@article{ObstSchadHuysetal.2018, author = {Obst, Elisabeth and Schad, Daniel and Huys, Quentin J. M. and Sebold, Miriam Hannah and Nebe, Stephan and Sommer, Christian and Smolka, Michael N. and Zimmermann, Ulrich S.}, title = {Drunk decisions}, series = {Journal of Psychopharmacology}, volume = {32}, journal = {Journal of Psychopharmacology}, number = {8}, publisher = {Sage Publ.}, address = {London}, issn = {0269-8811}, doi = {10.1177/0269881118772454}, pages = {855 -- 866}, year = {2018}, abstract = {Background: Studies in humans and animals suggest a shift from goal-directed to habitual decision-making in addiction. We therefore tested whether acute alcohol administration reduces goal-directed and promotes habitual decision-making, and whether these effects are moderated by self-reported drinking problems. Methods: Fifty-three socially drinking males completed the two-step task in a randomised crossover design while receiving an intravenous infusion of ethanol (blood alcohol level=80 mg\%), or placebo. To minimise potential bias by long-standing heavy drinking and subsequent neuropsychological impairment, we tested 18- to 19-year-old adolescents. Results: Alcohol administration consistently reduced habitual, model-free decisions, while its effects on goal-directed, model-based behaviour varied as a function of drinking problems measured with the Alcohol Use Disorders Identification Test. While adolescents with low risk for drinking problems (scoring <8) exhibited an alcohol-induced numerical reduction in goal-directed choices, intermediate-risk drinkers showed a shift away from habitual towards goal-directed decision-making, such that alcohol possibly even improved their performance. Conclusions: We assume that alcohol disrupted basic cognitive functions underlying habitual and goal-directed decisions in low-risk drinkers, thereby enhancing hasty choices. Further, we speculate that intermediate-risk drinkers benefited from alcohol as a negative reinforcer that reduced unpleasant emotional states, possibly displaying a novel risk factor for drinking in adolescence.}, language = {en} } @misc{SeboldGarbusowNebeetal.2018, author = {Sebold, Miriam Hannah and Garbusow, Maria and Nebe, S. and Sundmacher, L. and Kuitunen-Paul, S{\"o}ren and Wittchen, H. U. and Smolka, M. and Zimmermann, U. and Rapp, Michael Armin and Huys, Q. and Schlagenhauf, Florian and Heinz, A.}, title = {From goals to habits in alcohol dependence}, series = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {48}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, publisher = {Elsevier}, address = {Paris}, issn = {0924-9338}, pages = {S274 -- S274}, year = {2018}, language = {en} } @article{FriedelSeboldKuitunenPauletal.2017, author = {Friedel, Eva and Sebold, Miriam Hannah and Kuitunen-Paul, S{\"o}ren and Nebe, Stephan and Veer, Ilya M. and Zimmermann, Ulrich S. and Schlagenhauf, Florian and Smolka, Michael N. and Rapp, Michael Armin and Walter, Henrik and Heinz, Andreas}, title = {How Accumulated Real Life Stress Experience and Cognitive Speed Interact on Decision-Making Processes}, series = {Frontiers in human neuroscienc}, volume = {11}, journal = {Frontiers in human neuroscienc}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1662-5161}, doi = {10.3389/fnhum.2017.00302}, pages = {1 -- 9}, year = {2017}, abstract = {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.}, language = {en} } @article{SeboldDesernoNebeetal.2014, author = {Sebold, Miriam Hannah and Deserno, Lorenz and Nebe, Stefan and Schad, Daniel and Garbusow, Maria and Haegele, Claudia and Keller, Juergen and Juenger, Elisabeth and Kathmann, Norbert and Smolka, Michael N. and Rapp, Michael Armin and Schlagenhauf, Florian and Heinz, Andreas and Huys, Quentin J. M.}, title = {Model-based and model-free decisions in alcohol dependence}, series = {Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography}, volume = {70}, journal = {Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {0302-282X}, doi = {10.1159/000362840}, pages = {122 -- 131}, year = {2014}, abstract = {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.}, language = {en} } @misc{GarbusowSommerNebeetal.2018, author = {Garbusow, Maria and Sommer, Christian and Nebe, Stephan and Sebold, Miriam Hannah and Kuitunen-Paul, S{\"o}ren and Wittchen, Hans-Ulrich and Smolka, Michael N. and Zimmermann, Ulrich S. and Rapp, Michael Armin and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas}, title = {Multi-level evidence of general pavlovian-to-instrumental transfer in alcohol use disorder}, series = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, volume = {42}, journal = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, publisher = {Wiley}, address = {Hoboken}, issn = {0145-6008}, pages = {128A -- 128A}, year = {2018}, language = {en} } @article{SchadGarbusowFriedeletal.2018, author = {Schad, Daniel and Garbusow, Maria and Friedel, Eva and Sommer, Christian and Sebold, Miriam Hannah and H{\"a}gele, Claudia and Bernhardt, Nadine and Nebe, Stephan and Kuitunen-Paul, S{\"o}ren and Liu, Shuyan and Eichmann, Uta and Beck, Anne and Wittchen, Hans-Ulrich and Walter, Henrik and Sterzer, Philipp and Zimmermann, Ulrich S. and Smolka, Michael N. and Schlagenhauf, Florian and Huys, Quentin J. M. and Heinz, Andreas and Rapp, Michael Armin}, title = {Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk}, series = {European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry}, volume = {269}, journal = {European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry}, number = {3}, publisher = {Springer}, address = {Heidelberg}, issn = {0940-1334}, doi = {10.1007/s00406-017-0860-4}, pages = {295 -- 308}, year = {2018}, abstract = {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.