Abnormal brain activity during a reward and loss task in opiate dependent patients receiving methadone maintenance therapy

A core feature of human drug dependency is persistence in seeking and using drugs at the expense of other life goals. It has been hypothesised that addiction is associated with over-valuation of drug-related rewards and under-valuation of natural, non-drug related rewards. Humans additionally tend to persist in using drugs despite adverse consequences. This suggests that the processing of both rewarding and aversive information may be abnormal in addictions. We used fMRI to examine neural responses to reward and loss events in opiate dependent patients receiving Methadone Maintenance Treatment (MMT, n=30) and healthy controls (n=23) using non-drug related stimuli. Half of the patients were scanned after/before daily methadone intake (ADM/BDM patient groups). During reward trials, patients as a whole exhibited decreased neural discrimination between rewarding and non-rewarding outcomes in the dorsal caudate. Patients also showed reduced neural discrimination in the ventral striatum with regard to aversive and non-aversive outcomes, and failed to encode successful loss-avoidance as a reward signal in the ventral striatum. Patients additionally showed decreased insula activation during the anticipation/decision phase of loss events. ADM patients exhibited increased loss signals in the midbrain/para-hippocampal gyrus, possibly related to a disinhibition of dopamine neurons. This study suggests that patients with opiate dependency on MMT exhibit abnormal brain activations to non-drug related rewarding and loss events. Our findings add support to proposals that treatments for opiate addiction should aim to increase the reward value of non-drug related rewarding events, and highlights the importance of potential abnormalities in aversive information processing.