Acute stress alters probabilistic reversal learning in healthy male adults.

Behavioural adaptation is a fundamental cognitive ability, ensuring survival by allowing for flexible adjustment to changing environments. In laboratory settings, behavioural adaptation can be measured with reversal learning paradigms requiring agents to adjust reward learning to stimulus-action-outcome contingency changes. Stress is found to alter flexibility of reward learning, but effect directionality is mixed across studies. Here, we used model-based functional MRI (fMRI) in a within-subjects design to investigate the effect of acute psychosocial stress on flexible behavioural adaptation. Healthy male volunteers (n = 28) did a reversal learning task during fMRI in two sessions, once after the Trier Social Stress Test (TSST), a validated psychosocial stress induction method, and once after a control condition. Stress effects on choice behaviour were investigated using multilevel generalized linear models and computational models describing different learning processes that potentially generated the data. Computational models were fitted using a hierarchical Bayesian approach, and model-derived reward prediction errors (RPE) were used as fMRI regressors. We found that acute psychosocial stress slightly increased correct response rates. Model comparison revealed that double-update learning with altered choice temperature under stress best explained the observed behaviour. In the brain, model-derived RPEs were correlated with BOLD signals in striatum and ventromedial prefrontal cortex (vmPFC). Striatal RPE signals for win trials were stronger during stress compared with the control condition. Our study suggests that acute psychosocial stress could enhance reversal learning and RPE brain responses in healthy male participants and provides a starting point to explore these effects further in a more diverse population.

How do substance use disorders compare to other psychiatric conditions on structural brain abnormalities? A cross-disorder meta-analytic comparison using the ENIGMA consortium findings.

Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto-cerebellar and meso-cortico-limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large-scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case-control differences and to compare brain-correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta-analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age- and sex-matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case-control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co-variates . After correcting for multiple comparisons, AUD case-control meta-analysis of subcortical regions indicated significant differences in the thalamus, hippocampus, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta-analysis of CUD case-control studies indicated reliable reductions in amygdala, accumbens and hippocampus volumes, with the former effect size comparable to, and the latter effect size around half of that reported for alcohol and SCZ. CUD was associated with lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region, but this effect was not significant after correcting for multiple testing. This study allowed for an unbiased cross-disorder comparison of brain correlates of substance use disorders and showed alcohol-related brain anomalies equivalent in effect size to that found in SCZ in several subcortical and cortical regions and significantly greater alterations than those found in MDD in several subcortical and cortical regions. Although modest, CUD results overlapped with findings reported for AUD and other psychiatric conditions, but appear to be most robustly related to reduce thickness of the medial orbitofrontal cortex.

Predicting alcohol dependence from multi-site brain structural measures.

To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.

The exploration-exploitation trade-off in a foraging task is affected by mood-related arousal and valence.

The exploration-exploitation trade-off shows conceptual, functional, and neural analogies with the persistence-flexibility trade-off. We investigated whether mood, which is known to modulate the persistence-flexibility balance, would similarly affect the exploration-exploitation trade-off in a foraging task. More specifically, we tested whether interindividual differences in foraging behavior can be predicted by mood-related arousal and valence. In 119 participants, we assessed mood-related interindividual differences in exploration-exploitation using a foraging task that included minimal task constraints to reduce paradigm-induced biases of individual control tendencies. We adopted the marginal value theorem as a model-based analysis approach, which approximates optimal foraging behavior by tackling the patch-leaving problem. To assess influences of mood on foraging, participants underwent either a positive or negative mood induction. Throughout the experiment, we assessed arousal and valence levels as predictors for explorative/exploitative behavior. Our mood manipulation affected participants' arousal and valence ratings as expected. Moreover, mood-related arousal was found to predict exploration while valence predicted exploitation, which only partly matched our expectations and thereby the proposed conceptual overlap with flexibility and persistence, respectively. The current study provides a first insight into how processes related to arousal and valence differentially modulate foraging behavior. Our results imply that the relationship between exploration-exploitation and flexibility-persistence is more complicated than the semantic overlap between these terms might suggest, thereby calling for further research on the functional, neural, and neurochemical underpinnings of both trade-offs.

Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group.

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.

Metacontrol of human creativity: The neurocognitive mechanisms of convergent and divergent thinking.

Creativity is a complex construct that would benefit from a more comprehensive mechanistic approach. Two processes have been defined to be central to creative cognition: divergent and convergent thinking. These two processes are most often studied using the Alternate Uses Test (heavily relying on divergent thinking), and the Remote Associates Test (heavily relying on convergent thinking, at least with analytical solutions). Although creative acts should be regarded compound processes, most behavioral and neuroimaging studies ignore the composition of basic operations relevant for the task they investigate. In order to provide leverage for a more mechanistic, and eventually even comprehensive computational, approach to creative cognition, we compare findings from divergent and convergent thinking studies and review the similarities and differences between the two underlying types of processes, from a neurocognitive perspective with a strong focus on cortical structures. In this narrative review, we discuss a broad scope of neural correlates of divergent and convergent thinking. We provide a first step towards theoretical integration, by suggesting that creative cognition in divergent- and convergent-thinking heavy tasks is modulated by metacontrol states, where divergent thinking and insight solutions in convergent-thinking tasks seem to benefit from metacontrol biases towards flexibility, whereas convergent, analytical thinking seems to benefit from metacontrol biases towards persistence. These particular biases seem to be reflected by specific cortical brain-activation patterns, involving left frontal and right temporal/parietal networks. Our tentative framework could serve as a first proxy to guide neuroscientific creativity research into assessing more mechanistic details of human creative cognition.

Attentional blink and putative noninvasive dopamine markers: Two experiments to consolidate possible associations.

Adaptive behavioral control involves a balance between top-down persistence and flexible updating of goals under changing demands. According to the metacontrol state model (MSM), this balance emerges from the interaction between the frontal and the striatal dopaminergic system. The attentional blink (AB) task has been argued to tap into the interaction between persistence and flexibility, as it reflects overpersistence-the too-exclusive allocation of attentional resources to the processing of the first of two consecutive targets. Notably, previous studies are inconclusive about the association between the AB and noninvasive proxies of dopamine including the spontaneous eye blink rate (sEBR), which allegedly assesses striatal dopamine levels. We aimed to substantiate and extend previous attempts to predict individual sizes of the AB in two separate experiments with larger sample sizes (N = 71 & N = 65) by means of noninvasive behavioral and physiological proxies of dopamine (DA), such as sEBR and mood measures, which are likely to reflect striatal dopamine levels, and color discrimination, which has been argued to tap into the frontal dopamine levels. Our findings did not confirm the prediction that AB size covaries with sEBR, mood, or color discrimination. The implications of this inconsistency with previous observations are discussed.

Defining Compulsive Behavior.

Compulsive tendencies are a central feature of problematic human behavior and thereby are of great interest to the scientific and clinical community. However, no consensus exists about the precise meaning of 'compulsivity,' creating confusion in the field and hampering comparison across psychiatric disorders. A vague conceptualization makes compulsivity a moving target encompassing a fluctuating variety of behaviors, which is unlikely to improve the new dimension-based psychiatric or psychopathology approach. This article aims to help progress the definition of what constitutes compulsive behavior, cross-diagnostically, by analyzing different definitions in the psychiatric literature. We searched PubMed for articles in human psychiatric research with 'compulsive behavior' or 'compulsivity' in the title that focused on the broader concept of compulsivity-returning 28 articles with nine original definitions. Within the definitions, we separated three types of descriptive elements: phenomenological, observational and explanatory. The elements most applicable, cross-diagnostically, resulted in this definition: Compulsive behavior consists of repetitive acts that are characterized by the feeling that one 'has to' perform them while one is aware that these acts are not in line with one's overall goal. Having a more unified definition for compulsive behavior will make its meaning precise and explicit, and therefore more transferable and testable across clinical and non-clinical populations.

Loss of brain graph network efficiency in alcohol dependence.

