The Analysis Of Impulsive Behaviors Of Long-term Abstinent Heroin Addicts And MRI Study On Their Brain Structural And Functional Changes

Drug addiction is a chronic, relapsing brain disorder. Previous studies have demonstrated that imbalanced functional link between the brain networks persists in drug addicts, which is associated with their highly impulsive behaviors. However, whether the aberrant brain networks of the drug addicts, after multi-year abstinence, could be restored to the normal level remains unclear. Therefore, we examined the differences of impulsivity between long-term abstinent heroin addicts and healthy individuals. We also investigated the brain structural and functional characteristics of heroin addicts using magnetic resonance imaging. These findings may contribute to the development of effective treatment and rehabilitation strategies and provide new evidence to uncover the mechanisms of drug addiction and relapse.Chapter Ⅰ: The changes of impulsivity in multi-year abstinent heroin addictsObjective: The present study aims to evaluate the trait and state impulsivity of long–term abstinent heroin addicts.Methods: There were 37 heroin addicts and 37 healthy controls screened by clinical interviews and scales in the study. Each participant completed two clinical scales including Barratt Impulsiveness Scale(BIS-11) and the Sensitivity to Punishment and the Sensitivity to Reward Questionnaire(SPSRQ), and was also tested using delay discounting tasks.Results: There were no significant differences of BIS-11 and SPSRQ scores as well as delay discounting rates between the two groups.Conclusions: There was no difference in the impulsivity degree between the long-term abstinent addicts and healthy controls.Chapter Ⅱ: Alterations in rest-state functional connectivity in multi-year abstinent heroin addictsObjective: Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and ofrelapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence.Methods: In this study, whole-brain resting-state functional magnetic resonance images(8 min) were collected from 30 heroin-addicted individuals after a long period of abstinence(more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting-state functional connectivity(rs FC) of the nucleus accumbens(NAc), a brain region implicated in relapse-related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group.Results: We found that, compared with controls, heroin-dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen and left precuneus. However, with longer abstinence times, the strength of NAc functional connectivity with the left putamen increased to near-normal levels.Conclusions: These results indicate that brain lesions caused by drug misuse may be persistent and that a risk of relapse still exists in long-term abstinent heroin-addicted individuals. These findings may aid the development of treatment and rehabilitation strategies for those suffering from drug addiction.Chapter Ⅲ: Alterations in brain structure in multi-year abstinent heroin addictsObjective: Previous studies have suggested that heroin addiction is associated with structural and functional brain abnormalities. However, it is largely unknown whether these characteristics of brain abnormalities would be persistent or could be restored after long periods of abstinence. Considering the very high rates of relapse, we hypothesized that there may exist some latent neural vulnerabilities in abstinent heroin users.Methods: In this study, structural and resting-state functional MRI data were collected from 30 former heroin-dependent(FHD) subjects who were drug free for more than 3 years and 30 non-addicted cognitive normal(CN) volunteers.Voxel-based morphometry was used to identify possible gray matter volume differences between the FHD and CN groups. Alterations in resting-state functional connectivity in FHD were examined by using brain areas with gray matter deficits as seed regions.Results: Significantly reduced gray matter volume was observed in FHD in an area surrounding the parieto-occipital sulcus, which included the precuneus and cuneus. Functional connectivity analyses revealed that the FHD subjects showed reduced positive correlation within the default mode network and visual network, and decreased negative correlation between the default mode network, visual network and task positive network. Moreover, the altered functional connectivity was correlated with self-reported impulsivity scores in the FHD subjects.Conclusions: Our findings suggest that disruption of large-scale brain systems is present in former heroin users even after multi-year abstinence, which could serve as system-level neural underpinnings for behavioral dysfunctions associated with addiction.Chapter Ⅳ: The Brain Functional Connectivity in Response to Heroin-related Cues in Multi-year Abstinent Heroin AddictsObjective: Abnormal brain activity and functional connectivity to drug cues is a consequence of chronic drug abuse, which is associated with addiction severity and relapse. Although it has been well-studied in addicted and acute abstinent patients, little is known about the brain functional connectivity patterns to drug cues in long-term abstinent addicts.Methods: In this study, a total of 30 former heroin-dependent(FHD) subjects and 30 age- and sex-matched non-addicted cognitive normal(CN) volunteers were examined with a cue-reactivity functional magnetic resonance experiment with heroin-associated and neutral cues. Ratings of self-reported craving were assessed during scanning.Results: In comparison with healthy controls, heroin-dependent patients had no stronger craving for drug-related cues than for neutral cues. However, functional connectivity analysis using insula as a seed revealed increased connectivity with the DLPFC, bilateral angular, right inferior temporal gyrus, left fusiform gyri, left middle temporal gyrus during heroin cues compared with neutral cues. Heroin-related cuesf MRI contrast patients showed weaker connectivity between the insula and IFG in former abstinent addicts, while there was no difference during neutral cues. Furthermore, in heroin addicts, craving scores were negatively correlated with the strength of the insula connectivity with the IFG.Conclusions: Taken together, these findings demonstrated that abnormal brain areas functional connectivity to drug cues still persists in heroin addicts even after several years’ abstinence, which suggests that a risk of relapse still exists.