TY  - JOUR
A1  - Sekutowicz, Maria
A1  - Guggenmos, Matthias
A1  - Kuitunen-Paul, Sören
A1  - Garbusow, Maria
A1  - Sebold, Miriam
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  - 
TY  - JOUR
A1  - Garbusow, Maria
A1  - Nebe, Stephan
A1  - Sommer, Christian
A1  - Kuitunen-Paul, Sören
A1  - Sebold, Miriam
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  - Kaminski, Jakob A.
A1  - Schlagenhauf, Florian
A1  - Rapp, Michael A.
A1  - Awasthi, Swapnil
A1  - Ruggeri, Barbara
A1  - Deserno, Lorenz
A1  - Banaschewski, Tobias
A1  - Bokde, Arun L. W.
A1  - Bromberg, Uli
A1  - Büchel, Christian
A1  - Quinlan, Erin Burke
A1  - Desrivières, Sylvane
A1  - Flor, Herta
A1  - Frouin, Vincent
A1  - Garavan, Hugh
A1  - Gowland, Penny
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  - Smolka, Michael N.
A1  - Fröhner, Juliane H.
A1  - Walter, Henrik
A1  - Whelan, Robert
A1  - Ripke, Stephan
A1  - Schumann, Gunter
A1  - Heinz, Andreas
T1  - Epigenetic variance in dopamine D2 receptor
BT  - a marker of IQ malleability?
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 950 
KW  - genome-wide association
KW  - reward anticipation
KW  - human intelligence
KW  - human brain
KW  - stress
KW  - metaanalysis
KW  - striatum
KW  - psychopathology
KW  - prediction
KW  - volume
KW  - epigenetics and behaviour
KW  - human behaviour
KW  - learning and memory
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-425687
SN  - 1866-8372
IS  - 950
ER  - 
TY  - JOUR
A1  - Obst, Elisabeth
A1  - Schad, Daniel
A1  - Huys, Quentin J. M.
A1  - Sebold, Miriam
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
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  - Kaminski, Jakob A.
A1  - Schlagenhauf, Florian
A1  - Rapp, Michael A.
A1  - Awasthi, Swapnil
A1  - Ruggeri, Barbara
A1  - Deserno, Lorenz
A1  - Banaschewski, Tobias
A1  - Bokde, Arun L. W.
A1  - Bromberg, Uli
A1  - Büchel, Christian
A1  - Quinlan, Erin Burke
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 N.
A1  - Fröhner, Juliane H.
A1  - Walter, Henrik
A1  - Whelan, Robert
A1  - Ripke, Stephan
A1  - Schumann, Gunter
A1  - Heinz, Andreas
T1  - Epigenetic variance in dopamine D2 receptor
BT  - a marker of IQ malleability?
JF  - Translational Psychiatry
N2  - Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.
Y1  - 2018
U6  - https://doi.org/10.1038/s41398-018-0222-7
SN  - 2158-3188
VL  - 8
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - GEN
A1  - Garbusow, Maria
A1  - Sommer, Christian
A1  - Nebe, Stephan
A1  - Sebold, Miriam
A1  - Kuitunen-Paul, Sören
A1  - Wittchen, Hans-Ulrich
A1  - Smolka, Michael N.
A1  - Zimmermann, Ulrich S.
A1  - Rapp, Michael A.
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  - 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  - JOUR
A1  - Friedel, Eva
A1  - Sebold, Miriam
A1  - Kuitunen-Paul, Sören
A1  - Nebe, Stephan
A1  - Veer, Ilya M.
A1  - Zimmermann, Ulrich S.
A1  - Schlagenhauf, Florian
A1  - Smolka, Michael N.
A1  - Rapp, Michael A.
A1  - Walter, Henrik
A1  - Heinz, Andreas
T1  - How Accumulated Real Life Stress Experience and Cognitive Speed Interact on Decision-Making Processes
JF  - Frontiers in human neuroscienc
N2  - Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding. Acute stress reactivity is known to impair model-based but not model-free choice behavior, with higher working memory capacity protecting the model-based system from acute stress. However, it is not clear which impact accumulated real life stress has on model-free and model-based decision systems and how this influence interacts with cognitive abilities. Methods: We used a sequential decision-making task distinguishing relative contributions of both learning strategies to choice behavior, the Social Readjustment Rating Scale questionnaire to assess accumulated real life stress, and the Digit Symbol Substitution Test to test cognitive speed in 95 healthy subjects. Results: Individuals reporting high stress exposure who had low cognitive speed showed reduced model-based but increased model-free behavioral control. In contrast, subjects exposed to accumulated real life stress with high cognitive speed displayed increased model-based performance but reduced model-free control. Conclusion: These findings suggest that accumulated real life stress exposure can enhance reliance on cognitive speed for model-based computations, which may ultimately protect the model-based system from the detrimental influences of accumulated real life stress. The combination of accumulated real life stress exposure and slower information processing capacities, however, might favor model-free strategies. Thus, the valence and preference of either system strongly depends on stressful experiences and individual cognitive capacities.
KW  - chronic stress
KW  - model-based learning
KW  - model-free learning
KW  - decision making
KW  - cognitive speed
KW  - real-life events
Y1  - 2017
U6  - https://doi.org/10.3389/fnhum.2017.00302
SN  - 1662-5161
VL  - 11
SP  - 1
EP  - 9
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - GEN
A1  - Sebold, Miriam
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  -