Robust changes in reward circuitry during reward loss in current and former cocaine users during performance of a monetary incentive delay task.

BACKGROUND: Abnormal function in reward circuitry in cocaine addiction could predate drug use as a risk factor, follow drug use as a consequence of substance-induced alterations, or both. METHODS: We used a functional magnetic resonance imaging monetary incentive delay task (MIDT) to investigate reward-loss neural response differences among 42 current cocaine users, 35 former cocaine users, and 47 healthy subjects who also completed psychological measures and tasks related to impulsivity and reward. RESULTS: We found various reward processing-related group differences in several MIDT phases. Across task phases we found a control > current user > former user activation pattern, except for loss outcome, where former compared with current cocaine users activated ventral tegmental area more robustly. We also found regional prefrontal activation differences during loss anticipation between cocaine-using groups. Both groups of cocaine users scored higher than control subjects on impulsivity, compulsivity and reward-punishment sensitivity factors. In addition, impulsivity-related factors correlated positively with activation in amygdala and negatively with anterior cingulate activation during loss anticipation. CONCLUSIONS: Compared with healthy subjects, both former and current users displayed abnormal brain activation patterns during MIDT performance. Both cocaine groups differed similarly from healthy subjects, but differences between former and current users were localized to the ventral tegmental area during loss outcome and to prefrontal regions during loss anticipation, suggesting that long-term cocaine abstinence does not normalize most reward circuit abnormalities. Elevated impulsivity-related factors that relate to loss processing in current and former users suggest that these tendencies and relationships may pre-exist cocaine addiction.

Reward-related dorsal striatal activity differences between former and current cocaine dependent individuals during an interactive competitive game.

Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses).

Individuals family history positive for alcoholism show functional magnetic resonance imaging differences in reward sensitivity that are related to impulsivity factors.

BACKGROUND: Substance-abusing individuals tend to display abnormal reward processing and a vulnerability to being impulsive. Detoxified alcoholics show differences in regional brain activation during a monetary incentive delay task. However, there is limited information on whether this uncharacteristic behavior represents a biological predisposition toward alcohol abuse, a consequence of chronic alcohol use, or both. METHODS: We investigated proposed neural correlates of substance disorder risk by examining reward system activity during a monetary incentive delay task with separate reward prospect, reward anticipation, and reward outcome phases in 30 individuals with and 19 without family histories of alcoholism. All subjects were healthy, lacked DSM-IV past or current alcohol or substance abuse histories, and were free of illegal substances as verified by a urine toxicology screening at the time of scanning. Additionally, we explored specific correlations between task-related nucleus accumbens (NAcc) activation and distinct factor analysis-derived domains of behavioral impulsivity. RESULTS: During reward anticipation, functional magnetic resonance imaging data confirmed blunted NAcc activation in family history positive subjects. In addition, we found atypical activation in additional reward-associated brain regions during additional task phases. We further found a significant negative correlation between NAcc activation during reward anticipation and an impulsivity construct. CONCLUSIONS: Overall, results demonstrate that sensitivity of the reward circuit, including NAcc, is functionally different in alcoholism family history positive individuals in multiple regards.

Investigating the behavioral and self-report constructs of impulsivity domains using principal component analysis.

Impulsivity, often defined as a human behavior characterized by the inclination of an individual to act on urge rather than thought, with diminished regard to consequences, encompasses a range of maladaptive behaviors, which are in turn affected by distinct neural systems. Congruent with the above definition, behavioral studies have consistently shown that the underlying construct of impulsivity is multidimensional in nature. However, research to date has been inconclusive regarding the different domains or constructs that constitute this behavior. In addition there is also no clear consensus as to whether self-report and laboratory based measures of impulsivity measure the same or different domains. This study aimed to: (i) characterize the underlying multidimensional construct of impulsivity using a sample with varying degrees of putative impulsivity related to substance misuse, including subjects who were at-risk of substance use or addicted (ARA), and (ii) assess relationships between self-report and laboratory measures of impulsivity, using a principal component-based factor analysis. In addition, our supplementary goal was to evaluate the structural constructs of impulsivity within each group separately (healthy and ARA). We used five self-report measures (Behavioral Inhibition System/Behavioral Activation System, Barratt Impulsivity Scale-11, Padua Inventory, Zuckerman Sensation Seeking Scale, and Sensitivity to Punishment and Sensitivity to Reward Questionnaire) and two computer-based laboratory tasks (Balloon Analog Risk Task and the Experiential Discounting Task) to measure the aspects of impulsivity in a total of 176 adult subjects. Subjects included healthy controls (n = 89), nonalcoholic subjects with family histories of alcoholism (family history positive; n = 36) and both former (n = 20) and current (n = 31) cocaine users. Subjects with a family history of alcoholism and cocaine abusers were grouped together as 'at-risk/addicted' (ARA) to evaluate our supplementary goal. Our overall results revealed the multidimensional nature of the impulsivity construct as captured optimally through a five-factor solution that accounted for nearly 70% of the total variance. The five factors/components were imputed as follows 'Self-Reported Behavioral Activation', 'Self-Reported Compulsivity and Reward/Punishment', 'Self-Reported Impulsivity', 'Behavioral Temporal Discounting', and 'Behavioral Risk-Taking'. We also found that contrary to previously published reports, there was significant overlap between certain laboratory and self-report measures, indicating that they might be measuring the same impulsivity domain. In addition, our supplemental analysis also suggested that the impulsivity constructs were largely, but not entirely the same within the healthy and ARA groups.