甲基苯丙胺滥用形势日趋严峻，已成为我国严重的公共健康问题。精神依赖是甲基苯丙胺滥用、成瘾和复吸的关键原因，而药物线索的情绪和动机效应是精神依赖的核心成分。以往研究认为，成瘾个体的纹状体多巴胺系统功能的异常增强，使得药物线索获得了很强的诱因凸显性（incentive salience），从而能驱使成瘾个体趋近药物线索，并产生渴求和复吸行为；而执行功能的缺损可能加剧药物线索诱因凸显性在精神依赖中的影响。但是，甲基苯丙胺等成瘾药物的长期使用是否使得纹状体多巴胺系统发生普遍性的功能上调，从而增强了非药物奖赏线索的诱因凸显性的加工，目前尚不清楚；此外，执行功能对于药物线索诱因凸显性的调控作用，目前也缺乏明确的证据。解决这些问题，对于理解成瘾的本质以及指导临床干预具有重要意义。
药物线索引起的注意偏向是其诱因凸显性的标志之一，且能在成瘾个体戒断之后依然长期存在。因此，本研究以处于戒断状态下的甲基苯丙胺成瘾个体为被试，采用具有训练阶段和测试阶段的注意捕获行为实验范式及其变式，考察与非药物奖赏相关的线索以及与药物相关的线索所引起的注意偏向效应，以探讨成瘾个体的奖赏线索诱因凸显性加工是否发生了普遍性增强。另一方面，工作记忆是执行功能中能够调控选择性注意的关键成分，因此研究考察成瘾被试在工作记忆容量上的个体差异与注意偏向的关联性，并考察操纵工作记忆功能对注意偏向的影响，从而探讨工作记忆对药物线索注意偏向的调控作用。
本研究共设计了4 个行为实验。实验1 比较了甲基苯丙胺成瘾被试与健康控制组被试对于非药物奖赏线索的注意偏向。曾在训练阶段与高低奖赏（代币）进行匹配的奖赏线索，在测试阶段作为干扰刺激吸引注意，从而使被试的反应时延长。结果显示，成瘾被试对非药物奖赏线索的注意偏向效应弱于控制组，提示相较于健康人群，成瘾个体对自然奖赏线索的诱因凸显性加工发生下调。实验2 则在甲基苯丙胺成瘾被试中，进一步比较了药物二级线索和食物二级线索的注意偏向效应。结果显示，曾在训练阶段与药物图片匹配的药物二级线索能产生明显的注意偏向效应，而曾与食物图片匹配的食物二级线索不能产生显著的注意偏向效应。这再次说明成瘾个体对自然奖赏线索的诱因凸显性加工不足，而对药物线索的诱因凸显性加工则特异性增强。结果还显示，成瘾被试的工作记忆容量与药物二级线索注意偏向呈负相关，但与食物二级线索注意偏向效应没有显著相关性，提示工作记忆功能受损可能是药物线索诱因凸显性无法得到有效控制的重要原因。实验3 在甲基苯丙胺成瘾被试中，考察了工作记忆作为有限的执行功能资源，在调控药物二级线索注意偏向中的必要性。在注意捕获任务的测试阶段给成瘾被试增加工作记忆负荷，结果显示，增加负荷使得药物二级线索的注意偏向效应更为明显，且该效应仅在工作记忆容量较高的成瘾被试中有显著表现，说明足够的工作记忆资源对于调控药物相关线索的注意偏向是必要的。实验4 进一步探讨了在对药物二级线索注意偏向进行有针对性的抑制过程中，工作记忆可能发挥的作用。在任务的测试阶段，要求成瘾被试将药物二级线索及中性二级线索保持在工作记忆中，并在选择性注意过程中忽略这些线索。结果显示，成瘾被试的选择性注意可以逐渐对药物二级线索形成抑制，但这一过程慢于其对中性线索形成抑制的过程，而且工作记忆容量较高的成瘾被试能较快地形成对药物线索的注意抑制，提示在有针对性地抑制药物线索诱因凸显性加工中，工作记忆可以发挥重要作用。
以上实验结果表明，1）在甲基苯丙胺成瘾个体中，以注意偏向现象为代表，药物相关线索的诱因凸显性增强，而非药物奖赏相关线索的诱因凸显性减弱。对于甲基苯丙胺成瘾者而言，药物相关线索是一种特异性的奖赏线索，可能引起其纹状体多巴胺系统特异性的增强反应。2）工作记忆作为执行功能的核心成分之一，是调控药物线索注意偏向效应的关键因素。足够的工作记忆资源对于抑制该注意偏向不可或缺，且工作记忆的内容在有针对性地抑制该注意偏向中也可发挥重要作用。这些结果提示，工作记忆等认知控制能力不足导致成瘾个体不能抗拒药物相关线索的注意偏向，这将加剧药物相关线索诱因凸显性在成瘾行为中的不利影响；增强工作记忆功能可作为一种干预思路，在甲基苯丙胺成瘾的治疗以及预防复吸中具有较好的应用前景。

The escalating abuse of methamphetamine (MA) has been a severe public health problem in China. Psychological dependence is the key reason for abuse, addiction and relapse of MA. A core component of psychological dependence is the motivational effects of drug-related cues. Existing studies suggest that the abnormal hyper-functions of the striatal dopamine system of addictive individuals make the drug-related cues acquire powerful incentive salience, hence the cues can drive addictive individuals to approach and can induce craving and relapse. In addition, the impairment of executive functions in addicts probably exacerbates the detrimental effects of incentive salience. However, it is not clear whether chronic use of addictive drug such as MA will generally augment the function of striatal dopamine system thus increase the incentive salience of non-drug reward cues as well. Moreover, the evidence for the role of executive functions in regulating the incentive salience of drug cues is scarce. These problems are significant for understanding the nature of addiction and directing the clinical interventions.
