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Background A shift from goal-directed toward habitual control has been associated with alcohol dependence. Whether such a shift predisposes to risky drinking is not yet clear. We investigated how goal-directed and habitual control at age 18 predict alcohol use trajectories over the course of 3 years. Methods Goal-directed and habitual control, as informed by model-based (MB) and model-free (MF) learning, were assessed with a two-step sequential decision-making task during functional magnetic resonance imaging in 146 healthy 18-year-old men. Three-year alcohol use developmental trajectories were based on either a consumption score from the self-reported Alcohol Use Disorders Identification Test (assessed every 6 months) or an interview-based binge drinking score (grams of alcohol/occasion; assessed every year). We applied a latent growth curve model to examine how MB and MF control predicted the drinking trajectory. Results Drinking behavior was best characterized by a linear trajectory. MB behavioral control was negatively associated with the development of the binge drinking score; MF reward prediction error blood oxygen level–dependent signals in the ventromedial prefrontal cortex and the ventral striatum predicted a higher starting point and steeper increase of the Alcohol Use Disorders Identification Test consumption score over time, respectively. Conclusions We found that MB behavioral control was associated with the binge drinking trajectory, while the MF reward prediction error signal was closely linked to the consumption score development. These findings support the idea that unbalanced MB and MF control might be an important individual vulnerability in predisposing to risky drinking behavior.

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.

Significance In recent years, models have played an increasingly important role for understanding the brain in cognitive, behavioral, and systems neuroscience. Decision neuroscience in particular has benefitted greatly from the application of economic models of choice preferences to neural data. However, an often-overlooked aspect is that many models of preferences have a generic problem—they make extremely similar behavioral predictions. Here, we demonstrate that to understand the mechanisms of valuation in the brain, it is useful to compare models of choice preferences not only at the behavioral but also at the neural level., Decisions are based on the subjective values of choice options. However, subjective value is a theoretical construct and not directly observable. Strikingly, distinct theoretical models competing to explain how subjective values are assigned to choice options often make very similar behavioral predictions, which poses a major difficulty for establishing a mechanistic, biologically plausible explanation of decision-making based on behavior alone. Here, we demonstrate that model comparison at the neural level provides insights into model implementation during subjective value computation even though the distinct models parametrically identify common brain regions as computing subjective value. We show that frontal cortical regions implement a model based on the statistical distributions of available rewards, whereas intraparietal cortex and striatum compute subjective value signals according to a model based on distortions in the representations of probabilities. Thus, better mechanistic understanding of how cognitive processes are implemented arises from model comparisons at the neural level, over and above the traditional approach of comparing models at the behavioral level alone.

Background Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased approach behavior. However, it is yet unclear how aversive stimuli interact with complex learning and decision-making in the reward and avoidance domain. Moreover, the underlying computational mechanisms of these decision-making biases are unknown. Methods To elucidate these mechanisms, 54 healthy young male subjects performed a two-step sequential decision-making task, which allows to computationally model different aspects of learning, e.g., model-free, habitual, and model-based, goal-directed learning. We used a within-subject design, crossing task valence (reward vs. punishment learning) with emotional context (aversive vs. neutral background stimuli). We analyzed choice data, applied a computational model, and performed simulations. Results Whereas model-based learning was not affected, aversive stimuli interacted with model-free learning in a way that depended on task valence. Thus, aversive stimuli increased model-free avoidance learning but decreased model-free reward learning. The computational model confirmed this effect: the parameter lambda that indicates the influence of reward prediction errors on decision values was increased in the punishment condition but decreased in the reward condition when aversive stimuli were present. Further, by using the inferred computational parameters to simulate choice data, our effects were captured. Exploratory analyses revealed that the observed biases were associated with subclinical depressive symptoms. Conclusion Our data show that aversive environmental stimuli affect complex learning and decision-making, which depends on task valence. Further, we provide a model of the underlying computations of this affective modulation. Finally, our finding of increased decision-making biases in subjects reporting subclinical depressive symptoms matches recent reports of amplified Pavlovian influences on action selection in depression and suggests a potential vulnerability factor for mood disorders. We discuss our findings in the light of the involvement of the neuromodulators serotonin and dopamine. Electronic supplementary material The online version of this article (10.1007/s00213-019-05299-9) contains supplementary material, which is available to authorized users.