}, language = {en} } @article{SekutowiczGuggenmosKuitunenPauletal.2019, author = {Sekutowicz, Maria and Guggenmos, Matthias and Kuitunen-Paul, S{\"o}ren and Garbusow, Maria and Sebold, Miriam Hannah and Pelz, Patricia and Priller, Josef and Wittchen, Hans-Ulrich and Smolka, Michael N. and Zimmermann, Ulrich S. and Heinz, Andreas and Sterzer, Philipp and Schmack, Katharina}, title = {Neural Response Patterns During Pavlovian-to-Instrumental Transfer Predict Alcohol Relapse and Young Adult Drinking}, series = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, volume = {86}, journal = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, number = {11}, publisher = {Elsevier}, address = {New York}, issn = {0006-3223}, doi = {10.1016/j.biopsych.2019.06.028}, pages = {857 -- 863}, year = {2019}, abstract = {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.}, language = {en} } @misc{SeboldNebeGarbusowetal.2017, author = {Sebold, Miriam Hannah and Nebe, Stephan and Garbusow, Maria and Schad, Daniel and Sommer, Christian and Rapp, Michael Armin and Smolka, Michael N. and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas}, title = {Neurobiological correlates of learning and decision-making in alcohol dependence}, series = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {41}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, publisher = {Elsevier}, address = {Paris}, issn = {0924-9338}, doi = {10.1016/j.eurpsy.2017.01.084}, pages = {S11 -- S11}, year = {2017}, language = {en} } @article{NebeKroemerSchadetal.2017, author = {Nebe, Stephan and Kroemer, Nils B. and Schad, Daniel and Bernhardt, Nadine and Sebold, Miriam Hannah and Mueller, Dirk K. and Scholl, Lucie and Kuitunen-Paul, S{\"o}ren and Heinz, Andreas and Rapp, Michael Armin and Huys, Quentin J. M. and Smolka, Michael N.}, title = {No association of goal-directed and habitual control with alcohol consumption in young adults}, series = {Addiction biology}, volume = {23}, journal = {Addiction biology}, number = {1}, publisher = {Wiley}, address = {Hoboken}, issn = {1355-6215}, doi = {10.1111/adb.12490}, pages = {379 -- 393}, year = {2017}, abstract = {Alcohol dependence is a mental disorder that has been associated with an imbalance in behavioral control favoring model-free habitual over model-based goal-directed strategies. It is as yet unknown, however, whether such an imbalance reflects a predisposing vulnerability or results as a consequence of repeated and/or excessive alcohol exposure. We, therefore, examined the association of alcohol consumption with model-based goal-directed and model-free habitual control in 188 18-year-old social drinkers in a two-step sequential decision-making task while undergoing functional magnetic resonance imaging before prolonged alcohol misuse could have led to severe neurobiological adaptations. Behaviorally, participants showed a mixture of model-free and model-based decision-making as observed previously. Measures of impulsivity were positively related to alcohol consumption. In contrast, neither model-free nor model-based decision weights nor the trade-off between them were associated with alcohol consumption. There were also no significant associations between alcohol consumption and neural correlates of model-free or model-based decision quantities in either ventral striatum or ventromedial prefrontal cortex. Exploratory whole-brain functional magnetic resonance imaging analyses with a lenient threshold revealed early onset of drinking to be associated with an enhanced representation of model-free reward prediction errors in the posterior putamen. These results suggest that an imbalance between model-based goal-directed and model-free habitual control might rather not be a trait marker of alcohol intake per se.}, language = {en} } @misc{GarbusowSommerNebeetal.2018, author = {Garbusow, Maria and Sommer, C. and Nebe, S. and Sebold, Miriam Hannah and Kuitunen-Paul, S{\"o}ren and Wittchen, H. U. and Smolka, M. and Zimmermann, U. and Rapp, Michael Armin and Huys, Q. and Schlagenhauf, Florian and Heinz, A.}, title = {Pavlovian-instrumental transfer in the course of alcohol use disorder}, series = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {48}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, publisher = {Elsevier}, address = {ISSY-LES-MOULINEAUX}, issn = {0924-9338}, pages = {S546 -- S546}, year = {2018}, abstract = {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.}, language = {en} }