TY  - JOUR
A1  - Sommer, C.
A1  - Garbusow, Maria
A1  - Juenger, E.
A1  - Pooseh, S.
A1  - Bernhardt, Nadine
A1  - Birkenstock, J.
A1  - Schad, Daniel
A1  - Jabs, B.
A1  - Gloeckler, T.
A1  - Huys, Quentin J. M.
A1  - Heinz, A.
A1  - Smolka, Michael N.
A1  - Zimmermann, Ulrich S.
T1  - Strong seduction: impulsivity and the impact of contextual cues on instrumental behavior in alcohol dependence
JF  - Translational Psychiatry
N2  - 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.
Y1  - 2017
U6  - https://doi.org/10.1038/tp.2017.158
SN  - 2158-3188
VL  - 7
SP  - 1209
EP  - 1222
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - JOUR
A1  - Sekutowicz, Maria
A1  - Guggenmos, Matthias
A1  - Kuitunen-Paul, Sören
A1  - Garbusow, Maria
A1  - Sebold, Miriam Hannah
A1  - Pelz, Patricia
A1  - Priller, Josef
A1  - Wittchen, Hans-Ulrich
A1  - Smolka, Michael N.
A1  - Zimmermann, Ulrich S.
A1  - Heinz, Andreas
A1  - Sterzer, Philipp
A1  - Schmack, Katharina
T1  - Neural Response Patterns During Pavlovian-to-Instrumental Transfer Predict Alcohol Relapse and Young Adult Drinking
JF  - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry
N2  - 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.
KW  - Alcohol dependence
KW  - Future drinking behavior
KW  - Multivoxel classification
KW  - Pavlovian-to-instrumental transfer
KW  - Relapse
Y1  - 2019
U6  - https://doi.org/10.1016/j.biopsych.2019.06.028
SN  - 0006-3223
SN  - 1873-2402
VL  - 86
IS  - 11
SP  - 857
EP  - 863
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Sebold, Miriam Hannah
A1  - Spitta, G.
A1  - Gleich, T.
A1  - Dembler-Stamm, T.
A1  - Butler, Oisin
A1  - Zacharias, Kristin
A1  - Aydin, S.
A1  - Garbusow, Maria
A1  - Rapp, Michael Armin
A1  - Schubert, Florian
A1  - Buchert, Ralph
A1  - Gallinat, Jürgen
A1  - Heinz, A.
T1  - Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence
JF  - Journal of neural transmission
N2  - 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.
KW  - Stressful life events
KW  - Dopamine D2
KW  - D3 receptor
KW  - Positron emission tomography
KW  - Striatum
KW  - Alcohol dependence
Y1  - 2019
U6  - https://doi.org/10.1007/s00702-019-01985-2
SN  - 0300-9564
SN  - 1435-1463
VL  - 126
IS  - 9
SP  - 1127
EP  - 1134
PB  - Springer
CY  - Wien
ER  - 
TY  - JOUR
A1  - Sebold, Miriam Hannah
A1  - Schad, Daniel
A1  - Nebe, Stephan
A1  - Garbusow, Maria
A1  - Juenger, Elisabeth
A1  - Kroemer, Nils B.
A1  - Kathmann, Norbert
A1  - Zimmermann, Ulrich S.
A1  - Smolka, Michael N.
A1  - Rapp, Michael Armin
A1  - Heinz, Andreas
A1  - Huys, Quentin J. M.
T1  - Pavlovian-to-Instrumental Transfer Effects Rely Less on Model-based Reinforcement Learning
JF  - Journal of cognitive neuroscience
N2  - 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.
Y1  - 2016
U6  - https://doi.org/10.1162/jocn_a_00945
SN  - 0898-929X
SN  - 1530-8898
VL  - 28
SP  - 985
EP  - 995
PB  - MIT Press
CY  - Cambridge
ER  - 
TY  - GEN
A1  - Sebold, Miriam Hannah
A1  - Nebe, Stephan
A1  - Garbusow, Maria
A1  - Schad, Daniel
A1  - Sommer, Christian
A1  - Rapp, Michael Armin
A1  - Smolka, Michael N.
A1  - Huys, Quentin J. M.
A1  - Schlagenhauf, Florian
A1  - Heinz, Andreas
T1  - Neurobiological correlates of learning and decision-making in alcohol dependence
T2  - European psychiatry : the journal of the Association of European Psychiatrists
Y1  - 2017
U6  - https://doi.org/10.1016/j.eurpsy.2017.01.084
SN  - 0924-9338
SN  - 1778-3585
VL  - 41
SP  - S11
EP  - S11
PB  - Elsevier
CY  - Paris
ER  - 
TY  - JOUR
A1  - Sebold, Miriam Hannah
A1  - Nebe, Stephan
A1  - Garbusow, Maria
A1  - Guggenmos, Matthias
A1  - Schad, Daniel
A1  - Beck, Anne
A1  - Kuitunen-Paul, Sören
A1  - Sommer, Christian
A1  - Frank, Robin
A1  - Neu, Peter
A1  - Zimmermann, Ulrich S.
