TY - JOUR A1 - Sebold, Miriam 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 A. 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 - TY - JOUR A1 - Schad, Daniel A1 - Garbusow, Maria A1 - Friedel, Eva A1 - Sommer, Christian A1 - Sebold, Miriam 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 A. 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 - Heinz, Andreas A1 - Kiefer, Falk A1 - Smolka, Michael N. A1 - Endrass, Tanja A1 - Beste, Christian A1 - Beck, Anne A1 - Liu, Shuyan A1 - Genauck, Alexander A1 - Romund, Lydia A1 - Rapp, Michael A. A1 - Tost, Heike A1 - Spanagel, Rainer T1 - Addiction research consortium: losing and regaining control over drug intake (ReCoDe) - from trajectories to mechanisms and interventions JF - Addiction Biology N2 - One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake. KW - addiction KW - alternative rewards KW - animal and computational models KW - cognitive-behavioral control KW - craving and relapse KW - habit formation Y1 - 2019 VL - 25 IS - 2 PB - John Wiley & Sons, Inc. CY - New Jersey ER - TY - JOUR A1 - Legall, Herbert A1 - Stiel, Holger A1 - Beck, Michael A1 - Leupold, Dieter A1 - Gruszecki, Wieslaw I. A1 - Lokstein, Heiko T1 - Near edge X-ray absorption fine structure spectroscopy (NEXAFS) of pigment-protein complexes : peridinin- chlorophyll a-protein (PCP) of Amphidinium carterae N2 - Peridinin-chlorophyll a protein (PCP) is a unique water soluble antenna complex that employs the carotenoid peridinin as the main light-harvesting pigment. In the present study the near edge X-ray absorption fine structure (NEXAFS) spectrum of PCP was recorded at the carbon Kedge. Additionally, the NEXAFS spectra of the constituent pigments, chlorophyll a and peridinin, were measured. The energies of the lowest unoccupied molecular levels of these pigments appearing in the carbon NEXAFS spectrum were resolved. Individual contributions of the pigments and the protein to the measured NEXAFS spectrum of PCP were determined using a "building block" approach combining NEXAFS spectra of the pigments and the amino acids constituting the PCP apoprotein. The results suggest that absorption changes of the pigments in the carbon near K-edge region can be resolved following excitation using a suitable visible pump laser pulse. Consequently, it may be possible to study excitation energy transfer processes involving "optically dark" states of carotenoids in pigment-protein complexes by soft X-ray probe optical pump double resonance spectroscopy (XODR). Y1 - 2007 UR - http://www.sciencedirect.com/science/journal/0165022X U6 - https://doi.org/10.1016/j.jbbm.2006.08.005 SN - 0165-022X ER - TY - JOUR A1 - Hildebrandt, Niko A1 - Charbonniere, Loïc J. A1 - Beck, Michael A1 - Ziessel, Raymond F. A1 - Löhmannsröben, Hans-Gerd T1 - Quantum dots as efficient energy acceptors in a time-resolved fluoroimmunoassay Y1 - 2005 SN - 1433-7851 ER - TY - JOUR A1 - Gruszecki, Wieslaw I. A1 - Stiel, H. A1 - Niedzwiedzki, Dariusz A1 - Beck, Michael A1 - Milanowska, J. A1 - Lokstein, Heiko A1 - Leupold, Dieter T1 - Towards elucidating the energy of the first excited singlet state of xanthophyll cycle pigments investigated by x-ray absorption spectroscopy Y1 - 2005 ER - TY - JOUR A1 - Beck, Michael A1 - Stiel, H. A1 - Leupold, Dieter A1 - Winter, Bernd A1 - Pop, D. A1 - Vogt, U. A1 - Spitz, Christian T1 - Evaluation of the energetic position of the lowest excited singlet state of ß-carotene by NEXAFS and photoemission spectroscopy Y1 - 2001 ER - TY - JOUR A1 - Seitz, Aaron P. A1 - Schumacher, Fabian A1 - Baker, Jennifer A1 - Soddemann, Matthias A1 - Wilker, Barbara A1 - Caldwell, Charles C. A1 - Gobble, Ryan M. A1 - Kamler, Markus A1 - Becker, Katrin Anne A1 - Beck, Sascha A1 - Kleuser, Burkhard A1 - Edwards, Michael J. A1 - Gulbins, Erich T1 - Sphingosine-coating of plastic surfaces prevents ventilator-associated pneumonia JF - Journal of molecular medicine N2 - Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in critically ill patients. Here, we employed the broad antibacterial effects of sphingosine to prevent VAP by developing a novel method of coating surfaces of endotracheal tubes with sphingosine and sphingosine analogs. Sphingosine and phytosphingosine coatings of endotracheal tubes prevent adherence and mediate killing of Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus, even in biofilms. Most importantly, sphingosine-coating of endotracheal tubes also prevented P. aeruginosa and S. aureus pneumonia in vivo. Coating of the tubes with sphingosine was stable, without obvious side effects on tracheal epithelial cells and did not induce inflammation. In summary, we describe a novel method to coat plastic surfaces and provide evidence for the application of sphingosine and phytosphingosine as novel antimicrobial coatings to prevent bacterial adherence and induce killing of pathogens on the surface of endotracheal tubes with potential to prevent biofilm formation and VAP.Key messagesNovel dip-coating method to coat plastic surfaces with lipids.Sphingosine and phytosphingosine as novel antimicrobial coatings on plastic surface.Sphingosine coatings of endotracheal tubes prevent bacterial adherence and biofilms.Sphingosine coatings of endotracheal tubes induce killing of pathogens.Sphingosine coatings of endotracheal tubes ventilator-associated pneumonia. KW - Coating KW - Plastic surfaces KW - Sphingosine KW - Ventilation KW - Acinetobacter baumannii KW - Pseudomonas aeruginosa KW - Staphylococcus aureus Y1 - 2019 U6 - https://doi.org/10.1007/s00109-019-01800-1 SN - 0946-2716 SN - 1432-1440 VL - 97 IS - 8 SP - 1195 EP - 1211 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Sellrie, Frank A1 - Beck, Michael A1 - Hildebrandt, Niko A1 - Micheel, Burkhard T1 - A homogeneous time-resolved fluoroimmunoassay (TR-FIA) using antibody mediated luminescence quenching N2 - The determination of low-molecular weight substances (haptens) is demonstrated with a homogeneous time-resolved immunoassay using antibody-induced luminescence quenching. Our novel assay technology uses the newly developed monoclonal antibody (G24-BA9) to quench the luminescence of europium trisbipyridine (EuTBP). We performed a competitive biotin immunoassay including an EuTBP-biotin conjugate, the anti-EuTBP antibody G24-BA9 and streptavidin as assay components. Steric hindrance allows only the binding of either G24-BA9 (to the EuTBP moiety) or streptavidin (to the biotin moiety) to the EuTBP-biotin conjugate. Addition of the analyte biotin resulted in the binding of streptavidin to biotin and a concomitant preferred binding of G24-BA9 to EuTBP-biotin. Since G24-BA9 quenches the luminescence of EuTBP within the conjugate, the luminescence signal could be used to indicate and quantify the presence of free biotin in the system. All experiments were carried out in solution in the presence of 5% serum demonstrating the possibility of using our novel assay for a very fast determination of low molecular weight substances in biological fluids. Y1 - 2010 UR - http://www.rsc.org/Publishing/Journals/AY/Index.asp U6 - https://doi.org/10.1039/C0ay00306a SN - 1759-9660 ER - TY - JOUR A1 - Balta Beylergil, Sinem A1 - Beck, Anne A1 - Deserno, Lorenz A1 - Lorenz, Robert C. A1 - Rapp, Michael A. 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 -