Methadone maintenance treatment alters couplings of default mode and salience networks in individuals with heroin use disorder: A longitudinal self-controlled resting-state fMRI study.

Background: Methadone maintenance treatment (MMT) is a common treatment for heroin use disorder (HUD). Although individuals with HUD have been reported to show impaired coupling among the salience network (SN), executive control network (ECN), and default mode network (DMN), the effects of MMT on the coupling among three large-scale networks in individuals with HUD remains unclear. Methods: Thirty-seven individuals with HUD undergoing MMT and 57 healthy controls were recruited. The longitudinal one-year follow-up study aimed to evaluate the effects of methadone on anxiety, depression, withdrawal symptoms and craving and number of relapse, and brain function (SN, DMN and bilateral ECN) in relation to heroin dependence. The changes in psychological characteristics and the coupling among large-scale networks after 1 year of MMT were analyzed. The associations between the changes in coupling among large-scale networks and psychological characteristics and the methadone dose were also examined. Results: After 1 year of MMT, individuals with HUD showed a reduction in the withdrawal symptom score. The number of relapses was negatively correlated with the methadone dose over 1 year. The functional connectivity between the medial prefrontal cortex (mPFC) and the left middle temporal gyrus (MTG; both key nodes of the DMN) was increased, and the connectivities between the mPFC and the anterior insular and middle frontal gyrus (key nodes of the SN) were also increased. The mPFC-left MTG connectivity was negatively correlated with the withdrawal symptom score. Conclusion: Long-term MMT enhanced the connectivity within the DMN which might be related to reduced withdrawal symptoms, and that between the DMN and SN which might be related to increase in salience values of heroin cues in individuals with HUD. Long-term MMT may be a double-edged sword in treatment for HUD.

The effect of long-term methadone maintenance treatment on coupling among three large-scale brain networks in male heroin-dependent individuals: A resting-state fMRI study.

PURPOSE: Methadone maintenance treatment (MMT) is considered as an effective and mainstream therapy for heroin dependence. However, whether long-term MMT would improve the coupling among the three core large-scale brain networks (salience, default mode, and executive control) and its relationship with the craving for heroin is unknown. METHODS: Forty-four male heroin-dependent individuals during long-term MMT, 27 male heroin-dependent individuals after short-term detoxification/abstinence (SA), and 26 demographically matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging. We analyzed the difference in coupling among the salience, default mode, and executive control networks among the three groups and examined how the coupling among these large-scale networks was associated with craving before and after drug-cue exposure. RESULTS: Compared with the SA group, the MMT group showed lower craving before and after cue exposure and stronger connectivity between the dorsal anterior cingulate cortex (a key node of the salience network) and key regions of the bilateral executive control network, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and dorsomedial prefrontal cortex. Among the heroin-dependent individuals, the functional connectivity was negatively correlated with the craving before and after heroin-cue exposure. CONCLUSION: Our findings suggest that long-term MMT could increase the coupling between the salience and bilateral executive control networks and decrease craving for heroin. These findings contribute to the understanding of the neural mechanism of MMT, from the perspective of large-scale brain networks.

Assessing brain activity in male heroin-dependent individuals under methadone maintenance treatment: A resting-state fMRI study.

Methadone maintenance treatment (MMT) is recognized as an effective and mainstream alternative treatment for heroin addiction. However, the effect of long-term MMT on the local and global brain activity of heroin-dependent individuals during resting state remains unknown. Twenty-five heroin-dependent individuals under MMT, 26 heroin-dependent individuals after short-term abstinence (HA) and 42 healthy controls (HC) were included in the resting-state functional magnetic resonance imaging study. The craving before and after heroin cue exposure were evaluated among HA and MMT subjects. The difference in craving, regional homogeneity (ReHo) and related functional connectivity were analyzed among the three groups. We found that the craving before and after heroin cue exposure of MMT group was significantly lower than that of HA group. Compared with HA group, the MMT group showed higher ReHo value in the right orbitofrontal cortex and bilateral posterior central cortex. No significant difference in global brain connectivity based on differential ReHo regions was found among the three groups. This study demonstrated the long-term MMT could improve the local activity of executive control and somatosensory brain regions in heroin-dependent individuals. It suggested that MMT might be beneficial to restoring executive control and somatosensory function in the direction towards that of healthy controls.

Assessing effect of long-term abstinence on coupling of three core brain networks in male heroin addicts: A resting-state functional magnetic resonance imaging study.

Abstinence is one of the important measures for heroin addiction. However, it is unknown whether long-term abstinence (LA) would improve the coupling among three core brain networks (salience, default mode, and executive control) and decrease craving in treated heroin addicts. Forty-three heroin addicts with LA, 27 heroin addicts with short-term abstinence (SA), and 46 demographically matched healthy controls (HC) participated in the resting-state functional magnetic resonance imaging study. The authors compared the functional connectivity among the three groups and examined how the coupling among salience, default mode, and executive control networks related to duration of abstinence and craving before and after drug cue exposure among heroin addicts. Compared with the SA group, with a tendency toward the HC group, the LA group showed lower drug cue-induced craving, stronger connectivity between the dorsal anterior cingulate cortex (a key node of salience network) and left dorsolateral prefrontal cortex and right posterior parietal cortex (key nodes of executive control network), and stronger connectivity between the right dorsolateral prefrontal cortex and precuneus (a key node of default mode network). Meanwhile, the right dorsolateral prefrontal cortex-precuneus connectivity positively correlated with duration of abstinence. The LA and SA groups demonstrated lower connectivity between the left anterior insula (a key node of salience network) and dorsolateral prefrontal cortex and lower connectivity within the left dorsolateral prefrontal cortex, compared with the HC group. Our findings revealed that LA is associated with lower drug cue induced craving and improve the coupling among the three core brain networks in heroin addicts.

