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 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 - GEN A1 - Kaminski, Jakob A1 - Schlagenhauf, Florian A1 - Rapp, Michael A. A1 - Awasthi, Swapnil A1 - Ruggeri, Barbara A1 - Deserno, Lorenz A1 - Laura, Daedelow A1 - Banaschewski, Tobias A1 - Bokde, Arun A1 - Quinlan, Erin Burke A1 - Buechel, Christian A1 - Bromberg, Uli A1 - Desrivieres, Sylvane A1 - Flor, Herta A1 - Frouin, Vincent A1 - Garavan, Hugh A1 - Gowland, Penny A1 - Ittermann, Bernd A1 - Martinot, Jean-Luc A1 - Martinot, Marie-Laure Paillere A1 - Nees, Frauke A1 - Orfanos, Dimitri Papadopoulos A1 - Paus, Tomas A1 - Poustka, Luise A1 - Smolka, Michael A1 - Froehner, Juliane A1 - Walter, Henrik A1 - Whelan, Robert A1 - Ripke, Stephan A1 - Schumann, Gunter A1 - Heinz, Andreas T1 - Variance in Dopaminergic Markers BT - a possible marker of individual differences in IQ? T2 - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry KW - Intelligence KW - Dopamine KW - Epigenetic Biomarkers KW - Reward Anticipation KW - Polygenic Risk Score Y1 - 2018 U6 - https://doi.org/10.1016/j.biopsych.2018.02.311 SN - 0006-3223 SN - 1873-2402 VL - 83 IS - 9 SP - S118 EP - S118 PB - Elsevier CY - New York 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 - 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 - JOUR 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 JF - Addiction biology 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. KW - high‐risk drinking KW - interference control KW - Pavlovian‐to‐instrumental transfer Y1 - 2020 U6 - https://doi.org/10.1111/adb.12983 SN - 1355-6215 SN - 1369-1600 VL - 26 IS - 4 SP - 1 EP - 14 PB - Wiley CY - Hoboken ER - 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 - CHAP A1 - Schad, Daniel A1 - Juenger, Elisabeth A1 - Sebold, Miriam Hannah A1 - Garbusow, Maria A1 - Bernhart, 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 - Smart goals, slow habits? Individual differences in processing speed and working memory capacity moderate the balance between habitual and goal-directed choice behavior T2 - Cognitive processing : international quarterly of cognitive science Y1 - 2014 SN - 1612-4782 SN - 1612-4790 VL - 15 IS - 1 SP - S62 EP - S62 PB - Springer CY - Heidelberg ER - TY - GEN A1 - Xie, Chao A1 - Jia, Tianye A1 - Rolls, Edmund T. A1 - Robbins, Trevor W. A1 - Sahakian, Barbara J. A1 - Zhang, Jie A1 - Liu, Zhaowen A1 - Cheng, Wei A1 - Luo, Qiang A1 - Zac Lo, Chun-Yi A1 - Schumann, Gunter A1 - Feng, Jianfeng A1 - Wang, He A1 - Banaschewski, Tobias A1 - Barker, Gareth J. A1 - Bokde, Arun L.W. A1 - Büchel, Christian A1 - Quinlan, Erin Burke A1 - Desrivières, Sylvane A1 - Flor, Herta A1 - Grigis, Antoine A1 - Garavan, Hugh A1 - Gowland, Penny A1 - Heinz, Andreas A1 - Hohmann, Sarah A1 - Ittermann, Bernd A1 - Martinot, Jean-Luc A1 - Paillère Martinot, Marie-Laure A1 - Nees, Frauke A1 - Papadopoulos Orfanos, Dimitri A1 - Paus, Tomáš A1 - Poustka, Luise A1 - Fröhner, Juliane H. A1 - Smolka, Michael N. A1 - Walter, Henrik A1 - Whelan, Robert T1 - Reward versus nonreward sensitivity of the medial versus lateral orbitofrontal cortex relates to the severity of depressive symptoms T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe N2 - BACKGROUND: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms. METHODS: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14. RESULTS: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003). CONCLUSIONS: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 860 KW - adolescents KW - depression KW - monetary incentive delay task KW - nonreward sensitivity KW - orbitofrontal cortex KW - reward anticipation KW - reward sensitivity KW - ventral striatum Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-557882 SN - 1866-8364 IS - 3 ER - TY - JOUR A1 - Xie, Chao A1 - Jia, Tianye A1 - Rolls, Edmund T. A1 - Robbins, Trevor W. A1 - Sahakian, Barbara J. A1 - Zhang, Jie A1 - Liu, Zhaowen A1 - Cheng, Wei A1 - Luo, Qiang A1 - Zac Lo, Chun-Yi A1 - Schumann, Gunter A1 - Feng, Jianfeng A1 - Wang, He A1 - Banaschewski, Tobias