Background: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian–instrumental interactions. The A118G polymorphism of the OPRM1 gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the OPRM1 polymorphism is associated with the PIT effect and relapse in AD. Methods: Using a PIT task, we examined three independent samples: young healthy subjects (N = 161), detoxified alcohol-dependent patients (N = 186) and age-matched healthy controls (N = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the OPRM1 gene. Relapse was assessed after three months. Results: In all three samples, participants with the minor OPRM1 G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the OPRM1 polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse. Conclusion: These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD.

Background: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian–instrumental interactions. The A118G polymorphism of the OPRM1 gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the OPRM1 polymorphism is associated with the PIT effect and relapse in AD. Methods: Using a PIT task, we examined three independent samples: young healthy subjects ( N = 161), detoxified alcohol-dependent patients ( N = 186) and age-matched healthy controls ( N = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the OPRM1 gene. Relapse was assessed after three months. Results: In all three samples, participants with the minor OPRM1 G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the OPRM1 polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse. Conclusion: These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD.

Background: Neurodevelopmental and alcohol-induced changes in decision-making have been proposed to critically influence impulsive behaviour in adolescents. Objective: This study tested the influence of acute alcohol administration on impulsive choice in adolescents. Methods: Fifty-four males aged 18–19 years were tested in a single-blind placebo-controlled cross-over design. During alcohol administration (infusion resulting in an arterial blood alcohol concentration of 80 mg%) and placebo condition (saline infusion), participants performed a task battery providing estimates of delay discounting, probability discounting for gains, for losses and loss aversion, and also rated subjectively experienced alcohol effects. Additionally, baseline alcohol consumption (Alcohol Use Disorders Identification Test, blood phosphatidylethanol levels), motives (Drinking Motive Questionnaire, Alcohol Expectancy Questionnaire and Obsessive Compulsive Drinking Scale), family history and self-report measures of impulsivity (Barratt Impulsiveness Scale, Substance Use Risk Profile Scale) were provided. Results: No overall effects of treatment on choice behaviour were found. However, individual differences were observed. In the alcohol condition, more impulsive choice tendencies for delay discounting were associated with higher subjectively experienced alcohol effects. Further, higher risk aversion for probabilistic gains and higher loss aversion during alcohol condition were related to higher levels of real-life alcohol consumption and a family history of alcohol problems, respectively. Finally, the time to make a decision was substantially shortened for choices involving negative prospects. Conclusions: Contrary to common beliefs, acute alcohol intoxication did not generally incite impulsive decision-making. It rather appears that alcohol-induced behavioural changes in adolescents vary considerably depending on prior experiences and subjective effects of alcohol.

Value-based decision making (VBDM) is a principle that states that humans and other species adapt their behavior according to the dynamic subjective values of the chosen or unchosen options. The neural bases of this process have been extensively investigated using task-based fMRI and lesion studies. However, the growing field of resting-state functional connectivity (RSFC) may shed light on the organization and function of brain connections across different decision-making domains. With this aim, we used independent component analysis to study the brain network dynamics in a large cohort of young males (N = 145) and the relationship of these dynamics with VBDM. Participants completed a battery of behavioral tests that evaluated delay aversion, risk seeking for losses, risk aversion for gains, and loss aversion, followed by an RSFC scan session. We identified a set of large-scale brain networks and conducted our analysis only on the default mode network (DMN) and networks comprising cognitive control, appetitive-driven, and reward-processing regions. Higher risk seeking for losses was associated with increased connectivity between medial temporal regions, frontal regions, and the DMN. Higher risk seeking for losses was also associated with increased coupling between the left frontoparietal network and occipital cortices. These associations illustrate the participation of brain regions involved in prospective thinking, affective decision making, and visual processing in participants who are greater risk-seekers, and they demonstrate the sensitivity of RSFC to detect brain connectivity differences associated with distinct VBDM parameters.

