http://repub.eur.nl/res/aut/27065/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/38532/ 2012-11-27T00:00:00Z Contemporary theoretical models of substance dependence posit that deficits in inhibitory control play an important role in substance dependence. The neural network underlying inhibitory control and its association with substance dependence have been widely investigated. However, the pharmacology of inhibitory control is still insufficiently clear. The aims of the current study were twofold. First, we investigated the role of dopamine in inhibitory control and associated brain activation. Second, the proposed link between dopamine and impaired inhibitory control in nicotine dependence was investigated by comparing smokers and non-smoking controls. Haloperidol (2 mg), a dopamine D2/D3 receptor antagonist, and placebo were administered to 25 smokers and 25 non-smoking controls in a double-blind randomized cross-over design while performing a Go/NoGo task during fMRI scanning. Haloperidol reduced NoGo accuracy and associated brain activation in the ACC, right SFG and left IFG, showing that optimal dopamine levels are crucial to effectively implement inhibitory control. In addition, smokers showed behavioral deficits on the Go/NoGo task as well as hypoactivity in the left IFG, right MFG and ACC after placebo, supporting the hypothesis of a hypoactive prefrontal system in smokers. Haloperidol had a stronger impact on prefrontal brain activation in non-smoking controls compared to smokers, which is in line with the inverted 'U' curve theory of dopamine and cognitive control. The current findings suggest that altered baseline dopamine levels in addicted individuals may contribute to the often observed reduction in inhibitory control in these populations. http://repub.eur.nl/res/pub/37946/ 2012-11-23T00:00:00Z In the Netherlands, 27% of the population is currently smoking. Nicotine is among the most addictive substances of abuse. Thirty-two percent of the people who tried smoking develop nicotine dependence within ten year. This percentage is higher for nicotine than for other substances of abuse (e.g., 23 for heroin: Anthony, et al. 1994). Eighty percent of the smokers intend to quit smoking in the future while only 25% actually attempt to quit every year. Most of these quit attempts fail as 88-95% of the quitters smoke again in the year following the quit attempt (International Tobacco Control Policy Evaluation Project 2011). Although smoking rates are decreasing since 1970, the decline in smoking rates is less distinct in populations with a lower social economic status. Youngsters with lower educational levels start smoking more often and it could be that those with lower social economic status have more difficulties giving up smoking. Nicotine dependence is currently included in the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV-TR) as a ‘substance use disorder’. Examples of diagnostic criteria are tolerance, withdrawal, smoking more than one intended, and the continuation of smoking despite knowledge of adverse consequences. Although nicotine dependence is included in the DSM-IV, nicotine dependence is rarely diagnosed. In addition, many smokers do not meet the diagnostic criteria, although they do experience problems giving up smoking (Schmitz, et al. 2003) and have increased risks for serious health problems. All these characteristics of smoking imply that smoking is a serious and chronic condition that occurs in a substantial part of the population. http://repub.eur.nl/res/pub/32919/ 2012-06-29T00:00:00Z Excessive computer gaming has recently been proposed as a possible pathological illness. However, research on this topic is still in its infancy and underlying neurobiological mechanisms have not yet been identified. The determination of underlying mechanisms of excessive gaming might be useful for the identification of those at risk, a better understanding of the behavior and the development of interventions. Excessive gaming has been often compared with pathological gambling and substance use disorder. Both disorders are characterized by high levels of impulsivity, which incorporates deficits in error processing and response inhibition. The present study aimed to investigate error processing and response inhibition in excessive gamers and controls using a Go/NoGo paradigm combined with event-related potential recordings. Results indicated that excessive gamers show reduced error-related negativity amplitudes in response to incorrect trials relative to correct trials, implying poor error processing in this population. Furthermore, excessive gamers display higher levels of self-reported impulsivity as well as more impulsive responding as reflected by less behavioral inhibition on the Go/NoGo task. The present study indicates that excessive gaming partly parallels impulse control and substance use disorders regarding impulsivity measured on the self-reported, behavioral and electrophysiological level. Although the present study does not allow drawing firm conclusions on causality, it might be that trait impulsivity, poor error processing and diminished behavioral response inhibition underlie the excessive gaming patterns observed in certain individuals. They might be less sensitive to negative consequences of gaming and therefore continue their behavior despite adverse consequences. http://repub.eur.nl/res/pub/25755/ 2011-05-04T00:00:00Z Introduction: The role of inhibitory control in addictive behaviors is highlighted in several models of addictive behaviors. Although reduced inhibitory control has been observed in addictive behaviors, it is inconclusive whether this is evident in smokers. Furthermore, it has been proposed that drug abuse individuals with poor response inhibition may experience greater difficulties not consuming substances in the presence of drug cues. The major aim of the current study was to provide electrophysiological