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Behavioral adaptation is a fundamental cognitive ability, ensuring survival by allowing for flexible adjustment to changing environments. In laboratory settings, behavioral 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 behavioral 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 behavior 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 behavior. 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 to 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.

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., To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, we developed classifiers on data collected from multiple sites. Exploratory data analysis revealed that inclusion of case‐ and control‐only sites led to the inadvertent learning of site‐effects. Evolutionary‐based feature selection leveraging leave‐one‐site‐out cross‐validation, to combat unintentional learning, yielded a test‐set area under the receiver operating characteristic curve of 0.768.

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.

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. 9 p.

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.

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.

Highlights • We tested gender differences in brain volumes of alcohol dependent vs control groups. • Group differences in brain volumes emerged as gross and widespread. • Group-by-gender effects emerged in selected brain regions (cerebellum, amygdala) • In dependent users, greater alcohol use predicted smaller amygdala and larger cerebellum GM volume. • Our results highlight the need to account for gender differences in MRI studies of alcohol dependence., 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.

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.

IntroductionRecently popular sub-perceptual doses of psychedelic substances such as truffles, referred to as microdosing, allegedly have multiple beneficial effects including creativity and problem solving performance, potentially through targeting serotonergic 5-HT2Areceptors 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.MethodsDuring 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 manifested.ResultsWe found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected.ConclusionWhile 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.

[No abstract available] Funding Agencies|Flinders University; RU, Radboud Universiteit; NIU, Northern Illinois University; University of Nottingham; Universität zu Köln; Charité – Universitätsmedizin Berlin; SLU, Saint Louis University; TU/e, Technische Universiteit Eindhoven; University of Leeds; IUPUI, Indiana University-Purdue University Indianapolis; UiT, Universitetet i Tromsø; EUR, Erasmus Universiteit Rotterdam; UvT, Universiteit van Tilburg; University of Oxford; UNIL, Université de Lausanne; SEBM, Society for Experimental Biology and Medicine; NYU, New York University; UiT, Universitetet i Tromsø; RWTH Aachen University; KU Leuven; Universität Bielefeld; University of Louisiana at Lafayette; UA, University of Arkansas; Genentech Foundation for Biomedical Sciences; University of Bristol; UV, University of Virginia; City of Mobile; Université de Fribourg; Universiteit Gent; Yale University; VT, Virginia Polytechnic Institute and State University; DIBS, Duke Institute for Brain Sciences, Duke University; UCB UK; University of Leeds; BIBS, Brown Institute for Brain Science; UU, Universiteit Utrecht; Keele University; HRD, Division of Human Resource Development; WVU, West Virginia University; King’s College London; NTU, Nottingham Trent University; Rijksuniversiteit Groningen; KACST, King Abdulaziz City for Science and Technology; University of Edinburgh; UCONN, University of Connecticut; University of Kent; University of Cambridge; UNLV, University of Nevada, Las Vegas; Universiteit Leiden; UBC, University of British Columbia; HGS, Human Genome Sciences; AV CR, Akademie Ved Ceské Republiky; IUPUI, Indiana University-Purdue University Indianapolis; UK, University of Kentucky; University of Texas at Austin; DRS, Dahlem Research School, Freie Universität Berlin; Bangor University; RAND Corporation; University of Glasgow; University of Chester; CONICET, Consejo Nacional de Investigaciones Científicas y Técnicas; Massey University; UC, University of California; NIH, National Institutes of Health; UFSC, Universidade Federal de Santa Catarina; OU, Open University; Electroencephalography and Clinical Neuroscience Society; UNAB, Universidad Autónoma de Bucaramanga; KACST, King Abdulaziz City for Science and Technology; SU, Stanford University; CSIR, Council for Scientific and Industrial Research; FSU, Florida State University; UW, University of Wisconsin-Madison; LUMC, Leids Universitair Medisch Centrum; CERSI, Center of Excellence in Regulatory Science and Innovation; DePaul University; Baylor University; SU, Sahlgrenska Universitetssjukhuset; NINDS, National Institute of Neurological Disorders and Stroke