Gray matter alteration in heroin-dependent men: An atlas-based magnetic resonance imaging study.

Previous imaging studies on heroin addiction have reported brain morphological alterations. However, the effects of heroin exposure on gray matter volume varied among different studies due to different factors such as substitution treatment or mandatory abstinence. Meanwhile, the relationship between gray matter and heroin use history remains unknown. Thirty-three male heroin-dependent (HD) individuals who are not under any substitution treatment or mandatory abstinence and 40 male healthy controls (HC) were included in this structural magnetic resonance imaging study. With an atlas-based approach, gray matter structures up to individual functional area were delineated, and the differences in their volumes between the HD and HC groups were analyzed. In addition, the relationship between gray matter volume and duration of heroin use was explored. The HD group demonstrated significantly lower cortical volume mainly in the prefrontal cortex and mesolimbic dopaminergic regions across different parcellation levels, whereas several visual and somatosensory cortical regions in the HD group had greater volume relative to the HC group at a more detailed parcellation level. The duration of heroin use was negatively correlated with the gray matter volume of prefrontal cortex. These findings suggest that heroin addiction be related to gray matter alteration and might be related to damage/maladaption of the inhibitory control, reward, visual, and somatosensory functions of the brain, although cognitive correlates are warranted in future study. In addition, the atlas-based morphology analysis is a potential tool to help researchers search biomarkers of heroin addiction.

Differences in the amplitude of low-frequency fluctuation between methamphetamine and heroin use disorder individuals: A resting-state fMRI study.

INTRODUCTION: Methamphetamine has surpassed heroin as the most popular abused drug in China. Although the use of both heroin and methamphetamine leads to use disorders through dysfunction of the dopamine pathway, the incidence of psychiatric disorder caused by methamphetamine abuse is higher than the incidence of psychiatric disorder caused by heroin abuse. The difference in resting-state function between heroin use disorder (HUD) and methamphetamine use disorder (MAUD) and the relationship between resting-state function and psychiatric disorder related to MAUD are unknown. METHODS: In the present study, 21 male individuals with MAUD, 21 demographically matched individuals with HUD, and 21 normal controls (NC) were recruited. The amplitude of low-frequency fluctuation (ALFF) during resting-state brain function was measured by magnetic resonance imaging. Psychiatric status was evaluated by the Symptom Checklist-90 (SCL90). RESULTS: Individuals with MAUD had increased SCL90 scores compared to those of the NC for anxiety, paranoia, and additional items, and the hostility score was significantly increased compared to that of individuals with HUD. There is no significant difference between HUD and NC individuals. Individuals with MAUD had increased ALFF compared to those of the NC for thalamus, right postcentral, and right inferior temporal gyri, but a decreased ALFF in the cerebellum. Individuals with HUD had significantly increased ALFF compared to those of the NC for left middle frontal gyrus but a decreased ALFF in the left postcentral gyrus. Individuals with MAUD had significantly increased ALFF compared to those of the HUD for thalamus, the right inferior temporal, and bilateral postcentral gyri, and the ALFF of cerebellum and left middle frontal was significantly increased. CONCLUSIONS: Methamphetamine can induce more serious psychiatric disorders than heroin. The resting-state function involved in mood adjustment, the auditory, and memory-related brain regions may affect psychotic symptoms related to MAUD.

Assessing drug cue-induced brain response in heroin dependents treated by methadone maintenance and protracted abstinence measures.

Methadone maintenance treatment (MMT) and protracted abstinence (PA) are common methods of therapy in heroin addiction as both suppress the craving for drug use. However, the difference in patterns of brain function between two groups is unknown. Functional magnetic resonance imaging (fMRI) based drug cue-reactivity task is a good tool to understand the change of brain function during a certain period of treatment. Twenty-three heroin-dependent patients during PA, 18 heroin-dependent patients during MMT and 20 healthy control (HC) individuals were included to conduct the heroin cue-reactivity task during fMRI. The MMT and PA patients' subjective craving for heroin was evaluated. Differences among the three groups were analyzed with respect to heroin cue induced brain responses. Compared with HC group, MMT and PA groups commonly demonstrated significantly higher brain responses during exposure of heroin-related cues in the bilateral caudate, right thalamus, left hippocampus, parahippocampus, midbrain, left superior parietal lobule, right middle occipital gyrus, left posterior cingulate cortex and right cerebellum. However, compared with PA group, MMT group demonstrated significantly greater brain response mainly in right caudate, hippocampus, midbrain left fusiform, right inferior parietal lobule, left posterior cingulate cortex, cerebellum and postcentral gyrus. No difference in cue induced craving between MMT and PA groups was found. The findings suggest that MMT group demonstrated more enhanced drug cue induced brain responses than PA group, indicating that, these two treatments have different effect on patterns of brain response to heroin related cues in heroin-dependent individuals.