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Item does not contain fulltext, Background: Psychedelic-assisted therapy [e.g., with lysergic acid diethylamide (LSD)] has shown promising results as treatment for substance use disorders (SUDs). Previous systematic reviews assessing the efficacy of psilocybin in SUDs only included clinical trials conducted in the last 25 years, but they may have missed clinical trials assessing the efficacy of psilocybin that were conducted before the 1980s, given much research has been done with psychedelics in the mid-20th century. In this systematic review, we specifically assessed the efficacy of psilocybin in patients with a SUD or non-substance-related disorder with no publication date restrictions in our search strategy. Methods: A systematic literature search was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from the earliest published manuscript up to September 2, 2022, in seven electronic databases, including clinical trials in patients with a SUD or non-substance-related disorder evaluating the efficacy of psilocybin. Results: A total of four studies (six articles, of which two articles were long-term follow-up results from the same trial) were included in this systematic review. Psilocybin-assisted therapy was administered to n = 151 patients in a dose ranging from 6 to 40 mg. Three studies focused on alcohol use disorder, and one study on tobacco use disorder. In a pilot study (n = 10), the percentage of heavy drinking days decreased significantly between baseline and weeks 5-12 (mean difference of 26.0, 95% CI = 8.7-43.2, p = 0.008). In another single-arm study (n = 31), 32% (10/31) became completely abstinent from alcohol (mean duration of follow-up 6 years). In a double-blind, placebo-controlled randomized controlled trial (RCT, n = 95), the percentage of heavy drinking days during the 32-week double-blind period was significantly lower for psilocybin compared to placebo (mean difference of 13.9, 95% CI = 3.0–24.7, p = 0.01). In a pil

Contains fulltext : 253754.pdf (Publisher’s version ) (Open Access), Background and aims: Alcohol use disorder (AUD) is a chronic disorder with high relapse rates. There are currently few clinical trials of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) to reduce alcohol use among AUD patients, and results are mixed. The current study tested the effect of 10 add-on sessions of HF-rTMS over the right dorsolateral pre-frontal cortex (DLPFC) on alcohol use and craving. Design: Single-center, single blind sham-controlled parallel-group RCT (n = 80), with 3 and 6 months follow-up. Setting: Clinical treatment center in Amsterdam, the Netherlands. Participants: Eighty detoxified and abstinent AUD inpatients in clinical treatment (20 females, average age = 44.35 years). Intervention: Ten sessions of active or sham HF-rTMS (60 10 Hz trains of 5 sec at 110% motor threshold) over the right DLPFC on 10 consecutive work-days. Measurements: The primary outcome measure is the number of abstinent days over 6-month follow-up (FU). Secondary outcome measures are craving over 6-month FU (alcohol urge questionnaire and obsessive-compulsive drinking scale), time to first relapse over 6-month FU and grams of alcohol consumed over 6-month FU. Additional outcome measures: full abstinence over 6-month FU and treatment success over 12-month FU. Findings: HF-rTMS did not affect the number of abstinent days over 6 months FU [sham = 124 ± 65.9 days, active = 115 ± 69.8 days, difference: 9 days, 95% confidence interval (CI) = Poisson model: 0.578-3.547]. Moreover, HF-rTMS did not affect craving (AUQ/OCDS) (sham = 15.38/5.28, active = 17.48/4.75, differences = 2.1/-0.53, 95% CI mixed-effects model = -9.14 to 2.07/-1.44 to 2.40). Conclusions: There was no clear evidence that high-frequency repetitive transcranial magnetic stimulation over the right dorsolateral pre-frontal cortex treatment has a long-term positive effect on alcohol use or craving as add-on treatment for alcohol use disorder. High treatment response at 6-month follow-up could

