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1.  Elucidating Poor Decision-Making in a Rat Gambling Task 
PLoS ONE  2013;8(12):e82052.
Although poor decision-making is a hallmark of psychiatric conditions such as attention deficit/hyperactivity disorder, pathological gambling or substance abuse, a fraction of healthy individuals exhibit similar poor decision-making performances in everyday life and specific laboratory tasks such as the Iowa Gambling Task. These particular individuals may provide information on risk factors or common endophenotypes of these mental disorders. In a rodent version of the Iowa gambling task – the Rat Gambling Task (RGT), we identified a population of poor decision makers, and assessed how these rats scored for several behavioral traits relevant to executive disorders: risk taking, reward seeking, behavioral inflexibility, and several aspects of impulsivity. First, we found that poor decision-making could not be well predicted by single behavioral and cognitive characteristics when considered separately. By contrast, a combination of independent traits in the same individual, namely risk taking, reward seeking, behavioral inflexibility, as well as motor impulsivity, was highly predictive of poor decision-making. Second, using a reinforcement-learning model of the RGT, we confirmed that only the combination of extreme scores on these traits could induce maladaptive decision-making. Third, the model suggested that a combination of these behavioral traits results in an inaccurate representation of rewards and penalties and inefficient learning of the environment. Poor decision-making appears as a consequence of the over-valuation of high-reward-high-risk options in the task. Such a specific psychological profile could greatly impair clinically healthy individuals in decision-making tasks and may predispose to mental disorders with similar symptoms.
doi:10.1371/journal.pone.0082052
PMCID: PMC3855331  PMID: 24339988
2.  The Functional Anatomy of Impulse Control Disorders 
Impulsive–compulsive disorders such as pathological gambling, hypersexuality, compulsive eating, and shopping are side effects of the dopaminergic therapy for Parkinson’s disease. With a lower prevalence, these disorders also appear in the general population. Research in the last few years has discovered that these pathological behaviors share features similar to those of substance use disorders (SUD), which has led to the term “behavioral addictions”. As in SUDs, the behaviors are marked by a compulsive drive toward and impaired control over the behavior. Furthermore, animal and medication studies, research in the Parkinson’s disease population, and neuroimaging findings indicate a common neurobiology of addictive behaviors. Changes associated with addictions are mainly seen in the dopaminergic system of a mesocorticolimbic circuit, the so-called reward system. Here we outline neurobiological findings regarding behavioral addictions with a focus on dopaminergic systems, relate them to SUD theories, and try to build a tentative concept integrating genetics, neuroimaging, and behavioral results.
doi:10.1007/s11910-013-0386-8
PMCID: PMC3779310  PMID: 23963609
Behavioral addictions; Pathological gambling; Binge eating; Compulsive buying; Hypersexuality; Substance use disorders; Mesocorticolimbic circuit; Reward system; Dopamine; Parkinson; Parkinson’s disease; Neurobiology; Risk factors; Impulse control disorders; Functional anatomy
3.  Gambling 
Over the past several decades, and particularly during the last 10 to 15 years, there has been a rapid increase in the accessibility of legalized gambling in the United States and other parts of the world. Few studies have systematically explored the relationships between patterns of gambling and health status. Existing data support the notion that some gambling behaviors, particularly problem and pathological gambling, are associated with nongambling health problems. The purpose of this article is to provide a perspective on the relationship between gambling behaviors and substance use disorders, review the data regarding health associations and screening and treatment options for problem and pathological gambling, and suggest a role for generalist physicians in assessing problem and pathological gambling. A rationale for conceptualization of pathological gambling as an addictive disorder and a model proposing stress as a possible mediating factor in the relationship between gambling and health status are presented. More research is needed to investigate directly the biological and health correlates associated with specific types of gambling behaviors and to define the role for generalist physicians in the prevention and treatment of problem and pathological gambling.
doi:10.1046/j.1525-1497.2002.10812.x
PMCID: PMC1495100  PMID: 12220370
addiction; pathological gambling; treatment; prevention; substance abuse
4.  The Neurobiology of Impulse Control Disorders 
Objective
To review the neurobiological substrates of impulse control disorders (ICDs). Pathological gambling (PG) is a main focus of the review in that most biological studies of the formal ICDs have examined this disorder.
Methods
The medical database MedLine from 1966 to present was searched to identify relevant articles that were subsequently reviewed to generate this manuscript.
