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Contains fulltext : 242453.pdf (Publisher’s version ) (Open Access), The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods. https://www.trialregister.nl/trial/7955

14 december 2021, Item does not contain fulltext, Background and aims: Graph theoretic analysis of structural covariance networks (SCN) provides an assessment of brain organization that has not yet been applied to alcohol dependence (AD). We estimated whether SCN differences are present in adults with AD and heavy drinking adolescents at age 19 and age 14, prior to substantial exposure to alcohol. Design: Cross-sectional sample of adults and a cohort of adolescents. Correlation matrices for cortical thicknesses across 68 regions were summarized with graph theoretic metrics. Setting and participants: 745 adults with AD and 979 non-dependent controls from 24 sites curated by the ENIGMA-Addiction working group, and 297 hazardous drinking adolescents and 594 controls at age 14 and 19 from the IMAGEN study, all from Europe. Measurements: Metrics of network segregation (modularity, clustering coefficient, and local efficiency) and integration (average shortest path length and global efficiency). Findings: The younger AD adults had lower network segregation and higher integration relative to non-dependent controls. Compared with controls, the hazardous drinkers at age 19 showed lower modularity (Area-under-the-curve [AUC] difference = -0.0142, confidence interval [CI] 95% [-0.1333, 0.0092]; p-value = 0.017), clustering coefficient (AUC difference = -0.0164 CI 95% [-0.1456, 0.0043], p-value = 0.008), and local efficiency (AUC difference = -0.0141 CI 95% [-0.0097, 0.0034], p-value = 0.010), as well as lower average shortest path length (AUC difference = -0.0405 CI 95% [-0.0392, 0.0096]; p-value = 0.021) and higher global efficiency (AUC difference = 0.0044 CI 95% [-0.0011, 0.0043]; p-value = 0.023). The same pattern was present at age 14 with lower clustering coefficient (AUC difference = -0.0131 CI 95% [-0.1304, 0.0033]; p-value = 0.024), lower average shortest path length (AUC difference = -0.0362 CI 95% [-0.0334, 0.0118]; p-value = 0.019), and higher global efficiency (AUC difference = 0.0035 CI 95% [-0.0011, 0.0038]; p

31 januari 2021, Contains fulltext : 230060.pdf (Publisher’s version ) (Closed access), Many American and Dutch adolescents use marijuana regularly. There is concern that such use may impair cognitive function more in adolescents than adults. We examined effects of regular marijuana use on long-term memory and perseveration among American and Dutch adolescents. We administered Buschke's Selective Reminding Test (BSRT) to assess long-term memory and the Wisconsin Card Sorting Test (WCST) to assess perseveration in male teenagers. Usable test data were obtained for 12 American marijuana users, 13 American controls, 9 Dutch marijuana users, and 12 Dutch controls. In BSRT, users showed lower overall long-term storage than controls (adjusted means ± SE's for numbers of words per trial of 9.4 ± 0.2, 13.4 ± 0.3, 11.7 ± 0.2, and 12.4 ± 0.2 for American users, Dutch users, American controls, and Dutch controls, respectively). Marijuana was associated with memory effects only in American, not Dutch, users. Bivariate Pearson correlations for American and Dutch users combined showed associations of lower total recall with more uses in the previous year and lifetime (r = -0.61 and r = -0.53, respectively); and more perseverative errors with more uses in the previous year (r = 0.55). Some findings were consistent with the possibility that regular adolescent marijuana use causes deficits in cognition, especially memory. However, a causal interpretation cannot be inferred from our findings and is challenging to reconcile with the observation of memory deficits only in American users. Our study was novel in examining the influence of nationality on marijuana's cognitive effects. More studies of this topic should compare effects across nationalities or cultures.