Contains fulltext : 253485.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 253754.pdf (Publisher’s version ) (Open Access), Background and aims: Alcohol use disorder (AUD) is a chronic disorder with high relapse rates. There are currently few clinical trials of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) to reduce alcohol use among AUD patients, and results are mixed. The current study tested the effect of 10 add-on sessions of HF-rTMS over the right dorsolateral pre-frontal cortex (DLPFC) on alcohol use and craving. Design: Single-center, single blind sham-controlled parallel-group RCT (n = 80), with 3 and 6 months follow-up. Setting: Clinical treatment center in Amsterdam, the Netherlands. Participants: Eighty detoxified and abstinent AUD inpatients in clinical treatment (20 females, average age = 44.35 years). Intervention: Ten sessions of active or sham HF-rTMS (60 10 Hz trains of 5 sec at 110% motor threshold) over the right DLPFC on 10 consecutive work-days. Measurements: The primary outcome measure is the number of abstinent days over 6-month follow-up (FU). Secondary outcome measures are craving over 6-month FU (alcohol urge questionnaire and obsessive-compulsive drinking scale), time to first relapse over 6-month FU and grams of alcohol consumed over 6-month FU. Additional outcome measures: full abstinence over 6-month FU and treatment success over 12-month FU. Findings: HF-rTMS did not affect the number of abstinent days over 6 months FU [sham = 124 ± 65.9 days, active = 115 ± 69.8 days, difference: 9 days, 95% confidence interval (CI) = Poisson model: 0.578-3.547]. Moreover, HF-rTMS did not affect craving (AUQ/OCDS) (sham = 15.38/5.28, active = 17.48/4.75, differences = 2.1/-0.53, 95% CI mixed-effects model = -9.14 to 2.07/-1.44 to 2.40). Conclusions: There was no clear evidence that high-frequency repetitive transcranial magnetic stimulation over the right dorsolateral pre-frontal cortex treatment has a long-term positive effect on alcohol use or craving as add-on treatment for alcohol use disorder. High treatment response at 6-month follow-up could

Contains fulltext : 241718.pdf (Publisher’s version ) (Open Access), Background: Substance use disorders (SUDs) are prevalent in the general population, tend to follow a chronic course, are associated with many individual and social problems, and often have their onset in adolescence. However, the knowledge base from prospective population surveys and treatment-outcome studies on the course of SUD in adolescents is limited at best. The present study aims to fill this gap and focuses on a subgroup that is particularly at risk for chronicity: adolescents in addiction treatment. We will investigate the rate of persistent SUD and its predictors longitudinally from adolescence to young adulthood among youth with DSM-5 SUD from the start of their addiction treatment to 2 and 4 years following treatment-entry. In addition to SUD, we will investigate the course of comorbid mental disorders, social functioning, and quality of life and their association with SUD over time. Methods/design: In a naturalistic, multi-center prospective cohort design, we will include youths (n = 420), who consecutively enter addiction treatment at ten participating organizations in the Netherlands. Inclusion is prestratified by treatment organization, to ensure a nationally representative sample. Eligible youths are 16 to 22 years old and seek help for a primary DSM-5 cannabis, alcohol, cocaine or amphetamine use disorder. Assessments focus on lifetime and current substance use and SUD, non-SUD mental disorders, family history, life events, social functioning, treatment history, quality of life, chronic stress indicators (hair cortisol) and neuropsychological tests (computerized executive function tasks) and are conducted at baseline, end of treatment, and 2 and 4 years post-baseline. Baseline data and treatment data (type, intensity, duration) will be used to predict outcome - persistence of or desistance from SUD. Discussion: There are remarkably few prospective studies worldwide that investigated the course of SUD in adolescents in addiction treatment for longer

