Disrupted Functional Connectivity with Dopaminergic Midbrain in Cocaine Abusers

Background: Chronic cocaine use is associated with disrupted dopaminergic neurotransmission but how this disruption affects overall brain function (other than reward/motivation) is yet to be fully investigated. Here we test the hypothesis that cocaine addicted subjects will have disrupted functional connectivity between the midbrain (where dopamine neurons are located) and cortical and subcortical brain regions during the performance of a sustained attention task. Methodology/Principal Findings: We measured brain activation and functional connectivity with fMRI in 20 cocaine abusers and 20 matched controls. When compared to controls, cocaine abusers had lower positive functional connectivity of midbrain with thalamus, cerebellum, and rostral cingulate, and this was associated with decreased activation in thalamus and cerebellum and enhanced deactivation in rostral cingulate. Conclusions/Significance: These findings suggest that decreased functional connectivity of the midbrain interferes with the activation and deactivation signals associated with sustained attention in cocaine addicts

Executive Dysfunction and Reward Dysregulation: Interactions in Drug Addiction

Cocaine addiction is a serious public health hazard, and contributes to disastrous outcomes for individuals who suffer from it. Addiction is accompanied by an inability to control one\u27s own behavior, and a preoccupation with cocaine at the expense of other rewarding pursuits. Previous research has suggested that difficulties with executive function and reward processing may underlie these problems, but the extent to which each contributes to addiction severity, or how these two factors may interact, remains to be elucidated. By using event related potential (ERP) measures in combination with information about self-reported anhedonia over three experiments, we set out to more clearly define the phenotype of cocaine addiction and to investigate the extent to which executive dysfunction and reward dysregulation are associated with addiction severity. A model was designed to examine these factors. In addition, in a fourth study we investigated the integrity of executive functioning in both neutral and emotional contexts in abstinent cocaine users. We found that cocaine users show much more anhedonia than controls, and this anhedonia is associated with addiction severity. In addition, anhedonia is associated with poorer ability to monitor behavior when working toward reward, with increased reward motivation in both controls and cocaine users, and also with reduced consummatory reward response in cocaine users. Intriguingly, however, anhedonia is not associated with executive function deficits that are found in cocaine users, and these same executive function deficits are not associated with addiction severity. Finally, we show these executive function deficits to be normalized in abstinent cocaine abusers, and show that abstinent cocaine abusers do not modulate inhibitory response in response to emotional stimuli. Combined, these findings suggest that addiction is a phenotype defined by the presence of both reward dysregulation and executive dysfunction, and that reward dysregulation especially is associated with increased severity of the syndrome. These findings are then discussed in terms of a possible mechanistic model

Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence

A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n = 60) with data on healthy volunteers (n = 60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption

The relationship between executive functioning and substance abuse

Substance use disorders are a widespread issue in society today with approximately 20 million people in the U.S. alone experiencing drug-related problems (Substance Abuse and Mental Health Services Administration, 2012). However, treatment is often ineffectual with approximately 50% of addicted individuals returning to substance use. One factor found to impact individuals\u27 treatment response is their neuropsychological functioning. Drug-abusers frequently exhibit severe executive functioning impairments across a number of domains, and there is evidence that these deficits may be time and substance-dependent. Executive functions are mental processes critical in motivation, planning, and goal-directed behaviors. With extended abstinence, research suggests cognitive improvements will occur for many addicts. The goal of the present study was to evaluate specific impairments in cognitive abilities and executive functions associated with substance abuse for individuals entering residential treatment and to assess the relationship between self-report executive functioning problems and functioning observed on neuropsychological tests. It was hypothesized that participants would exhibit significant impairments in the areas of working memory, set-shifting, inhibition, planning, verbal fluency, and sustained attention. Further, it was hypothesized that improvements in executive functioning would be observed after approximately 45 days of treatment. Moreover, it was hypothesized that executive functioning measures, both self-report and performance-based, would predict substance-related problems, years of abuse, and problematic personality traits. Finally, better neurocognitive functioning at intake was hypothesized to be related to treatment retention. This study examined adult participants receiving treatment within a private residential addiction center. Findings generally did not provide support for hypotheses. Results found participants reported significant levels of executive functioning problems but exhibited significantly poorer performance on only one neuropsychological measure (Comprehensive Trail-Making Task) compared to established norms which indicated deficits in set-shifting ability. Further, significant improvements at follow-up testing were observed in only three executive functioning tasks, although fewer executive functioning problems were reported by participants across multiple domains. It may be that more extensive cognitive improvements were not observed given the generally average performance of the sample across the neuropsychological battery administered. Further, the only executive functioning measure found to be a significant predictor of substance-related problems and problematic personality traits was the self-report Barkley Deficits in Executive Functioning Scales. Finally, scores on initial executive functioning measures were not found to be predictive of treatment retention. One possible explanation for these results may be the characteristics of the sample studied as the participants were generally well-educated with likely higher levels of general cognitive functioning compared to similar research