Results
Preclinical studies suggest that differential brain monoamine neuromodulation is associated with impulsive decision-making and risk-taking behaviors. Clinical studies implicate multiple neurotransmitter systems (serotonergic, dopaminergic, adrenergic, and opioidergic) in the pathophysiology of PG and other ICDs. Initial neuroimaging studies have implicated the ventromedial prefrontal cortex and ventral striatum in the pathophysiology of PG and other ICDs. Genetic contributions to PG seem substantial and initial studies have implicated specific allelic polymorphisms, although genome-wide analyses have yet to be published.
Conclusion
Although significant advances have been made in our understanding of the neurobiology of ICDs, more research is needed to extend existing knowledge and translate these findings into clinical advances.
PMCID: PMC3676928  PMID: 18278382
Pathological Gambling; Serotonin; Norepinephrine; Dopamine; Opioids; Impulsivity; Stress; Genetics; Brain Imaging; Biochemistry
5.  Similarities and Differences between Pathological Gambling and Substance Use Disorders: A Focus on Impulsivity and Compulsivity 
Psychopharmacology  2011;219(2):469-490.
Rationale
Pathological gambling (PG) has recently been considered as a “behavioral” or non-substance addiction. A comparison of characteristics of PG and substance use disorders (SUDs) has clinical ramifications and could help advance future research on these conditions. Specific relationships with impulsivity and compulsivity may be central to understanding PG and SUDs.
Objectives
To compare and contrast research findings in PG and SUDs pertaining to neurocogntive tasks, brain function and neurochemistry, with a focus on impulsivity and compulsivity.
Results
Multiple similarities were found between PG and SUDs, including poor performance on neurocognitive tasks, specifically with respect to impulsive choice and response tendencies and compulsive features (e.g., response perseveration and action with diminished relationship to goals or reward). Findings suggest dysfunction involving similar brain regions, including the ventromedial prefrontal cortex (PFC) and striatum and similar neurotransmitter systems, including dopaminergic and serotonergic. Unique features exist which may in part reflect influences of acute or chronic exposures to specific substances.
Conclusions
Both similarities and differences exist between PG and SUDs. Understanding these similarities more precisely may facilitate treatment development across addictions, whereas understanding differences may provide insight into treatment development for specific disorders. Individual differences in features of impulsivity and compulsivity may represent important endophenotypic targets for prevention and treatment strategies.
doi:10.1007/s00213-011-2550-7
PMCID: PMC3249521  PMID: 22057662
Iowa Gambling Task; delay discounting; neuroimaging; alcohol; cocaine; dopamine; serotonin; glutamate; frontal cortex; striatum
6.  Fronto-striatal dysregulation in drug addiction and pathological gambling: Consistent inconsistencies?☆ 
NeuroImage : Clinical  2013;2:385-393.
Alterations in appetitive processing are central to the major psychological theories of addiction, with differential predictions made by the reward deficiency, incentive salience, and impulsivity hypotheses. Functional MRI has become the chief means of testing these predictions, with experiments reliably highlighting disturbances at the level of the striatum, medial prefrontal cortex, and affiliated regions. However, demonstrations of hypo-reactivity and hyper-reactivity of this circuitry in drug addicted groups are reported in approximately equal measure. Similar findings are echoed in the emergent neuroimaging literature on pathological gambling, which has recently witnessed a coming of age. The first aim of this article is to consider some of the methodological aspects of these experiments that could influence the observed direction of group-level effects, including the baseline condition, trial structure and timing, and the nature of the appetitive cues (drug-related, monetary, or primary rewards). The second aim is to highlight the conceptual traction that is offered by pathological gambling, as a model of a ‘toxicity free’ addiction and an illness where tasks of monetary reinforcement afford a more direct mapping to the abused commodity. Our conclusion is that relatively subtle decisions in task design appear capable of driving group differences in fronto-striatal circuitry in entirely opposing directions, even with tasks and task variants that look ostensibly similar. Differentiation between the psychological theories of addiction will require a greater breadth of experimental designs, with more research needed on processing of primary appetitive cues, aversive processing, and in vulnerable/at-risk groups.
