and endogenous opiates. Several brain regions are likely involved in the effect, including mesolimbic terminals and the central nucleus of the amygdala. Further study of the incubation of food craving could facilitate development of treatments for cravings that precede relapse characteristic of drug and food addictions.     

The mirror neuron system: grasping others’ actions from birth?

In the adult human brain, the presence of a system matching the observation and the execution of actions is well established. This mechanism is thought to rely primarily on the contribution of so-called 'mirror neurons', cells that are active when a specific gesture is executed as well as when it is seen or heard. Despite the wealth of evidence detailing the existence of a mirror neuron system (MNS) in the adult brain, little is known about its normal development. Yet, a better understanding of the MNS in infants would be of considerable theoretical and clinical interest, as dysfunctions within the MNS have been demonstrated in neurodevelopmental disorders such as autism spectrum disorder. Arguments in favor of an innate, or very early, mechanism underlying action understanding mainly come from studies of neonatal imitation, the existence of which has been questioned by some. Here, we review evidence suggesting the presence of an MNS in the human child, as well as work that suggests, although indirectly, the existence of a mechanism matching the perception and the execution of actions in the human newborn.     

Role of dopamine,the frontal cortex and memory circuits in drug addiction: insight from imaging studies

Drug addiction is characterized by a set of recurring processes (intoxication, withdrawal, craving) that lead to the relapsing nature of the disorder. We have used positron emission tomography to investigate in humans the role of dopamine (DA) and the brain circuits it regulates in these processes. We have shown that increases in DA are associated with the subjective reports of drug reinforcement corroborating the relevance of drug-induced DA increases in the rewarding effects of drugs in humans. During withdrawal we have shown in drug abusers significant reductions in DA D2 receptors and in DA release. We postulate that this hypodopaminergic state would result in a decreased sensitivity to natural reinforcers perpetuating the use of the drug as a means to compensate for this deficit and contributing to the anhedonia and dysphoria seen during withdrawal. Because the D2 reductions are associated with decreased activity in the anterior cingulate gyrus and in the orbitofrontal cortex we postulate that this is one of the mechanisms by which DA disruption leads to compulsive drug administration and the lack of control over drug intake in the drug-addicted individual. This is supported by studies showing that during craving these frontal regions become hyperactive in proportion to the intensity of the craving. Craving is also associated with activation of memory circuits including the amygdala (implicated in conditioned learning), hippocampus (implicated in declarative learning), and dorsal striatum (implicated in habit learning) all of which receive DA innervation. We therefore postulate that dopamine contributes to addiction by disrupting the frontal cortical circuits that regulate motivation, drive, and self-control and by memory circuits that increase the motivational salience of the drug and drug-associated stimuli.