TY  - JOUR
A1  - Balta Beylergil, Sinem
A1  - Beck, Anne
A1  - Deserno, Lorenz
A1  - Lorenz, Robert C.
A1  - Rapp, Michael Armin
A1  - Schlagenhauf, Florian
A1  - Heinz, Andreas
A1  - Obermayer, Klaus
T1  - Dorsolateral prefrontal cortex contributes to the impaired behavioral adaptation in alcohol dependence
JF  - NeuroImage: Clinical : a journal of diseases affecting the nervous system
N2  - Substance-dependent individuals often lack the ability to adjust decisions flexibly in response to the changes in reward contingencies. Prediction errors (PEs) are thought to mediate flexible decision-making by updating the reward values associated with available actions. In this study, we explored whether the neurobiological correlates of PEs are altered in alcohol dependence. Behavioral, and functional magnetic resonance imaging (fMRI) data were simultaneously acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy controls (HC) during a probabilistic reward-guided decision-making task with dynamically changing reinforcement contingencies. A hierarchical Bayesian inference method was used to fit and compare learning models with different assumptions about the amount of task-related information subjects may have inferred during the experiment. Here, we observed that the best-fitting model was a modified Rescorla-Wagner type model, the “double-update” model, which assumes that subjects infer the knowledge that reward contingencies are anti-correlated, and integrate both actual and hypothetical outcomes into their decisions. Moreover, comparison of the best-fitting model's parameters showed that ADP were less sensitive to punishments compared to HC. Hence, decisions of ADP after punishments were loosely coupled with the expected reward values assigned to them. A correlation analysis between the model-generated PEs and the fMRI data revealed a reduced association between these PEs and the BOLD activity in the dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was observed in the DLPFC when positive and negative PE signals were analyzed separately. The right DLPFC activity in ADP showed a reduced correlation with positive PEs. On the other hand, ADP, particularly the patients with high dependence severity, recruited the left DLPFC to a lesser extent than HC for processing negative PE signals. These results suggest that the DLPFC, which has been linked to adaptive control of action selection, may play an important role in cognitive inflexibility observed in alcohol dependence when reinforcement contingencies change. Particularly, the left DLPFC may contribute to this impaired behavioral adaptation, possibly by impeding the extinction of the actions that no longer lead to a reward.
KW  - Alcohol dependence
KW  - Prediction error
KW  - Reinforcement learning
KW  - Reversal learning
KW  - Dorsolateral prefrontal cortex
KW  - Decision-making
Y1  - 2017
U6  - https://doi.org/10.1016/j.nicl.2017.04.010
SN  - 2213-1582
VL  - 15
SP  - 80
EP  - 94
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - 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  - 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 Armin
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  -