Alcohol dependence (AD) is characterized by corticostriatal impairments in individual brain areas such as the striatum. As yet however, complex brain network topology in AD and its association with disease progression are unknown. We applied graph theory to resting-state functional magnetic resonance imaging (RS-fMRI) to examine weighted global efficiency and local (clustering coefficient, degree and eigenvector centrality) network topology and the functional role of the striatum in 24 AD patients compared with 20 matched healthy controls (HCs), and their association with dependence characteristics. Graph analyses were performed based on Pearson's correlations between RS-fMRI time series, while correcting for age, gender and head motion. We found no significant group differences between AD patients and HCs in network topology. Notably, within the patient group, but not in HCs, the whole-brain network showed reduced average cluster coefficient with more severe alcohol use, whereas longer AD duration within the patient group was associated with a global decrease in efficiency, degree and clustering coefficient. Additionally, within four a-priori chosen bilateral striatal nodes, alcohol use severity was associated with lower clustering coefficient in the left caudate. Longer AD duration was associated with reduced clustering coefficient in caudate and putamen, and reduced degree in bilateral caudate, but with increased eigenvector centrality in left posterior putamen. Especially changes in global network topology and clustering coefficient in anterior striatum remained strikingly robust after exploratory variations in network weight. Our results show adverse effects of AD on overall network integration and possibly on striatal efficiency, putatively contributing to the increasing behavioral impairments seen in chronically addicted patients.

Functional connectivity alterations between default mode network and occipital cortex in patients with obsessive-compulsive disorder (OCD).

Altered brain network connectivity is a potential biomarker for obsessive-compulsive disorder (OCD). A meta-analysis of resting-state MRI studies by Gürsel et al. (2018) described altered functional connectivity in OCD patients within and between the default mode network (DMN), the salience network (SN), and the frontoparietal network (FPN), as well as evidence for aberrant fronto-striatal circuitry. Here, we tested the replicability of these meta-analytic rsfMRI findings by measuring functional connectivity during resting-state fMRI in a new sample of OCD patients (n = 24) and matched controls (n = 33). We performed seed-to-voxel analyses using 30 seed regions from the prior meta-analysis. OCD patients showed reduced functional connectivity between the SN and the DMN compared to controls, replicating previous findings. We did not observe significant group differences of functional connectivity within the DMN, SN, nor FPN. Additionally, we observed reduced connectivity between the visual network to both the DMN and SN in OCD patients, in particular reduced functional connectivity between lateral parietal seeds and the left inferior lateral occipital pole. Furthermore, the right lateral parietal seed (associated with the DMN) was more strongly correlated with a cluster in the right lateral occipital cortex and precuneus (a region partly overlapping with the Dorsal Attentional Network (DAN)) in patients. Importantly, this latter finding was positively correlated to OCD symptom severity. Overall, our study partly replicated prior meta-analytic findings, highlighting hypoconnectivity between SN and DMN as a potential biomarker for OCD. Furthermore, we identified changes between the SN and the DMN with the visual network. This suggests that abnormal connectivity between cortex regions associated with abstract functions (transmodal regions such as the DMN), and cortex regions associated with constrained neural processing (unimodal regions such as the visual cortex), may be important in OCD.

Cognitive Control of Working Memory: A Model-Based Approach.

Working memory (WM)-based decision making depends on a number of cognitive control processes that control the flow of information into and out of WM and ensure that only relevant information is held active in WM's limited-capacity store. Although necessary for successful decision making, recent work has shown that these control processes impose performance costs on both the speed and accuracy of WM-based decisions. Using the reference-back task as a benchmark measure of WM control, we conducted evidence accumulation modeling to test several competing explanations for six benchmark empirical performance costs. Costs were driven by a combination of processes, running outside of the decision stage (longer non-decision time) and showing the inhibition of the prepotent response (lower drift rates) in trials requiring WM control. Individuals also set more cautious response thresholds when expecting to update WM with new information versus maintain existing information. We discuss the promise of this approach for understanding cognitive control in WM-based decision making.

