TY  - JOUR
A1  - Wyckmans, Florent
A1  - Otto, A. Ross
A1  - Sebold, Miriam Hannah
A1  - Daw, Nathaniel
A1  - Bechara, Antoine
A1  - Saeremans, Mélanie
A1  - Kornreich, Charles
A1  - Chatard, Armand
A1  - Jaafari, Nemat
A1  - Noël, Xavier
T1  - Reduced model-based decision-making in gambling disorder
JF  - Scientific reports
N2  - Compulsive behaviors (e.g., addiction) can be viewed as an aberrant decision process where inflexible reactions automatically evoked by stimuli (habit) take control over decision making to the detriment of a more flexible (goal-oriented) behavioral learning system. These behaviors are thought to arise from learning algorithms known as "model-based" and "model-free" reinforcement learning. Gambling disorder, a form of addiction without the confound of neurotoxic effects of drugs, showed impaired goal-directed control but the way in which problem gamblers (PG) orchestrate model-based and model-free strategies has not been evaluated. Forty-nine PG and 33 healthy participants (CP) completed a two-step sequential choice task for which model-based and model-free learning have distinct and identifiable trial-by-trial learning signatures. The influence of common psychopathological comorbidities on those two forms of learning were investigated. PG showed impaired model-based learning, particularly after unrewarded outcomes. In addition, PG exhibited faster reaction times than CP following unrewarded decisions. Troubled mood, higher impulsivity (i.e., positive and negative urgency) and current and chronic stress reported via questionnaires did not account for those results. These findings demonstrate specific reinforcement learning and decision-making deficits in behavioral addiction that advances our understanding and may be important dimensions for designing effective interventions.
Y1  - 2019
U6  - https://doi.org/10.1038/s41598-019-56161-z
SN  - 2045-2322
VL  - 9
PB  - Nature Publ. Group
CY  - London
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  - Chen, Ke
A1  - Hollunder, Barbara
A1  - Garbusow, Maria
A1  - Sebold, Miriam Hannah
A1  - Heinz, Andreas
T1  - The physiological responses to acute stress in alcohol-dependent patients
BT  - a systematic review
JF  - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
N2  - 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/)
KW  - acute stress
KW  - alcohol dependence
KW  - hypothalamic- pituitary-adrenal axis
KW  - physiological reactivity
Y1  - 2020
U6  - https://doi.org/10.1016/j.euroneuro.2020.09.003
SN  - 0924-977X
SN  - 1873-7862
VL  - 41
SP  - 1
EP  - 15
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Obst, Elisabeth
A1  - Schad, Daniel
A1  - Huys, Quentin J. M.
A1  - Sebold, Miriam Hannah
A1  - Nebe, Stephan
A1  - Sommer, Christian
A1  - Smolka, Michael N.
A1  - Zimmermann, Ulrich S.
T1  - Drunk decisions
BT  - Alcohol shifts choice from habitual towards goal-directed control in adolescent intermediate-risk drinkers
JF  - Journal of Psychopharmacology
N2  - 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.
KW  - Computer-assisted Alcohol Infusion System
KW  - habitual learning
KW  - model-free and model-based decision-making
KW  - two-stage Markov decision task
KW  - subjective response to ethanol
KW  - drinking problems
KW  - real-life drinking behaviour
Y1  - 2018
U6  - https://doi.org/10.1177/0269881118772454
SN  - 0269-8811
SN  - 1461-7285
VL  - 32
IS  - 8
SP  - 855
EP  - 866
PB  - Sage Publ.
CY  - London
ER  - 
TY  - JOUR
A1  - Garbusow, Maria
A1  - Nebe, Stephan
A1  - Sommer, Christian
A1  - Kuitunen-Paul, Sören
A1  - Sebold, Miriam Hannah
A1  - Schad, Daniel
A1  - Friedel, Eva
A1  - Veer, Ilya M.
A1  - Wittchen, Hans-Ulrich
A1  - Rapp, Michael A.