Highlights
•We outline the current psychological theories of addiction and their predictions.•We review recent fMRI literature of substance addictions and appetitive processing.•Reasons for opposing results (hyper- vs hypo-active reward regions) are discussed.•Recent fMRI findings of appetitive processing in pathological gambling are reviewed.•Pathological gambling is suggested as a prototypical addiction for imaging research.
doi:10.1016/j.nicl.2013.02.005
PMCID: PMC3777686  PMID: 24179792
Addiction; Pathological gambling; fMRI; Ventral striatum; Appetitive processing
7.  Dispositional Mindfulness as a Predictor of the Severity of Gambling Outcomes 
Two studies were conducted to test and explain the relation of mindfulness to the severity of gambling outcomes among frequent gamblers. In both studies, dispositional mindfulness related to less severe gambling outcomes as measured by a DSM-IV-based screen for pathological gambling, even after controlling for gambling frequency and dispositional self-control. Study 2 extended this finding in showing that the association between mindfulness and lower pathological gambling was partially mediated by better performance on two risk-taking tasks that capture overconfidence, risky bet acceptance, and myopic focus on reward. These studies suggest a role for mindfulness in lessening the severity of gambling problems and making adaptive decisions, especially in risk-relevant contexts.
doi:10.1016/j.paid.2007.05.007
PMCID: PMC2748809  PMID: 19777140
MINDFULNESS; OVERCONFIDENCE; RISK-TAKING; GAMBLING; DECISION-MAKING
8.  Delay and Probability Discounting in Pathological Gamblers With and Without a History of Substance Use Problems 
Psychopharmacology  2011;219(2):491-499.
Rationale
Pathological gambling and substance use disorders are highly comorbid, possibly because they both stem from a similar process—impulsivity. Although much data exist regarding the association between delay discounting and these psychiatric disorders, relatively little research has examined probability discounting and its relationship with either substance use or gambling.
Objectives
The goal of the current study was to compare rates of probability and delay discounting in a large population of pathological gamblers with and without a history of substance use problems.
Methods
Treatment-seeking pathological gamblers with (n=117) and without (n=119) a history of substance use problems completed questionnaires about discounting of hypothetical monetary outcomes and the Eysenck Impulsivity Questionnaire. The delay discounting questionnaire involved choices between a smaller amount of money delivered immediately versus a larger amount delivered later, and the probability questionnaire was comprised of choices between a smaller certain versus a larger probabilistic monetary outcome. Hyperbolic functions estimated delay and probability discounting rates based on the indifference points obtained through the questionnaires.
Results
Results revealed significant effects of substance use problem status on delay but not on probability discounting, with no significant correlation noted between the two discounting processes. Only delay discounting correlated with Eysenck impulsivity scores.
Conclusions
These data suggest that delay and probability discounting tap different dimensions, and delay discounting is more closely linked with substance use problem histories in pathological gamblers.
doi:10.1007/s00213-011-2508-9
PMCID: PMC3629698  PMID: 21952671
pathological gamblers; substance use problems; choice; delay discounting; probability discounting; impulsivity
9.  The Iowa Gambling Task and the three fallacies of dopamine in gambling disorder 
Gambling disorder sufferers prefer immediately larger rewards despite long term losses on the Iowa Gambling Task (IGT), and these impairments are associated with dopamine dysfunctions. Dopamine is a neurotransmitter linked with temporal and structural dysfunctions in substance use disorder, which has supported the idea of impaired decision-making and dopamine dysfunctions in gambling disorder. However, evidence from substance use disorders cannot be directly transferred to gambling disorder. This article focuses on three hypotheses of dopamine dysfunctions in gambling disorder, which appear to be “fallacies,” i.e., have not been supported in a series of positron emission tomography (PET) studies. The first “fallacy” suggests that gambling disorder sufferers have lower dopamine receptor availability, as seen in substance use disorders. However, no evidence supported this hypothesis. The second “fallacy” suggests that maladaptive decision-making in gambling disorder is associated with higher dopamine release during gambling. No evidence supported the hypothesis, and the literature on substance use disorders offers limited support for this hypothesis. The third “fallacy” suggests that maladaptive decision-making in gambling disorder is associated with higher dopamine release during winning. The evidence did not support this hypothesis either. Instead, dopaminergic coding of reward prediction and uncertainty might better account for dopamine dysfunctions in gambling disorder. Studies of reward prediction and reward uncertainty show a sustained dopamine response toward stimuli with maximum uncertainty, which may explain the continued dopamine release and gambling despite losses in gambling disorder. The findings from the studies presented here are consistent with the notion of dopaminergic dysfunctions of reward prediction and reward uncertainty signals in gambling disorder.
doi:10.3389/fpsyg.2013.00709
PMCID: PMC3792697  PMID: 24115941
gambling disorder; Iowa Gambling Task (IGT); dopamine; addiction; positron-emission tomography
10.  Individual Differences and Decision Making: When the Lure Effect of Gain Is a Matter of Size 
PLoS ONE  2013;8(3):e58946.