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Objective: Economic evaluations of interventions for dual diagnosis patients are scarce. A recent randomized controlled trial has supported the effectiveness of the Self-wise, Otherwise, Streetwise (SOS) training to reduce victimization in dual diagnosis patients. The purpose of the current study was to analyze the cost-effectiveness and cost-utility of the SOS training as an add-on to care as usual (CAU). Methods: We performed an economic evaluation from a societal perspective alongside the SOS trial. Participants were 250 dual diagnosis patients recruited at three locations from a large urban psychiatric service in the Netherlands. The main outcomes were treatment response for victimization and quality-adjusted life years (QALYs). Both costs and effects were measured across a 14-month follow-up. Results: There was no significant difference between CAU + SOS and CAU in total costs (mean difference €4,859; 95% CI [−€4,795 to €14,513]) and QALY gains (mean difference 0.0012; 95% CI [−0.05 to 0.05]). Significantly more participants in CAU + SOS achieved treatment response for victimization compared to CAU (68% vs. 54%; mean difference 0.14; 95% CI [0.02 to 0.26]). The cost-effectiveness analysis indicated an 83% likelihood that CAU + SOS resulted in a higher treatment response rate for victimization at higher costs compared to CAU. The cost-utility analysis indicated that adding SOS-training to CAU is probably not cost-effective at conventional willingness-to-pay levels for QALYs. Conclusions: At a societal willingness-to-pay of €38,000 or more per extra treatment responder, adding SOS-training to usual care is probably more attractive than usual care alone with regard to cost-effectiveness. This is a considerable willingness to pay. However, the direct costs of offering the SOS training are expected to be minor. Our findings should be interpreted with caution due to the short follow-up period and absence of data on potential reductions in police and judicial costs ot

Contains fulltext : 221828.pdf (Publisher’s version ) (Open Access)

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Contains fulltext : 200963.pdf (publisher's version ) (Closed access), Objective: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. Method: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. Results: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent contr

Item does not contain fulltext, Cannabis exerts its psychoactive effect through cannabinoid receptors that are widely distributed across the cortical surface of the human brain. It is suggested that cannabis use may contribute to structural alterations across the cortical surface. In a large, multisite dataset of 120 controls and 141 cannabis users, we examined whether differences in key characteristics of the cortical surface - including cortical thickness, surface area, and gyrification index were related to cannabis use characteristics, including (i) cannabis use vs. non-use, (ii) cannabis dependence vs. non-dependence vs. non-use, and (iii) early adolescent vs. late adolescent onset of cannabis use vs. non-use. Our results revealed that cortical morphology was not associated with cannabis use, dependence, or onset age. The lack of effect of regular cannabis use, including problematic use, on cortical structure in our study is contrary to previous evidence of cortical morphological alterations (particularly in relation to cannabis dependence and cannabis onset age) in cannabis users. Careful reevaluation of the evidence on cannabis-related harm will be necessary to address concerns surrounding the long-term effects of cannabis use and inform policies in a changing cannabis regulation climate.

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.

Item does not contain fulltext, Background: The party drug gamma hydroxybutyrate (GHB) is highly addictive. GHB use disorder (GUD) has poor treatment outcome, with relapse rates over 60% within 3 months after detoxification. In order to get a better understanding of the limited treatment success, we explored GUD patients' illness perceptions and treatment needs. Methods: In a qualitative cross-sectional observational study, using a semi-structured interview based on the works of Kleinmann, illness perceptions were explored among treatment seeking GUD patients (n = 20). The analysis was based on the principles of Grounded Theory by the 2 interviewers and an independent researcher. Results: GUD patients had mainly positive views toward GHB. GHB was perceived as strongly rewarding and perceived as the solution to psychosocial problems, rather than the cause. After repeated readmissions, GUD patients perceived themselves as addicted to GHB and GHB use as more problematic. They reported a need for personalized treatment goals, which were mainly aimed toward dealing with psychiatric symptoms and social reintegration. Conclusion: GUD shares many characteristics with other substance use disorders, in line with gradual development from positive reinforcement in early-stage GUD to negative reinforcement in later stages of more compulsive GHB use. Future studies should investigate whether personalization of treatment goals, such as social reintegration, lead to better treatment outcomes.

