Neural Correlates of Drug-Related Attentional Bias in Heroin Dependence.
ABSTRACT: The attention of drug-dependent persons tends to be captured by stimuli associated with drug consumption. This involuntary cognitive process is considered as attentional bias (AB). AB has been hypothesized to have causal effects on drug abuse and drug relapse, but its underlying neural mechanisms are still unclear. This study investigated the neural basis of AB in abstinent heroin addicts (AHAs), combining event-related potential (ERP) analysis and source localization techniques. Electroencephalography data were collected in 21 abstinent heroin addicts and 24 age- and gender-matched healthy controls (HCs) during a dot-probe task. In the task, a pair of drug-related image and neutral image was presented randomly in left and right side of the cross fixation, followed by a dot probe replacing one of the images. Behaviorally, AHAs had shorter reaction times (RTs) for the congruent condition compared to the incongruent condition, whereas this was not the case in the HCs. This finding demonstrated the presence of AB towards drug cues in AHAs. Furthermore, the image-evoked ERPs in AHAs had significant shorter P1 latency compared to HCs, as well as larger N1, N2, and P2 amplitude, suggesting that drug-related stimuli might capture attention early and overall require more attentional resources in AHAs. The target-related P3 had significantly shorter latency and lower amplitude in the congruent than incongruent condition in AHAs compared to HCs. Moreover, source localization of ERP components revealed increased activity for AHAs as compared to HCs in the dorsal posterior cingulate cortex (dPCC), superior parietal lobule and inferior frontal gyrus (IFG) for image-elicited responses, and decreased activity in the occipital and the medial parietal lobes for target-elicited responses. Overall, the results of our study confirmed that AHAs may exhibit AB in drug-related contexts, and suggested that the bias might be related to an abnormal neural activity, both in early and late attention processing stages.
Project description:Abnormal decision making is a behavioral characteristic of drug addiction. Indeed, drug addicts prefer immediate rewards at the expense of future interests. Assessing the neurocognitive basis of decision-making related to drug dependence, combining event-related potential (ERP) analysis and source localization techniques, may provide new insights into understanding decision-making deficits in drug addicts and further guide withdrawal treatment. In this study, EEG was performed in 20 abstinent heroin addicts (AHAs) and 20 age-, education- and gender-matched healthy controls (HCs) while they participated in a simple two-choice gambling task (99 vs. 9). Our behavioral results showed that AHAs tend to select higher-risk choices compared with HCs (i.e., more "99" choices than "9"). ERP results showed that right hemisphere preponderance of stimulus-preceding negativity was disrupted in AHAs, but not in HCs. Feedback-related negativity of difference wave was higher in AHAs than HCs, with the P300 amplitude associated with risk magnitude and valence. Using source localization that allows identification of abnormal brain activity in consequential cognitive stages, including the reward expectation and outcome evaluation stages, we found abnormalities in both behavioral and neural responses on gambling in AHAs. Taken together, our findings suggest AHAs have risk-prone tendency and dysfunction in adaptive decision making, since they continue to choose risky options even after accruing considerable negative scores, and fail to shift to a safer strategy to avoid risk. Such abnormal decision-making bias to risk and immediate reward seeking may be accompanied by abnormal reward expectation and evaluation in AHAs, which explains their high risk-seeking and impulsivity.
Project description:Drug use and relapse involve learned associations between drug-associated environmental cues and drug effects. Extinction procedures in the clinic can suppress conditioned responses to drug cues, but the extinguished responses typically reemerge after exposure to the drug itself (reinstatement), the drug-associated environment (renewal), or the passage of time (spontaneous recovery). We describe a memory retrieval-extinction procedure that decreases conditioned drug effects and drug seeking in rat models of relapse, and drug craving in abstinent heroin addicts. In rats, daily retrieval of drug-associated memories 10 minutes or 1 hour but not 6 hours before extinction sessions attenuated drug-induced reinstatement, spontaneous recovery, and renewal of conditioned drug effects and drug seeking. In heroin addicts, retrieval of drug-associated memories 10 minutes before extinction sessions attenuated cue-induced heroin craving 1, 30, and 180 days later. The memory retrieval-extinction procedure is a promising nonpharmacological method for decreasing drug craving and relapse during abstinence.