Alcohol consumption is pivotal for the subsequent development of alcohol use disorders (AUD). The Alcohol Use Disorders Identification Test (AUDIT) is a recommended AUD screening tool for prevention and primary care settings. The objectives of this study were to test how many participants with heavy drinking are unidentified by the AUDIT, if proportions of unidentified participants vary over time, and whether this unidentified risk group (URG) was clinically relevant in terms of drinking behavior reports and AUD risk factors, as well as future adverse outcomes, such as craving, dependence symptoms, or depression.Our prospective cohort study followed 164 German males aged 18-19years without an alcohol dependence diagnosis over 24months. Only men were included due to higher AUD prevalence and gender-specific differences in metabolism, drinking patterns, and progression to AUD. All participants were screened via telephone interview and answered questionnaires both in person and via internet. Heavy drinking was classified using the AUDIT consumption score (AUDIT-C≥4.50). Standardized AUD diagnoses and symptoms, as well as alcohol use-related outcome criteria were assessed via standardized Composite International Diagnostic Interview (CIDI), and self-report questionnaires.One in four participants (22-28% across all four follow-ups) reported heavy drinking but was unidentified by AUDIT total score (i.e. score8), thus qualifying for URG status. The URG status did not fluctuate considerably across follow-ups (repeated-measures ANOVA, p=0.293). URG participants identified at the six-month follow-up did not generally differ from participants without URG status in terms of AUD family history or temperament (multivariate ANOVA, p=0.114), except for anxiety sensitivity (pDespite the considerable number of heavy-drinking individuals unidentified by AUDIT total scores, an additional classification according to AUDIT-C values did not prove useful. Combining AUDIT and AUDIT-C scores might not be sufficient for identifying AUD risk groups among young adult German males. There is an urgent need for a replication of our findings among female participants.

Individuals differ in how they learn from experience. In Pavlovian conditioning models, where cues predict reinforcer delivery at a different goal location, some animals-called sign-trackers-come to approach the cue, whereas others, called goal-trackers, approach the goal. In sign-trackers, model-free phasic dopaminergic reward-prediction errors underlie learning, which renders stimuli 'wanted'. Goal-trackers do not rely on dopamine for learning and are thought to use model-based learning. We demonstrate this double dissociation in 129 male humans using eye-tracking, pupillometry and functional magnetic resonance imaging informed by computational models of sign- and goal-tracking. We show that sign-trackers exhibit a neural reward prediction error signal that is not detectable in goal-trackers. Model-free value only guides gaze and pupil dilation in sign-trackers. Goal-trackers instead exhibit a stronger model-based neural state prediction error signal. This model-based construct determines gaze and pupil dilation more in goal-trackers.

Alcohol consumption during adolescence might impede normal brain development, while more excessive drinking during this period poses a risk for developing alcohol use disorder. Here it was tested whether nucleus accumbens (NAcc) resting-state functional connectivity could be associated with lifetime drinking behavior in young adults, and whether it could predict their alcohol consumption during a one-year follow-up period. The current investigation was part of the bicentric Learning and Alcohol Dependence (LeAD) population-based prospective cohort study. One hundred and eighty-four 18-year-old male social drinking volunteers without a lifetime diagnosis of psychotic, bipolar, or alcohol use disorder were recruited from the general population. Seed-based resting-state functional connectivity was calculated for the bilateral NAcc in each participant. Across the group, the association between NAcc functional connectivity and lifetime alcohol consumption was assessed (p .05, whole-brain FWE-corrected). Individual connectivity values were then extracted from regions that demonstrated a significant association to predict drinking behavior during a one-year follow-up period (n = 143), correcting for lifetime alcohol consumption. Weaker connectivity between the left NAcc and bilateral dorsolateral prefrontal cortex, inferior frontal gyrus, left caudate nucleus, left putamen, and left insula was associated with greater lifetime alcohol consumption, as well as with greater alcohol consumption during the one-year follow-up period. Our findings underscore the relevance of fronto-striatal connectivity to the field of alcohol research. Impaired prefrontal cognitive control might mediate excessive drinking behavior and may prove a promising biomarker for risk of future alcohol (ab)use.