The attentional bias to drug cues is a marker of its incentive salience, which can persist even after a long abstinence in addicts. Hence, in order to explore whether the incentive salience of reward cues augment generally in MA addiction, the present study recruited MA addicts in compulsory rehabilitation as participants, and used the attention capture paradigm which consists a training phase and a test phase and its modified versions to investigate their attentional bias to cues related with drug and non-drug reward. On the other hand, working memory (WM) is a crucial component for regulating selective attention in executive functions. Hence, to identify the role of WM in regulating the attentional bias to drug cues, the present study investigated the relevance between the individual differences in WM capacity and the attentional bias, and observed the effects of manipulating WM function on the attentional bias.
Four behavioral experiments were designed in the present study. Experiment 1 compared the attentional bias effects of non-drug reward cues between MA addictive participants and healthy participants. Paired with tokens in training phase, the reward cues acted as distractors to attract attention and prolonged the response time in test phase. The results showed that, the attentional bias to reward cues was weaker in addicts than in healthy participants, suggesting the incentive salience of natural reward cues was attenuated in addicts. Experiment 2 further compared the attentional biases to the second-order cues of drug and food in addictive participants. The results showed that only the cues which paired with drug pictures in training phase attracted attention significantly in test phase, but the cues which paired with food pictures did not bias the attention. These finds indicated again that non-drug reward cues had insufficient incentive salience in addicts. Moreover, the WM capacity was negatively correlated with the attentional bias to drug-related cues, but had no significant correlation with the attentional bias to food-related cues. It suggested that WM impairment was responsible for the ineffective control on incentive salience of drug-related cues.
Experiment 3 explored the necessity of WM in regulating the attentional bias to second-order drug cues in addictive participants. A WM load was added during the test phase. The results showed that the attentional bias to drug-related cues was augmented when the WM load was added, and the effect was significant only in addictive participants with relative higher WM capacity. These finds provided explicit evidence that sufficient WM resource was indispensable for the inhibition of attentional bias. In order to further examine the role of WM in specifically inhibitory control on attentional bias, the test phase of Experiment 4 asked addictive participants to sustain the secondorder drug cues and neutral cues in their WM contents, and to ignore these cues in the selective attention processes. The results showed that addictive participants could progressively establish the attentional inhibition on drug cues, but the process was slower than the process of inhibition on neutral cue. Furthermore, the addictive participants with relative higher WM capacity could establish the attentional inhibition faster. These finds suggested WM could take an important part in specifically inhibition on the incentive salience of drug cues.
In sum, the results of present study suggested that 1) in MA addictive individuals, represented by attentional bias, the incentive salience of drug related cues increases while the incentive salience of non-drug reward cues attenuates. Drug-related cues are a specific category of reward cues which induced augmented activities of striatal dopamine system. 2) As a core component of executive functions, working memory is a key cognitive factor for regulating the attentional bias to drug-related cues. Sufficient WM resource is indispensable for inhibiting the attentional bias, and the content of WM can play an important role in targeted inhibition of attentional bias. These results suggested that the insufficiency of cognitive control such as WM is responsible for the inability to resist the attentional bias to drug-related cues, which exacerbates the adverse effects of incentive salience of drug-related cues in MA addiction. Enhancing the function of working memory is a promising intervention approach in the treatment and relapse prevention of methamphetamine addiction.