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Background: The US National Institutes of Mental Health Research Domain Criteria (RDoC) seek to stimulate research into biologically validated neuropsychological dimensions across mental illness symptoms and diagnoses. The RDoC framework comprises 39 functional constructs designed to be revised and refined, with the overall goal of improving diagnostic validity and treatments. This study aimed to reach a consensus among experts in the addiction field on the ‘primary’ RDoC constructs most relevant to substance and behavioural addictions. Methods: Forty-four addiction experts were recruited from Australia, Asia, Europe and the Americas. The Delphi technique was used to determine a consensus as to the degree of importance of each construct in understanding the essential dimensions underpinning addictive behaviours. Expert opinions were canvassed online over three rounds (97% completion rate), with each consecutive round offering feedback for experts to review their opinions. Results: Seven constructs were endorsed by ≥ 80% of experts as ‘primary’ to the understanding of addictive behaviour: five from the Positive Valence System (reward valuation, expectancy, action selection, reward learning, habit); one from the Cognitive Control System (response selection/inhibition); and one expert-initiated construct (compulsivity). These constructs were rated to be related differentially to stages of the addiction cycle, with some linked more closely to addiction onset and others more to chronicity. Experts agreed that these neuropsychological dimensions apply across a range of addictions. Conclusions: The study offers a novel and neuropsychologically informed theoretical framework, as well as a cogent step forward to test transdiagnostic concepts in addiction research, with direct implications for assessment, diagnosis, staging of disorder, and treatment.

Contains fulltext : 216292.pdf (Publisher’s version ) (Open Access), Gambling disorder (GD) is characterized by an inability to stop or control gambling behaviour and is often accompanied by gambling-related cognitive distortions. Task-based functional Magnetic Resonance Imaging (fMRI) studies have revealed abnormal responses within the prefrontal and insular cortex, and mesolimbic reward regions. Studies examining resting-state functional connectivity in GD, although limited in number, have so far applied seed-based analysis approaches which revealed altered brain functioning. Here, we applied data-driven Independent Components Analysis to resting-state multi-echo fMRI data. Networks of interest were selected by spatially correlating them to independently derived network templates. Using dual regression, we compared connectivity strength between 20 GD patients and 20 healthy controls within 4 well-known networks (the ventral attention, limbic, frontoparietal control, and default mode network) and an additional basal ganglia component. Compared to controls, GD patients showed increased integration of the right middle insula within the ventral attention network, an area suggested to play an important role in addiction-related drive. Moreover, our findings indicate that gambling-related cognitive distortions - a hallmark of GD - were positively related to stronger integration of the amygdala, medial prefrontal cortex and insula within various resting-state networks.

Contains fulltext : 177182.pdf (publisher's version ) (Open Access), Glutamate and GABA play an important role in substance dependence. However, it remains unclear whether this holds true for different substance use disorders and how this is related to risk-related traits such as impulsivity. We, therefore, compared Glx (as a proxy measure for glutamate) and GABA concentrations in the dorsal anterior cingulate cortex (dACC) of 48 male cigarette smokers, 61 male smoking polysubstance users, and 90 male healthy controls, and investigated the relationship with self-reported impulsivity and substance use. Glx and GABA concentrations were measured using proton Magnetic Resonance Spectroscopy. Impulsivity, smoking, alcohol and cocaine use severity and cannabis use were measured using self-report instruments. Results indicate a trend towards group differences in Glx. Post-hoc analyses showed a difference between smokers and healthy controls (p=0.04) and a trend towards higher concentrations in smoking polysubstance users and healthy controls (p=0.09), but no differences between smokers and smoking polysubstance users. dACC GABA concentrations were not significantly different between groups. Smoking polysubstance users were more impulsive than smokers, and both groups were more impulsive than controls. No significant associations were observed between dACC neurotransmitter concentrations and impulsivity and level and severity of smoking, alcohol or cocaine use or the presence of cannabis use. The results indicate that differences in dACC Glx are unrelated to type and level of substance use. No final conclusion can be drawn on the lack of GABA differences due to assessment difficulties. The relationship between dACC neurotransmitter concentrations and cognitive impairments other than self-reported impulsivity should be further investigated.

