@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}
}
@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{GarbusowSchadSeboldetal.2016,
  author    = {Garbusow, Maria and Schad, Daniel and Sebold, Miriam and Friedel, Eva and Bernhardt, Nadine and Koch, Stefan P. and Steinacher, Bruno and Kathmann, Norbert and Geurts, Dirk E. M. and Sommer, Christian and Mueller, Dirk K. and Nebe, Stephan and Paul, Soeren and Wittchen, Hans-Ulrich and Zimmermann, Ulrich S. and Walter, Henrik and Smolka, Michael N. and Sterzer, Philipp and Rapp, Michael A. and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas},
  title     = {Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence},
  series = {Addiction biology},
  volume    = {21},
  journal   = {Addiction biology},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1355-6215},
  doi       = {10.1111/adb.12243},
  pages     = {719 -- 731},
  year      = {2016},
  abstract  = {In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.},
  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}
}
@misc{GarbusowNebeSommeretal.2019,
  author    = {Garbusow, Maria and Nebe, Stephan and Sommer, Christian and Kuitunen-Paul, S{\"o}ren and Sebold, Miriam and Schad, Daniel and Friedel, Eva and Veer, Ilya M. and Wittchen, Hans-Ulrich and Rapp, Michael A. and Ripke, Stephan and Walter, Henrik and Huys, Quentin J. M. and Schlagenhauf, Florian and Smolka, Michael N. and Heinz, Andreas},
  title     = {Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  number    = {841},
  issn      = {1866-8364},
  doi       = {10.25932/publishup-47328},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-473280},
  pages     = {14},
  year      = {2019},
  abstract  = {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.},
  language  = {en}
}
@article{SeboldDesernoNebeetal.2014,
  author    = {Sebold, Miriam 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 A. 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}
}
@article{SchadGarbusowFriedeletal.2018,
  author    = {Schad, Daniel and Garbusow, Maria and Friedel, Eva and Sommer, Christian and Sebold, Miriam 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 A.},
  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{SeboldSchadNebeetal.2016,
  author    = {Sebold, Miriam 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 A. 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}
}
@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}
}