TY - GEN A1 - Awasthi, Swapnil A1 - Kaminski, Jakob A1 - Rapp, Michael A. A1 - Schlagenhauf, Florian A1 - Walter, Henrik A1 - Ruggeri, Barbara A1 - Ripke, Stephan A1 - Schumann, Gunter A1 - Heinz, Andreas T1 - A neural signature of malleability BT - general intelligence correlates with ventral striatal activation and epigenetic makers of dopamine neurotransmission T2 - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology N2 - General intelligence has a substantial genetic background in children, adolescents, and adults, but environmental factors also strongly correlate with cognitive performance as evidenced by a strong (up to one SD) increase in average intelligence test results in the second half of the previous century. This change occurred in a period apparently too short to accommodate radical genetic changes. It is highly suggestive that environmental factors interact with genotype by possible modification of epigenetic factors that regulate gene expression and thus contribute to individual malleability. This modification might as well be reflected in recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. Y1 - 2019 U6 - https://doi.org/10.1016/j.euroneuro.2017.08.139 SN - 0924-977X SN - 1873-7862 VL - 29 SP - S858 EP - S859 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Deserno, Lorenz A1 - Beck, Anne A1 - Huys, Quentin J. M. A1 - Lorenz, Robert C. A1 - Buchert, Ralph A1 - Buchholz, Hans-Georg A1 - Plotkin, Michail A1 - Kumakara, Yoshitaka A1 - Cumming, Paul A1 - Heinze, Hans-Jochen A1 - Grace, Anthony A. A1 - Rapp, Michael A. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum JF - European journal of neuroscience N2 - Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N=27). All participants also underwent 6-[F-18]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake. KW - alcohol addiction KW - dopamine KW - fMRI KW - PET KW - prediction error Y1 - 2015 U6 - https://doi.org/10.1111/ejn.12802 SN - 0953-816X SN - 1460-9568 VL - 41 IS - 4 SP - 477 EP - 486 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Haegele, Claudia A1 - Schlagenhauf, Florian A1 - Rapp, Michael A. A1 - Sterzer, Philipp A1 - Beck, Anne A1 - Bermpohl, Felix A1 - Stoy, Meline A1 - Stroehle, Andreas A1 - Wittchen, Hans-Ulrich A1 - Dolan, Raymond J. A1 - Heinz, Andreas T1 - Dimensional psychiatry: reward dysfunction and depressive mood across psychiatric disorders JF - Psychopharmacology N2 - A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries. We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment. During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation. Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities. KW - Dimensional KW - fMRI KW - Reward system KW - Ventral striatum KW - Monetary incentive delay task KW - Depressive symptoms Y1 - 2015 U6 - https://doi.org/10.1007/s00213-014-3662-7 SN - 0033-3158 SN - 1432-2072 VL - 232 IS - 2 SP - 331 EP - 341 PB - Springer CY - New York ER - TY - JOUR A1 - Balta Beylergil, Sinem A1 - Beck, Anne A1 - Deserno, Lorenz A1 - Lorenz, Robert C. A1 - Rapp, Michael A. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas A1 - Obermayer, Klaus T1 - Dorsolateral prefrontal cortex contributes to the impaired behavioral adaptation in alcohol dependence JF - NeuroImage: Clinical : a journal of diseases affecting the nervous system N2 - Substance-dependent individuals often lack the ability to adjust decisions flexibly in response to the changes in reward contingencies. Prediction errors (PEs) are thought to mediate flexible decision-making by updating the reward values associated with available actions. In this study, we explored whether the neurobiological correlates of PEs are altered in alcohol dependence. Behavioral, and functional magnetic resonance imaging (fMRI) data were simultaneously acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy controls (HC) during a probabilistic reward-guided decision-making task with dynamically changing reinforcement contingencies. A hierarchical Bayesian inference method was used to fit and compare learning models with different assumptions about the amount of task-related information subjects may have inferred during the experiment. Here, we observed that