A1  - Rapp, Michael Armin
A1  - Smolka, Michael N.
A1  - Huys, Quentin J. M.
A1  - Schlagenhauf, Florian
A1  - Heinz, Andreas
T1  - When Habits Are Dangerous: Alcohol Expectancies and Habitual Decision Making Predict Relapse in Alcohol Dependence
JF  - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry
N2  - 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.
KW  - Alcohol dependence
KW  - Alcohol expectancy
KW  - Goal-directed control
KW  - Medial prefrontal cortex
KW  - Reinforcement learning
KW  - Treatment outcome
Y1  - 2017
U6  - https://doi.org/10.1016/j.biopsych.2017.04.019
SN  - 0006-3223
SN  - 1873-2402
VL  - 82
SP  - 847
EP  - 856
PB  - Elsevier
CY  - New York
ER  - 
TY  - GEN
A1  - Sebold, Miriam Hannah
A1  - Garbusow, Maria
A1  - Nebe, S.
A1  - Sundmacher, L.
A1  - Kuitunen-Paul, Sören
A1  - Wittchen, H. U.
A1  - Smolka, M.
A1  - Zimmermann, U.
A1  - Rapp, Michael Armin
A1  - Huys, Q.
A1  - Schlagenhauf, Florian
A1  - Heinz, A.
T1  - From goals to habits in alcohol dependence
BT  - association with treatment outcome and cognitive bias modification training
T2  - European psychiatry : the journal of the Association of European Psychiatrists
Y1  - 2018
SN  - 0924-9338
SN  - 1778-3585
VL  - 48
SP  - S274
EP  - S274
PB  - Elsevier
CY  - Paris
ER  - 
TY  - JOUR
A1  - Sebold, Miriam Hannah
A1  - Garbusow, Maria
A1  - Jetzschmann, P.
A1  - Schad, Daniel
A1  - Nebe, S.
A1  - Schlagenhauf, Florian
A1  - Heinz, A.
A1  - Rapp, Michael Armin
A1  - Romanczuk-Seiferth, Nina
T1  - Reward and avoidance learning in the context of aversive environments and possible implications for depressive symptoms
JF  - Psychopharmacology
N2  - 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.
KW  - Reward learning
KW  - Avoidance learning
KW  - Reinforcement learning
KW  - Computational psychiatry
KW  - Decision-making
KW  - Affective modulation
KW  - Depression symptoms
Y1  - 2019
U6  - https://doi.org/10.1007/s00213-019-05299-9
SN  - 0033-3158
SN  - 1432-2072
VL  - 236
IS  - 8
SP  - 2437
EP  - 2449
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Sebold, Miriam Hannah
A1  - Deserno, Lorenz
A1  - Nebe, Stefan
A1  - Schad, Daniel
A1  - Garbusow, Maria
A1  - Haegele, Claudia
A1  - Keller, Juergen
A1  - Juenger, Elisabeth
A1  - Kathmann, Norbert
A1  - Smolka, Michael N.
A1  - Rapp, Michael Armin
A1  - Schlagenhauf, Florian
A1  - Heinz, Andreas
A1  - Huys, Quentin J. M.
T1  - Model-based and model-free decisions in alcohol dependence
JF  - Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography
N2  - 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.
KW  - Alcohol dependence
KW  - Decision-making
KW  - Reinforcement learning
KW  - Dopamine
KW  - Computational psychiatry
Y1  - 2014
U6  - https://doi.org/10.1159/000362840
SN  - 0302-282X
SN  - 1423-0224
VL  - 70
IS  - 2
SP  - 122
EP  - 131
PB  - Karger
CY  - Basel
ER  - 
TY  - CHAP
A1  - Schad, Daniel
A1  - Juenger, Elisabeth
A1  - Sebold, Miriam Hannah
A1  - Garbusow, Maria
A1  - Bernhart, Nadine
A1  - Javadi, Amir Homayoun
A1  - Zimmermann, Ulrich S.
A1  - Smolka, Michael N.
A1  - Heinz, Andreas
A1  - Rapp, Michael Armin
A1  - Huys, Quentin J. M.
T1  - Smart goals, slow habits? Individual differences in processing speed and working memory capacity moderate the balance between habitual and goal-directed choice behavior
T2  - Cognitive processing : international quarterly of cognitive science
Y1  - 2014
SN  - 1612-4782
SN  - 1612-4790
VL  - 15
IS  - 1
SP  - S62
EP  - S62
PB  - Springer
CY  - Heidelberg
ER  -