TY - GEN A1 - Garbusow, Maria A1 - Sommer, Christian A1 - Nebe, Stephan A1 - Sebold, Miriam Hannah A1 - Kuitunen-Paul, Sören A1 - Wittchen, Hans-Ulrich A1 - Smolka, Michael N. A1 - Zimmermann, Ulrich S. A1 - Rapp, Michael Armin A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - Multi-level evidence of general pavlovian-to-instrumental transfer in alcohol use disorder T2 - Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism Y1 - 2018 SN - 0145-6008 SN - 1530-0277 VL - 42 SP - 128A EP - 128A 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 Armin 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 - 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 - Schad, Daniel A1 - Garbusow, Maria A1 - Friedel, Eva A1 - Sommer, Christian A1 - Sebold, Miriam Hannah A1 - Hägele, Claudia A1 - Bernhardt, Nadine A1 - Nebe, Stephan A1 - Kuitunen-Paul, Sören A1 - Liu, Shuyan A1 - Eichmann, Uta A1 - Beck, Anne A1 - Wittchen, Hans-Ulrich A1 - Walter, Henrik A1 - Sterzer, Philipp A1 - Zimmermann, Ulrich S. A1 - Smolka, Michael N. A1 - Schlagenhauf, Florian A1 - Huys, Quentin J. M. A1 - Heinz, Andreas A1 - Rapp, Michael Armin T1 - Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk JF - European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry N2 - 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. KW - Alcohol dependence KW - Human neuroimaging KW - Nucleus accumbens KW - Pavlovian-instrumental transfer KW - Relapse Y1 - 2018 U6 - https://doi.org/10.1007/s00406-017-0860-4 SN - 0940-1334 SN - 1433-8491 VL - 269 IS - 3 SP - 295 EP - 308 PB - Springer CY - Heidelberg 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 Armin 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 - 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 -