Anna E. Goudriaan

Pathological gambling; A comprehensive review of biobehavioral findings

In this review, findings of biobehavioral research into pathological gambling (PG) are discussed, focusing on neuropsychological, psychophysiological, neuroimaging, neurochemical and genetic studies. Neuropsychological studies indicate deficiencies in certain executive functions. Psychophysiological studies indicate that arousal in PG is of importance when reward is present. Neuroimaging studies point to abnormalities in brain functioning. Recent research into the neurochemistry of PG indicates that abnormalities exist in different neurotransmitter systems. Finally, genetic studies indicate the existence of abnormal dopamine receptor genes in PG. Methodological and theoretical factors that may explain discrepancies between studies include differences in screening and assessment, heterogeneity of gambling problems and different underlying cognitive or motivational mechanisms. Results from the PG studies fit in with recent theoretical models of addiction and PG, which stress the involvement of brain reward pathways, neurotransmitter abnormalities, the frontal cortex and the psychophysiological stress system. A framework for future studies is suggested, indicating the need for studies that integrate knowledge from different research areas, and that employ stricter diagnostic screening methods and inclusion of clinical control groups.

Why gamblers fail to win: A review of cognitive and neuroimaging findings in pathological gambling

The purpose of this review is to gain more insight in the neuropathology of pathological gambling (PG) and problem gambling, and to discuss challenges in this research area. Results from the reviewed PG studies show that PG is more than just an impulse control disorder. PG seems to fit very well with recent theoretical models of addiction, which stress the involvement of the ventral tegmental-orbito frontal cortex. Differentiating types of PG on game preferences (slot machines vs. casino games) seems to be useful because different PG groups show divergent results, suggesting different neurobiological pathways to PG. A framework for future studies is suggested, indicating the need for hypothesis driven pharmacological and functional imaging studies in PG and integration of knowledge from different research areas to further elucidate the neurobiological underpinnings of this disorder.

Response Perseveration and Ventral Prefrontal Sensitivity to Reward and Punishment in Male Problem Gamblers and Smokers

Pathological gambling (PG) is associated with maladaptive perseverative behavior, but the underlying mechanism and neural circuitry is not completely clear. Here, the hypothesis was tested that PG is characterized by response perseveration and abnormalities in reward and/or punishment sensitivity in the ventral frontostriatal circuit. Executive functioning was assessed to verify if these effects are independent of the dorsal frontostriatal circuit. A group of smokers was also included to examine whether impairments in PG generalize to substance use disorders. Response perseveration and reward/punishment sensitivity were measured with a probabilistic reversal-learning task, in which subjects could win and lose money. Executive functioning was measured with a planning task, the Tower of London. Performance and fMRI data were acquired in 19 problem gamblers, 19 smokers, and 19 healthy controls. Problem gamblers showed severe response perseveration, associated with reduced activation of right ventrolateral prefrontal cortex in response to both monetary gain and loss. Results did not fully generalize to smokers. Planning performance and related activation of the dorsal frontostriatal circuit were intact in both problem gamblers and smokers. PG is related to response perseveration and diminished reward and punishment sensitivity as indicated by hypoactivation of the ventrolateral prefrontal cortex when money is gained and lost. Moreover, intact planning abilities and normal dorsal frontostriatal responsiveness indicate that this deficit is not due to impaired executive functioning. Response perseveration and ventral prefrontal hyporesponsiveness to monetary loss may be markers for maladaptive behavior seen in chemical and nonchemical addictions.

The role of self-reported impulsivity and reward sensitivity versus neurocognitive measures of disinhibition and decision-making in the prediction of relapse in pathological gamblers.

BACKGROUND Disinhibition and decision-making skills play an important role in theories on the cause and outcome of addictive behaviors such as substance use disorders and pathological gambling. In recent studies, both disinhibition and disadvantageous decision-making strategies, as measured by neurocognitive tests, have been found to influence the course of substance use disorders. Research on factors affecting relapse in pathological gambling is scarce. METHOD This study investigated the effect of both self-reported impulsivity and reward sensitivity, and neurocognitively assessed disinhibition and decision-making under conflicting contingencies, on relapse in a group of 46 pathological gamblers. RESULTS Logistic regression analysis indicated that longer duration of the disorder and neurocognitive indicators of disinhibition (Stop Signal Reaction Time) and decision-making (Card Playing Task) were significant predictors of relapse (explaining 53% of the variance in relapse), whereas self-reported impulsivity and reward sensitivity did not significantly predict relapse. Overall classification accuracy was 76%, with a positive classification accuracy of 76% and a negative classification accuracy of 75%. CONCLUSIONS Duration of the disorder and neurocognitive measures of disinhibition and decision-making are powerful predictors of relapse in pathological gambling. The results suggest that endophenotypical neurocognitive characteristics are more promising in the prediction of relapse in pathological gambling than phenotypical personality characteristics. Neurocognitive predictors may be useful to guide treatment planning of follow-up contacts and booster sessions.

