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.