Altered brain intrinsic functional hubs and connectivity associated with relapse risk in heroin dependents undergoing methadone maintenance treatment: A resting-state fMRI study.

BACKGROUND:The neural substrates underlying the relapse behavior of heroin dependents (HD) who received long-term methadone maintenance treatment (MMT) have yet to be thoroughly expounded. This study investigated the relapse-related intrinsic functional hubs of HD and their functional integration feature at whole brain network level. METHODS:57 male HD receiving MMT and 49 matched healthy controls (HC) were enrolled. All of the subjects received resting-state functional magnetic resonance imaging scan. And the 57 patients were assigned a 26-month follow-up for collecting illegal drug use information. Of them, 11 were non-relapsers and 46 relapsers. We analyzed the voxel-based degree centrality (DC) to reveal the differences in nodule centrality between HD and HC, conducted Pearson partial-correlation analysis to confirm the relationship between relapse frequency and DC value of the nodes with significant intergroup differences, and finally compared the functional connectivity (FC) of the relapse-related hubs between non-relapsers and relapsers. RESULTS:We found the DC values of right insula and left nucleus accumbens (NAc) were negatively correlated with relapse frequency. Compared with the non-relapsers, the relapsers had a significant decreased FC between left NAc and inhibitory control circuitry, including left dorsolateral prefrontal cortex, left inferior frontal gyrus and motor regions. CONCLUSIONS:These findings suggest that the neural substrates of relapse vulnerability in HD undergoing MMT are the intrinsic functional hubs of introceptive and reward systems and the latter modulates relapse behavior via interaction with inhibitory control circuit.