Contains fulltext : 226697.pdf (publisher's version ) (Closed access), Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD) often co-occur and are associated with treatment resistance. Both disorders are characterized by similar reward-processing deficits with decreased striatal responses to reward anticipation, though literature is inconsistent. It is unclear whether substance misuse exaggerates reward-processing deficits observed in ADHD. The aim of this study was to examine substance misuse effects on reward-processing in ADHD. Functional MRI data in a Monetary Incentive Delay (MID) task from a multi-site study were compared across ADHD groups with and without substance misuse (ADHD + SM and ADHD-only, respectively) and healthy controls (n = 40/group, 74 males and 46 females, aged 13.7-25.9 years). Substance misuse was defined as misuse of alcohol, nicotine, or drugs. Groups were matched with presence/absence of parental SUD to avoid interference with SUD trait effects. Compared to ADHD-only and controls, ADHD + SM showed hyperactivation in putamen during reward anticipation. Compared to controls, the ADHD groups showed hypoactivation in motor/sensory cortices and hyperactivation in frontal pole and OFC during reward outcome. ADHD + SM also showed hyperactivation in frontal pole during neutral outcome. Moreover, ADHD + SM patients showed higher callous-unemotional (CU) traits that were positively correlated with putamen responses to reward anticipation. Our results show distinct condition-independent neural activation profile for ADHD + SM compared to ADHD-only and controls. Effects of comorbid substance misuse and variability of its prevalence across ADHD studies might have contributed to inconsistencies in ADHD literature. Contrasted with findings for reward-processing in SUD literature, results potentially suggest distinct underlying mechanisms for SUD subgroups with different characteristics, like antisocial/psychopathic traits.

24 juni 2021, Item does not contain fulltext, Background: Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol. Pre-existing differences in subcortical brain volume may affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. Aims We assess the causal nature of the complex relationship of subcortical brain volume with smoking and alcohol use, using bi-directional Mendelian randomisation. Method: Mendelian randomisation uses genetic variants predictive of a certain 'exposure' as instrumental variables to test causal effects on an 'outcome'. Because of random assortment at meiosis, genetic variants should not be associated with confounders, allowing less biased causal inference. We used summary-level data of genome-wide association studies of subcortical brain volumes (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus; n = 50 290) and smoking and alcohol use (smoking initiation, n = 848 460; cigarettes per day, n = 216 590; smoking cessation, n = 378 249; alcoholic drinks per week, n = 630 154; alcohol dependence, n = 46 568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. Results: There was strong evidence that liability to alcohol dependence decreased amygdala and hippocampal volume, and smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. Conclusions: Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and likely mental health, warranting more recognition in public health efforts.

Contains fulltext : 230497.pdf (Publisher’s version ) (Open Access), Introduction: Despite its well-established negative effects, environmental tobacco smoke (ETS) exposure remains highly prevalent worldwide. ETS exposure is associated with a wide range of physical and mental health-related problems among youth, including an increased likelihood to develop nicotine dependence. Up till now, neurocognitive effects of ETS exposure are largely unknown, while such effects could explain the role of ETS exposure in the development of nicotine dependence. Therefore, this preregistered study investigated the role of current ETS exposure in brain functioning associated with smoking cue-reactivity and inhibitory control. Method: Concurrent with functional magnetic resonance imaging, nonsmoking adolescents aged 14-18 years (N = 51) performed a smoking cue-reactivity task, assessing brain functioning to smoking cues, and a Go/NoGo task measuring inhibitory control. ETS exposure was measured using a self-report questionnaire and biochemically verified. Results: No significant associations were observed between current ETS exposure and brain functioning associated with smoking cue-reactivity and inhibitory control. Conclusion: These findings suggest that low-to-moderate levels of current ETS exposure are not associated with increased salience of smoking cues or deficits in inhibitory control in nonsmoking adolescents. Longitudinal research is needed to further clarify the exact effect of lifetime ETS exposure on brain functioning, as well as research focusing on the effects of higher levels of ETS exposure.