A1 - Barker, Gareth J. A1 - Bokde, Arun L.W. A1 - Büchel, Christian A1 - Quinlan, Erin Burke A1 - Desrivières, Sylvane A1 - Flor, Herta A1 - Grigis, Antoine A1 - Garavan, Hugh A1 - Gowland, Penny A1 - Heinz, Andreas A1 - Hohmann, Sarah A1 - Ittermann, Bernd A1 - Martinot, Jean-Luc A1 - Paillère Martinot, Marie-Laure A1 - Nees, Frauke A1 - Papadopoulos Orfanos, Dimitri A1 - Paus, Tomáš A1 - Poustka, Luise A1 - Fröhner, Juliane H. A1 - Smolka, Michael N. A1 - Walter, Henrik A1 - Whelan, Robert T1 - Reward versus nonreward sensitivity of the medial versus lateral orbitofrontal cortex relates to the severity of depressive symptoms JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging N2 - BACKGROUND: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms. METHODS: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14. RESULTS: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003). CONCLUSIONS: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores. KW - adolescents KW - depression KW - monetary incentive delay task KW - nonreward sensitivity KW - orbitofrontal cortex KW - reward anticipation KW - reward sensitivity KW - ventral striatum Y1 - 2021 U6 - https://doi.org/10.1016/j.bpsc.2020.08.017 SN - 0006-3223 SN - 1873-2402 VL - 6 IS - 3 SP - 259 EP - 269 PB - Elsevier Science CY - Amsterdam 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 - 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 - 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 - 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 - 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 - Garbusow, Maria A1 - Ebrahimi, Claudia A1 - Riemerschmid, Carlotta A1 - Daldrup, Luisa A1 - Rothkirch, Marcus A1 - Chen, Ke A1 - Chen, Hao A1 - Belanger, Matthew J. A1 - Hentschel, Angela A1 - Smolka, Michael A1 - Heinz, Andreas A1 - Pilhatsch, Maximilan A1 - Rapp, Michael A. T1 - Pavlovian-to-instrumental transfer across mental disorders BT - a review JF - Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography N2 - A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects. Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity. In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects. We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability. Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting. To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions. KW - Pavlovian-to-instrumental transfer KW - dimensional psychopathology KW - mental disorders KW - reliability Y1 - 2022 U6 - https://doi.org/10.1159/000525579 SN - 0302-282X SN - 1423-0224 VL - 81 IS - 5 SP - 418 EP - 437 PB - Karger CY - Basel ER - TY - JOUR A1 - Deeken, Friederike A1 - Reichert, Markus A1 - Zech, Hilmar A1 - Wenzel, Julia A1 - Wedemeyer, Friederike A1 - Aguilera, Alvaro A1 - Aslan, Acelya A1 - Bach, Patrick A1 - Bahr, Nadja Samia A1 - Ebrahimi, Claudia A1 - Fischbach, Pascale Christine A1 - Ganz, Marvin A1 - Garbusow, Maria A1 - Großkopf, Charlotte M. A1 - Heigert, Marie A1 - Hentschel, Angela A1 - Karl, Damian A1 - Pelz, Patricia A1 - Pinger, Mathieu A1 - Riemerschmid, Carlotta A1 - Rosenthal, Annika A1 - Steffen, Johannes A1 - Strehle, Jens A1 - Weiss,, Franziska A1 - Wieder, Gesine A1 - Wieland, Alfred A1 - Zaiser, Judith A1 - Zimmermann, Sina A1 - Walter, Henrik A1 - Lenz, Bernd A1 - Deserno, Lorenz A1 - Smolka, Michael N. A1 - Liu, Shuyan A1 - Ebner-Priemer, Ulrich Walter A1 - Heinz, Andreas A1 - Rapp, Michael A. T1 - Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany JF - JAMA Network Open N2 - Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002). Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals. Y1 - 2022 U6 - https://doi.org/10.1001/jamanetworkopen.2022.24641 SN - 2574-3805 VL - 5 SP - 1 EP - 11 PB - JAMA Network / American Medical Association CY - Chicago, Illinois, USA ET - 8 ER - TY - GEN A1 - Deeken, Friederike A1 - Reichert, Markus A1 - Zech, Hilmar A1 - Wenzel, Julia A1 - Wedemeyer, Friederike A1 - Aguilera, Alvaro A1 - Aslan, Acelya A1 - Bach, Patrick A1 - Bahr, Nadja Samia A1 - Ebrahimi, Claudia A1 - Fischbach, Pascale Christine A1 - Ganz, Marvin A1 - Garbusow, Maria A1 - Großkopf, Charlotte M. A1 - Heigert, Marie A1 - Hentschel, Angela A1 - Karl, Damian A1 - Pelz, Patricia A1 - Pinger, Mathieu A1 - Riemerschmid, Carlotta A1 - Rosenthal, Annika A1 - Steffen, Johannes A1 - Strehle, Jens A1 - Weiss, Franziska A1 - Wieder, Gesine A1 - Wieland, Alfred A1 - Zaiser, Judith A1 - Zimmermann, Sina A1 - Walter, Henrik A1 - Lenz, Bernd A1 - Deserno, Lorenz A1 - Smolka, Michael N. A1 - Liu, Shuyan A1 - Ebner-Priemer, Ulrich Walter A1 - Heinz, Andreas A1 - Rapp, Michael A. T1 - Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe N2 - Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002). Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 805 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-571460 SN - 1866-8364 IS - 805 ER - TY - JOUR A1 - Nebe, Stephan A1 - Kroemer, Nils B. A1 - Schad, Daniel A1 - Bernhardt, Nadine A1 - Sebold, Miriam Hannah A1 - Mueller, Dirk K. A1 - Scholl, Lucie A1 - Kuitunen-Paul, Sören A1 - Heinz, Andreas A1 - Rapp, Michael A. A1 - Huys, Quentin J. M. A1 - Smolka, Michael N. T1 - No association of goal-directed and habitual control with alcohol consumption in young adults JF - Addiction biology N2 - Alcohol dependence is a mental disorder that has been associated with an imbalance in behavioral control favoring model-free habitual over model-based goal-directed strategies. It is as yet unknown, however, whether such an imbalance reflects a predisposing vulnerability or results as a consequence of repeated and/or excessive alcohol exposure. We, therefore, examined the association of alcohol consumption with model-based goal-directed and model-free habitual control in 188 18-year-old social drinkers in a two-step sequential decision-making task while undergoing functional magnetic resonance imaging before prolonged alcohol misuse could have led to severe neurobiological adaptations. Behaviorally, participants showed a mixture of model-free and model-based decision-making as observed previously. Measures of impulsivity were positively related to alcohol consumption. In contrast, neither model-free nor model-based decision weights nor the trade-off between them were associated with alcohol consumption. There were also no significant associations between alcohol consumption and neural correlates of model-free or model-based decision quantities in either ventral striatum or ventromedial prefrontal cortex. Exploratory whole-brain functional magnetic resonance imaging analyses with a lenient threshold revealed early onset of drinking to be associated with an enhanced representation of model-free reward prediction errors in the posterior putamen. These results suggest that an imbalance between model-based goal-directed and model-free habitual control might rather not be a trait marker of alcohol intake per se. KW - alcohol KW - goal-directed KW - reinforcement learning Y1 - 2017 U6 - https://doi.org/10.1111/adb.12490 SN - 1355-6215 SN - 1369-1600 VL - 23 IS - 1 SP - 379 EP - 393 PB - Wiley CY - Hoboken 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 - JOUR A1 - Sekutowicz, Maria A1 - Guggenmos, Matthias A1 - Kuitunen-Paul, Sören A1 - Garbusow, Maria A1 - Sebold, Miriam Hannah A1 - Pelz, Patricia A1 - Priller, Josef A1 - Wittchen, Hans-Ulrich A1 - Smolka, Michael N. A1 - Zimmermann, Ulrich S. A1 - Heinz, Andreas A1 - Sterzer, Philipp A1 - Schmack, Katharina T1 - Neural Response Patterns During Pavlovian-to-Instrumental Transfer Predict Alcohol Relapse and Young Adult Drinking JF - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry N2 - BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Delta = -24.4 +/- 6.0 g vs. -5.7 +/- 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states. KW - Alcohol dependence KW - Future drinking behavior KW - Multivoxel classification KW - Pavlovian-to-instrumental transfer KW - Relapse Y1 - 2019 U6 - https://doi.org/10.1016/j.biopsych.2019.06.028 SN - 0006-3223 SN - 1873-2402 VL - 86 IS - 11 SP - 857 EP - 863 PB - Elsevier CY - New York ER -