Brain responses to drug cues predict craving changes in abstinent heroin users: A preliminary study

Background: Loss of control over drug intake occurring in drug addiction is believed to result from disruption of reward circuits, including reduced responsiveness to natural rewards (e.g., monetary, sex) and heightened responsiveness to drug reward. Yet few studies have assessed reward deficiency and related brain responses in abstinent heroin users with opioid use disorder, and less is known whether the brain responses can predict cue-induced craving changes following by prolonged abstinence. Method: 31 heroin users (age: 44.13 +/- 7.68 years, male: 18 (58%), duration of abstinence: 85.2 +/- 52.5 days) were enrolled at a mandatory detoxification center. By employing a cue-reactivity paradigm including three types of cues (drug, sexual, neutral), brain regional activations and circuit-level functional coupling were extracted. Among the 31 heroin users, 15 were followed up longitudinally to assess cue induced craving changes in the ensuing 6 months. Results: One way analysis of variance results showed that heroin users have differential brain activations to the three cues (neutral, drug and sexual) in the left dorsolateral prefrontal cortex (DLPFC), insula, orbiotofrontal cortex (OFC) and the bilateral thalamus. Drug cue induced greater activations in left DLPFC, insula and OFC compared to sexual cue. The psychophysiological interactions (PPI) analysis revealed negative couplings of the left DLPFC and the left OFC, bilateral thalamus, putamen in heroin users during drug cue exposure. In the 6-month follow-up study, both drug cue induced activation of the left DLPFC and the functional coupling of the left DLPFC-bilateral thalamus at baseline was correlated with craving reductions, which were not found for sexual cues. Conclusion: Our preliminary study provided novel evidence for the reward deficiency theory of opioid use disorder. Our findings also have clinical implications, as drug cue induced activation of the left DLPFC and functional coupling of left DLPFC-bilateral thalamus may be potential neuroimaging markers for craving changes during prolonged abstinence. Evidently, the findings in the current preliminary study should be confirmed by large sample size in the future.