The Iowa Gambling Task (IGT) is widely used in investigations of decision making. A growing number of studies have linked performance on this task to personality differences, with the aim of explaining the large degree of variability in healthy individuals' performance of the task. However, this line of research has yielded inconsistent results. In the present study, we tested whether increasing the conflict between short-term and long-term gains in the IGT can clarify personality-related modulations of decision making. We assessed performance on the original IGT as a function of the personality traits typically involved in risky decision making (i.e., impulsivity, sensation seeking, sensitivity to reward and punishment). The impact of these same personality traits was also evaluated on a modified version of the task in which the difference in immediate reward magnitude between disadvantageous and advantageous decks was increased, while keeping the net gain fixed. The results showed that only in this latter IGT variant were highly impulsive individuals and high sensation seekers lured into making disadvantageous choices. The opposite seems to be the case for participants who were highly sensitive to punishment, although further data are needed to corroborate this finding. The present preliminary results suggest that the IGT variant used in this study could be more effective than the original task at identifying personality effects in decision making. Implications for dispositional and situational effects on decision making are discussed.
doi:10.1371/journal.pone.0058946
PMCID: PMC3590131  PMID: 23484058
11.  The neurobiology of pathological gambling and drug addiction: an overview and new findings 
Gambling is a prevalent recreational behaviour. Approximately 5% of adults have been estimated to experience problems with gambling. The most severe form of gambling, pathological gambling (PG), is recognized as a mental health condition. Two alternate non-mutually exclusive conceptualizations of PG have considered it as an obsessive-compulsive spectrum disorder and a ‘behavioural’ addiction. The most appropriate conceptualization of PG has important theoretical and practical implications. Data suggest a closer relationship between PG and substance use disorders than exists between PG and obsessive-compulsive disorder. This paper will review data on the neurobiology of PG, consider its conceptualization as a behavioural addiction, discuss impulsivity as an underlying construct, and present new brain imaging findings investigating the neural correlates of craving states in PG as compared to those in cocaine dependence. Implications for prevention and treatment strategies will be discussed.
doi:10.1098/rstb.2008.0100
PMCID: PMC2607329  PMID: 18640909
gambling; addiction; impulsivity; impulse control disorder; brain imaging; functional magnetic resonance imaging
12.  Increased Functional Connectivity between Prefrontal Cortex and Reward System in Pathological Gambling 
PLoS ONE  2013;8(12):e84565.
Pathological gambling (PG) shares clinical characteristics with substance-use disorders and is thus discussed as a behavioral addiction. Recent neuroimaging studies on PG report functional changes in prefrontal structures and the mesolimbic reward system. While an imbalance between these structures has been related to addictive behavior, whether their dysfunction in PG is reflected in the interaction between them remains unclear. We addressed this question using functional connectivity resting-state fMRI in male subjects with PG and controls. Seed-based functional connectivity was computed using two regions-of-interest, based on the results of a previous voxel-based morphometry study, located in the prefrontal cortex and the mesolimbic reward system (right middle frontal gyrus and right ventral striatum). PG patients demonstrated increased connectivity from the right middle frontal gyrus to the right striatum as compared to controls, which was also positively correlated with nonplanning aspect of impulsiveness, smoking and craving scores in the PG group. Moreover, PG patients demonstrated decreased connectivity from the right middle frontal gyrus to other prefrontal areas as compared to controls. The right ventral striatum demonstrated increased connectivity to the right superior and middle frontal gyrus and left cerebellum in PG patients as compared to controls. The increased connectivity to the cerebellum was positively correlated with smoking in the PG group. Our results provide further evidence for alterations in functional connectivity in PG with increased connectivity between prefrontal regions and the reward system, similar to connectivity changes reported in substance use disorder.
doi:10.1371/journal.pone.0084565
PMCID: PMC3868704  PMID: 24367675
13.  Effects of Acute Pramipexole on Male Rats’ Preference for Gambling-like Rewards II 
Pramipexole (PPX) is a dopamine agonist medication that has been implicated in the development of pathological gambling and other impulse control disorders. Johnson, Madden, Brewer, Pinkston, and Fowler (2011) reported that PPX increased male rats’ preference for gambling-like rewards (those arranged according to a variable-ratio schedule) over predictable rewards (those obtained from a fixed-ratio schedule). The present experiment explored the possibility that Johnson et al. underestimated the effects of PPX on gambling-like choices by constraining their rats’ daily income. In the present experiment conducted in a closed economy, PPX produced a dose-related increase in choice of the gambling-like alternative. In a control condition, PPX did not disrupt choice, suggesting the increased preference for gambling-like rewards was not due to nonspecific drug effects. Our findings are qualitatively consistent with those of Johnson et al., although the dose-related effect and larger effect size in the current study suggest that the effect of PPX on gambling-like choices is more pronounced when income was not constrained. This finding is consistent with clinical reports suggesting PPX is related to the development of problem gambling in humans.
doi:10.1037/a0027117
PMCID: PMC3482126  PMID: 22288460
pramipexole; dopamine agonist; gambling; Parkinson’s disease; rat
14.  A neurocognitive comparison of cognitive flexibility and response inhibition in gamblers with varying degrees of clinical severity 
Psychological Medicine  2011;41(10):2111-2119.