Contains fulltext : 229772.pdf (publisher's version ) (Closed access), Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

Item does not contain fulltext, Objective: Smoking is a major cause of worldwide morbidity and mortality. Evidence-based intervention programs to help young adults quit smoking are largely lacking; identifying targets for intervention is therefore critical. A candidate target is inhibitory control, with previous studies on Go/No-Go trainings showing behavior change in the food and alcohol domain. The current study examined the mechanisms of change of HitnRun, a Go/No-Go game, in a smoking population that was motivated to quit. Method: A 2-armed experimental study (n = 106) was conducted and young adults (Mage = 22.15; SDage = 2.59) were randomly assigned to either play HitnRun or to read a psychoeducational brochure. Prior to and directly following the intervention period, smoking-specific and general inhibitory control, perceived attractiveness of smoking pictures, and weekly smoking behavior were assessed. Results: Results indicated that Go/No-Go training seems to decrease evaluations of smoking stimuli rather than top-down smoking-specific and general control processes. Similar reductions for weekly smoking were found in both groups. Conclusions: Go/No-Go training did not differentially influence smoking-specific inhibitory control, general inhibitory control and weekly smoking behavior. Go/No-Go training might be able to decrease evaluations of smoking stimuli, yet based on the current study we cannot rule out the possibility of regression to the mean. More research and iterative design is needed to better understand the potential role of Go/No-Go training in smoking cessation interventions, as well as exploring other evidence-based mechanisms (e.g., peer processes, self-efficacy) that might be an important addition to smoking cessation interventions for young people.

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

Contains fulltext : 242453.pdf (Publisher’s version ) (Open Access), The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods. https://www.trialregister.nl/trial/7955

The adverse outcome pathway (AOP) is a conceptual construct that facilitates organisation and interpretation of mechanistic data representing multiple biological levels and deriving from a range of methodological approaches including in silico, in vitro and in vivo assays. AOPs are playing an increasingly important role in the chemical safety assessment paradigm and quantification of AOPs is an important step towards a more reliable prediction of chemically induced adverse effects. Modelling methodologies require the identification, extraction and use of reliable data and information to support the inclusion of quantitative considerations in AOP development. An extensive and growing range of digital resources are available to support the modelling of quantitative AOPs, providing a wide range of information, but also requiring guidance for their practical application. A framework for qAOP development is proposed based on feedback from a group of experts and three qAOP case studies. The proposed framework provides a harmonised approach for both regulators and scientists working in this area.

Contains fulltext : 219494.pdf (Publisher’s version ) (Closed access), While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics - the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD) - that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

Contains fulltext : 220223.pdf (publisher's version ) (Open Access), Introduction: Brain functioning, as indexed by event-related potentials (ERPs) representing smoking cue reactivity, inhibitory control, and reward processing, has been found to be compromised in smokers. However, whether environmental tobacco smoke (ETS) exposure in never smokers results in similar brain changes is unknown. This question is particularly relevant during adolescence, given ongoing brain maturation and a high risk of smoking initiation. The present study tested the associations between ETS exposure and ERPs reflecting cue reactivity (P3, LPP), inhibitory control (N2, P3), and reward processing (anticipation P3 (P3), feedback-related negativity (FRN)) among never-smoking adolescents. Methods: Eighty-four never-smoking adolescents (nonexposed = 32, exposed = 52) performed a smoking cue reactivity, a Go/NoGo, and a monetary incentive delay (MID) task while ERPs were measured. Results: Exposed and nonexposed groups did not differ in ERPs reflecting smoking cue reactivity, inhibitory control, and reward processing. A negative correlation between ETS exposure and the anticipatory P3 suggests reduced anticipatory reward sensitivity for nondrug rewards with increased levels of ETS exposure. However, since this effect was not consistent across analyses, no strong conclusions can be formulated. In the current study, few participants reported high levels of ETS exposure; therefore, further study is necessary. Conclusions: Nevertheless, from this study, it can be concluded that low-to-moderate exposure to ETS during adolescence does not result in functional brain changes related to smoking cue reactivity, inhibitory control, and reward processing.

