Acute alcohol effects on explicit and implicit motivation to drink alcohol in socially drinking adolescents.

Alcohol-related cues can evoke explicit and implicit motivation to drink alcohol. Concerning the links between explicit and implicit motivation, there are mixed findings. Therefore, we investigated both concepts in 51 healthy 18- to 19-year-old males, who are less affected by neuropsychological deficits in decision-making that are attributed to previous alcohol exposure than older participants. In a randomized crossover design, adolescents were infused with either alcohol or placebo. Self-ratings of alcohol desire, thirst, well-being and alcohol effects comprised our explicit measures of motivation. To measure implicit motivation, we used money and drink stimuli in a Pavlovian conditioning (Pc) task and an Approach-Avoidance Task (AAT). Alcohol administration increased explicit motivation to drink alcohol, reduced Pc choices of alcoholic drink-conditioned stimuli, but had no effect on the AAT. This combination of results might be explained by differences between goal-directed and habitual behavior or a temporary reduction in rewarding outcome expectancies. Further, there was no association between our measures of motivation to drink alcohol, indicating that both self-reported motivation to drink and implicit approach tendencies may independently contribute to adolescents' actual alcohol intake. Correlations between Alcohol Use Disorders Identification Test (AUDIT) scores and our measures of motivation to drink alcohol suggest that interventions should target high-risk adolescents after alcohol intake. Clinical trials: Project 4: Acute Effects of Alcohol on Learning and Habitization in Healthy Young Adults (LeAD_P4); NCT01858818; https://clinicaltrials.gov/ct2/show/NCT01858818.

Adolescent Women Induce Lower Blood Alcohol Levels Than Men in a Laboratory Alcohol Self-Administration Experiment.

BACKGROUND: Adolescence is a critical period for the development of alcohol use disorders; drinking habits are rather unstable and genetic influences, such as male sex and a positive family history of alcoholism (FH), are often masked by environmental factors such as peer pressure. METHODS: We investigated how sex and FH modulate alcohol use in a sample of 18- to 19-year-olds from the Dresden Longitudinal Study on Alcohol use in Young Adults. Adolescents reported their real-life drinking in a TimeLine Follow-Back interview. They subsequently completed a training and an experimental session of free-access intravenous alcohol self-administration (i.v. ASA) using the computer-assisted alcohol infusion system to control for environmental cues as well as for biological differences in alcohol pharmacokinetics. During i.v. ASA, we assessed subjective alcohol effects at 8 time points. RESULTS: Women reported significantly less real-life drinking than men and achieved significantly lower mean arterial blood alcohol concentrations (aBACs) in the laboratory. At the same time, women reported greater sedation relative to men and rated negative effects as high as did men. A positive FH was associated with lower real-life drinking in men but not in women. In the laboratory, FH was not linked to i.v. ASA. Greater real-life drinking was significantly positively associated with higher mean aBACs in the laboratory, and all i.v. ASA indices were highly correlated across the 2 sessions. CONCLUSIONS: We conclude that adolescent women chose lower aBACs because they experienced adverse alcohol effects, namely sedation and negative effects, at lower aBACs than men. A positive FH was not apparent as risk factor for drinking in our young sample. The i.v. ASA method demonstrated good external validity as well as test-retest reliability, the latter indicating that a separate training session is not required when employing the i.v. ASA paradigm.

Don't Think, Just Feel the Music: Individuals with Strong Pavlovian-to-Instrumental Transfer Effects Rely Less on Model-based Reinforcement Learning.

Behavioral choice can be characterized along two axes. One axis distinguishes reflexive, model-free systems that slowly accumulate values through experience and a model-based system that uses knowledge to reason prospectively. The second axis distinguishes Pavlovian valuation of stimuli from instrumental valuation of actions or stimulus-action pairs. This results in four values and many possible interactions between them, with important consequences for accounts of individual variation. We here explored whether individual variation along one axis was related to individual variation along the other. Specifically, we asked whether individuals' balance between model-based and model-free learning was related to their tendency to show Pavlovian interferences with instrumental decisions. In two independent samples with a total of 243 participants, Pavlovian-instrumental transfer effects were negatively correlated with the strength of model-based reasoning in a two-step task. This suggests a potential common underlying substrate predisposing individuals to both have strong Pavlovian interference and be less model-based and provides a framework within which to interpret the observation of both effects in addiction.

Laboratory alcohol self-administration experiments do not increase subsequent real-life drinking in young adult social drinkers.