Background
As a behavioral addiction with clinical and phenomenological similarities to substance addiction, recreational and pathological gambling represent models for studying the neurobiology of addiction, without the confounding deleterious brain effects which may occur from chronic substance abuse.
Method
A community sample of individuals aged 18–65 years who gamble was solicited through newspaper advertising. Subjects were grouped a priori into three groups (no-risk, at-risk, and pathological gamblers) based on a diagnostic interview. All subjects underwent a psychiatric clinical interview and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Subjects with a current axis I disorder, history of brain injury/trauma, or implementation or dose changes of psychoactive medication within 6 weeks of study enrollment were excluded.
Results
A total of 135 no-risk, 69 at-risk and 46 pathological gambling subjects were assessed. Pathological gamblers were significantly older, and exhibited significant deficiencies in motor impulse control (stop-signal reaction times), response speed (median ‘go’ trial response latency) and cognitive flexibility [total intra-dimensional/extra-dimensional (IDED) errors] versus controls. The finding of impaired impulse control and cognitive flexibility was robust in an age-matched subgroup analysis of pathological gamblers. The no-risk and at-risk gambling groups did not significantly differ from each other on task performance.
Conclusions
Impaired response inhibition and cognitive flexibility exist in people with pathological gambling compared with no-risk and at-risk gamblers. The early identification of such illness in adolescence or young adulthood may aid in the prevention of addiction onset of such disabling disorders.
doi:10.1017/S0033291711000316
PMCID: PMC3381334  PMID: 21426627
Cognition; gambling; impulsivity
15.  Selective decision-making deficits in at-risk gamblers 
Psychiatry Research  2011;189(1):115-120.
Despite reasonable knowledge of pathological gambling (PG), little is known of its cognitive antecedents. We evaluated decision-making and impulsivity characteristics in people at risk of developing PG using neuropsychological tests. Non-treatment seeking volunteers (18-29 years) who gamble ≥5 times/year were recruited from the general community, and split into two groups: those “at risk” of developing PG (n=74) and those social, non-problem gamblers (n=112). Participants undertook the Cambridge Gamble and Stop-signal tasks and were assessed with the Mini-International Neuropsychiatric Interview and the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling. On the Cambridge Gamble task, the at- risk subjects gambled more points overall, were more likely to go bankrupt, and made more irrational decisions under situations of relative risk ambiguity. On the Stop-signal task, at- risk gamblers did not differ from the social, non-problem gamblers in terms of motor impulse control (stop-signal reaction times). Findings suggest that selective cognitive dysfunction may already be present in terms of decision-making in at-risk gamblers, even before psychopathology arises. These findings implicate selective decision-making deficits and dysfunction of orbitofronto-limbic circuitry in the chain of pathogenesis between social, non-problematic and pathological gambling.
doi:10.1016/j.psychres.2011.05.034
PMCID: PMC3401062  PMID: 21715016
Pathological Gambling; Pathogenesis; Addiction; Cognitive Dysfunction; Cognition; Inhibition
16.  Reviewing Two Types of Addiction – Pathological Gambling and Substance Use 
Gambling, including pathological gambling and problem gambling, has received increased attention from clinicians and researchers over the past three decades since gambling opportunities have expanded around the world. Gambling disorders affect 0.2–5.3% of adults worldwide, although measurement and prevalence varies according to the screening instruments and methods used, and availability and accessibility of gambling opportunities. Several distinct treatment approaches have been favorably evaluated, such as cognitive behavioral and brief treatment models and pharmacological interventions. Although promising, family therapy and support from Gamblers Anonymous are less well empirically supported. Gambling disorders are highly comorbid with other mental health and substance use disorders, and a further understanding is needed of both the causes and treatment implications of this disorder. This article reviews definition, causes and associated features with substance abuse, screening and diagnosis, and treatment approaches.
doi:10.4103/0253-7176.96147
PMCID: PMC3361844  PMID: 22661800
Addiction; gambling; substance use
17.  Diminished fronto-striatal activity during processing of monetary rewards and losses in pathological gambling 
Biological psychiatry  2012;71(8):749-757.