Radboud University, 10 september 2020, Promotor : Engels, R.C.M.E. Co-promotores : Luijten, M., Sescousse, G.T., Contains fulltext : 221892.pdf (publisher's version ) (Open Access)

Contains fulltext : 216178.pdf (publisher's version ) (Open Access), Harmful behavior such as smoking may reflect a disturbance in the balance of goal-directed and habitual control. Animal models suggest that habitual control develops after prolonged substance use. In this study, we investigated whether smokers (N = 49) differ from controls (N = 46) in the regulation of goal-directed and habitual behavior. It was also investigated whether individual differences in nicotine dependence levels were associated with habitual responding.We used two different multistage instrumental learning tasks that consist of an instrumental learning phase, subsequent outcome devaluation, and a testing phase to measure the balance between goal-directed and habitual responding. The testing phases of these tasks occurred after either appetitive versus avoidance instrumental learning. The appetitive versus aversive instrumental learning stages in the two different tasks modeled positive versus negative reinforcement, respectively.Smokers and nonsmoking controls did not differ on habitual versus goal-directed control in either task. Individual differences in nicotine dependence within the group of smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. The current finding highlights the importance of individual differences within smokers. For future research, neuroimaging studies are suggested to further unravel the nature of the imbalance between goal-directed versus habitual control in severely dependent smokers by directly measuring activity in the corresponding brain systems.Goal-directed versus habitual behavior in substance use and addiction is highly debated. This study investigated goal-directed versus habitual control in smokers. The findings suggest that smokers do not differ from controls in goal-directed versus habitual control. In

Contains fulltext : 217238pub.pdf (publisher's version ) (Open Access), Alcohol is mainly consumed in social settings, in which people often adapt their drinking behavior to that of others, also called imitation of drinking. Yet, it remains unclear what drives this drinking in a social setting. In this study, we expected to see stronger brain and behavioral responses to social compared to non-social alcohol cues, that would be associated with drinking in a social setting. The sample consisted of 153 beer-drinking males, aged 18-25 years. Brain responses to social alcohol cues were measured during an alcohol cue exposure task in the scanner. Behavioral responses to social alcohol cues were measured using a stimulus-response compatibility task, providing an index of approach bias towards these cues. Drinking in a social setting was measured in a laboratory mimicking a bar environment. Specific brain responses to social alcohol cues were observed in the bilateral superior temporal sulcus and the left inferior parietal lobe. There was no approach bias towards social alcohol cues specifically, however, we did find an approach bias towards alcohol (versus soda) cues in general. Brain responses and approach bias towards social alcohol cues were unrelated and not associated with actual drinking. Thus, we found no support for a relation between drinking in a social setting on the one hand, and brain cue-reactivity or behavioral approach biases to social alcohol cues on the other hand. This suggests that, in contrast to our hypothesis, drinking in a social setting may not be driven by brain or behavioral responses to social alcohol cues.

Introduction: Harmful behavior such as smoking may reflect a disturbance in the balance of goaldirected and habitual control. Animal models suggest that habitual control develops after prolonged substance use. In this study, we investigated whether smokers (N = 49) differ from controls (N = 46) in the regulation of goal-directed and habitual behavior. It was also investigated whether individual differences in nicotine dependence levels were associated with habitual responding. Methods: We used two different multistage instrumental learning tasks that consist of an instrumental learning phase, subsequent outcome devaluation, and a testing phase to measure the balance between goal-directed and habitual responding. The testing phases of these tasks occurred after either appetitive versus avoidance instrumental learning. The appetitive versus aversive instrumental learning stages in the two different tasks modeled positive versus negative reinforcement, respectively. Results: Smokers and nonsmoking controls did not differ on habitual versus goal-directed control in either task. Individual differences in nicotine dependence within the group of smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. Conclusions: The current finding highlights the importance of individual differences within smokers. For future research, neuroimaging studies are suggested to further unravel the nature of the imbalance between goal-directed versus habitual control in severely dependent smokers by directly measuring activity in the corresponding brain systems. Implications: Goal-directed versus habitual behavior in substance use and addiction is highly debated. This study investigated goal-directed versus habitual control in smokers. The findings suggest that smokers do not diff