BACKGROUND: While the utility of experimental free-access alcohol self-administration paradigms is well established, little data exist addressing the question of whether study participation influences subsequent natural alcohol consumption. We here present drinking reports of young adults before and after participation in intravenous alcohol self-administration studies. METHODS: Timeline Follow-back drinking reports for the 6 weeks immediately preceding the first, and the 6 weeks after the last experimental alcohol challenge were examined from subjects completing 1 of 2 similar alcohol self-administration paradigms. In study 1, 18 social drinkers (9 females, mean age 24.1 years) participated in 3 alcohol self-infusion sessions up to a maximum blood alcohol concentration (BAC) of 160 mg%. Study 2 involved 60 participants (30 females, mean age 18.3 years) of the Dresden Longitudinal Study on Alcohol Use in Young Adults (D-LAYA), who participated in 2 sessions of alcohol self-infusion up to a maximum BAC of 120 mg%, and a nonexposed age-matched control group of 42 (28 females, mean age 18.4 years) subjects. RESULTS: In study 1, participants reported (3.7%) fewer heavy drinking days as well as a decrease of 2.5 drinks per drinking day after study participation compared to prestudy levels (p < 0.05, respectively). In study 2, alcohol-exposed participants reported 7.1% and non-alcohol-exposed controls 6.5% fewer drinking days at poststudy measurement (p < 0.001), while percent heavy drinking days and drinks per drinking day did not differ. CONCLUSIONS: These data suggest that participation in intravenous alcohol self-administration experiments does not increase subsequent real-life drinking of young adults.

XRCC5 as a risk gene for alcohol dependence: evidence from a genome-wide gene-set-based analysis and follow-up studies in Drosophila and humans.

Genetic factors have as large role as environmental factors in the etiology of alcohol dependence (AD). Although genome-wide association studies (GWAS) enable systematic searches for loci not hitherto implicated in the etiology of AD, many true findings may be missed owing to correction for multiple testing. The aim of the present study was to circumvent this limitation by searching for biological system-level differences, and then following up these findings in humans and animals. Gene-set-based analysis of GWAS data from 1333 cases and 2168 controls identified 19 significantly associated gene-sets, of which 5 could be replicated in an independent sample. Clustered in these gene-sets were novel and previously identified susceptibility genes. The most frequently present gene, ie in 6 out of 19 gene-sets, was X-ray repair complementing defective repair in Chinese hamster cells 5 (XRCC5). Previous human and animal studies have implicated XRCC5 in alcohol sensitivity. This phenotype is inversely correlated with the development of AD, presumably as more alcohol is required to achieve the desired effects. In the present study, the functional role of XRCC5 in AD was further validated in animals and humans. Drosophila mutants with reduced function of Ku80-the homolog of mammalian XRCC5-due to RNAi silencing showed reduced sensitivity to ethanol. In humans with free access to intravenous ethanol self-administration in the laboratory, the maximum achieved blood alcohol concentration was influenced in an allele-dose-dependent manner by genetic variation in XRCC5. In conclusion, our convergent approach identified new candidates and generated independent evidence for the involvement of XRCC5 in alcohol dependence.

Pavlovian-to-instrumental transfer in alcohol dependence: a pilot study.

BACKGROUND: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. METHODS: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. RESULTS: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. CONCLUSION: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.

Model-based and model-free decisions in alcohol dependence.

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.

Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex.

BACKGROUND: A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. METHODS: We measured inhibitory control in 50 young adults with a stop-signal task during functional magnetic resonance imaging. In a single-blind placebo-controlled cross-over design, all participants performed the stop-signal task once under alcohol with a breath alcohol concentration of .6 g/kg and once under placebo. In addition, alcohol consumption was assessed with a free-access alcohol self-administration paradigm in the same participants. RESULTS: Inhibitory control was robustly decreased under alcohol compared with placebo, indicated by longer stop-signal reaction times. On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. CONCLUSIONS: We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans, which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control might enhance alcohol consumption in young adults, which might promote future alcohol problems.

No evidence for feature overwriting in visual working memory.

The effect of repeating features in a short-term memory task was tested in three experiments. Experiments 1 and 2 used a recognition paradigm. Participants encoded four serially presented objects and then decided whether a probe matched one of them with regard to all three features. In the control condition no feature was repeated; in the experimental condition features were repeated in two memory objects. Experiment 3 used a cued recall paradigm with the same list design. After list presentation one feature was used as a cue uniquely indicating one of the memory objects. Participants recalled the remaining two features of the probed object. Feature overwriting as one component of the interference model of Oberauer and Kliegl (2006) predicts worse performance in the experimental compared to the control condition. Results of all three experiments did not support this hypothesis. Recognition performances in Experiments 1 and 2 were not impaired by repeating features. Recall performance in Experiment 3 was better for repeated features, contrary to the predictions of feature overwriting. Predictions from feature overwriting for the shape of serial position curves were also not confirmed.

Processing speed enhances model-based over model-free reinforcement learning in the presence of high working memory functioning.

Theories of decision-making and its neural substrates have long assumed the existence of two distinct and competing valuation systems, variously described as goal-directed vs. habitual, or, more recently and based on statistical arguments, as model-free vs. model-based reinforcement-learning. Though both have been shown to control choices, the cognitive abilities associated with these systems are under ongoing investigation. Here we examine the link to cognitive abilities, and find that individual differences in processing speed covary with a shift from model-free to model-based choice control in the presence of above-average working memory function. This suggests shared cognitive and neural processes; provides a bridge between literatures on intelligence and valuation; and may guide the development of process models of different valuation components. Furthermore, it provides a rationale for individual differences in the tendency to deploy valuation systems, which may be important for understanding the manifold neuropsychiatric diseases associated with malfunctions of valuation.