A.E. Goudriaan

Individual differences in decision making and reward processing predict changes in cannabis use: a prospective functional magnetic resonance imaging study

Decision‐making deficits are thought to play an important role in the development and persistence of substance use disorders. Individual differences in decision‐making abilities and their underlying neurocircuitry may, therefore, constitute an important predictor for the course of substance use and the development of substance use disorders. Here, we investigate the predictive value of decision making and neural mechanisms underlying decision making for future cannabis use and problem severity in a sample of heavy cannabis users. Brain activity during a monetary decision‐making task (Iowa gambling task) was compared between 32 heavy cannabis users and 41 matched non‐using controls using functional magnetic resonance imaging. In addition, within the group of heavy cannabis users, associations were examined between task‐related brain activations, cannabis use and cannabis use‐related problems at baseline, and change in cannabis use and problem severity after a 6‐month follow‐up. Despite normal task performance, heavy cannabis users compared with controls showed higher activation during wins in core areas associated with decision making. Moreover, within the group of heavy cannabis users, win‐related activity and activity anticipating loss outcomes in areas generally involved in executive functions predicted change in cannabis use after 6 months. These findings are consistent with previous studies and point to abnormal processing of motivational information in heavy cannabis users. A new finding is that individuals who are biased toward immediate rewards have a higher probability of increasing drug use, highlighting the importance of the relative balance between motivational processes and regulatory executive processes in the development of substance use disorders.

Cannabis dependence, cognitive control and attentional bias for cannabis words

One of the characteristics of people suffering from addictive behaviors is the tendency to be distracted by drug cues. This attentional bias for drug cues is thought to lead to increased craving and drug use, and may draw individuals into a vicious cycle of drug addiction. In the current study we developed a Dutch version of the cannabis Stroop task and measured attentional bias for cannabis words in a group of heavy cannabis users and matched controls. The classical Stroop task was used as a global measure of cognitive control and we examined the relationship between cognitive control, cannabis-related problems, cannabis craving and cannabis attentional bias. Using our version of the cannabis Stroop task, a group of heavy cannabis users showed attentional bias to cannabis words, whereas a control group of non-users did not. Furthermore, within the group of cannabis users, those who were clinically recognized as dependent showed a stronger attentional bias than the heavy, non-dependent users. Cannabis users who displayed reduced cognitive control (as measured with the classical Stroop task) showed increased session-induced craving. Contrary to expectations, however, cognitive control did not appear to modulate the relationship between attentional bias to cannabis words (cannabis Stroop task) and cannabis dependence. This study confirmed the relationship between cannabis dependence and attentional bias and extends this by highlighting a moderating role for cognitive control, which may make some more vulnerable to craving.

The relationship between impulsivity and craving in alcohol dependent patients

RationaleImpulsivity and craving are both associated with higher relapse rates and a worse prognosis in patients with a substance use disorder, but the relationship between these two phenomena has been largely ignored in the field of alcohol use disorders.ObjectivesThe primary aim of this study was to investigate the relationship between different dimensions of impulsivity and different forms of self-reported craving. Additionally, the influence of the severity of alcohol dependence on impulsivity, craving, and on their relationship was exploed.MethodsImpulsivity and craving levels were investigated in 87 abstinent alcohol-dependent (AD) patients using a broad range of self-report questionnaires and behavioral impulsivity measures. Alcohol use was measured by means of the timeline followback method.ResultsHigher scores of emotional craving (Alcohol Urge Questionnaire—AUQ) were significantly related to higher self-reported impulsivity (Barratt Impulsiveness Scale, version 11) and to higher cognitive impulsivity (information sampling task). Additionally, exploratory analyses suggest that these relationships are more pronounced in severe AD patients compared to less severe AD patients. No significant relationships were found between emotional craving (AUQ) and motor impulsivity (stop signal task) or delay discounting and between obsessive-compulsive craving (Obsessive Compulsive Drinking Scale) and measures of impulsivity.ConclusionsEmotional craving is related to self-reported impulsivity and to cognitive impulsivity. These relationships seem to be more pronounced in AD patients with severe alcohol dependence. Further research is needed to explore the effect of this relationship on treatment outcome and relapse.