Evaluation of attention bias in morphine and methamphetamine abusers towards emotional scenes during early abstinence: An eye-tracking study

Introduction: We hypothesized that inappropriate attention during the period of abstinence in individuals with substance use disorder can result in an inadequate perception of emotion and unsuitable reaction to emotional scenes. The main aim of this research was to evaluate the attentional bias towards emotional images in former substance abusers and compare it to healthy adults. Methods: Paired images of general scenes consisting of pleasant, unpleasant, and neutral images were presented to subjects for 3 s while their attentional bias and eye movements were measured by eye tracking. The participants were 72 male adults consisting of 23 healthy control, 24 morphine former abusers, and 25 methamphetamine former abusers. The former abusers were recruited from a private addiction quitting center and addiction rehabilitation campus. The healthy individuals were selected from general population. Number and duration of first fixation, duration of first gaze, and sustained attention towards emotional scenes were measured as the main variables and the data were analyzed using the repeated measures ANOVA. Results: A significant difference was observed between former morphine abusers and healthy control in terms of number and duration of first fixations and first gaze duration towards pleasant images. Discussion: Individuals with morphine use disorder have more problems with attending to emotional images compared to methamphetamine abusers and healthy people

Risk-taking and fairness among cocaine-dependent patients in dual diagnoses: Schizophrenia and Anti-Social Personality Disorder

This study reports experimental results from a clinical sample of patients with a cocaine-related disorder and dual diagnosis: Schizophrenia and Anti-Social Personality Disorder. Both types of patients as well as a non-clinical group of students performed two incentivized decision-making tasks. In the first part of the experiment, they performed a lottery-choice task in order to elicit their degree of risk aversion. In the second part, they decided in two modified dictator games aimed at eliciting their aversion to advantageous and disadvantageous inequality. It is found that the Anti-Social Personality Disorder group exhibits no significant differences from the non-clinical sample in either task. However, compared with the students’ sample, subjects from the group with schizophrenia show more risk aversion and exhibit more aversion towards disadvantageous inequality

Competing neurobehavioral decision systems and the neuroeconomics of craving in opioid addiction

Craving is typically thought of as a classically conditioned response characterized by an elevated mesolimbic dopamine response to drug-related stimuli. Although this definition has spurred considerable research, the clinical impact of the research conducted has been less robust. The current review takes a more contemporary approach by conceptualizing craving as the breakdown of executive function and relative strengthening of the limbic system, occurring in the presence of conditioned cues, leading to a maladaptive craving response (ie, an increased likelihood of drug consumption). Working from this framework, the present review focuses on four issues in drug craving research: pivotal findings and limitations of cue-reactivity and neurocognitive tasks; two main processes of craving that include self-control and reward-based explanations; integration of neuroeconomic approaches to craving; and the theoretical implications and future directions of drug craving research