@article{SeboldSpittaGleichetal.2019, author = {Sebold, Miriam Hannah and Spitta, G. and Gleich, T. and Dembler-Stamm, T. and Butler, Oisin and Zacharias, Kristin and Aydin, S. and Garbusow, Maria and Rapp, Michael Armin and Schubert, Florian and Buchert, Ralph and Gallinat, J{\"u}rgen and Heinz, A.}, title = {Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence}, series = {Journal of neural transmission}, volume = {126}, journal = {Journal of neural transmission}, number = {9}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-019-01985-2}, pages = {1127 -- 1134}, year = {2019}, abstract = {Stress plays a key role in modulating addictive behavior and can cause relapse following periods of abstinence. Common effects of stress and alcohol on the dopaminergic system have been suggested, although the precise mechanisms are unclear. Here, we investigated 20 detoxified alcohol-dependent patients and 19 matched healthy controls and assessed striatal D2/D3 availability using [F-18]-fallypride positron emission tomography and stressful life events. We found a strong association between striatal D2/D3 availability and stress in patients, but not in healthy controls. Interestingly, we found increased D2/D3 receptor availability in patients with higher stress levels. This mirrors complex interactions between stress and alcohol intake in animal studies and emphasizes the importance to investigate stress exposure in neurobiological studies of addiction.}, language = {en} } @article{SeboldSchadNebeetal.2016, author = {Sebold, Miriam Hannah and Schad, Daniel and Nebe, Stephan and Garbusow, Maria and Juenger, Elisabeth and Kroemer, Nils B. and Kathmann, Norbert and Zimmermann, Ulrich S. and Smolka, Michael N. and Rapp, Michael Armin and Heinz, Andreas and Huys, Quentin J. M.}, title = {Pavlovian-to-Instrumental Transfer Effects Rely Less on Model-based Reinforcement Learning}, series = {Journal of cognitive neuroscience}, volume = {28}, journal = {Journal of cognitive neuroscience}, publisher = {MIT Press}, address = {Cambridge}, issn = {0898-929X}, doi = {10.1162/jocn_a_00945}, pages = {985 -- 995}, year = {2016}, abstract = {Behavioral choice can be characterized along two axes. One axis distinguishes reflexive, model-free systems that slowly accumulate values through experience and a model-based system that uses knowledge to reason prospectively. The second axis distinguishes Pavlovian valuation of stimuli from instrumental valuation of actions or stimulus-action pairs. This results in four values and many possible interactions between them, with important consequences for accounts of individual variation. We here explored whether individual variation along one axis was related to individual variation along the other. Specifically, we asked whether individuals' balance between model-based and model-free learning was related to their tendency to show Pavlovian interferences with instrumental decisions. In two independent samples with a total of 243 participants, Pavlovian-instrumental transfer effects were negatively correlated with the strength of model-based reasoning in a two-step task. This suggests a potential common underlying substrate predisposing individuals to both have strong Pavlovian interference and be less model-based and provides a framework within which to interpret the observation of both effects in addiction.}, 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{SeboldNebeGarbusowetal.2017, author = {Sebold, Miriam Hannah and Nebe, Stephan and Garbusow, Maria and Guggenmos, Matthias and Schad, Daniel and Beck, Anne and Kuitunen-Paul, S{\"o}ren and Sommer, Christian and Frank, Robin and Neu, Peter and Zimmermann, Ulrich S. and Rapp, Michael Armin and Smolka, Michael N. and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas}, title = {When Habits Are Dangerous: Alcohol Expectancies and Habitual Decision Making Predict Relapse in Alcohol Dependence}, series = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, volume = {82}, journal = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, publisher = {Elsevier}, address = {New York}, issn = {0006-3223}, doi = {10.1016/j.biopsych.2017.04.019}, pages = {847 -- 856}, year = {2017}, abstract = {BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies.