TY - JOUR A1 - Wyckmans, Florent A1 - Otto, A. Ross A1 - Sebold, Miriam Hannah A1 - Daw, Nathaniel A1 - Bechara, Antoine A1 - Saeremans, Mélanie A1 - Kornreich, Charles A1 - Chatard, Armand A1 - Jaafari, Nemat A1 - Noël, Xavier T1 - Reduced model-based decision-making in gambling disorder JF - Scientific reports N2 - Compulsive behaviors (e.g., addiction) can be viewed as an aberrant decision process where inflexible reactions automatically evoked by stimuli (habit) take control over decision making to the detriment of a more flexible (goal-oriented) behavioral learning system. These behaviors are thought to arise from learning algorithms known as "model-based" and "model-free" reinforcement learning. Gambling disorder, a form of addiction without the confound of neurotoxic effects of drugs, showed impaired goal-directed control but the way in which problem gamblers (PG) orchestrate model-based and model-free strategies has not been evaluated. Forty-nine PG and 33 healthy participants (CP) completed a two-step sequential choice task for which model-based and model-free learning have distinct and identifiable trial-by-trial learning signatures. The influence of common psychopathological comorbidities on those two forms of learning were investigated. PG showed impaired model-based learning, particularly after unrewarded outcomes. In addition, PG exhibited faster reaction times than CP following unrewarded decisions. Troubled mood, higher impulsivity (i.e., positive and negative urgency) and current and chronic stress reported via questionnaires did not account for those results. These findings demonstrate specific reinforcement learning and decision-making deficits in behavioral addiction that advances our understanding and may be important dimensions for designing effective interventions. Y1 - 2019 U6 - https://doi.org/10.1038/s41598-019-56161-z SN - 2045-2322 VL - 9 PB - Nature Publ. Group CY - London ER - TY - GEN A1 - Garbusow, Maria A1 - Sommer, Christian A1 - Nebe, Stephan A1 - Sebold, Miriam Hannah A1 - Kuitunen-Paul, Sören A1 - Wittchen, Hans-Ulrich A1 - Smolka, Michael N. A1 - Zimmermann, Ulrich S. A1 - Rapp, Michael Armin 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 - GEN A1 - Garbusow, Maria A1 - Sommer, C. A1 - Nebe, S. A1 - Sebold, Miriam Hannah A1 - Kuitunen-Paul, Sören A1 - Wittchen, H. U. A1 - Smolka, M. A1 - Zimmermann, U. A1 - Rapp, Michael Armin A1 - Huys, Q. A1 - Schlagenhauf, Florian A1 - Heinz, A. T1 - Pavlovian-instrumental transfer in the course of alcohol use disorder T2 - European psychiatry : the journal of the Association of European Psychiatrists N2 - Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping on- going thought and behavior. The influence of Pavlovian stimuli on on-going behavior is paradigmatically measured by Pavlovian-to-instrumental-transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent, and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced Pavlovian-Instrumental transfer. Methods: 32 recently detoxified alcohol-dependent patients and 32 age and gender matched healthy controls performed a PIT task with instrumental go/no-go approach behaviours. The task involved both Pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol- dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT. Y1 - 2018 SN - 0924-9338 SN - 1778-3585 VL - 48 SP - S546 EP - S546 PB - Elsevier CY - ISSY-LES-MOULINEAUX ER - TY - JOUR A1 - Sekutowicz, Maria A1 - Guggenmos, Matthias A1 - Kuitunen-Paul, Sören A1 - Garbusow, Maria A1 - Sebold, Miriam Hannah A1 - Pelz, Patricia A1 - Priller, Josef A1 - Wittchen, Hans-Ulrich A1 - Smolka, Michael N. A1 - Zimmermann, Ulrich S. A1 - Heinz, Andreas A1 - Sterzer, Philipp A1 - Schmack, Katharina T1 - Neural Response Patterns During Pavlovian-to-Instrumental Transfer Predict Alcohol Relapse and Young Adult Drinking JF - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry N2 - BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Delta = -24.4 +/- 6.0 g vs. -5.7 +/- 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states. KW - Alcohol dependence KW - Future drinking behavior KW - Multivoxel classification KW - Pavlovian-to-instrumental transfer KW - Relapse Y1 - 2019 U6 - https://doi.org/10.1016/j.biopsych.2019.06.028 SN - 0006-3223 SN - 1873-2402 VL - 86 IS - 11 SP - 857 EP - 863 PB - Elsevier CY - New York ER - TY - JOUR A1 - Friedel, Eva A1 - Sebold, Miriam Hannah 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 Armin 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 - Chen, Ke A1 - Hollunder, Barbara A1 - Garbusow, Maria A1 - Sebold, Miriam Hannah A1 - Heinz, Andreas T1 - The physiological responses to acute stress in alcohol-dependent patients BT - a systematic review JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology N2 - Dysregulation of physiological stress reactivity plays a key role in the development and relapse risk of alcohol dependence. This article reviews studies investigating physiological responses to experimentally induced acute stress in patients with alcohol dependence. A systematic search from electronic databases resulted in 3641 articles found and after screening 62 articles were included in our review. Studies are analyzed based on stress types (i.e., social stress tasks and nonsocial stress tasks) and physiological markers (i.e., the nervous system, the endocrine system, somatic responses and the immune system). In studies applying nonsocial stress tasks, alcohol-dependent patients were reported to show a blunted stress response compared with healthy controls in the majority of studies applying markers of adrenocorticotropic hormone and cortisol. In studies applying social stress tasks, findings are inconsistent, with less than half of the studies reporting altered physiological stress responses in patients. We discuss the impact of duration of abstinence, comorbidities, baseline physiological arousal and intervention on the discrepancy of study findings. Furthermore, we review evidence for an associationbetween blunted physiological stress responses and the relapse risk among patients with alcohol dependence. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) KW - acute stress KW - alcohol dependence KW - hypothalamic- pituitary-adrenal axis KW - physiological reactivity Y1 - 2020 U6 - https://doi.org/10.1016/j.euroneuro.2020.09.003 SN - 0924-977X SN - 1873-7862 VL - 41 SP - 1 EP - 15 PB - Elsevier CY - Amsterdam ER - TY - GEN A1 - Sebold, Miriam Hannah 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 Armin A1 - Huys, Q. A1 - Schlagenhauf, Florian A1 - Heinz, A. 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 - Garbusow, Maria A1 - Schad, Daniel A1 - Sommer, Christian A1 - Juenger, Elisabeth A1 - Sebold, Miriam Hannah A1 - Friedel, Eva A1 - Wendt, Jean A1 - Kathmann, Norbert A1 - Schlagenhauf, Florian A1 - Zimmermann, Ulrich S. A1 - Heinz, Andreas A1 - Huys, Quentin J. M. A1 - Rapp, Michael Armin T1 - Pavlovian-to-instrumental transfer in alcohol dependence: a pilot study JF - Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography N2 - Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT. KW - Pavlovian-to-instrumental transfer KW - Alcohol dependence KW - Human Y1 - 2014 U6 - https://doi.org/10.1159/000363507 SN - 0302-282X SN - 1423-0224 VL - 70 IS - 2 SP - 111 EP - 121 PB - Karger CY - Basel ER - TY - CHAP A1 - Schad, Daniel A1 - Juenger, Elisabeth A1 - Sebold, Miriam Hannah A1 - Garbusow, Maria A1 - Bernhart, Nadine A1 - Javadi, Amir Homayoun A1 - Zimmermann, Ulrich S. A1 - Smolka, Michael N. A1 - Heinz, Andreas A1 - Rapp, Michael Armin A1 - Huys, Quentin J. M. T1 - Smart goals, slow habits? Individual differences in processing speed and working memory capacity moderate the balance between habitual and goal-directed choice behavior T2 - Cognitive processing : international quarterly of cognitive science Y1 - 2014 SN - 1612-4782 SN - 1612-4790 VL - 15 IS - 1 SP - S62 EP - S62 PB - Springer CY - Heidelberg ER - TY - GEN A1 - Garbusow, Maria A1 - Nebe, Stephan A1 - Sommer, Christian A1 - Kuitunen-Paul, Sören A1 - Sebold, Miriam Hannah A1 - Schad, Daniel A1 - Friedel, Eva A1 - Veer, Ilya M. A1 - Wittchen, Hans-Ulrich A1 - Rapp, Michael Armin A1 - Ripke, Stephan A1 - Walter, Henrik A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Smolka, Michael N. A1 - Heinz, Andreas T1 - Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers BT - Behavioral, Neural and Polygenic Correlates T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe N2 - In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 841 KW - Pavlovian-to-instrumental transfer KW - amygdala KW - alcohol KW - polygenic risk KW - high risk drinkers Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-473280 SN - 1866-8364 IS - 841 ER -