Gender-related neuroanatomical differences in alcohol dependence: findings from the ENIGMA Addiction Working Group.

Gender-related differences in the susceptibility, progression and clinical outcomes of alcohol dependence are well-known. However, the neurobiological substrates underlying such differences remain unclear. Therefore, this study aimed to investigate gender differences in the neuroanatomy (i.e. regional brain volumes) of alcohol dependence. We examined the volume of a priori regions of interest (i.e., orbitofrontal cortex, hippocampus, amygdala, nucleus accumbens, caudate, putamen, pallidum, thalamus, corpus callosum, cerebellum) and global brain measures (i.e., total grey matter (GM), total white matter (WM) and cerebrospinal fluid). Volumes were compared between 660 people with alcohol dependence (228 women) and 326 controls (99 women) recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age and education years. Compared to controls, individuals with alcohol dependence on average had (3-9%) smaller volumes of the hippocampus (bilateral), putamen (left), pallidum (left), thalamus (right), corpus callosum, total GM and WM, and cerebellar GM (bilateral), the latter more prominently in women (right). Alcohol-dependent men showed smaller amygdala volume than control men, but this effect was unclear among women. In people with alcohol dependence, more monthly standard drinks predicted smaller amygdala and larger cerebellum GM volumes. The neuroanatomical differences associated with alcohol dependence emerged as gross and widespread, while those associated with a specific gender may be confined to selected brain regions. These findings warrant future neuroscience research to account for gender differences in alcohol dependence to further understand the neurobiological effects of alcohol dependence.

Sex differences in the neuroanatomy of alcohol dependence: hippocampus and amygdala subregions in a sample of 966 people from the ENIGMA Addiction Working Group.

Males and females with alcohol dependence have distinct mental health and cognitive problems. Animal models of addiction postulate that the underlying neurobiological mechanisms are partially distinct, but there is little evidence of sex differences in humans with alcohol dependence as most neuroimaging studies have been conducted in males. We examined hippocampal and amygdala subregions in a large sample of 966 people from the ENIGMA Addiction Working Group. This comprised 643 people with alcohol dependence (225 females), and a comparison group of 323 people without alcohol dependence (98 females). Males with alcohol dependence had smaller volumes of the total amygdala and its basolateral nucleus than male controls, that exacerbated with alcohol dose. Alcohol dependence was also associated with smaller volumes of the hippocampus and its CA1 and subiculum subfield volumes in both males and females. In summary, hippocampal and amygdalar subregions may be sensitive to both shared and distinct mechanisms in alcohol-dependent males and females.

How metacontrol biases and adaptivity impact performance in cognitive search tasks.

Cognitive control requires a balance between persistence and flexibility. We studied inter- and intraindividual differences in the metacontrol bias towards persistence or flexibility in cognitive search tasks from various cognitive domains that require continuous switching between persistence and flexibility. For each task, clustering and switching scores were derived to assess persistence and flexibility, respectively, as well as a total performance score to reflect general performance. We compared two, not mutually exclusive accounts according to which the balance between clustering and switching scores is affected by (1) individual, trait-like metacontrol biases towards persistence or flexibility and/or (2) the metacontrol adaptivity to bias states according to changing situational demands. We found that clustering and switching scores failed to generalize across tasks. However, clustering and switching were inversely related and predicted the total performance scores in most of the tasks, which in turn partially generalized across tasks and task domains. We conclude that metacontrol-biases towards persistence or flexibility can be adapted easily to specific task demands and individual resources, possibly overwriting individual metacontrol trait biases. Moreover, we suggest that total performance scores might serve to measure metacontrol adaptivity in future studies if task-restrictions and resources are known and/or well balanced.

A transdiagnostic dimensional approach towards a neuropsychological assessment for addiction: an international Delphi consensus study.

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

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects.

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 control subjects. CONCLUSIONS: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

Acute and past subjective stress influence working memory and related neural substrates.