IntroductionAltered reward-based learning and stress play an important role in psychiatric illnesses, such as psychosis or addiction. Stress sometimes increases learning from rewards, other times it does not show an effect (Starcke & Brand, 2016). A task addressing reward-based learning is the reversal learning task, which uses probabilistic rewards as feedback and incorporates sudden changes in reward contingencies. The effects of acute stress on reversal learning have rarely been addressed.ObjectivesHere, we investigated the effect of acute social stress in a within-subject design in healthy participants.MethodsA sample of n = 28 male non-clinical participants performed the task in a control condition versus the Trier Social Stress Test (TSST), a validated method to induce psychosocial stress. In our version of the reversal learning task (Reiter, 2016), participants choose between two anti-correlated stimuli in order to obtain rewards in three blocks. Reward contingencies remain stable for the first 55 trials and the last 35 trials. During the second block, in between the stable blocks, four changes of reward contingencies require participants to flexibly adapt their behavior. Performance was measured in correct responses, switches after losses and wins.ResultsCortisol and subjective stress responses showed that the stress induction was successful. Preliminary analyses showed no significant effect of stress induction on any of the performance measures.ConclusionsThese results demonstrate that reversal learning, at least regarding overall performance measures in our task, is robust to stress-related changes. Modeling and fMRI analyses could yield further insights into more subtle changes after stress induction.DisclosureNo significant relationships.

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. Electronic supplementary material The online version of this article (10.3758/s13415-019-00717-z) contains supplementary material, which is available to authorized users.

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.

Creativity is a compelling but heterogeneous phenomenon. As opposed to big-C creativity, which is regarded as limited to the rare brilliant mind, little-c creativity is indispensable in adaptive everyday behavior, serving to adjust to changing circumstances and challenges. Computational approaches help demystify human creativity by offering insights into the underlying mechanisms and their characteristics. Recently proposed computational models to creative cognition often focus on either divergent or convergent problem-solving, but some start to integrate these processes into broader cognitive frameworks. We briefly review the state-of-the-art in the field and point out theoretical overlap. We extract basic principles that most existing models agree on and desiderata on the way towards a comprehensive model.

IntroductionA meta-analysis by Gürsel et al. (2018) found altered functional connectivity in OCD patients within and between default mode (DMN), salience (SN), and frontoparietal networks (FPN), as well as evidence for aberrant fronto-striatal circuitry.ObjectivesTesting the replicability of meta-analysis rsfMRI findings in OCD patients.MethodsWe measured functional connectivity during resting-state fMRI in a sample of OCD patients (n=24) and controls matched for age and sex (n=33). The CONN toolbox implemented in SPM was used to perform seed-to-voxel analysis using 30 seed regions based on the previous meta-analytic findings.ResultsOCD patients showed reduced functional connectivity between SN and DMN compared to controls, replicating previous findings. We did not observe significant group differences of functional connectivity within the DMN, SN, or FPN. The strongest finding consisted of altered connectivity between DMN and SN to the visual network. OCD patients showed reduced functional connectivity between the left lateral parietal seed (LPl) and the inferior lateral occipital pole left (iLOCl) compared to controls. Furthermore, the LPl was found to be hyperconnected with the right superior lateral occipital cortex (sLOCr) and the right precuneus. This finding was positively correlated to OCD symptom severity, especially compulsions.ConclusionsOur findings replicated partly the meta-analysis findings, specifically reduced connectivity between SN and DMN. Using seeds based on the meta-analysis, we identified aberrations between the SN and, in particular, the DMN to the visual network. This raises the question about the visual system’s involvement in OCD symptoms and the abnormal connectivity of a unimodal region to the multimodal DMN.DisclosureNo significant relationships.

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.

Cognitive control requires a balance between persistence andflexibility. 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.

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.

Contains fulltext : 150694.pdf (Publisher’s version ) (Closed access) Het huidige systeem voor psychiatrische diagnostiek en nosologie is voornamelijk gebaseerd op extern waarneembare symptomen en een categorische classificatie. Dit leidt tot heterogeniteit en comorbiditeit tussen diagnosen. Om classificatie te verbeteren en individuele behandeling te bevorderen, is er behoefte aan een meer dimensionale en kwantitatieve benadering, waarmee onderliggende (niet direct waarneembare) processen en mechanismen worden gedefinieerd. Een dergelijke benadering zal leiden tot toepasbare diagnostische tests die zich richten op pathofysiologische mechanismen die ten grondslag liggen aan verstoorde observeerbare cognitieve en emotionele processen en de daaruit voortkomende psychopathologie. Computationele psychiatrie biedt een handvat tot een dergelijke mechanistische benadering. Door middel van non-lineaire wiskundige modellen wordt informatie geïntegreerd over latente processen die ten grondslag liggen aan (verstoord) gedrag, simultaan gemeten breinactiviteit, en zelfs effecten van interventies, zoals hersenstimulatie en farmacologie. De hoop is dat deze benadering zal leiden tot een beter begrip van psychiatrische stoornissen op het niveau van (latente) cognitieve processen en de onderliggende neurobiologie en, daaruit volgend, een verbetering van diagnose en behandeling. In dit artikel introduceren wij eerst de rationale en werkwijze van de computationele psychiatrie, om vervolgens de stappen te bespreken die naar onze mening genomen moeten worden om een succesvolle bijdrage te leveren aan de psychiatrie en gerelateerde specialismen. 12 p.

