@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}
}
@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}
}
@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{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}
}
@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}
}
@misc{GarbusowNebeSommeretal.2019,
  author    = {Garbusow, Maria and Nebe, Stephan and Sommer, Christian and Kuitunen-Paul, S{\"o}ren and Sebold, Miriam Hannah and Schad, Daniel and Friedel, Eva and Veer, Ilya M. and Wittchen, Hans-Ulrich and Rapp, Michael Armin 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{GarbusowNebeSommeretal.2019,
  author    = {Garbusow, Maria and Nebe, Stephan and Sommer, Christian and Kuitunen-Paul, S{\"o}ren and Sebold, Miriam Hannah and Schad, Daniel and Friedel, Eva and Veer, Ilya M. and Wittchen, Hans-Ulrich and Rapp, Michael Armin 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 = {Journal of Clinical Medicine},
  volume    = {8},
  journal   = {Journal of Clinical Medicine},
  number    = {8},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2077-0383},
  doi       = {10.3390/jcm8081188},
  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{ChenNebeMojtahedzadehetal.2020,
  author    = {Chen, Hao and Nebe, Stephan and Mojtahedzadeh, Negin and Kuitunen-Paul, Soren and Garbusow, Maria and Schad, Daniel and Rapp, Michael Armin 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 Armin 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}
}