Background
Mesocorticolimbic neurocircuitry and impulsivity have both been implicated in pathological gambling (PG) and in reward processing. However, the neural underpinnings of specific phases of reward and loss processing in PG and their relationships to impulsivity remain only partially understood. The present functional magnetic resonance imaging study examined brain activity associated with different phases of reward and loss processing in PG. Given an inverse relationship between ventral striatal recruitment during anticipation of monetary rewards and impulsivity in alcohol dependence, the current study explored whether a similar association might also be present in PG.
Methods
Fourteen adults with PG and 14 control comparison (CC) participants performed the Monetary Incentive Delay Task (MIDT) to identify brain activation changes associated with reward/loss prospect, reward/loss anticipation and reward/loss notification. Impulsivity was assessed separately using the Barratt Impulsiveness Scale.
Results
Relative to the CC group, the PG group exhibited significantly reduced activity in the ventromedial prefrontal cortex, insula and ventral striatum during several phases, including the prospect and anticipation phases of both gain and losses. Activity in the ventral striatum correlated inversely with levels of impulsivity in PG participants, consistent with prior findings in alcohol dependence.
Conclusions
Relatively decreased activity in cortico-striatal neurocircuitry during multiple phases of reward processing suggests consistent alterations in neurocircuitry underlying incentive valuation and loss prediction. Together with findings in alcohol dependence, these results suggest that impulsive tendencies in addictions may be reflected in diminished ventral striatal activations to reward anticipation and may represent targets for treatment development in addictions.
doi:10.1016/j.biopsych.2012.01.006
PMCID: PMC3460522  PMID: 22336565
fMRI; vmPFC; ventral striatum; insula; incentive; gambling
18.  Impulsive Action but Not Impulsive Choice Determines Problem Gambling Severity 
PLoS ONE  2012;7(11):e50647.
Background
Impulsivity is a hallmark of problem gambling. However, impulsivity is not a unitary construct and this study investigated the relationship between problem gambling severity and two facets of impulsivity: impulsive action (impaired ability to withhold a motor response) and impulsive choice (abnormal aversion for the delay of reward).
Methods
The recruitment includes 65 problem gamblers and 35 normal control participants. On the basis of DSM-IV-TR criteria, two groups of gamblers were distinguished: problem gamblers (n = 38) and pathological gamblers (n = 27) with similar durations of gambling practice. Impulsive action was assessed using a response inhibition task (the stop-signal task). Impulsive choice was estimated with the delay-discounting task. Possible confounds (e.g., IQ, mood, ADHD symptoms) were recorded.
Results
Both problem and pathological gamblers discounted reward at a higher rate than their controls, but only pathological gamblers showed abnormally low performance on the most demanding condition of the stop-signal task. None of the potential confounds covaried with these results.
Conclusions
These results suggest that, whereas abnormal impulsive choice characterizes all problem gamblers, pathological gamblers' impairments in impulsive action may represent an important developmental pathway of pathological gambling.
doi:10.1371/journal.pone.0050647
PMCID: PMC3507734  PMID: 23209796
19.  Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review 
Neuropsychopharmacology  2009;35(3):591-604.
Failures in cortical control of fronto-striatal neural circuits may underpin impulsive and compulsive acts. In this narrative review, we explore these behaviors from the perspective of neural processes and consider how these behaviors and neural processes contribute to mental disorders such as obsessive–compulsive disorder (OCD), obsessive–compulsive personality disorder, and impulse-control disorders such as trichotillomania and pathological gambling. We present findings from a broad range of data, comprising translational and human endophenotypes research and clinical treatment trials, focussing on the parallel, functionally segregated, cortico-striatal neural projections, from orbitofrontal cortex (OFC) to medial striatum (caudate nucleus), proposed to drive compulsive activity, and from the anterior cingulate/ventromedial prefrontal cortex to the ventral striatum (nucleus accumbens shell), proposed to drive impulsive activity, and the interaction between them. We suggest that impulsivity and compulsivity each seem to be multidimensional. Impulsive or compulsive behaviors are mediated by overlapping as well as distinct neural substrates. Trichotillomania may stand apart as a disorder of motor-impulse control, whereas pathological gambling involves abnormal ventral reward circuitry that identifies it more closely with substance addiction. OCD shows motor impulsivity and compulsivity, probably mediated through disruption of OFC-caudate circuitry, as well as other frontal, cingulate, and parietal connections. Serotonin and dopamine interact across these circuits to modulate aspects of both impulsive and compulsive responding and as yet unidentified brain-based systems may also have important functions. Targeted application of neurocognitive tasks, receptor-specific neurochemical probes, and brain systems neuroimaging techniques have potential for future research in this field.