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, pSVC = 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 (rs = 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.

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.

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 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.

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.

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

BackgroundAddiction 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.MethodsNinety 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.ResultsPatients 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.ConclusionsThese 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.

Individuals differ in how they learn from experience. In Pavlovian conditioning models, where cues predict reinforcer delivery at a different goal location, some animals-called sign-trackers-come to approach the cue, whereas others, called goal-trackers, approach the goal. In sign-trackers, model-free phasic dopaminergic reward-prediction errors underlie learning, which renders stimuli 'wanted'. Goal-trackers do not rely on dopamine for learning and are thought to use model-based learning. We demonstrate this double dissociation in 129 male humans using eye-tracking, pupillometry and functional magnetic resonance imaging informed by computational models of sign- and goal-tracking. We show that sign-trackers exhibit a neural reward prediction error signal that is not detectable in goal-trackers. Model-free value only guides gaze and pupil dilation in sign-trackers. Goal-trackers instead exhibit a stronger model-based neural state prediction error signal. This model-based construct determines gaze and pupil dilation more in goal-trackers.

Background Impulsive decision making relates to problematic substance use. Specifically, altered delay discounting (DD) has been suggested as a behavioral marker for addiction, while other relevant facets of choice impulsivity such as probability discounting (PD) or loss aversion are clearly understudied. Methods Two studies were performed collecting behavioral data on choice impulsivity with a value-based decision-making battery providing estimates of DD, PD for gains and losses, and loss aversion. Study (1): In a sample of 198 male 18-year-old social drinkers, we analyzed impulsive choice behavior and its association with alcohol consumption and self-report measures of substance use-related personality traits on a cross-sectional level. Additionally, the predictive value of baseline choice behavior for the trajectories of alcohol consumption over a 12-month follow-up period was evaluated. Study (2): Behavioral data on choice impulsivity were collected for 114 detoxified patients with alcohol use disorder (AUD) and 98 control participants. We analyzed group differences at baseline and assessed the predictive value of choice impulsivity for relapse to heavy alcohol use in patients during a follow-up period of 48 weeks. Results Study (1): Only DD was associated with baseline alcohol use, but no measure of choice impulsivity predicted the drinking trajectories over the following 12 months. Study (2): Compared to the control group, AUD patients showed higher DD, lower risk aversion regarding probabilistic gains, lower risk seeking regarding probabilistic losses, and lower loss aversion facing mixed prospects. Further, shallow discounting of probabilistic losses at baseline was predictive for relapse in patients. Conclusions All 4 domains of impulsive decision making were considerably altered in AUD patients though mostly not related to alcohol use in young adult social drinkers. This suggests that these facets of impulsive behavior may develop as consequences of chronic alcohol consumption. Furthermore, discounting of probabilistic losses might prove valuable in identifying patients vulnerable for relapse.

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.