It is suggested that acute stress shifts behavioral control from goal-directed, model-based toward habitual, model-free strategies. Recent findings indicate that interindividual differences in the cortisol stress response influence model-based decision-making. Although not yet investigated in humans, animal studies show that chronic stress also shifts decision-making toward more habitual behavior. Here, we ask whether acute stress and individual vulnerability factors, such as stress reactivity and previous exposure to stressful life events, impact the balance between model-free and model-based control systems. To test this, 39 male participants (21-30 years old) were exposed to a potent psychosocial stressor (Trier Social Stress Test) and a control condition in a within-subjects design before they performed a sequential decision-making task which evaluates the balance between the two systems. Physiological and subjective stress reactivity was assessed before, during, and after acute stress exposure. By means of computational modeling, we demonstrate that interindividual variability in stress reactivity predicts impairments in model-based decision-making. Whereas acute psychosocial stress did not alter model-based behavioral control, we found chronic and acute stress to interact in their detrimental effect on decision-making: subjects with high but not low chronic stress levels as indicated by stressful life events exhibited reduced model-based control in response to acute psychosocial stress. These findings emphasize that stress reactivity and chronic stress play an important role in mediating the relationship between stress and decision-making. Our results might stimulate new insights into the interplay between chronic and acute stress, attenuated model-based control, and the pathogenesis of various psychiatric diseases.

Post-traumatic stress disorder (PTSD) is associated with impaired memory performance coupled with functional changes in brain areas involved in declarative memory and emotion regulation. It is not yet clear how symptom severity and comorbidity affect neurocognitive functioning in PTSD. We performed a functional magnetic resonance imaging (fMRI) study with an emotional declarative memory task in 28 Complex PTSD patients with comorbid depressive and personality disorders, and 21 healthy nontrauma-exposed controls. In Complex PTSD patients-compared to controls-encoding of later remembered negative words vs baseline was associated with increased blood oxygenation level dependent (BOLD) response in the left ventral anterior cingulate cortex (ACC) and dorsal ACC extending to the dorsomedial prefrontal cortex (dmPFC) together with a trend for increased left hippocampus activation. Patients tended to commit more False Alarms to negative words compared to controls, which was associated with enhanced left ventrolateral prefrontal and orbitofrontal cortex (vlPFC/OFC) responses. Severity of child abuse was positively correlated with left ventral ACC activity and severity of depression with (para) hippocampal and ventral ACC activity. Presented results demonstrate functional abnormalities in Complex PTSD in the frontolimbic brain circuit also implicated in fear conditioning models, but generally in the opposite direction, which may be explained by severity of the trauma and severity of comorbid depression in Complex PTSD.©The Author (2011). Published by Oxford University Press.

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.

Pathological gambling (PG) is associated with maladaptive perseverative behavior, but the underlying mechanism and neural circuitry is not completely clear. Here, the hypothesis was tested that PG is characterized by response perseveration and abnormalities in reward and/or punishment sensitivity in the ventral frontostriatal circuit. Executive functioning was assessed to verify if these effects are independent of the dorsal frontostriatal circuit. A group of smokers was also included to examine whether impairments in PG generalize to substance use disorders. Response perseveration and reward/punishment sensitivity were measured with a probabilistic reversal-learning task, in which subjects could win and lose money. Executive functioning was measured with a planning task, the Tower of London. Performance and fMRI data were acquired in 19 problem gamblers, 19 smokers, and 19 healthy controls. Problem gamblers showed severe response perseveration, associated with reduced activation of right ventrolateral prefrontal cortex in response to both monetary gain and loss. Results did not fully generalize to smokers. Planning performance and related activation of the dorsal frontostriatal circuit were intact in both problem gamblers and smokers. PG is related to response perseveration and diminished reward and punishment sensitivity as indicated by hypoactivation of the ventrolateral prefrontal cortex when money is gained and lost. Moreover, intact planning abilities and normal dorsal frontostriatal responsiveness indicate that this deficit is not due to impaired executive functioning. Response perseveration and ventral prefrontal hyporesponsiveness to monetary loss may be markers for maladaptive behavior seen in chemical and nonchemical addictions.Neuropsychopharmacology advance online publication, 1 October 2008; doi:10.1038/npp.2008.175