Contains fulltext : 217797pub.pdf (publisher's version ) (Open Access), Impaired brain processing of alcohol-related rewards has been suggested to play a central role in alcohol use disorder. Yet, evidence remains inconsistent and mainly originates from studies in which participants passively observe alcohol cues or taste alcohol. Here, we designed a protocol in which beer consumption was predicted by incentive cues and contingent on instrumental action closer to real life situations. We predicted that anticipating and receiving beer (compared with water) would elicit activity in the brain reward network and that this activity would correlate with drinking level across participants. The sample consisted of 150 beer-drinking males, aged 18 to 25 years. Three groups were defined based on alcohol use disorders identification test (AUDIT) scores: light drinkers (n = 39), at-risk drinkers (n = 64), and dependent drinkers (n = 47). fMRI measures were obtained while participants engaged in the beer incentive delay task involving beer- and water-predicting cues followed by real sips of beer or water. During anticipation, outcome notification and delivery of beer compared with water, higher activity was found in a reward-related brain network including the dorsal medial prefrontal cortex, orbitofrontal cortex, and amygdala. Yet, no activity was observed in the striatum, and no differences were found between the groups. Our results reveal that anticipating, obtaining, and tasting beer activates parts of the brain reward network, but that these brain responses do not differentiate between different drinking levels.

Radboud University, 30 januari 2020, Promotor : Granic, I. Co-promotor : Luijten, M., Contains fulltext : 214860.pdf (publisher's version ) (Open Access), In her PhD thesis, Hanneke Scholten designed and tested the game HitnRun to help youth quit smoking. A combined theory-driven and engagement-driven approach was taken aiming to design an experience that youth could authentically connect and engage with. In contrast to our expectations, participants in both the HitnRun and brochure group showed equal improvements in smoking behavior over time. Yet, participants who played HitnRun for a longer period of time also showed lower weekly smoking levels than participants who played HitnRun for a shorter period of time. The effects of HitnRun shows most promise for youth who connected with and were engaged by the game. Our promising findings are highly important given the current paucity of evidence-based interventions. In the future we need to work towards a "pull" instead of "push" model which will honor youths' autonomy, and give them the opportunity to choose the tools that have actual value to them.

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

Contains fulltext : 204838.pdf (publisher's version ) (Open Access), Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly “recreational” substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants’ age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics.

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

Contains fulltext : 212485.pdf (Publisher’s version ) (Open Access), Smoking is a major cause of worldwide morbidity and mortality. Almost no evidence-based intervention programs are available to help youth quit smoking. We argue that ineffective targeting of peer influence and engagement difficulties are significant barriers to successful youth smoking cessation. To address these barriers, we developed the mobile game intervention HitnRun. A two-armed randomized controlled trial (RCT; n = 144) was conducted and young smokers (Mage = 19.39; SDage = 2.52) were randomly assigned to either play HitnRun or read a psychoeducational brochure. Prior to, directly following the intervention period, and after three-month follow-up, weekly smoking behavior, abstinence rates, intervention dose, and peer- and engagement-related factors were assessed. Results indicated similar reductions in weekly smoking levels and similar abstinence rates for both groups. Yet, we found a dose effect with HitnRun only: The longer participants played HitnRun, the lower their weekly smoking levels were. In the brochure group, a higher dose was related to higher weekly smoking levels at all measurement moments. Exploratory analyses showed the most powerful effects of HitnRun for participants who connected with and were engaged by the intervention. Future work should build on the promising potential of HitnRun by increasing personalization efforts and strengthening peer influence components.

Contains fulltext : 209839.pdf (publisher's version ) (Open Access), In everyday decision-making, individuals make trade-offs between short-term and long-term benefits or costs. Depending on many factors, individuals may choose to wait for larger delayed reward, yet in other situations they may prefer the smaller, immediate reward. In addition to within-subject variation in the short-term versus long-term reward trade-off, there are also interindividual differences in delay discounting (DD), which have been shown to be quite stable. The extent to which individuals discount the value of delayed rewards turns out to be associated with important health and disorder-related outcomes: the more discounting, the more unhealthy or problematic choices. This has led to the hypothesis that DD can be conceptualized as trans-disease process. The current systematic review presents an overview of behavioral trainings and manipulations that have been developed to reduce DD in human participants aged 12 years or older. Manipulation studies mostly contain one session and measure DD directly after the manipulation. Training studies add a multiple session training component that is not per se related to DD, in between two DD task measurements. Ninety-eight studies (151 experiments) were identified that tested behavioral trainings and manipulations to decrease DD. Overall, results indicated that DD can be decreased, showing that DD is profoundly context dependent and changeable. Most promising avenues to pursue in future research seem to be acceptance-based/mindfulness-based trainings, and even more so manipulations involving a future orientation. Limitations and recommendations are discussed to identify the mechanistic processes that allow for changes in discount rate and behavior accordingly.

