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 - 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 Armin 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 - 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 - 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 - 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 - 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 Armin 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 - 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 -