doi:10.1038/npp.2009.185
PMCID: PMC3055606  PMID: 19940844
impulsive; compulsive; endophenotypes; serotonin; dopamine; Cognition; Psychiatry & Behavioral Sciences; Animal models; Biological Psychiatry; OCD; impulsivity; compulsivity; translational
20.  Effect of executive functioning, decision-making and self-reported impulsivity on the treatment outcome of pathologic gambling 
Background
Impairments in self-regulatory behaviour reflect a deficit in executive functioning and decision-making, as well as higher levels of self-reported impulsivity, and may be involved in the development and maintenance of addictive disorders. We sought to explore the association between self-reported impulsivity and neurocognitive measures, and their association with treatment outcome in pathologic gambling.
Methods
We assessed patients with pathologic gambling using executive functioning and decision-making tests and self-report measures of impulsivity. Patients underwent cognitive–behavioural therapy (CBT) for pathologic gambling.
Results
We included 88 patients (8% women) in our study. High self-reported extravagance was associated with poor performance in the Iowa Gambling Task (IGT)-ABCD version. High impulsiveness, low disorderliness, high exploratory excitability (trend), poor backward block span and poor IGT-EFGH scores (trend) predicted dropout. We observed no self-reported or neurocognitive predictors of relapse or number of treatment sessions attended.
Limitations
Most participants were slot-machine gamblers seeking treatment. No follow-up data and no control group were included in the study. The missing sample (i.e., individuals who were recruited and assessed in the pretreatment stage but who chose not to begin treatment) had higher extravagance scores than the final sample.
Conclusion
Neurocognitive reward sensitivity was related to self-reported overspending behaviour. Self-regulatory impairments (especially rash impulsiveness and punishment sensitivity) and executive dysfunction predicted only dropout of CBT in participants with pathologic gambling. Different neurocognitive processes and personality traits might mediate treatment response to psychological therapy of pathologic gambling according to the specific target variable assessed.
doi:10.1503/jpn.090095
PMCID: PMC3080512  PMID: 21138656
21.  Discounting of probabilistic rewards is associated with gambling abstinence in treatment-seeking pathological gamblers 
Journal of abnormal psychology  2011;121(1):151-159.
Individuals with addictive disorders, including substance abusers and pathological gamblers, discount or devalue rewards delayed in time more than controls. Theoretically, preference for probabilistic rewards is directly related to gambling, but limited empirical research has examined probabilistic discounting in individuals with pathological gambling. This study evaluated probability and delay discounting in treatment-seeking pathological gamblers and their association with gambling treatment outcomes during and following treatment. At time of treatment entry, 226 pathological gamblers completed probability and delay discounting tasks. They were then randomized to one of three treatment conditions, and gambling behavior was measured throughout treatment and at a one-year follow-up assessment. After controlling for possibly confounding variables and treatment condition, more shallow probability discounting was associated with greater reductions in amounts wagered during treatment and likelihood of gambling abstinence at the end of treatment and throughout the follow-up period. No associations were noted between delay discounting and gambling treatment outcomes. These data suggest that probability discounting may be an important construct in understanding pathological gambling and its treatment.
doi:10.1037/a0024782
PMCID: PMC3773696  PMID: 21842965
probability discounting; pathological gambling; treatment
22.  Recreational gamblers with and without parental addiction 
Psychiatry Research  2012;196(2-3):290-295.
Research has found that children who have parents with an addiction may be more vulnerable to developing psychopathology compared to children without parental addiction. We compared young adult, recreational gamblers with and without parental addiction on measures of gambling behavior and impulsivity. A total of 286 recreational gamblers (defined as having gambled at least five times in the past 12 months) between the ages of 18 and 29 participated in an initial intake of a longitudinal study assessing susceptibility to pathological gambling. Trained staff interviewed subjects and subjects completed cognitive testing and self-report measures. Fifty-three subjects (18.53%) reported at least one parent with an addiction (including alcohol and substance dependence and pathological gambling). Subjects with at least one addicted parent were significantly more likely to report problems resulting from gambling, have significantly greater rates of psychiatric comorbidity, and report significantly more current marijuana and tobacco use. Subjects with an addicted parent were not significantly different on measures of impulsivity. These findings suggest that even at a stage of low-risk gambling, before what has been considered a psychopathology arises, those with a possible environmental and/or genetic risk of addiction exhibit a range of problematic behaviors.
