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 Armin
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  - Obst, Elisabeth
A1  - Schad, Daniel
A1  - Huys, Quentin J. M.
A1  - Sebold, Miriam Hannah
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  - Kaminski, Jakob A.
A1  - Schlagenhauf, Florian
A1  - Rapp, Michael Armin
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  - JOUR
A1  - Friedel, Eva
A1  - Sebold, Miriam Hannah
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 Armin
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  - JOUR
A1  - Sebold, Miriam Hannah
A1  - Deserno, Lorenz
A1  - Nebe, Stefan
A1  - Schad, Daniel
A1  - Garbusow, Maria
A1  - Haegele, Claudia
A1  - Keller, Juergen
A1  - Juenger, Elisabeth
A1  - Kathmann, Norbert
A1  - Smolka, Michael N.
A1  - Rapp, Michael Armin
A1  - Schlagenhauf, Florian
A1  - Heinz, Andreas
A1  - Huys, Quentin J. M.
T1  - Model-based and model-free decisions in alcohol dependence
JF  - Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography
N2  - Background: Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive. Methods: Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns. Results: Alcohol-dependent patients showed less evidence of goal-directed choices than healthy controls, particularly after losses. There was no difference in the strength of the habitual component. The group differences did not survive controlling for performance on the Digit Symbol Substitution Task. Conclusion: Chronic alcohol use appears to selectively impair goal-directed function, rather than promoting habitual responding. It appears to do so particularly after nonrewards, and this may be mediated by the effects of alcohol on more general cognitive functions subserved by the prefrontal cortex.
KW  - Alcohol dependence
KW  - Decision-making
KW  - Reinforcement learning
KW  - Dopamine
KW  - Computational psychiatry
Y1  - 2014
U6  - https://doi.org/10.1159/000362840
SN  - 0302-282X
SN  - 1423-0224
VL  - 70
IS  - 2
SP  - 122
EP  - 131
PB  - Karger
CY  - Basel
ER  - 
TY  - GEN
A1  - Garbusow, Maria
A1  - Sommer, Christian
A1  - Nebe, Stephan
A1  - Sebold, Miriam Hannah
A1  - Kuitunen-Paul, Sören
A1  - Wittchen, Hans-Ulrich
A1  - Smolka, Michael N.
A1  - Zimmermann, Ulrich S.
A1  - Rapp, Michael Armin
A1  - Huys, Quentin J. M.
A1  - Schlagenhauf, Florian
A1  - Heinz, Andreas
T1  - Multi-level evidence of general pavlovian-to-instrumental transfer in alcohol use disorder
T2  - Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism
Y1  - 2018
SN  - 0145-6008
SN  - 1530-0277
VL  - 42
SP  - 128A
EP  - 128A
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Schad, Daniel
A1  - Garbusow, Maria
A1  - Friedel, Eva
A1  - Sommer, Christian
A1  - Sebold, Miriam Hannah
A1  - Hägele, Claudia
A1  - Bernhardt, Nadine
A1  - Nebe, Stephan
A1  - Kuitunen-Paul, Sören
A1  - Liu, Shuyan
A1  - Eichmann, Uta
A1  - Beck, Anne
A1  - Wittchen, Hans-Ulrich
A1  - Walter, Henrik
A1  - Sterzer, Philipp
A1  - Zimmermann, Ulrich S.
A1  - Smolka, Michael N.
A1  - Schlagenhauf, Florian
A1  - Huys, Quentin J. M.
A1  - Heinz, Andreas
A1  - Rapp, Michael Armin
T1  - Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk
JF  - European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry
N2  - The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.
KW  - Alcohol dependence
KW  - Human neuroimaging
KW  - Nucleus accumbens
KW  - Pavlovian-instrumental transfer
KW  - Relapse
Y1  - 2018
U6  - https://doi.org/10.1007/s00406-017-0860-4
SN  - 0940-1334
SN  - 1433-8491
VL  - 269
IS  - 3
SP  - 295
EP  - 308
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - 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  - 
TY  - GEN
A1  - Sebold, Miriam Hannah
A1  - Nebe, Stephan
A1  - Garbusow, Maria
A1  - Schad, Daniel
A1  - Sommer, Christian
A1  - Rapp, Michael Armin
A1  - Smolka, Michael N.
A1  - Huys, Quentin J. M.
A1  - Schlagenhauf, Florian
A1  - Heinz, Andreas
T1  - Neurobiological correlates of learning and decision-making in alcohol dependence
T2  - European psychiatry : the journal of the Association of European Psychiatrists
Y1  - 2017
U6  - https://doi.org/10.1016/j.eurpsy.2017.01.084
SN  - 0924-9338
SN  - 1778-3585
VL  - 41
SP  - S11
EP  - S11
PB  - Elsevier
CY  - Paris
ER  - 
TY  - JOUR
A1  - 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 Armin
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  -