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 - 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 - GEN A1 - Chen, Hao A1 - Nebe, Stephan A1 - Mojtahedzadeh, Negin A1 - Kuitunen-Paul, Soren A1 - Garbusow, Maria A1 - Schad, Daniel A1 - Rapp, Michael A. A1 - Huys, Quentin J. M. A1 - Heinz, Andreas A1 - Smolka, Michael N. T1 - Susceptibility to interference between Pavlovian and instrumental control is associated with early hazardous alcohol use T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 855 KW - high‐risk drinking KW - interference control KW - Pavlovian‐to‐instrumental transfer Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-569609 SN - 1866-8364 IS - 4 ER - TY - GEN A1 - Sebold, Miriam Hannah A1 - Nebe, Stephan A1 - Garbusow, Maria A1 - Schad, Daniel A1 - Sommer, Christian A1 - Rapp, Michael A. 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 - GEN 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 T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 841 KW - Pavlovian-to-instrumental transfer KW - amygdala KW - alcohol KW - polygenic risk KW - high risk drinkers Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-473280 SN - 1866-8364 IS - 841 ER - TY - JOUR A1 - Chen, Hao A1 - Belanger, Matthew J. A1 - Garbusow, Maria A1 - Kuitunen-Paul, Soeren A1 - Huys, Quentin J. M. A1 - Heinz, Andreas A1 - Rapp, Michael A. A1 - Smolka, Michael N. T1 - Susceptibility to interference between Pavlovian and instrumental control predisposes risky alcohol use developmental trajectory from ages 18 to 24 JF - Addiction biology N2 - 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. KW - interference control KW - Pavlovian-to-instrumental transfer KW - risky drinking Y1 - 2023 U6 - https://doi.org/10.1111/adb.13263 SN - 1355-6215 SN - 1369-1600 VL - 28 IS - 2 PB - Wiley CY - Hoboken 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 -