TY - JOUR A1 - Balta Beylergil, Sinem A1 - Beck, Anne A1 - Deserno, Lorenz A1 - Lorenz, Robert C. A1 - Rapp, Michael Armin A1 - Schlagenhauf, Florian A1 - Heinz, Andreas A1 - Obermayer, Klaus T1 - Dorsolateral prefrontal cortex contributes to the impaired behavioral adaptation in alcohol dependence JF - NeuroImage: Clinical : a journal of diseases affecting the nervous system N2 - Substance-dependent individuals often lack the ability to adjust decisions flexibly in response to the changes in reward contingencies. Prediction errors (PEs) are thought to mediate flexible decision-making by updating the reward values associated with available actions. In this study, we explored whether the neurobiological correlates of PEs are altered in alcohol dependence. Behavioral, and functional magnetic resonance imaging (fMRI) data were simultaneously acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy controls (HC) during a probabilistic reward-guided decision-making task with dynamically changing reinforcement contingencies. A hierarchical Bayesian inference method was used to fit and compare learning models with different assumptions about the amount of task-related information subjects may have inferred during the experiment. Here, we observed that the best-fitting model was a modified Rescorla-Wagner type model, the “double-update” model, which assumes that subjects infer the knowledge that reward contingencies are anti-correlated, and integrate both actual and hypothetical outcomes into their decisions. Moreover, comparison of the best-fitting model's parameters showed that ADP were less sensitive to punishments compared to HC. Hence, decisions of ADP after punishments were loosely coupled with the expected reward values assigned to them. A correlation analysis between the model-generated PEs and the fMRI data revealed a reduced association between these PEs and the BOLD activity in the dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was observed in the DLPFC when positive and negative PE signals were analyzed separately. The right DLPFC activity in ADP showed a reduced correlation with positive PEs. On the other hand, ADP, particularly the patients with high dependence severity, recruited the left DLPFC to a lesser extent than HC for processing negative PE signals. These results suggest that the DLPFC, which has been linked to adaptive control of action selection, may play an important role in cognitive inflexibility observed in alcohol dependence when reinforcement contingencies change. Particularly, the left DLPFC may contribute to this impaired behavioral adaptation, possibly by impeding the extinction of the actions that no longer lead to a reward. KW - Alcohol dependence KW - Prediction error KW - Reinforcement learning KW - Reversal learning KW - Dorsolateral prefrontal cortex KW - Decision-making Y1 - 2017 U6 - https://doi.org/10.1016/j.nicl.2017.04.010 SN - 2213-1582 VL - 15 SP - 80 EP - 94 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Lorenz, Robert C. A1 - Gleich, Tobias A1 - Beck, Anne A1 - Poehland, Lydia A1 - Raufelder, Diana A1 - Sommer, Werner A1 - Rapp, Michael Armin A1 - Kuehn, Simone A1 - Gallinat, Jürgen T1 - Reward anticipation in the adolescent and aging brain JF - Human brain mapping : a journal devoted to functional neuroanatomy and neuroimaging N2 - Processing of reward is the basis of adaptive behavior of the human being. Neural correlates of reward processing seem to be influenced by developmental changes from adolescence to late adulthood. The aim of this study is to uncover these neural correlates during a slot machine gambling task across the lifespan. Therefore, we used functional magnetic resonance imaging to investigate 102 volunteers in three different age groups: 34 adolescents, 34 younger adults, and 34 older adults. We focused on the core reward areas ventral striatum (VS) and ventromedial prefrontal cortex (VMPFC), the valence processing associated areas, anterior cingulate cortex (ACC) and insula, as well as information integration associated areas, dorsolateral prefrontal cortex (DLPFC), and inferior parietal lobule (IPL). Results showed that VS and VMPFC were characterized by a hyperactivation in adolescents compared with younger adults. Furthermore, the ACC and insula were characterized by a U-shape pattern (hypoactivation in younger adults compared with adolescents and older adults), whereas the DLPFC and IPL were characterized by a J-shaped form (hyperactivation in older adults compared with younger groups). Furthermore, a functional connectivity analysis revealed an elevated negative functional coupling between the inhibition-related area rIFG and VS in younger adults compared with adolescents. Results indicate that lifespan-related changes during reward anticipation are characterized by different trajectories in different reward network modules and support the hypothesis of an imbalance in maturation of striatal and prefrontal cortex in adolescents. Furthermore, these results suggest compensatory age-specific effects in fronto-parietal regions. Hum Brain Mapp 35:5153-5165, 2014. (c) 2014 Wiley Periodicals, Inc. KW - reward anticipation KW - lifespan KW - aging KW - adolescence KW - fMRI KW - connectivity Y1 - 2014 U6 - https://doi.org/10.1002/hbm.22540 SN - 1065-9471 SN - 1097-0193 VL - 35 IS - 10 SP - 5153 EP - 5165 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Deserno, Lorenz A1 - Beck, Anne A1 - Huys, Quentin J. M. A1 - Lorenz, Robert C. A1 - Buchert, Ralph A1 - Buchholz, Hans-Georg A1 - Plotkin, Michail A1 - Kumakara, Yoshitaka A1 - Cumming, Paul A1 - Heinze, Hans-Jochen A1 - Grace, Anthony A. A1 - Rapp, Michael Armin A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum JF - European journal of neuroscience N2 - Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N=27). All participants also underwent 6-[F-18]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake. KW - alcohol addiction KW - dopamine KW - fMRI KW - PET KW - prediction error Y1 - 2015 U6 - https://doi.org/10.1111/ejn.12802 SN - 0953-816X SN - 1460-9568 VL - 41 IS - 4 SP - 477 EP - 486 PB - Wiley-Blackwell CY - Hoboken ER -