We used a novel computerized decision-making task to

Groups of subjects whose primary drug of abuse was

Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiatedependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants were administered the Tower of London (TOL) planning task and the 3D-IDED attentional set-shifting task to assess executive function, and Paired Associates Learning and Delayed Pattern Recognition Memory tasks to assess visual memory function. The three groups of substance users showed significant impairments on TOL planning, Pattern Recognition Memory and Paired Associates Learning. Current amphetamine users displayed a greater degree of impairment than current opiate users. Consistent with previous research showing that healthy men are performing better on visuo-spatial tests than women, our male controls remembered significantly more paired associates than their female counterparts. This relationship was reversed in drug users. While performance of female drug users was normal, male drug users showed significant impairment compared to both their female counterparts and male controls. There was no difference in performance between current and former drug users. Neither years of drug abuse nor years of drug abstinence were associated with performance. Chronic drug users display pronounced neuropsychological impairment in the domains of executive and memory function. Impairment persists after several years of drug abstinence and may reflect neuropathology in frontal and temporal cortices.

Rationale-There is converging evidence for impairments in decision-making in chronic substance users. In the light of findings that substance abuse is associated with disruptions of the functioning of the striato-thalamo-orbitofrontal circuits, it has been suggested that decision- Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts making impairments are linked to frontal lobe dysfunction. We sought to investigate this possibility using functional neuroimaging.Methods-Decision-making was investigated using the Cambridge Risk Task during H 2 15 O PET scans. A specific feature of the Risk Task is the decisional conflict between an unlikely high reward option and a likely low reward option. Four groups, each consisting of 15 participants, were compared: chronic amphetamine users, chronic opiate users, ex-drug users who had been long-term amphetamine/opiate users but are abstinent from all drugs of abuse for at least 1 year and healthy matched controls without a drug-taking history.Results-During decision-making, control participants showed relatively greater activation in the right dorsolateral prefrontal cortex, whereas participants engaged in current or previous drug use showed relatively greater activation in the left orbitofrontal cortex.Conclusion-Our results indicate a disturbance in the mediation by the prefrontal cortex of a risky decision-making task associated with amphetamine and opiate abuse. Moreover, this disturbance was observed in a group of former drug users who had been abstinent for at least 1 year.

Reinforcing properties of psychoactive substances are considered to be critically involved in the development and maintenance of substance dependence. While accumulating evidence suggests that the sensitivity to reinforcement values may generally be altered in chronic substance users, relatively little is known about the influence reinforcing feedback exerts on ongoing decision-making in these individuals. Decision-making was investigated using the Cambridge Risk Task, in which there is a conflict between an unlikely large reward option and a likely small reward option. Responses on a given trial were analyzed with respect to the outcome on the previous trial, providing a measure of the impact of prior feedback in modulating behavior. Five different groups were compared: (i) chronic amphetamine users, (ii) chronic opiate users in methadone maintenance treatment (MMT), (iii) chronic users of illicit heroin, (iv) ex-drug users who had been long-term amphetamine/opiate users but were abstinent from all drugs of abuse for at least 1 year and (v) matched controls without a history of illicit substance use. Contrary to our predictions, choice preference was modified in response to feedback only in opiate users enrolled in MMT. Following a loss, the MMT opiate group chose the likely small reward option significantly less frequently than controls and heroin users. Our results suggest that different opiates are associated with distinctive behavioral responses to feedback. These findings are discussed with respect to the different mechanisms of action of heroin and methadone.