Project description:Drug addiction is widely linked to the orbitofrontal cortex (OFC), which is essential for regulating reward-related behaviors, emotional responses, and anxiety. Over the past two decades, neuroimaging has provided significant contributions revealing functional and structural alternations in the brains of drug addicts. However, the underlying neural mechanism in the OFC and its correlates with drug addiction and anxiety still require further elucidation. We first presented a pilot investigation to examine local networks in OFC regions through resting-state functional connectivity (rsFC) using functional near-infrared spectroscopy (fNIRS) from eight abstinent addicts in a heroin-dependent group (HD) and seven subjects in a control group (CG). We discovered that the HDs manifested enhanced interhemispheric correlation and rsFC. Moreover, small-worldness was explored in the brain networks. In addition to the altered rsFC in the OFC networks, our examinations demonstrated associations in the functional connectivity between the left inferior frontal gyrus and other OFC regions related to anxiety in the HDs. The study provides important preliminary evidence of the complex OFC networks in heroin addiction and suggests neural correlates of anxiety. It opens a window in application of fNIRS to predict psychiatric trajectories and may create new insights into neural adaptations resulting from chronic opiate intake.
Project description:<h4>Objective</h4>Heroin abuse is associated with cognitive deficits. These might play a role in relapse after abstinence, which could be reduced by cognitive trainings. A previous study assessed effects of working memory (WM) training on executive functioning (EF) in heroin addicts undergoing methadone treatment, potentially limiting training effects. The present study assessed WM training effects in abstinent heroin addicts currently no longer receiving pharmacological treatment.<h4>Method</h4>Inpatients were randomly assigned to a WM training or active control condition and performed EF tasks before and after training.<h4>Results</h4>Trained participants improved their performance on the trained task. Using the control group as reference, they showed short-lived beneficial near- but no far-transfer effects to non-trained cognitive tasks. Participants with a strong baseline WM showed stronger training but smaller transfer effects than participants with a weak baseline WM.<h4>Conclusion</h4>The combined results suggest limited cognitive transfer effects of WM training in heroin addicts irrespective of current methadone treatment status. They also suggest individual differences in training and transfer benefits dependent on baseline EF.
Project description:Recently, Willuhn et al. reported that cocaine use and even non-substance-related addictive behavior increases as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors and was also associated with lower activation of cues in occipital cortex and cerebellum, in a recent PET study by Volkow's et al. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of 10 heroin addicts undergoing protracted abstinence (average 16.9 months). In a randomized placebo-controlled crossover study of KB220Z, five subjects completed a triple-blinded experiment in which the subject, the person administering the treatment, and the person evaluating the response to treatment were blinded to the treatment that any particular subject was receiving. In addition, nine subjects were genotyped utilizing the GARSDX™ test. We preliminarily report that KB220Z induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following 1-hour acute administration. Furthermore, KB220Z also reduced resting-state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all 10 abstinent heroin-dependent subjects, we observed that three brain regions of interest were significantly activated from resting state by KB220Z compared to placebo (p < 0.05). Increased functional connectivity was observed in a putative network that included the dorsal anterior cingulate, medial frontal gyrus, nucleus accumbens, posterior cingulate, occipital cortical areas, and cerebellum. These results and other quantitative electroencephalogy (qEEG) study results suggest a putative anti-craving/anti-relapse role of KB220Z in addiction by direct or indirect dopaminergic interaction. Due to small sample size, we caution definitive interpretation of these preliminary results, and confirmation with additional research and ongoing rodent and human studies of KB220Z is required.
Project description:OBJECTIVE: To compare HCV and HIV infection among heroin addicts in MMT and not in MMT in two large cities in central China. METHODS: A total of 541 heroin addicts were recruited from MMT clinics and voluntary detoxification centers in Changsha and Wuhan, China. Structured questionnaires collected data on their socio-demographics, clinical status, risk behaviors, and their knowledge of HIV. Their HIV serostatus and Hepatitis C virus (HCV) serostatus were determined by testing antibodies in blood serum. RESULTS: We observed a higher prevalence of HCV infection among MMT heroin addicts (82.3%) than that in the non-MMT group (50.6%). However, our findings indicated that the heroin addicts in MMT had less drug or sexual HIV/HCV risk behaviors and more knowledge about HIV than non-MMT addicts. The heroin addicts in MMT had a significantly higher percentage of individuals who always used condoms (44.9%) compared with patients in the non-MMT group (14.6%, p = 0.039), and they had more knowledge about HIV than non-MMT individuals (p<.001). The percentage of HIV-positive addicts in the MMT group (0.7%) and non-MMT group (0.8%) were almost same. CONCLUSION: Our study indicated that the rate of HCV infection among heroin addicts among MMT or non-MMT settings in central China is very high. The non-MMT heroin addicts have higher risk of becoming infected with HCV in the future, while at present they have lower rates of HCV infection than MMT heroin addicts. Although rates of HIV infection among MMT and non-MMT heroin addicts are low now, they are all at great risk of becoming infected with HIV in the future, especially for non-MMT heroin addicts. We should use the MMT sites as a platform to improve the control of HCV and HIV infection in heroin addicts.
