The difference in the effect of methadone and protracted abstinence on the coupling among key large-scale brain networks of individuals with heroin use disorder: A resting-state fMRI study

Background Methadone maintenance treatment (MMT) and protracted abstinence (PA) effectively reduce the craving for heroin among individuals with heroin use disorder (HUD). However, the difference in their effects on brain function, especially the coupling among the large-scale brain networks (default mode [DMN], salience [SN], and executive control [ECN] networks), remains unclear. This study analyzed the effects of the MMT and PA on these networks and the predictive value of the bilateral resource allocation index (RAI) for craving for heroin. Methods Twenty-five individuals undergoing the MMT, 22 undergoing the PA, and 51 healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Independent component analysis identified the ECN, DMN, and SN. The SN-ECN and SN-DMN connectivity and the bilateral RAI were evaluated. The relationships between network coupling and clinical and psychological characteristics were analyzed. The multiple linear regression model identified significant variables for predicting craving scores. Results The MMT group showed significantly stronger SN-left ECN (lECN) coupling and left RAI than the PA group. In the MMT group, SN-lECN connectivity and bilateral RAI were positively correlated with the total methadone dose. In both treatment groups, SN-right ECN (rECN) connectivity and right RAI were negatively correlated with craving. The models revealed that the bilateral RAI and the MMT and PA were associated with the craving. Conclusions The MMT enhances SN-lECN coupling and the left RAI more than the PA, possibly due to higher control modulation. The RAI could help predict heroin craving in individuals with HUD undergoing either treatment program.