Maartje Luijten

Cannabis Use and Memory Brain Function in Adolescent Boys: A Cross-Sectional Multicenter Functional Magnetic Resonance Imaging Study

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.

Neurobiological substrate of smoking-related attentional bias

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 self-reported 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.

Individual Differences in Anterior Cingulate Activation Associated with Attentional Bias Predict Cocaine Use After Treatment

Drug-dependent patients often relapse into drug use after treatment. Behavioral studies show that enhanced attentional bias to drug cues is a precursor of relapse. The present functional magnetic resonance imaging (fMRI) study examined whether brain regions involved in attentional bias are predictive of cocaine use after treatment. Attentional bias-related brain activity was measured—with a cocaine Stroop task—in cocaine-dependent patients during their first week in detoxification treatment and was used to predict cocaine use at 3-month follow-up. The predictive value of attentional bias-related brain activity in a priori defined regions of interest, in addition to other measures such as self-reports of substance severity, craving, and behavioral attentional bias were examined. The results show that craving in the week before treatment and individual variability in attentional bias-related activity in the dorsal anterior cingulate cortex (dACC) were significant predictors of days of cocaine use at 3-month follow-up and accounted for 45% in explained variance. Brain activity in the dACC uniquely contributed 22% of explained variance to the prediction model. These findings suggest that hyperactive attentional bias-related brain activity in the dACC might be a biomarker of relapse vulnerability as early as in the first week of detoxification treatment. Ultimately, this may help to develop individually tailored treatment interventions to reduce relapse risk.

Error processing and response inhibition in excessive computer game players: an event-related potential study

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.

Deficits in Inhibitory Control in Smokers During a Go/NoGo Task: An Investigation Using Event-Related Brain Potentials

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.

Diminished error processing in smokers during smoking cue exposure.

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.

Disruption of Reward Processing in Addiction : An Image-Based Meta-analysis of Functional Magnetic Resonance Imaging Studies

Importance Disrupted reward processing, mainly driven by striatal dysfunction, is a key characteristic of addictive behaviors. However, functional magnetic resonance imaging (fMRI) studies have reported conflicting results, with both hypoactivations and hyperactivations during anticipation and outcome notification of monetary rewards in addiction. Objective To determine the nature and direction of reward-processing disruptions during anticipation and outcome notification of monetary rewards in individuals with addiction using image-based meta-analyses of fMRI studies. Data Sources Relevant publications were identified searching PubMed (inclusion until March 2015) using the following terms: reward, fMRI, substance use, cocaine, cannabis, opiates, alcohol, nicotine, smokers, gambling, gamblers, gaming, and gamers. Authors of included articles were contacted to obtain statistical fMRI maps. Study Selection Inclusion criteria: reward task involving monetary reward anticipation and/or outcome; participants showing addictive behaviors; and healthy control group. Exclusion criteria: participants aged younger than 18 years; recreational substance use or gambling; participants at risk for addictive behaviors; and studies using the same patient data as other included studies. Data Extraction and Synthesis Study procedures were conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. Using Seed-based d Mapping software, meta-analyses were performed using random-effect nonparametric statistics with group whole brain T-maps from individual studies as input. Analyses were performed across all addictions and for substance and gambling addictions separately. Main Outcomes and Measures Group differences (individuals with addiction vs control individuals) in reward-related brain activation during reward anticipation and outcome using fMRI (planned before data collection). Results Twenty-five studies were included in the meta-analysis, representing 643 individuals with addictive behaviors and 609 healthy control individuals. During reward anticipation, individuals with substance and gambling addictions showed decreased striatal activation compared with healthy control individuals. During reward outcome, individuals with substance addiction showed increased activation in the ventral striatum, whereas individuals with gambling addiction showed decreased activation in the dorsal striatum compared with healthy control individuals. Conclusions and Relevance Striatal hypoactivation in individuals with addiction during reward anticipation and in individuals with gambling addiction during reward outcome is in line with the reward-deficiency theory of addiction. However, the combination of hypoactivation during reward anticipation and hyperactivation during reward outcome in the striatum of individuals with substance addiction may be explained using learning-deficit theory.

The clinical relevance of neurocognitive measures in addiction

One of the major challenges in addiction treatment is relapse prevention, as rates of relapse following treatment remain very high across the main classes of drugs of abuse. Relapse prevention could be improved by a better understanding of the factors that influence treatment outcomes, including better predictors of risk of relapse following treatment. Recent developments in cognitive neuroscience point to neurocognitive measures (i.e., brain-imaging measures during cognitive-task performance) as potential predictors of relapse. These might even be better predictors than self-report measures, such as craving. We first give an overview of the current state of the field, and then discuss the outstanding challenges and future directions in this area of research.

An fMRI study of cognitive control in problem gamers

A small proportion of video game players develop uncontrolled gaming behavior. A dysfunctional cognitive control circuit may explain this excessive behavior. Therefore, the current study investigated whether problem gamers are characterized by deficits in various aspects of cognitive control (inhibitory control, error processing, attentional control) by measuring brain activation using functional magnetic resonance imaging during Go-NoGo and Stroop task performance. In addition, both impulsivity and attentional control were measured using self-reports. Participants comprised 18 problem gamers who were compared with 16 matched casual gaming controls. Results indicate significantly increased self-reported impulsivity levels and decreased inhibitory control accompanied by reduced brain activation in the left inferior frontal gyrus (IFG) and right inferior parietal lobe (IPL) in problem gamers relative to controls. Significant hypoactivation in the left IFG in problem gamers was also observed during Stroop task performance, but groups did not differ on behavioral and self-reported measures of attentional control. No evidence was found for reduced error processing in problem gamers. In conclusion, the current study provides evidence for reduced inhibitory control in problem gamers, while attentional control and error processing were mostly intact. These findings implicate that reduced inhibitory control and elevated impulsivity may constitute a neurocognitive weakness in problem gamers.

Neural correlates of attentional bias in addiction.

A small but growing neuroimaging literature has begun to examine the neural mechanisms underlying the difficulty that substance-use dependent (SUD) groups have with ignoring salient, drug-related stimuli. Drug-related attentional bias appears to implicate the countermanding forces of cognitive control and reward salience. Basic cognitive neuroscience research suggests that ignoring emotionally evocative stimuli in our environment requires both up-regulation of control networks and down-regulation of processing in emotion and reward regions. Research to date suggests that attentional biases for drug-related stimuli emerge from a failure to sufficiently increase control of attention over salient, but task-irrelevant stimuli. While SUD samples have typically shown increased activity in the cognitive control regions (ie, lateral prefrontal and dorsal anterior cingulate), during attentional bias such increases appear to have been insufficient for the concomitant increases in processing by the emotion/reward regions (ie, amygdala, insula, and striatum). Given the potential contribution of attentional biases to perpetuating drug use and the development of interventions (both pharmaceutical and cognitive-behavioral) to treat biases, understanding the neural basis of successfully reducing bias remains an important, but as yet unanswered, question for our field.