Abnormal Brain Activity During a Reward and Loss Task in Opiate-Dependent Patients Receiving Methadone Maintenance Therapy

Abstract

A core feature of human drug dependency is persistence in seeking and using drugs at the expense of other life goals. It has been hypothesized that addiction is associated with overvaluation of drug-related rewards and undervaluation of natural, nondrug-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 ¼ 30) and healthy controls (n ¼ 23) using nondrug-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 nonrewarding outcomes in the dorsal caudate. Patients also showed reduced neural discrimination in the ventral striatum with regard to aversive and nonaversive outcomes and failed to encode successful loss avoidance as a reward signal in the ventral striatum. Patients also showed decreased insula activation during the anticipation/decision phase of loss events. ADM patients exhibited increased loss signals in the midbrain/ parahippocampal gyrus, possibly related to a disinhibition of dopamine neurons. This study suggests that patients with opiate dependency on MMT exhibit abnormal brain activations to nondrug-related rewarding and loss events. Our findings add support to proposals that treatments for opiate addiction should aim to increase the reward value of nondrug-related rewarding events and highlight the importance of potential abnormalities in aversive information processing.

Acute naltrexone does not remediate fronto‐striatal disturbances in alcoholic and alcoholic polysubstance‐dependent populations during a monetary incentive delay task

“…The current result concurs with previous research findings of altered striatal activity for non-drug rewards in substance dependence (Buhler et al, 2010;Bustamante et al, 2014;Diekhof et al, 2008;Gradin et al, 2014;Peters et al, 2011;Wrase et al, 2007) and may be consistent with a sustained striatal reward deficiency syndrome (Blum et al, 2000;Koob et al, 2004) in long-term substance abstinence. There are also high levels of MORs in the caudate (Arvidsson et al, 1995), making this region a credible target for modulation with naltrexone.…”

Exaggerated Acquisition and Resistance to Extinction of Avoidance Behavior in Treated Heroin-Dependent Men

“…However, decreased reward-seeking behavior is insufficient to explain avoidance differences on the current task, since female controls obtained less reward (fewer points) than male controls but showed no differences on avoidance responding. It is possible that male patients had abnormal learning of both the appetitive and aversive components of the current task 53 or had lower learning rates, which impaired the ability of reinforcement to alter their behavior. 54 …”

Smokers and ex‐smokers have shared differences in the neural substrates for potential monetary gains and losses

“…Previous research has reported altered striatal activity for non-drug rewards in substance dependence (Buhler et al, 2010;Bustamante et al, 2014;Diekhof et al, 2008;Gradin et al, 2014;Peters et al, 2011;Wrase et al, 2007) with some evidence for a sustained striatal reward deficiency syndrome (Blum et al, 2000) in long-term substance abstinence. The current finding of increased ventral putamen and caudate activation in ex-smokers suggests that they have an increased motivational signal in a reward-motor network where preparatory responses might be optimized to avoid loss.…”