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.