the best-fitting model was a modified Rescorla-Wagner type model, the “double-update” model, which assumes that subjects infer the knowledge that reward contingencies are anti-correlated, and integrate both actual and hypothetical outcomes into their decisions. Moreover, comparison of the best-fitting model's parameters showed that ADP were less sensitive to punishments compared to HC. Hence, decisions of ADP after punishments were loosely coupled with the expected reward values assigned to them. A correlation analysis between the model-generated PEs and the fMRI data revealed a reduced association between these PEs and the BOLD activity in the dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was observed in the DLPFC when positive and negative PE signals were analyzed separately. The right DLPFC activity in ADP showed a reduced correlation with positive PEs. On the other hand, ADP, particularly the patients with high dependence severity, recruited the left DLPFC to a lesser extent than HC for processing negative PE signals. These results suggest that the DLPFC, which has been linked to adaptive control of action selection, may play an important role in cognitive inflexibility observed in alcohol dependence when reinforcement contingencies change. Particularly, the left DLPFC may contribute to this impaired behavioral adaptation, possibly by impeding the extinction of the actions that no longer lead to a reward. KW - Alcohol dependence KW - Prediction error KW - Reinforcement learning KW - Reversal learning KW - Dorsolateral prefrontal cortex KW - Decision-making Y1 - 2017 U6 - https://doi.org/10.1016/j.nicl.2017.04.010 SN - 2213-1582 VL - 15 SP - 80 EP - 94 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Kaminski, Jakob A. A1 - Schlagenhauf, Florian A1 - Rapp, Michael A. A1 - Awasthi, Swapnil A1 - Ruggeri, Barbara A1 - Deserno, Lorenz A1 - Banaschewski, Tobias A1 - Bokde, Arun L. W. A1 - Bromberg, Uli A1 - Büchel, Christian A1 - Quinlan, Erin Burke A1 - Desrivieres, Sylvane A1 - Flor, Herta A1 - Frouin, Vincent A1 - Garavan, Hugh A1 - Gowland, Penny A1 - Ittermann, Bernd A1 - Martinot, Jean-Luc A1 - Martinot, Marie-Laure Paillere A1 - Nees, Frauke A1 - Orfanos, Dimitri Papadopoulos A1 - Paus, Tomas A1 - Poustka, Luise A1 - Smolka, Michael N. A1 - Fröhner, Juliane H. A1 - Walter, Henrik A1 - Whelan, Robert A1 - Ripke, Stephan A1 - Schumann, Gunter A1 - Heinz, Andreas T1 - Epigenetic variance in dopamine D2 receptor BT - a marker of IQ malleability? JF - Translational Psychiatry N2 - Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure. Y1 - 2018 U6 - https://doi.org/10.1038/s41398-018-0222-7 SN - 2158-3188 VL - 8 PB - Nature Publ. Group CY - New York ER - TY - GEN A1 - Sebold, Miriam A1 - Garbusow, Maria A1 - Nebe, S. A1 - Sundmacher, L. A1 - Kuitunen-Paul, Sören A1 - Wittchen, H. U. A1 - Smolka, M. A1 - Zimmermann, U. A1 - Rapp, Michael A. A1 - Huys, Q. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - From goals to habits in alcohol dependence BT - association with treatment outcome and cognitive bias modification training T2 - European psychiatry : the journal of the Association of European Psychiatrists Y1 - 2018 SN - 0924-9338 SN - 1778-3585 VL - 48 SP - S274 EP - S274 PB - Elsevier CY - Paris ER - TY - JOUR A1 - Friedel, Eva A1 - Sebold, Miriam A1 - Kuitunen-Paul, Sören A1 - Nebe, Stephan A1 - Veer, Ilya M. A1 - Zimmermann, Ulrich S. A1 - Schlagenhauf, Florian A1 - Smolka, Michael N. A1 - Rapp, Michael A. A1 - Walter, Henrik A1 - Heinz, Andreas T1 - How Accumulated Real Life Stress Experience and Cognitive Speed Interact on Decision-Making Processes JF - Frontiers in human neuroscienc N2 - Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding. Acute stress reactivity is known to impair model-based but not model-free choice behavior, with higher working memory capacity protecting the model-based system from acute stress. However, it is not clear which impact accumulated real life stress has on model-free and model-based decision systems and how this influence interacts with cognitive abilities. Methods: We used a sequential decision-making task distinguishing relative contributions of both learning strategies to choice