Item does not contain fulltext, Orbitofrontal cortex (OFC) sulcogyral patterns are stable morphological variations established early in life. They consist of three distinct pattern types, with Type III in particular being associated with poor regulatory control (e.g., high sensation seeking and negative emotionality, low constraint), which may confer risk for earlier onset of cannabis (CB) use and greater use in later life. The OFC sulcogyral pattern may therefore be a stable trait marker in understanding individual differences in substance-use vulnerability and associated affective disturbances in users. In a large multisite cross-sectional study, we compared OFC pattern type distribution between 128 healthy controls (HC) and 146 CB users. Within users (n=140), we explored the association between OFC pattern type and CB use level, and subsequently if level of CB use informed by OFC pattern type may mediate disturbances in affective tone, as indexed by depressive symptoms. While OFC pattern distribution did not distinguish between HC and CB groups, it informed greater lifetime use within users. Specifically, CB users with pattern Type III in the right OFC tended to use more CB over their lifetime, than did CB users with pattern Type I or II. Greater lifetime CB use was subsequently associated with higher depressive symptoms, such that it mediated an indirect association between right OFC pattern Type III and higher depressive symptoms. The present study provides evidence for neurobiological differences, specifically sulcogyral pattern of the OFC, to modulate level of CB use, which may subsequently influence the expression of depressive symptoms.

Contains fulltext : 135384.pdf (publisher's version ) (Open Access), In problem gamblers, diminished cognitive control and increased impulsivity is present compared to healthy controls. Moreover, impulsivity has been found to be a vulnerability marker for the development of pathological gambling (PG) and problem gambling (PrG) and to be a predictor of relapse. In this review, the most recent findings on functioning of the brain circuitry relating to impulsivity and cognitive control in PG and PrG are discussed. Diminished functioning of several prefrontal areas and of the anterior cingulate cortex (ACC) indicate that cognitive-control related brain circuitry functions are diminished in PG and PrG compared to healthy controls. From the available cue reactivity studies on PG and PrG, increased responsiveness towards gambling stimuli in fronto-striatal reward circuitry and brain areas related to attentional processing is present compared to healthy controls. At this point it is unresolved whether PG is associated with hyper- or hypo-activity in the reward circuitry in response to monetary cues. More research is needed to elucidate the complex interactions for reward responsivity in different stages of gambling and across different types of reward. Conflicting findings from basic neuroscience studies are integrated in the context of recent neurobiological addiction models. Neuroscience studies on the interface between cognitive control and motivational processing are discussed in light of current addiction theories. CLINICAL IMPLICATIONS: We suggest that innovation in PG therapy should focus on improvement of dysfunctional cognitive control and/or motivational functions. The implementation of novel treatment methods like neuromodulation, cognitive training and pharmacological interventions as add-on therapies to standard treatment in PG and PrG, in combination with the study of their effects on brain-behavior mechanisms could prove an important clinical step forward towards personalizing and improving treatment results in PG.

Contains fulltext : 137689.pdf (publisher's version ) (Open Access), BACKGROUND: Patients with alcohol dependence (AD) and pathological gambling (PG) are characterized by dysfunctional reward processing and their ability to adapt to alterations of reward contingencies is impaired. However, most neurocognitive tasks investigating reward processing involve a complex mix of elements, such as working memory, immediate and delayed rewards, and risk-taking. As a consequence, it is not clear whether contingency learning is altered in AD or PG. Therefore, the current study aimed to examine performance in a deterministic contingency learning task, investigating discrimination, reversal, and extinction learning. METHODS: Thirty-three alcohol-dependent patients (ADs), 28 pathological gamblers (PGs), and 18 healthy controls (HCs) performed a contingency learning task in which they learned stimulus-reward associations that were first reversed and later extinguished while receiving deterministic feedback throughout. Accumulated points, number of perseverative errors and trials required to reach a criterion in each learning phase were compared between groups using nonparametric Kruskal-Wallis rank-sum tests. Regression analyses were performed to compare learning curves. RESULTS: PGs and ADs did not differ from HCs in discrimination learning, reversal learning, or extinction learning, on the nonparametric tests. Regression analyses, however, showed differences in the initial speed of learning: PGs were significantly faster in discrimination learning compared to ADs, and both PGs and ADs learned slower than HCs in the reversal learning and extinction phases of the task. CONCLUSIONS: Learning rates for reversal and extinction were slower for the alcohol-dependent group and PG group compared to HCs, suggesting that reversing and extinguishing learned contingencies require more effort in ADs and PGs. This implicates a diminished flexibility to overcome previously learned contingencies.