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Contains fulltext : 202218pub.pdf (publisher's version ) (Closed access), Drinking heavily in a short period is associated with significant health risks. However, little is known about when heavy drinking occurs during an evening. Recently, research found that individuals increase their drinking pace across the evening, speeding up their drinking. The current study examines whether this speeding up is different depending on when individuals start to drink in the evening. Data on alcohol consumption were collected among 197 young adults in the Netherlands (48.7% female, Mage = 20.8 SD = 1.7) on Thursday, Friday and Saturday evenings for 5 consecutive weeks using questionnaires send to participants' smartphone every hour between 9 p.m.-1 a.m. The final sample consisted of 10,144 questionnaires across 2,781 evenings. On evenings when individuals started to drink early (between 8 and 9 p.m.), more alcohol was consumed in the first drinking hour, yet no increase in acceleration was found compared to evenings when individuals started later. Moreover, starting later resulted in a lower overall evening consumption and less binge-drinking episodes compared to starting earlier. The results indicate that when individuals start drinking later in the evening they do not tend to catch up the "missed" drinks, that is they do not increase their drinking faster when starting later in the evening, and they drink less heavily. Therefore, motivating young adults to postpone their first drink in the evening could help heavy drinking young adults to drink less on weekend evenings.

Alcohol is mainly consumed in social settings, in which people often adapt their drinking behaviour to that of others, also called imitation of drinking. Yet, it remains unclear what drives this drinking in a social setting. In this study, we expected to see stronger brain and behavioural responses to social compared to non-social alcohol cues, and these responses to be associated with drinking in a social setting. The sample consisted of 153 beer-drinking males, aged 18–25 years. Brain responses to social alcohol cues were measured during an alcohol cue-exposure task performed in an fMRI scanner. Behavioural responses to social alcohol cues were measured using a stimulus-response compatibility task, providing an index of approach bias towards these cues. Drinking in a social setting was measured in a laboratory mimicking a bar environment. Specific brain responses to social alcohol cues were observed in the bilateral superior temporal sulcus and the left inferior parietal lobe. There was no approach bias towards social alcohol cues specifically; however, we did find an approach bias towards alcohol (versus soda) cues in general. Brain responses and approach bias towards social alcohol cues were unrelated and not associated with actual drinking. Thus, we found no support for a relation between drinking in a social setting on the one hand, and brain cue-reactivity or behavioural approach biases to social alcohol cues on the other hand. This suggests that, in contrast to our hypothesis, drinking in a social setting may not be driven by brain or behavioural responses to social alcohol cues.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly “recreational” substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants’ age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics.

Contains fulltext : 203460.pdf (publisher's version ) (Open Access), Objective: Smoking is one of the leading public health problems worldwide. The inability to quit smoking may be the result of the amplified value of smoking-related cues and inhibitory control deficits. Previous research has shown that pairing substance-related cues with no-go trials in go/no-go training reduces the value of these cues, an effect known as devaluation. The current experiment investigated the devaluation effect of go/no-go training on smoking-related cues, and compared this effect between smokers and nonsmokers. Design and Main Outcome Measures: 39 smokers and 43 nonsmokers were trained to respond immediately to neutral stimuli, but inhibit their reaction when smoking stimuli were presented. Before and after training, participants evaluated smoking and neutral stimuli, where part of these stimuli were subsequently presented in the training, and the other part was not used in training. Results: Not responding to smoking stimuli in go/no-go training decreased subsequent evaluations of trained smoking stimuli compared to untrained smoking stimuli, thereby replicating food and alcohol studies and extending the devaluation effect to smoking-related cues. This devaluation effect was found for both smokers and non-smokers. Conclusion: Smoking-related cues can be devaluated in smokers and non-smokers, thereby showing the potential for Go/No-Go training in smoking cessation interventions.