behavior, the Social Readjustment Rating Scale questionnaire to assess accumulated real life stress, and the Digit Symbol Substitution Test to test cognitive speed in 95 healthy subjects. Results: Individuals reporting high stress exposure who had low cognitive speed showed reduced model-based but increased model-free behavioral control. In contrast, subjects exposed to accumulated real life stress with high cognitive speed displayed increased model-based performance but reduced model-free control. Conclusion: These findings suggest that accumulated real life stress exposure can enhance reliance on cognitive speed for model-based computations, which may ultimately protect the model-based system from the detrimental influences of accumulated real life stress. The combination of accumulated real life stress exposure and slower information processing capacities, however, might favor model-free strategies. Thus, the valence and preference of either system strongly depends on stressful experiences and individual cognitive capacities. KW - chronic stress KW - model-based learning KW - model-free learning KW - decision making KW - cognitive speed KW - real-life events Y1 - 2017 U6 - https://doi.org/10.3389/fnhum.2017.00302 SN - 1662-5161 VL - 11 SP - 1 EP - 9 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Sebold, Miriam A1 - Deserno, Lorenz A1 - Nebe, Stefan A1 - Schad, Daniel A1 - Garbusow, Maria A1 - Haegele, Claudia A1 - Keller, Juergen A1 - Juenger, Elisabeth A1 - Kathmann, Norbert A1 - Smolka, Michael N. A1 - Rapp, Michael A. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas A1 - Huys, Quentin J. M. T1 - Model-based and model-free decisions in alcohol dependence JF - Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography N2 - Background: Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive. Methods: Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns. Results: Alcohol-dependent patients showed less evidence of goal-directed choices than healthy controls, particularly after losses. There was no difference in the strength of the habitual component. The group differences did not survive controlling for performance on the Digit Symbol Substitution Task. Conclusion: Chronic alcohol use appears to selectively impair goal-directed function, rather than promoting habitual responding. It appears to do so particularly after nonrewards, and this may be mediated by the effects of alcohol on more general cognitive functions subserved by the prefrontal cortex. KW - Alcohol dependence KW - Decision-making KW - Reinforcement learning KW - Dopamine KW - Computational psychiatry Y1 - 2014 U6 - https://doi.org/10.1159/000362840 SN - 0302-282X SN - 1423-0224 VL - 70 IS - 2 SP - 122 EP - 131 PB - Karger CY - Basel ER - TY - GEN A1 - Garbusow, Maria A1 - Sommer, Christian A1 - Nebe, Stephan A1 - Sebold, Miriam A1 - Kuitunen-Paul, Sören A1 - Wittchen, Hans-Ulrich A1 - Smolka, Michael N. A1 - Zimmermann, Ulrich S. A1 - Rapp, Michael A. A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - Multi-level evidence of general pavlovian-to-instrumental transfer in alcohol use disorder T2 - Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism Y1 - 2018 SN - 0145-6008 SN - 1530-0277 VL - 42 SP - 128A EP - 128A PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Schad, Daniel A1 - Garbusow, Maria A1 - Friedel, Eva A1 - Sommer, Christian A1 - Sebold, Miriam A1 - Hägele, Claudia A1 - Bernhardt, Nadine A1 - Nebe, Stephan A1 - Kuitunen-Paul, Sören A1 - Liu, Shuyan A1 - Eichmann, Uta A1 - Beck, Anne A1 - Wittchen, Hans-Ulrich A1 - Walter, Henrik A1 - Sterzer, Philipp A1 - Zimmermann, Ulrich S. A1 - Smolka, Michael N. A1 - Schlagenhauf, Florian A1 - Huys, Quentin J. M. A1 - Heinz, Andreas A1 - Rapp, Michael A. T1 - Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk JF - European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry N2 - The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors. KW - Alcohol dependence KW - Human neuroimaging KW - Nucleus accumbens KW - Pavlovian-instrumental transfer KW - Relapse Y1 - 2018 U6 - https://doi.org/10.1007/s00406-017-0860-4 SN - 0940-1334 SN - 1433-8491 VL - 269 IS - 3 SP - 295 EP - 308 PB - Springer CY - Heidelberg ER -