}, 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{SeboldGarbusowJetzschmannetal.2019, author = {Sebold, Miriam Hannah and Garbusow, Maria and Jetzschmann, P. and Schad, Daniel and Nebe, S. and Schlagenhauf, Florian and Heinz, A. and Rapp, Michael Armin and Romanczuk-Seiferth, Nina}, title = {Reward and avoidance learning in the context of aversive environments and possible implications for depressive symptoms}, series = {Psychopharmacology}, volume = {236}, journal = {Psychopharmacology}, number = {8}, publisher = {Springer}, address = {New York}, issn = {0033-3158}, doi = {10.1007/s00213-019-05299-9}, pages = {2437 -- 2449}, year = {2019}, abstract = {Background Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased approach behavior. However, it is yet unclear how aversive stimuli interact with complex learning and decision-making in the reward and avoidance domain. Moreover, the underlying computational mechanisms of these decision-making biases are unknown. Methods To elucidate these mechanisms, 54 healthy young male subjects performed a two-step sequential decision-making task, which allows to computationally model different aspects of learning, e.g., model-free, habitual, and model-based, goal-directed learning. We used a within-subject design, crossing task valence (reward vs. punishment learning) with emotional context (aversive vs. neutral background stimuli). We analyzed choice data, applied a computational model, and performed simulations. Results Whereas model-based learning was not affected, aversive stimuli interacted with model-free learning in a way that depended on task valence. Thus, aversive stimuli increased model-free avoidance learning but decreased model-free reward learning. The computational model confirmed this effect: the parameter lambda that indicates the influence of reward prediction errors on decision values was increased in the punishment condition but decreased in the reward condition when aversive stimuli were present. Further, by using the inferred computational parameters to simulate choice data, our effects were captured. Exploratory analyses revealed that the observed biases were associated with subclinical depressive symptoms. Conclusion Our data show that aversive environmental stimuli affect complex learning and decision-making, which depends on task valence. Further, we provide a model of the underlying computations of this affective modulation. Finally, our finding of increased decision-making biases in subjects reporting subclinical depressive symptoms matches recent reports of amplified Pavlovian influences on action selection in depression and suggests a potential vulnerability factor for mood disorders. We discuss our findings in the light of the involvement of the neuromodulators serotonin and dopamine.}, 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} } @inproceedings{SchadJuengerSeboldetal.2014, author = {Schad, Daniel and Juenger, Elisabeth and Sebold, Miriam Hannah and Garbusow, Maria and Bernhart, Nadine and Javadi, Amir Homayoun and Zimmermann, Ulrich S. and Smolka, Michael N. and Heinz, Andreas and Rapp, Michael Armin and Huys, Quentin J. M.}, title = {Smart goals, slow habits? Individual differences in processing speed and working memory capacity moderate the balance between habitual and goal-directed choice behavior}, series = {Cognitive processing : international quarterly of cognitive science}, volume = {15}, booktitle = {Cognitive processing : international quarterly of cognitive science}, number = {1}, publisher = {Springer}, address = {Heidelberg}, issn = {1612-4782}, pages = {S62 -- S62}, year = {2014}, language = {en} } @article{SchadJuengerSeboldetal.2014, author = {Schad, Daniel and Juenger, Elisabeth and Sebold, Miriam Hannah and Garbusow, Maria and Bernhardt, Nadine and Javadi, Amir-Homayoun and Zimmermann, Ulrich S. and Smolka, Michael N. and Heinz, Andreas and Rapp, Michael Armin and Huys, Quentin J. M.}, title = {Processing speed enhances model-based over model-free reinforcement learning in the presence of high working memory functioning}, series = {Frontiers in psychology}, volume = {5}, journal = {Frontiers in psychology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-1078}, doi = {10.3389/fpsyg.2014.01450}, pages = {10}, year = {2014}, abstract = {Theories of decision-making and its neural substrates have long assumed the existence of two distinct and competing valuation systems, variously described as goal-directed vs. habitual, or, more recently and based on statistical arguments, as model-free vs. model-based reinforcement-learning. Though both have been shown to control choices, the cognitive abilities associated with these systems are under ongoing investigation. Here we examine the link to cognitive abilities, and find that individual differences in processing speed covary with a shift from model-free to model-based choice control in the presence of above-average working memory function. This suggests shared cognitive and neural processes; provides a bridge between literatures on intelligence and valuation; and may guide the development of process models of different valuation components. Furthermore, it provides a rationale for individual differences in the tendency to deploy valuation systems, which may be important for understanding the manifold neuropsychiatric diseases associated with malfunctions of valuation.}, 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} }