A1  - Ripke, Stephan
A1  - Walter, Henrik
A1  - Huys, Quentin J. M.
A1  - Schlagenhauf, Florian
A1  - Smolka, Michael N.
A1  - Heinz, Andreas
T1  - Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers
BT  - Behavioral, Neural and Polygenic Correlates
JF  - Journal of Clinical Medicine
N2  - 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.
KW  - Pavlovian-to-instrumental transfer
KW  - amygdala
KW  - alcohol
KW  - polygenic risk
KW  - high risk drinkers
Y1  - 2019
U6  - https://doi.org/10.3390/jcm8081188
SN  - 2077-0383
VL  - 8
IS  - 8
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Garbusow, Maria
A1  - Schad, Daniel
A1  - Sebold, Miriam Hannah
A1  - Friedel, Eva
A1  - Bernhardt, Nadine
A1  - Koch, Stefan P.
A1  - Steinacher, Bruno
A1  - Kathmann, Norbert
A1  - Geurts, Dirk E. M.
A1  - Sommer, Christian
A1  - Mueller, Dirk K.
A1  - Nebe, Stephan
A1  - Paul, Soeren
A1  - Wittchen, Hans-Ulrich
A1  - Zimmermann, Ulrich S.
A1  - Walter, Henrik
A1  - Smolka, Michael N.
A1  - Sterzer, Philipp
A1  - Rapp, Michael A.
A1  - Huys, Quentin J. M.
A1  - Schlagenhauf, Florian
A1  - Heinz, Andreas
T1  - Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence
JF  - Addiction biology
N2  - 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.
KW  - human Pavlovian-to-instrumental transfer
KW  - nucleus accumbens
KW  - relapse in alcohol use disorder
Y1  - 2016
U6  - https://doi.org/10.1111/adb.12243
SN  - 1355-6215
SN  - 1369-1600
VL  - 21
SP  - 719
EP  - 731
PB  - Wiley-Blackwell
CY  - Hoboken
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 A.
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  - JOUR
A1  - Garbusow, Maria
A1  - Schad, Daniel
A1  - Sommer, Christian
A1  - Juenger, Elisabeth
A1  - Sebold, Miriam Hannah
A1  - Friedel, Eva
A1  - Wendt, Jean
A1  - Kathmann, Norbert
A1  - Schlagenhauf, Florian
A1  - Zimmermann, Ulrich S.
A1  - Heinz, Andreas
A1  - Huys, Quentin J. M.
A1  - Rapp, Michael A.
T1  - Pavlovian-to-instrumental transfer in alcohol dependence: a pilot study
JF  - Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography
N2  - Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
KW  - Pavlovian-to-instrumental transfer
KW  - Alcohol dependence
KW  - Human
Y1  - 2014
U6  - https://doi.org/10.1159/000363507
SN  - 0302-282X
SN  - 1423-0224
VL  - 70
IS  - 2
SP  - 111
EP  - 121
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Schad, Daniel
A1  - Juenger, Elisabeth
A1  - Sebold, Miriam Hannah
A1  - Garbusow, Maria
A1  - Bernhardt, Nadine
A1  - Javadi, Amir-Homayoun
A1  - Zimmermann, Ulrich S.
A1  - Smolka, Michael N.
A1  - Heinz, Andreas
A1  - Rapp, Michael A.
A1  - Huys, Quentin J. M.
T1  - Processing speed enhances model-based over model-free reinforcement learning in the presence of high working memory functioning
JF  - Frontiers in psychology
N2  - 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.
KW  - decision-making
KW  - reward
KW  - cognitive abilities
KW  - model-based and model-free learning
KW  - fluid intelligence
KW  - habitual and goal-directed system
Y1  - 2014
U6  - https://doi.org/10.3389/fpsyg.2014.01450
SN  - 1664-1078
VL  - 5
PB  - Frontiers Research Foundation
CY  - Lausanne
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 A.
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  -