@article{SeboldNebeGarbusowetal.2017, author = {Sebold, Miriam 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 A. 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} } @article{ChenHollunderGarbusowetal.2020, author = {Chen, Ke and Hollunder, Barbara and Garbusow, Maria and Sebold, Miriam and Heinz, Andreas}, title = {The physiological responses to acute stress in alcohol-dependent patients}, series = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {41}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-977X}, doi = {10.1016/j.euroneuro.2020.09.003}, pages = {1 -- 15}, year = {2020}, abstract = {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/)}, language = {en} } @article{ChenBelangerGarbusowetal.2023, author = {Chen, Hao and Belanger, Matthew J. and Garbusow, Maria and Kuitunen-Paul, Soeren and Huys, Quentin J. M. and Heinz, Andreas and Rapp, Michael A. and Smolka, Michael N.}, title = {Susceptibility to interference between Pavlovian and instrumental control predisposes risky alcohol use developmental trajectory from ages 18 to 24}, series = {Addiction biology}, volume = {28}, journal = {Addiction biology}, number = {2}, publisher = {Wiley}, address = {Hoboken}, issn = {1355-6215}, doi = {10.1111/adb.13263}, pages = {18}, year = {2023}, abstract = {Pavlovian cues can influence ongoing instrumental behaviour via Pavlovian-to-instrumental transfer (PIT) processes. While appetitive Pavlovian cues tend to promote instrumental approach, they are detrimental when avoidance behaviour is required, and vice versa for aversive cues. We recently reported that susceptibility to interference between Pavlovian and instrumental control assessed via a PIT task was associated with risky alcohol use at age 18. We now investigated whether such susceptibility also predicts drinking trajectories until age 24, based on AUDIT (Alcohol Use Disorders Identification Test) consumption and binge drinking (gramme alcohol/drinking occasion) scores. The interference PIT effect, assessed at ages 18 and 21 during fMRI, was characterized by increased error rates (ER) and enhanced neural responses in the ventral striatum (VS), the lateral and dorsomedial prefrontal cortices (dmPFC) during conflict, that is, when an instrumental approach was required in the presence of an aversive Pavlovian cue or vice versa. We found that a stronger VS response during conflict at age 18 was associated with a higher starting point of both drinking trajectories but predicted a decrease in binge drinking. At age 21, high ER and enhanced neural responses in the dmPFC were associated with increasing AUDIT-C scores over the next 3 years until age 24. Overall, susceptibility to interference between Pavlovian and instrumental control might be viewed as a predisposing mechanism towards hazardous alcohol use during young adulthood, and the identified high-risk group may profit from targeted interventions.}, language = {en} } @article{ChenNebeMojtahedzadehetal.2020, author = {Chen, Hao and Nebe, Stephan and Mojtahedzadeh, Negin and Kuitunen-Paul, Soren and Garbusow, Maria and Schad, Daniel and Rapp, Michael A. and Huys, Quentin J. M. and Heinz, Andreas and Smolka, Michael N.}, title = {Susceptibility to interference between Pavlovian and instrumental control is associated with early hazardous alcohol use}, series = {Addiction biology}, volume = {26}, journal = {Addiction biology}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {1355-6215}, doi = {10.1111/adb.12983}, pages = {1 -- 14}, year = {2020}, abstract = {Pavlovian-to-instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high-risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18-year-old male adults. Participants (N = 191) were instructed to 'collect good shells' and 'leave bad shells' during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high-risk and low-risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high-risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high-risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High-risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom-up), decreased lPFC response (top-down), and their altered interplay may contribute to poor interference control in the high-risk drinkers.}, language = {en} } @misc{ChenNebeMojtahedzadehetal.2020, author = {Chen, Hao and Nebe, Stephan and Mojtahedzadeh, Negin and Kuitunen-Paul, Soren and Garbusow, Maria and Schad, Daniel and Rapp, Michael A. and Huys, Quentin J. M. and Heinz, Andreas and Smolka, Michael N.}, title = {Susceptibility to interference between Pavlovian and instrumental control is associated with early hazardous alcohol use}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {4}, issn = {1866-8364}, doi = {10.25932/publishup-56960}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-569609}, pages = {16}, year = {2020}, abstract = {Pavlovian-to-instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high-risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18-year-old male adults. Participants (N = 191) were instructed to 'collect good shells' and 'leave bad shells' during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high-risk and low-risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high-risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high-risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High-risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom-up), decreased lPFC response (top-down), and their altered interplay may contribute to poor interference control in the high-risk drinkers.