How Top-Down and Bottom-Up Regulation in Fronto-Amygdalar Network Changes over Time during Drug Cue-Exposure: An fMRI Study among Abstinent Heroin User

Top-down regulation is one of the major neural cores in drug-craving management and relapse prevention. The dynamic temporal behavior of top-down regulation between the dorso-lateral and ventro-medial prefrontal cortices (DLPFC and VMPFC) and amygdala during drug cue-exposure has not been studied yet. Fifteen abstinent participants with heroin use disorder were scanned using drug cue-induced craving fMRI task. Using Dynamic Causal Modelling (DCM), the winning model showed a significant reciprocal connection between the VMPFC and DLPFC while there was a one-way effect of the VMPFC on the amygdala. There is also a top-down modulation by DLPFC on the VMPFC-Amygdala connection. Craving contrast input only modulated amygdala directly. Using sliding-window for temporal evaluation, craving input to amygdala increased over time, simultaneously, DLPFC top-down modulatory effect on VMPFC-amygdala connection decreased. Temporal changes in the network connectivity during cue exposure with enhancement in craving input to amygdala and reduction in top-down modulatory effects of DLPFC, could provide us with new insights towards the dynamic nature of the cue-reactivity and failure to control its motivational consequences. Dynamic response of top-down regulatory networks during cue exposure can be considered as a new potential biomarker in the future addiction fMRI studies.