Stress has been proposed to affect cognitive control capacities, including working memory (WM) maintenance. This effect may depend on variability in stress reactivity and past subjective stress. However, as most studies employed between-subjects designs, evidence for within-subject stress effects remains scarce. To understand the role of intra-individual stress effects on WM, we adopted a within-subject design to study how acute stress, variability in stress reactivity, and past subjective stress influence behavioral and neural WM mechanisms. Thirty-four healthy males performed a WM task during functional magnetic resonance imaging (fMRI) in a control versus acute stress condition following the Trier Social Stress Test, a validated psychosocial stressor method. We tested for stress effects on WM performance and related neural activation by associating them with individual acute stress responsivity and past subjective stress experience using retrospective self-report questionnaires. We found no evidence of an effect of acute stress or related stress-reactivity on intra-individual WM performance. However, past subjective stress negatively influenced acute stress-induced changes to WM. On the neural level, acute stress reduced WM-related activation in the dorsolateral prefrontal cortex (dlPFC). The observed negative influence of inter-individual variability in past subjective stress experience on changes in WM performance, suggests that past subjective stress might induce vulnerability for impairing effects of acute stress on cognitive functioning. Because acute stress reduced WM-related dlPFC activation while WM performance remained unaffected, acute stress might boost neural processing efficiency in this group of high performing healthy individuals. Our study suggests that measures of past subjective stress should be considered when studying and interpreting the effects of acute stress on cognition.

Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting.

INTRODUCTION: Taking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including creativity and problem-solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics, it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults. METHODS: During a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were expected to be manifested. RESULTS: We found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected. CONCLUSION: While this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.

Slips of Action and Sequential Decisions: A Cross-Validation Study of Tasks Assessing Habitual and Goal-Directed Action Control.

Instrumental learning and decision-making rely on two parallel systems: a goal-directed and a habitual system. In the past decade, several paradigms have been developed to study these systems in animals and humans by means of e.g., overtraining, devaluation procedures and sequential decision-making. These different paradigms are thought to measure the same constructs, but cross-validation has rarely been investigated. In this study we compared two widely used paradigms that assess aspects of goal-directed and habitual behavior. We correlated parameters from a two-step sequential decision-making task that assesses model-based (MB) and model-free (MF) learning with a slips-of-action paradigm that assesses the ability to suppress cue-triggered, learnt responses when the outcome has been devalued and is therefore no longer desirable. MB control during the two-step task showed a very moderately positive correlation with goal-directed devaluation sensitivity, whereas MF control did not show any associations. Interestingly, parameter estimates of MB and goal-directed behavior in the two tasks were positively correlated with higher-order cognitive measures (e.g., visual short-term memory). These cognitive measures seemed to (at least partly) mediate the association between MB control during sequential decision-making and goal-directed behavior after instructed devaluation. This study provides moderate support for a common framework to describe the propensity towards goal-directed behavior as measured with two frequently used tasks. However, we have to caution that the amount of shared variance between the goal-directed and MB system in both tasks was rather low, suggesting that each task does also pick up distinct aspects of goal-directed behavior. Further investigation of the commonalities and differences between the MF and habit systems as measured with these, and other, tasks is needed. Also, a follow-up cross-validation on the neural systems driving these constructs across different paradigms would promote the definition and operationalization of measures of instrumental learning and decision-making in humans.

Genetic imaging consortium for addiction medicine: From neuroimaging to genes.

Since the sample size of a typical neuroimaging study lacks sufficient statistical power to explore unknown genomic associations with brain phenotypes, several international genetic imaging consortia have been organized in recent years to pool data across sites. The challenges and achievements of these consortia are considered here with the goal of leveraging these resources to study addiction. The authors of this review have joined together to form an Addiction working group within the framework of the ENIGMA project, a meta-analytic approach to multisite genetic imaging data. Collectively, the Addiction working group possesses neuroimaging and genomic data obtained from over 10,000 subjects. The deadline for contributing data to the first round of analyses occurred at the beginning of May 2015. The studies performed on this data should significantly impact our understanding of the genetic and neurobiological basis of addiction.