Project description:Heroin and methylamphetamine (METH) are two addictive drugs that cause serious problems for society. Dopamine receptor D4 (DRD4), a key receptor in the dopaminergic system, may facilitate the development of drug addiction. The aim of the present study was to investigate the association between the promoter methylation level of DRD4 gene and drug addiction. Bisulfite pyrosequencing technology was used to measure the methylation levels of DRD4 promoter in 60 drug addicts and 52 matched controls. Significantly higher levels of DRD4 CpG1 and CpG4 methylation were detected in METH and heroin drug addicts compared with controls (P<0.05). Male METH addicts exhibited significantly higher DRD4 CpG1, CpG2 and CpG4 methylation levels compared with sex-matched controls (P<0.05). In heroin addicts, a positive correlation was observed between depression-dejection and DRD4 CpG5 methylation (r=0.537, P=0.039) whereas there was a negative correlation between drug usage frequency and CpG1 methylation (r=-0.632, P=0.011). In METH addicts, methylation levels were not significantly associated with depression-dejection and drug usage frequency. In addition, luciferase assays demonstrated that the target sequence of the DRD4 promoter upregulates gene expression. The results of the present study suggest that DNA methylation of DRD4 may be responsible for the pathophysiology of drug addiction.
Project description:Previous studies show that the acute administration of N-acetylcysteine (NAC) inhibits the desire for cocaine in addicts and cocaine-seeking in animals.Rats were trained to self-administer heroin, and the reinstatement model of drug seeking was used to determine whether chronic NAC treatment inhibited heroin-seeking.Daily NAC administration inhibited cue- and heroin-induced seeking. Moreover, repeated NAC administration during extinction training reduced extinction-responding and inhibited cue- and heroin-induced reinstatement for up to 40 days after discontinuing daily NAC injection.These data show that daily NAC inhibits heroin-induced reinstatement and produces an enduring reduction in cue- and heroin-induced drug seeking for over 1 month after the last injection of NAC. Both the inhibitory effect of NAC on the reinstatement of heroin-seeking and the ability of NAC to reduce extinction-responding support clinical evaluation of repeated NAC administration to decrease in drug-seeking in heroin addicts.
Project description:Objective:Aerobic exercise is considered a potential adjunctive treatment for heroin addicts, but little is known about its mechanisms. Less severe cravings and greater inhibitory control have been associated with reduced substance use. The aim of the current study was to determine the effects, as measured by behavioral and neuroelectric measurements, of acute aerobic exercise on heroin cravings and inhibitory control induced by heroin-related conditions among heroin addicts. Design:The present study used a randomized controlled design. Methods:Sixty male heroin addicts who met the DSM-V criteria were recruited from the Isolated Detoxification Center in China and randomly assigned to one of two groups; one group completed a 20-min bout of acute stationary cycle exercise with vigorous intensity (70-80% of maximum heart rate, exercise group), and the other group rested (control group). The self-reported heroin craving levels and inhibitory control outcomes (measured by a heroin-related Go/No-Go task) were assessed pre- and post-exercise. Results:The heroin craving levels in the exercise group were significantly attenuated during, immediately following, and 40 min after vigorous exercise compared with before exercise; moreover, during exercise, a smaller craving was observed in the exercise group than in the control group. Acute exercise also facilitated inhibition performance in the No-Go task. After exercise, the participants' accuracy, the N2d amplitudes, and the theta two band spectral power during the No-Go conditions were higher in the exercise group than in the control group. Interestingly, significant correlations between the changes in these sensitive measurements and the changes in cravings were observed. Conclusions:This is the first empirical study to demonstrate that aerobic exercise may be efficacious for reducing heroin cravings and promoting inhibitory control among heroin addicts.
Project description:Stress is a significant risk factor in the development of drug addictions and in addiction relapse susceptibility. This hypothesis-driven study was designed to determine if specific SNPs in genes related to stress response are associated with heroin and/or cocaine addiction in African Americans. The analysis included 27 genes (124 SNPs) and was performed independently for each addiction. The sample consisted of former heroin addicts in methadone maintenance treatment (n = 314), cocaine addicts (n = 281), and controls (n = 208). Fourteen SNPs showed nominally significant association with heroin addiction (p < 0.05), including the African-specific, missense SNP rs5376 (Asn334Ser) in the galanin receptor type 1 gene (GALR1) and the functional FKBP5 intronic SNP rs1360780. Thirteen SNPs showed association with cocaine addiction, including the synonymous SNPs rs237902, in the oxytocin receptor gene (OXTR), and rs5374 in GALR1. No signal remained significant after correction for multiple testing. Four additional SNPs (GALR1 rs2717162, AVP rs2282018, CRHBP rs1875999, and NR3C2 rs1040288) were associated with both addictions and may indicate common liability. The study provides preliminary evidence for novel association of variants in several stress-related genes with heroin and/or cocaine addictions and may enhance the understanding of the interaction between stress and addictions.