Einleitung: Modellfreies und modellbasiertes Lernen sowie Entscheidungs-Strategien rucken zunehmend in den Fokus der Suchtforschung. Erste Kontakte mit Drogen finden in der Regel zielgerichtet, willentlich oder „reflektiv“ statt. Dabei werden Assoziation spezifischer Situationen mit Handlungen und deren Konsequenzen gelernt (wodurch ein Modell der Welt aufgebaut wird, daher „modellbasiert“). Durch haufige Wiederholung kann solches Verhalten zunehmend von seinen Konsequenzen abgekoppelt werden und sich zu einer „reflexiven“ Gewohnheit entwickeln, bei der („modellfrei“ gelernte) Reiz-Reaktions-Schemata das Verhalten einer Person ohne Rucksicht auf ihre aktuellen Ziele kontrollieren. Methoden: Im Rahmen unserer fMRT-Studie wurde bei 201 psychisch und neurologisch gesunden 18-jahrigen Mannern instrumentelles Lernen und Entscheidungsverhalten mit der 2-Step Task (Daw et al., 2011) untersucht. Dabei mussten sie durch Versuch und Irrtum lernen, welche Entscheidungssequenz am wahrscheinlichsten zu Geldgewinnen fuhrt, wobei die Gewinnwahrscheinlichkeit im Verlauf des Experiments variierte. Mithilfe computationaler Modellierung des Wahlverhaltens der Probanden untersuchten wir das Gleichgewicht zwischen modellfreien und modellbasierten Einflussen auf ihre Entscheidungen. Auserdem erlaubt unser Vorgehen, Vorhersagefehler von Verstarkern fur jeden Durchgang zu berechnen und dessen neurale Korrelate aufzuzeigen. Als Vorhersagefehler bezeichnet man die Abweichung vom erwarteten Ergebnis: Er ist positiv, falls die erhaltene Belohnung hoher als erwartet ausfallt und negativ bei unvorhergesehen geringer Belohnung und stellt die Grundlage modellfreien instrumentellen Lernens dar. Ergebnisse: Wir konnten die Ergebnisse von Daw et al. (2011) replizieren, dass das BOLD-Signal im Striatum wahrend 2-Step Task sowohl mit dem modellfreien Vorhersagefehler als auch daruber hinaus mit einem modellbasierten Einfluss auf dieses Lernsignal assoziiert ist. Vorlaufige Ergebnisse unserer Studie zeigen eine negative Korrelation dieses modellbasierten Einflusses mit der Haufigkeit von Rauschtrinken in den vergangenen 12 Monaten. Auserdem zeigt sich im Zusammenhang mit einer von uns entwickelten Testbatterie zur Erfassung impulsiven Wahlverhaltens, dass die neuronale Kodierung des modellfreien Vorhersagefehlers bei impulsiven Probanden schwacher ist. Diskussion: Unsere Ergebnisse deuten darauf hin, dass die neuralen Systeme, die modellfreiem und modellbasiertem Lernen zugrunde liegen, uberlappen. Weiterhin zeigt sich ein negativer Zusammenhang zwischen der Starke des modellbasierten Einflusses auf modellfreies Lernen sowohl mit der Haufigkeit von Rauschtrinken als auch mit Impulsivitat, einem Risikofaktor fur Abhangigkeitserkrankungen, jedoch keinerlei Korrelation mit dem modellfreien Vorhersagefehler selbst. Diese Ergebnisse deuten an, dass der zugrunde liegende Mechanismus beim Ubergang von „reflektiver“, modellbasierter zu „reflexiver“, modellfreier Verhaltenskontrolle weniger eine Verstarkung des modellfreien Systems als vermutlich viel mehr eine Abnahme des modellbasierten Systems ist.

The mesolimbic dopaminergic system has been implicated in two kinds of reward processing, one in reinforcement learning (e.g prediction error) and another in incentive salience attribution (e.g. cue-reactivity). Both functions have been implicated in alcohol dependence with the former contributing to the persistence of chronic alcohol intake despite severe negative consequences and the latter playing a crucial role in cue-induced craving and relapse. The bicentric study “Learning in alcohol dependence (LeAD)” aims to bridge a gap between these processes by investigating reinforcement learning mechanisms and the influence that Pavlovian cues exert over behavior. We here demonstrate that alcohol dependent subjects show alterations in goal-directed, model-based reinforcement learning (Sebold et al., 2014) and demonstrate that prospective relapsing patients show reductions in the medial prefrontal cortex activation during goal-directed control. Moreover we show that in alcohol dependent patients compared to healthy controls, Pavlovian cues exert pronounced control over behavior (Garbusow et al., 2016). Again, prospective relapsing patients showed increased Nucleus accumbens activation during these cue-induced responses. These findings point to an important role of the mesolimbic dopaminergic system as a predictor of treatment outcome in alcohol dependence.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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. © 2014 S. Karger AG, Basel