doi:10.1016/j.psychres.2011.12.019
PMCID: PMC3380340  PMID: 22401973
Pathological Gambling; Psychopathology; Addiction; Family History; Young Adults
23.  Endogenous cortisol levels are associated with an imbalanced striatal sensitivity to monetary versus non-monetary cues in pathological gamblers 
Pathological gambling is a behavioral addiction characterized by a chronic failure to resist the urge to gamble. It shares many similarities with drug addiction. Glucocorticoid hormones including cortisol are thought to play a key role in the vulnerability to addictive behaviors, by acting on the mesolimbic reward pathway. Based on our previous report of an imbalanced sensitivity to monetary versus non-monetary incentives in the ventral striatum of pathological gamblers (PGs), we investigated whether this imbalance was mediated by individual differences in endogenous cortisol levels. We used functional magnetic resonance imaging (fMRI) and examined the relationship between cortisol levels and the neural responses to monetary versus non-monetary cues, while PGs and healthy controls were engaged in an incentive delay task manipulating both monetary and erotic rewards. We found a positive correlation between cortisol levels and ventral striatal responses to monetary versus erotic cues in PGs, but not in healthy controls. This indicates that the ventral striatum is a key region where cortisol modulates incentive motivation for gambling versus non-gambling related stimuli in PGs. Our results extend the proposed role of glucocorticoid hormones in drug addiction to behavioral addiction, and help understand the impact of cortisol on reward incentive processing in PGs.
doi:10.3389/fnbeh.2014.00083
PMCID: PMC3971166  PMID: 24723862
cortisol; reward; pathological gambling; fMRI; ventral striatum; addiction; incentive; glucocorticoid hormones
24.  Aboriginal Gambling and Problem Gambling: A Review 
The prevention of gambling-related problems amongst Aboriginal communities has been neglected by most public health strategies which concentrate on mainstream populations. Research indicates that rates of problem gambling are higher for Aboriginal groups than the general population. Specific cultural, familial, and social patterns influence gambling by Aboriginal groups, which are individually different, making it difficult to implement a cohesive strategy to address gambling-related harms. Because of this complexity, a thorough literature review is necessary to identify gaps in policy and research. This paper uses a public health framework to consider multi-dimensional influences (personal, environmental, economic, cultural and social) that affect gambling uptake. Such analysis is also important for identifying risk factors which facilitate the development and maintenance of problem gambling and potentially for underpinning protection, prevention and treatment programs. It is advised that strategies be developed in consultation with Aboriginal peoples to guide public health policy and research to minimise any gambling-related harms.
doi:10.1007/s11469-012-9400-7
PMCID: PMC3971442
Gambling; Aboriginal; Indigenous; Culture; Risk factors; Public health
25.  Decision Making in the Reward and Punishment Variants of the Iowa Gambling Task: Evidence of “Foresight” or “Framing”? 
Surface-level differences in the reward and punishment variants, specifically greater long-term decision making in the punishment variant of the Iowa Gambling Task (IGT) observed in previous studies led to the present comparison of long-term decision making in the two IGT variants (n = 320, male = 160). It was contended that risk aversion triggered by a positive frame of the reward variant and risk seeking triggered by a negative frame of the punishment variant appears as long-term decision making in the two IGT variants. Apart from the frame of the variant as a within-subjects factor (variant type: reward and punishment), the order in which the frame was triggered (order type: reward–punishment or punishment–reward), and the four types of instructions that delineated motivation toward reward from that of punishment (reward, punishment, reward and punishment, and no-hint) were hypothesized to have an effect on foresighted decision making in the IGT. As expected, long-term decision making differed across the two IGT variants suggesting that the frame of the variant has an effect on long-term decision making in the IGT (p < 0.001). The order in which a variant was presented, and the type of the instructions that were used both had an effect on long-term decision making in the two IGT variants (p < 0.05). A post hoc test suggested that the instructions that differentiated between reward and punishment resulted in greater foresight than the commonly used IGT instructions that fail to distinguish between reward and punishment. As observed in previous studies, there were more number of participants (60%) who showed greater foresight in the punishment variant than in the reward variant (p < 0.001). The results suggest that foresight in IGT decision making is sensitive to reward and punishment frame in an asymmetric manner, an observation that is aligned with the behavioral decision making framework. Benefits of integrating findings from behavioral studies in decision neuroscience are discussed, and a need to investigate cultural differences in the IGT studies is pointed out.
doi:10.3389/fnins.2012.00107
PMCID: PMC3400253  PMID: 22833714
Iowa gambling task; reward–punishment; instructions; decision making; framing effect

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