}, language = {en} } @article{SeboldChenOenaletal.2022, author = {Sebold, Miriam and Chen, Hao and {\"O}nal, Aleyna and Kuitunen-Paul, S{\"o}ren and Mojtahedzadeh, Negin and Garbusow, Maria and Nebe, Stephan and Wittchen, Hans-Ulrich and Huys, Quentin J. M. and Schlagenhauf, Florian and Rapp, Michael A. and Smolka, Michael N. and Heinz, Andreas}, title = {Stronger prejudices are associated with decreased model-based control}, series = {Frontiers in psychology}, volume = {12}, journal = {Frontiers in psychology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-1078}, doi = {10.3389/fpsyg.2021.767022}, pages = {10}, year = {2022}, abstract = {Background: Prejudices against minorities can be understood as habitually negative evaluations that are kept in spite of evidence to the contrary. Therefore, individuals with strong prejudices might be dominated by habitual or "automatic" reactions at the expense of more controlled reactions. Computational theories suggest individual differences in the balance between habitual/model-free and deliberative/model-based decision-making. Methods: 127 subjects performed the two Step task and completed the blatant and subtle prejudice scale. Results: By using analyses of choices and reaction times in combination with computational modeling, subjects with stronger blatant prejudices showed a shift away from model-based control. There was no association between these decision-making processes and subtle prejudices. Conclusion: These results support the idea that blatant prejudices toward minorities are related to a relative dominance of habitual decision-making. This finding has important implications for developing interventions that target to change prejudices across societies.}, language = {en} } @article{SommerGarbusowJuengeretal.2017, author = {Sommer, C. and Garbusow, Maria and Juenger, E. and Pooseh, S. and Bernhardt, Nadine and Birkenstock, J. and Schad, Daniel and Jabs, B. and Gloeckler, T. and Huys, Quentin J. M. and Heinz, A. and Smolka, Michael N. and Zimmermann, Ulrich S.}, title = {Strong seduction: impulsivity and the impact of contextual cues on instrumental behavior in alcohol dependence}, series = {Translational Psychiatry}, volume = {7}, journal = {Translational Psychiatry}, publisher = {Nature Publ. Group}, address = {New York}, issn = {2158-3188}, doi = {10.1038/tp.2017.158}, pages = {1209 -- 1222}, year = {2017}, abstract = {Alcohol-related cues acquire incentive salience through Pavlovian conditioning and then can markedly affect instrumental behavior of alcohol-dependent patients to promote relapse. However, it is unclear whether similar effects occur with alcohol-unrelated cues. We tested 116 early-abstinent alcohol-dependent patients and 91 healthy controls who completed a delay discounting task to assess choice impulsivity, and a Pavlovian-to-instrumental transfer (PIT) paradigm employing both alcohol-unrelated and alcohol-related stimuli. To modify instrumental choice behavior, we tiled the background of the computer screen either with conditioned stimuli (CS) previously generated by pairing abstract pictures with pictures indicating monetary gains or losses, or with pictures displaying alcohol or water beverages. CS paired to money gains and losses affected instrumental choices differently. This PIT effect was significantly more pronounced in patients compared to controls, and the group difference was mainly driven by highly impulsive patients. The PIT effect was particularly strong in trials in which the instrumental stimulus required inhibition of instrumental response behavior and the background CS was associated to monetary gains. Under that condition, patients performed inappropriate approach behavior, contrary to their previously formed behavioral intention. Surprisingly, the effect of alcohol and water pictures as background stimuli resembled that of aversive and appetitive CS, respectively. These findings suggest that positively valenced background CS can provoke dysfunctional instrumental approach behavior in impulsive alcohol-dependent patients. Consequently, in real life they might be easily seduced by environmental cues to engage in actions thwarting their long-term goals. Such behaviors may include, but are not limited to, approaching alcohol.}, language = {en} } @article{SeboldSpittaGleichetal.2019, author = {Sebold, Miriam 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 A. 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} } @inproceedings{SchadJuengerSeboldetal.2014, author = {Schad, Daniel and Juenger, Elisabeth and Sebold, Miriam and Garbusow, Maria and Bernhart, Nadine and Javadi, Amir Homayoun and Zimmermann, Ulrich S. and Smolka, Michael N. and Heinz, Andreas and Rapp, Michael A. 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{SeboldGarbusowJetzschmannetal.2019, author = {Sebold, Miriam and Garbusow, Maria and Jetzschmann, P. and Schad, Daniel and Nebe, S. and Schlagenhauf, Florian and Heinz, A. and Rapp, Michael A. 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} }