Compulsivity in obsessive-compulsive disorder and addictions

Compulsive behaviors are driven by repetitive urges and typically involve the experience of limited voluntary control over these urges, a diminished ability to delay or inhibit these behaviors, and a tendency to perform repetitive acts in a habitual or stereotyped manner. Compulsivity is not only a central characteristic of obsessive-compulsive disorder (OCD) but is also crucial to addiction. Based on this analogy, OCD has been proposed to be part of the concept of behavioral addiction along with other non-drug-related disorders that share compulsivity, such as pathological gambling, skin-picking, trichotillomania and compulsive eating. In this review, we investigate the neurobiological overlap between compulsivity in substance-use disorders, OCD and behavioral addictions as a validation for the construct of compulsivity that could be adopted in the Research Domain Criteria (RDoC). The reviewed data suggest that compulsivity in OCD and addictions is related to impaired reward and punishment processing with attenuated dopamine release in the ventral striatum, negative reinforcement in limbic systems, cognitive and behavioral inflexibility with diminished serotonergic prefrontal control, and habitual responding with imbalances between ventral and dorsal frontostriatal recruitment. Frontostriatal abnormalities of compulsivity are promising targets for neuromodulation and other interventions for OCD and addictions. We conclude that compulsivity encompasses many of the RDoC constructs in a trans-diagnostic fashion with a common brain circuit dysfunction that can help identifying appropriate prevention and treatment targets.

Grey Matter Changes Associated with Heavy Cannabis Use: A Longitudinal sMRI Study

Cannabis is the most frequently used illicit drug worldwide. Cross-sectional neuroimaging studies suggest that chronic cannabis exposure and the development of cannabis use disorders may affect brain morphology. However, cross-sectional studies cannot make a conclusive distinction between cause and consequence and longitudinal neuroimaging studies are lacking. In this prospective study we investigate whether continued cannabis use and higher levels of cannabis exposure in young adults are associated with grey matter reductions. Heavy cannabis users (N = 20, age baseline M = 20.5, SD = 2.1) and non-cannabis using healthy controls (N = 22, age baseline M = 21.6, SD = 2.45) underwent a comprehensive psychological assessment and a T1- structural MRI scan at baseline and 3 years follow-up. Grey matter volumes (orbitofrontal cortex, anterior cingulate cortex, insula, striatum, thalamus, amygdala, hippocampus and cerebellum) were estimated using the software package SPM (VBM-8 module). Continued cannabis use did not have an effect on GM volume change at follow-up. Cross-sectional analyses at baseline and follow-up revealed consistent negative correlations between cannabis related problems and cannabis use (in grams) and regional GM volume of the left hippocampus, amygdala and superior temporal gyrus. These results suggests that small GM volumes in the medial temporal lobe are a risk factor for heavy cannabis use or that the effect of cannabis on GM reductions is limited to adolescence with no further damage of continued use after early adulthood. Long-term prospective studies starting in early adolescence are needed to reach final conclusions.

Cue-induced striatal activity in frequent cannabis users independently predicts cannabis problem severity three years later

Cannabis is the most frequently used illicit drug worldwide, but little is known about the mechanisms underlying continued cannabis use. Cue-reactivity (the physical, psychological, behavioural and neural reaction to substance-related cues) might be related to continued cannabis use. In this 3-year prospective neuroimaging study we investigated whether cannabis cue-induced brain activity predicted continued cannabis use and associated problem severity 3 years later. In addition, baseline brain activations were compared between dependent and non-dependent cannabis users at follow-up. Analyses were focussed on brain areas known to be important in cannabis cue-reactivity: anterior cingulate cortex, orbitofrontal cortex, ventral tegmental area, amygdala and striatum. At baseline, 31 treatment-naive frequent cannabis users performed a cue-reactivity functional magnetic resonance imaging task. Of these participants, 23 completed the 3-year follow-up. None of the cue-induced region of interest activations predicted the amount of cannabis use at follow-up. However, cue-induced activation in the left striatum (putamen) significantly and independently predicted problem severity at follow-up (p < 0.001) as assessed with the Cannabis Use Disorder Identification Test. Also, clinically dependent cannabis users at follow-up showed higher baseline activation at trend level in the left striatum compared with non-dependent users. This indicates that neural cue-reactivity in the dorsal striatum is an independent predictor of cannabis use-related problems. Given the relatively small sample size, these results are preliminary and should be replicated in larger samples of cannabis users.

The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation : A randomized, double-blind, placebo-controlled trial

Using data form a 14-day double-blind trial with 48 smokers randomized to either N-acetylcysteine (2400 mg) or placebo, we tested the effect of N-acetylcysteine on glutamate and gamma-aminobutyric acid concentrations in the dorsal anterior cingulate cortex and on smoking cessation. Smoking related behaviors and neurotransmitter concentrations in the dorsal anterior cingulate cortex were assessed before and after treatment. Forty-seven non-smoking males served as baseline controls. Smokers showed higher baseline glutamate but similar gamma-aminobutyric acid concentrations than non-smokers. There were no treatment effects on dorsal anterior cingulate cortex neurotransmitter concentrations, smoking cessation, craving, or withdrawal symptoms. These results confirm glutamate disbalance in smokers, but not efficacy of N-acetylcysteine.