Grey matter alterations associated with cannabis use: results of a VBM study in heavy cannabis users and healthy controls

Cannabis abuse is related to impairments in a broad range of cognitive functions. However, studies on cannabis abuse in relation to brain structure are sparse and results are inconsistent, probably due to differences in imaging methodology, severity of cannabis abuse, and use of other substances. The goal of the current MRI study was to investigate brain morphology related to current and lifetime severity of cannabis use and dependence in heavy cannabis users without intensive use of other illicit drugs. Voxel-based morphometry was used to assess differences in regional grey and white matter volume between 33 heavy cannabis users and 42 matched controls. Within heavy cannabis users, grey and white matter volume was correlated with measures of cannabis use and dependence. Analyses were focused a priori on the orbitofrontal cortex, anterior cingulate cortex, striatum, amygdala, hippocampus, and cerebellum, regions implicated in substance dependence and/or with high cannabinoid receptor-1 concentrations. Regional grey matter volume in the anterior cerebellum was larger in heavy cannabis users. Within the group of heavy cannabis users, grey matter volume in the amygdala and hippocampus correlated negatively with the amount of cannabis use or dependence. No associations were found between white matter volume and measures of cannabis use or dependence. These findings indicate that associations between heavy cannabis use and altered brain structure are complex. Differential patterns of structural changes for various cannabis use levels imply that alterations in brain structure are associated with specific characteristics of cannabis use and dependence.

The relationship between impulsive choice and impulsive action: a cross-species translational study.

Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task) and impulsive action (five-choice serial reaction time task) paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT) and impulsive action (immediate and delayed memory task, IMT/DMT). Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action) and filled out the Barratt impulsiveness scale (BIS-11). Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1) self-reported impulsivity (BIS-11); (2) impulsive action (IMT/DMT and SST); (3) impulsive choice (DDT). This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology.

New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity

Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, which are mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this article, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive, and addictive disorders and indicate new directions for research.

Effects of non-invasive neurostimulation on craving: A meta-analysis

This meta-analysis was conducted to evaluate the available evidence regarding the effects of non-invasive neurostimulation of the dorsolateral prefrontal cortex (DLPFC), on craving in substance dependence and craving for high palatable food. Non-invasive neurostimulation techniques were restricted to repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS). A total of 17 eligible studies were identified. Random effects analysis revealed a pooled standardized effect size (Hedges g) of 0.476 (CI: 0.316-0.636), indicating a medium effect size favouring active non-invasive neurostimulation over sham stimulation in the reduction of craving (z=5.832, p<0.001). No significant differences were found between rTMS and tDCS, between the various substances of abuse and between substances of abuse and food, or between left and right DLPFC stimulation. In conclusion, this meta-analysis provides the first clear evidence that non-invasive neurostimulation of the DLPFC decreases craving levels in substance dependence.

Impulsivity as a vulnerability factor for poor addiction treatment outcomes : a review of neurocognitive findings among individuals with substance use disorders

With the current review, we explore the hypothesis that individual differences in neurocognitive aspects of impulsivity (i.e., cognitive and motor disinhibition, delay discounting and impulsive decision-making) among individuals with a substance use disorder are linked to unfavorable addiction treatment outcomes, including high drop-out rates and difficulties in achieving and maintaining abstinence. A systematic review of the literature was carried out using PubMed, PsycINFO and Web of Knowledge searches. Twenty-five unique empirical papers were identified and findings were considered in relation to the different impulsivity dimensions. Although conceptual/methodological heterogeneity and lack of replication are key limitations of studies in this area, findings speak for a prominent role of cognitive disinhibition, delay discounting and impulsive decision-making in the ability to successfully achieve and maintain abstinence during and following addiction treatment. In contrast, indices of motor disinhibition appear to be unrelated to abstinence levels. Whereas the relationship between impulsivity and treatment retention needs to be examined more extensively, preliminary evidence suggests that impulsive/risky decision-making is unrelated to premature treatment drop-out among individuals with a substance use disorder. The reviewed findings are discussed in terms of their clinical implications.

Reaching out towards cannabis: approach-bias in heavy cannabis users predicts changes in cannabis use

Aims Repeated drug exposure can lead to an approach-bias, i.e. the relatively automatically triggered tendencies to approach rather that avoid drug-related stimuli. Our main aim was to study this approach-bias in heavy cannabis users with the newly developed cannabis Approach Avoidance Task (cannabis-AAT) and to investigate the predictive relationship between an approach-bias for cannabis-related materials and levels of cannabis use, craving, and the course of cannabis use. Design, settings and participants Cross-sectional assessment and six-month follow-up in 32 heavy cannabis users and 39 non-using controls. Measurements Approach and avoidance action-tendencies towards cannabis and neutral images were assessed with the cannabis AAT. During the AAT, participants pulled or pushed a joystick in response to image orientation. To generate additional sense of approach or avoidance, pulling the joystick increased picture size while pushing decreased it. Craving was measured pre- and post-test with the multi-factorial Marijuana Craving Questionnaire (MCQ). Cannabis use frequencies and levels of dependence were measured at baseline and after a six-month follow-up. Findings Heavy cannabis users demonstrated an approach-bias for cannabis images, as compared to controls. The approach-bias predicted changes in cannabis use at six-month follow-up. The pre-test MCQ emotionality and expectancy factor were associated negatively with the approach-bias. No effects were found on levels of cannabis dependence. Conclusions Heavy cannabis users with a strong approach-bias for cannabis are more likely to increase their cannabis use. This approach-bias could be used as a predictor of the course of cannabis use to identify individuals at risk from increasing cannabis use.