Contains fulltext : 135381.pdf (publisher's version ) (Closed access), Individuals with alcohol dependence are known to make disadvantageous decisions, possibly caused by alterations in either reward or punishment sensitivity, which lead to persistent alcohol use despite its adverse consequences. Previous studies in alcohol dependence have mainly focused on reward anticipation processing and results from these studies are mixed. To clarify the nature of the motivational deficit that underlies disadvantageous choice in alcohol dependence, the current study sought to characterize the neural representation of expected value in individuals with alcohol dependence, separating expectancy-related processing of gains and losses, as a function of outcome magnitude and outcome probability. METHOD: Functional MRI was used to examine brain responses during the expectation of gains and losses in patients with alcohol dependence (n=19) and healthy controls (n=19). The task manipulated outcome magnitude (euro1 and euro5) and outcome probability (30% and 70%). RESULTS: Compared to healthy controls, patients with alcohol dependence were more responsive to the expectancy of large wins, in the caudate and putamen. This effect was driven by a higher caudate activity in the contrast comparing euro5 vs. euro1 trials in patients with alcohol dependence. There were no group differences in the responses to the expectancy for loss. The patient group reported lower expectancies of winning in the trial-by-trial ratings. CONCLUSIONS: Patients with alcohol dependence showed caudate hyperactivity when expecting wins. The result contrasts with past work using the monetary incentive delay task, showing caudate hypoactivity; the passive nature of our task contrasts with an active response requirement in the MIDT studies., BACKGROUND: Individuals with alcohol dependence are known to make disadvantageous decisions, possibly caused by alterations in either reward or punishment sensitivity, which lead to persistent alcohol use despite its adverse consequences. Previous studies in alcohol dependence have mainly focused on reward anticipation processing and results from these studies are mixed. To clarify the nature of the motivational deficit that underlies disadvantageous choice in alcohol dependence, the current study sought to characterize the neural representation of expected value in individuals with alcohol dependence, separating expectancy-related processing of gains and losses, as a function of outcome magnitude and outcome probability. METHOD: Functional MRI was used to examine brain responses during the expectation of gains and losses in patients with alcohol dependence (n=19) and healthy controls (n=19). The task manipulated outcome magnitude (euro1 and euro5) and outcome probability (30% and 70%). RESULTS: Compared to healthy controls, patients with alcohol dependence were more responsive to the expectancy of large wins, in the caudate and putamen. This effect was driven by a higher caudate activity in the contrast comparing euro5 vs. euro1 trials in patients with alcohol dependence. There were no group differences in the responses to the expectancy for loss. The patient group reported lower expectancies of winning in the trial-by-trial ratings. CONCLUSIONS: Patients with alcohol dependence showed caudate hyperactivity when expecting wins. The result contrasts with past work using the monetary incentive delay task, showing caudate hypoactivity; the passive nature of our task contrasts with an active response requirement in the MIDT studies.

One hallmark of gambling disorder (GD) is the observation that gamblers have problems stopping their gambling behavior once it is initiated. On a neuropsychological level, it has been hypothesized that this is the result of a cognitive inflexibility.The present study investigated cognitive inflexibility in patients with GD using a task involving cognitive inflexibility with a reward element (i.e., reversal learning) and a task measuring general cognitive inflexibility without such a component (i.e., response perseveration). For this purpose, scores of a reward-based reversal learning task (probabilistic reversal learning task) and the Wisconsin card sorting task were compared between a group of treatment seeking patients with GD and a gender and age matched control group. The results show that pathological gamblers have impaired performance on the neurocognitive task measuring reward-based cognitive inflexibility. However, no difference between the groups is observed regarding non-reward-based cognitive inflexibility. This suggests that cognitive inflexibility in GD is the result of an aberrant reward-based learning, and not based on a more general problem with cognitive flexibility. The pattern of observed problems is suggestive of a dysfunction of the orbitofrontal cortex, the ventrolateral prefrontal cortex, and the ventral regions of the striatum in gamblers. Relevance for the neurocognition of problematic gambling is discussed.