evidence for reduced inhibitory control in smokers and to investigate whether this is more pronounced during smoking cue exposure. Methods: Participants (19 smokers and 20 non-smoking controls) performed a smoking Go/NoGo task. Behavioral accuracy and amplitudes of the N2 and P3 event-related potential (ERP), both reflecting aspects of response inhibition, were the main variables of interest. Results: Reduced NoGo N2 amplitudes in smokers relative to controls were accompanied by decreased task performance, whereas no differences between groups were found in P3 amplitudes. This was found to represent a general lack of inhibition in smokers, and not dependent on the presence of smoking cues. Conclusions: The current results suggest that smokers have difficulties with response inhibition, which is an important finding that eventually can be implemented in smoking cessation programs. More research is needed to clarify the exact role of cue exposure on response inhibition. http://repub.eur.nl/res/pub/22094/ 2011-02-01T00:00:00Z Substance-dependent patients automatically and involuntarily allocate their attention to drug cues in the environment, a process referred to as attentional bias. Attentional bias is increased during periods of subjective craving and predictive of treatment outcome and relapse in substance dependence. Despite recent theoretical and clinical advances with regard to attentional bias, the underlying neurobiological mechanisms are largely unknown. The objective of the current study was to investigate the neural substrate of attentional bias and associated subjective craving in smokers. A group of smokers (n=20) and a group of age- and gender-matched nonsmoking controls (n=22) were recruited from the general population and participated in a single session of fMRI scanning while attentional processes were manipulated. Main outcome measures were blood oxygen level-dependent (BOLD) fMRI activation during an attentional bias paradigm and selfreported cigarette craving. Results of the current study show that the dorsal anterior cingulate cortex, the superior parietal gyrus, and the superior temporal gyrus were more strongly activated in smokers, as compared to controls, when they had to pay attention to task-relevant information (line counting) while smoking cues were present as distracters (attentional bias). Subjective craving measures during attentional bias correlated with brain activation in the insula and putamen. To our knowledge, this is the first controlled study that shows the brain regions involved in attentional bias in smokers. The current study demonstrates that brain regions contributing to top-down attentional processing are implicated in attentional bias in smokers, suggesting that smokers have to employ more attentional resources to focus on a standard cognitive task when smoking cues are present. http://repub.eur.nl/res/pub/22034/ 2010-06-01T00:00:00Z Objective: Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and executive control. Prefrontal and temporal regions are critically involved in these functions. Maturational processes leave these brain areas prone to the potentially harmful effects of cannabis use. Method: We performed a two-site (United States and the Netherlands; pooled data) functional magnetic resonance imaging (MRI) study with a cross-sectional design, investigating the effects of adolescent cannabis use on working memory (WM) and associative memory (AM) brain function in 21 abstinent but frequent cannabis–using boys (13–19) years of age and compared them with 24 nonusing peers. Brain activity during WM was assessed before and after rule-based learning (automatization). AM was assessed using a pictorial hippocampal-dependent memory task. Results: Cannabis users performed normally on both memory tasks. During WM assessment, cannabis users showed excessive activity in prefrontal regions when a task was novel, whereas automatization of the task reduced activity to the same level in users and controls. No effect of cannabis use on AM-related brain function was found. Conclusions: In adolescent cannabis users, the WM system was overactive during a novel task, suggesting functional compensation. Inefficient WM recruitment was not related to a failure in automatization but became evident when processing continuously changing information. The results seem to confirm the vulnerability of still developing frontal lobe functioning for early-onset cannabis use. http://repub.eur.nl/res/pub/21798/ 2010-01-01T00:00:00Z Deficits in error processing may contribute to the continuation of impulsive behaviors such as smoking. Previous studies show deficits in error processing among substance abuse patients. However, these studies were all conducted during affectively neutral conditions. Deficits in error processing in smokers may become more pronounced under affectively challenging conditions, such as during smoking cue exposure. The aim of the present study was to investigate whether smokers showed initial error processing deficits, as measured with the error-related negativity (ERN), and decreased motivational significance attributed to an error, as measured with the error positivity (Pe) when exposed to smoking cues. Additionally, we examined the nature of the ERN and Pe amplitudes in more detail by investigating their associations with trait impulsivity, nicotine dependence levels and cigarette craving. Event-related potentials were measured during a modified Erikson flanker task in both smokers and non-smoking controls. Smokers showed reduced ERN and Pe amplitudes after making an error, accompanied by diminished post-error slowing of reaction times. These results suggest that initial error processing and motivational significance attributed to an error are affected in smokers during smoking cue exposure. Furthermore, individual variation in impulsivity and nicotine dependence was associated with reduced ERN amplitudes.