Longitudinal study of hippocampal volumes in heavy cannabis users

Background: Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. Methods: Twenty heavy cannabis users (mean age 21 years, range 18–24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. Results: Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes. Conclusions: Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.

Differential effects of left and right prefrontal magnetic stimulation on resting state connectivity in healthy individuals

Introduction High frequency repetitive transcranial magnetic stimulation (HF-rTMS) has gained great interest in multiple clinical and research fields. With HF-rTMS a coil – wherein an alternating current is running – is placed on top of the skull, creating a magnetic field that influences the perpendicular neural tissue, thereby stimulating the neuronal activity of the targeted cortical area [1]. Although it is believed that HF-rTMS accomplishes its effect by influencing entire neuronal networks [2]. One cortical area frequently chosen as stimulation target is the dorsolateral prefrontal cortex (dlPFC), as it is part of the control network. However, despite its popularity and frequent use, very little is known about the differential effect of HF-rTMS over the left and right dlPFC on intrinsic functional connectivity networks in healthy individuals. Therefore the current study will address this issue. Methods The current study assessed the differential effects of left or right dlPFC HF-rTMS (corrected for sham) on intrinsic functional connectivity networks in a sample of 45 healthy individuals. The study was a randomized, single-blind trial with two sessions. During the first session demographic data were obtained and a baseline resting state functional magnetic resonance imaging (rsfMRI) scan was performed. During the second session subjects were randomized to either sham dlPFC HF-rTMS (n=15), left active dlPFC HF-rTMS (n=15) or right active dlPFC HF-rTMS (n=15) directly followed by a second rsfMRI scan. A HF-rTMS session consisted of sixty trains of 5 seconds at a frequency of 10Hz. During the sham condition the coil was tilted 90 degrees relative to the skull. This condition was used in order to correct for time and placebo effects. Independent Component Analysis (ICA) were performed to assess baseline differences and stimulation effects on within and between network functional connectivity. The five components of interest were the left frontal parietal network, right frontal parietal network, default mode network, salience network and reward network. Results The three stimulation groups did not differ on within as well as between functional connectivity of the five components of interest at baseline. Regarding the stimulation effects on within network connectivity, stimulation of the left dlPFC resulted in decreased functional connectivity in the salience network whereas right dlPFC stimulation resulted in increased functional connectivity within this network. Regarding the stimulation effects on between network connectivity, no differences between left or right dlPFC stimulation were found. Discussion Stimulation of either the left or the right dlPFC (compared to sham stimulation) thus seems to lead to opposite effects within the salience network. Since the role of this network in directing attention between internal and external processes [3], and decreased functional connectivity is associated with worsened cognitive functioning in aging [4], the results of this study might have implications for the clinical effects of HF-rTMS over the dlPFC. Therefore future (clinical) studies should implement questionnaires and/ or neurocognitive tasks in order to be able to relate changes in functional connectivity to changes in cognitive functioning.

The relation between gray matter volume and the use of alcohol, tobacco, cocaine and cannabis in male polysubstance users

BACKGROUND Neuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is known about the relation between GM volume abnormalities and polysubstance use. METHODS In this study we assessed the relation between GM volume, and the use of alcohol, tobacco, cocaine and cannabis as well as the total number of substances used, in a sample of 169 males: 15 non-substance users, 89 moderate drinkers, 27 moderate drinkers who also smoke tobacco, 13 moderate drinkers who also smoke tobacco and use cocaine, 10 heavy drinkers who smoke tobacco and use cocaine and 15 heavy drinkers who smoke tobacco, cannabis and use cocaine. RESULTS Regression analyses showed that there was a negative relation between the number of substances used and volume of the dorsal medial prefrontal cortex (mPFC) and the ventral mPFC. Without controlling for the use of other substances, the volume of the dorsal mPFC was negatively associated with the use of alcohol, tobacco, and cocaine. After controlling for the use of other substances, a negative relation was found between tobacco and cocaine and volume of the thalami and ventrolateral PFC, respectively. CONCLUSION These findings indicate that mPFC alterations may not be substance-specific, but rather related to the number of substances used, whereas, thalamic and ventrolateral PFC pathology is specifically associated with tobacco and cocaine use, respectively. These findings are important, as the differential alterations in GM volume may underlie different cognitive deficits associated with substance use disorders.