Objectives. Alcohol-use disorders in adolescents are associated with gray matter (GM) abnormalities suggesting neurotoxicity by alcohol. However, recently similar GM abnormalities were found in non-drinking children with a family history (FH) of alcohol dependence (AD). The question thus rises whether these abnormalities represent a transient delay in brain maturation or a persistent risk factor for developing neuropsychiatric disorders, rather than a (neurotoxic) consequence of AD. This study investigated whether a FH of AD in non-drinking adults is associated with abnormal GM-volumes similar to those observed in drinking and non-drinking adolescents with a FH of AD. Methods. GM-images were analyzed using Voxel-Based Morphometry in non-alcoholics with (FH+; N = 36) and without (FH-; N = 107) familial AD. Additionally we controlled for possible confounders: diagnosis of depression/anxiety, childhood trauma and familial depression/anxiety. Results. Smaller GM-volumes were shown in the right parahippocampal gyrus in FH+ compared with FH-. Results were unaffected by confounders. Conclusions. We demonstrated an effect of familial AD in non-alcoholic adults on GM volume in the parahippocampal gyrus, similar to drinking and non-drinking FH+ adolescents. These findings suggest that GM abnormalities in the parahippocampal gyrus represent a persistent biological susceptibility for AD or related psychopathology and not neurotoxicity of alcohol or delayed brain maturation. © 2013 Informa Healthcare.

Introduction With the progression of substance dependence, drug cue-related brain activation is thought to shift from motivational towards habit pathways. However, a direct association between cue-induced brain activation and dependence duration has not yet been shown. We therefore examined the relationship between alcohol cue-reactivity in the brain, cue-induced subjective craving and alcohol dependence duration and severity. Since alcohol dependence is highly comorbid with depression/anxiety, which may modulate brain responses to alcohol cues, we also examined the relation between comorbid depression/anxiety and cue-reactivity. Methods We compared 30 alcohol dependent patients with 15 healthy controls and 15 depression/anxiety patients during a visual alcohol cue-reactivity task using functional magnetic resonance imaging blood oxygenated level-dependent responses and subjective craving as outcomes. Within the alcohol dependent group we correlated cue-reactivity with alcohol dependence severity and duration, with cue-induced craving and with depression/anxiety levels. Results Alcohol dependent patients showed greater cue-reactivity in motivational brain pathways and stronger subjective craving than depression/anxiety patients and healthy controls. Depression/anxiety was not associated with cue-reactivity, but depression severity in alcohol dependent patients was positively associated with craving. Within alcohol dependence, longer duration of alcohol dependence was associated with stronger cue-related activation of the posterior putamen, a structure involved in habits, whereas higher alcohol dependence severity was associated with lower cue-reactivity in the anterior putamen, an area implicated in goal-directed behavior preceding habit formation. Conclusion Cue-reactivity in alcohol dependence is not modulated by comorbid depression or anxiety. More importantly, the current data confirm the hypothesis of a ventral to dorsal striatal shift of learning processes with longer dependence duration, which could underlie increasingly habitual substance use with progressing substance dependence.

Substance dependence is characterized by compulsive drug-taking despite negative consequences. Animal research suggests an underlying imbalance between goal-directed and habitual action control with chronic drug use. However, this imbalance, and its associated neurophysiological mechanisms, has not yet been experimentally investigated in human drug abusers. The aim of the present study therefore was to assess the balance between goal-directed and habit-based learning and its neural correlates in abstinent alcohol-dependent (AD) patients. A total of 31 AD patients and 19 age, gender and education matched healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during completion of an instrumental learning task designed to study the balance between goal-directed and habit learning. Task performance and task-related blood oxygen level-dependent activations in the brain were compared between AD patients and healthy matched controls. Findings were additionally associated with duration and severity of alcohol dependence. The results of this study provide evidence for an overreliance on stimulusresponse habit learning in AD compared with HC, which was accompanied by decreased engagement of brain areas implicated in goal-directed action (ventromedial prefrontal cortex and anterior putamen) and increased recruitment of brain areas implicated in habit learning (posterior putamen) in AD patients. In conclusion, this is the first human study to provide experimental evidence for a disturbed balance between goal-directed and habitual control by use of an instrumental learning task, and to directly implicate cortical dysfunction to overreliance on inflexible habits in AD patients. © 2013 Macmillan Publishers Limited All rights reserved.