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Intact corticostriatal control of goal-directed action in Alcohol Use Disorder: a Pavlovian-to-instrumental transfer and outcome-devaluation study.

ABSTRACT: Deficits in instrumental, goal-directed control, combined with the influence of drug-associated Pavlovian-conditioned stimuli, are thought to influence the development and maintenance of addiction. However, direct evidence has mainly come from animal studies. We sought to establish whether alcohol use disorder (AUD) is characterized by behavioral or neurobiological deficits in (i) the integration of Pavlovian and instrumental values and (ii) goal-directed control; and (iii) whether duration or severity of AUD is associated with such deficits. The influence of cues predicting food rewards on instrumental action was assessed in a Pavlovian-to-instrumental transfer (PIT) test, measuring both specific and general PIT, and goal-directed behavior in an outcome-devaluation test. Brain activity was measured using functional MRI in 38 abstinent individuals with AUD and 22 matched healthy control individuals (HCs). We found significant specific and general PIT and outcome-devaluation effects across groups indicating goal-directed control, mediated by distinct corticostriatal signals, but no significant differences between individuals with AUD and healthy controls. Bayesian analyses provided substantial-to-strong evidence for the absence of group differences for these effects, or any relationship with duration or severity of AUD. These results suggest intact ability to integrate action-outcome associations on specific and general PIT and goal-directed learning in AUD during abstinence.

SUBMITTER: van Timmeren T

PROVIDER: S-EPMC7087408 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Intact corticostriatal control of goal-directed action in Alcohol Use Disorder: a Pavlovian-to-instrumental transfer and outcome-devaluation study.

van Timmeren Tim T Quail Stephanie L SL Balleine Bernard W BW Geurts Dirk E M DEM Goudriaan Anna E AE van Holst Ruth J RJ

Scientific reports 20200318 1

Deficits in instrumental, goal-directed control, combined with the influence of drug-associated Pavlovian-conditioned stimuli, are thought to influence the development and maintenance of addiction. However, direct evidence has mainly come from animal studies. We sought to establish whether alcohol use disorder (AUD) is characterized by behavioral or neurobiological deficits in (i) the integration of Pavlovian and instrumental values and (ii) goal-directed control; and (iii) whether duration or s ...[more]

PMID: 32188908

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Project description:The acquired motivational impact of conditioned stimuli has been studied using the Pavlovian-to-instrumental transfer (PIT) task, where a cue paired with a reward is consistently shown to energize responses separately trained with that same reward ("specific" PIT). However, most alcohol studies have shown that alcohol-related cues elevate responses trained with either the same alcohol reward or with other non-alcoholic rewards ("general" PIT). The effects of extinction on this alcohol PIT effect have not been fully explored. We tested the hypothesis that cues signaling different-tasting alcohols might acquire specific craving reactions for those alcohols leading to specific PIT, but that these effects might be sensitive to extinction. Three experiments examined the specificity of PIT using alcohol and non-alcohol outcomes. Rats first consumed different-flavored alcohol solutions in their home cages. Then they were trained to perform two responses, each reinforced with distinctly flavored solutions, using a Polycose fading procedure. The outcomes were sweet (4% sucrose) or salty (0.9% NaCl) ethanol (10% v/v) solutions (Experiments 1 and 2) or one plain or salty alcohol vs. a non-alcoholic sweet solution (Experiment 3). Then, two cues were each differentially paired with these outcomes. In PIT tests, animals performed both responses in the presence and absence of these cues without any rewards. Experiments 1, 2, and 3 showed that a cue paired with a flavored alcohol produced a small but consistent bias toward the response trained with the same alcohol solution (specific PIT). Experiment 2 showed that extinction eliminated this effect. Experiment 3 demonstrated that specific PIT occurred when contrasting salty, or plain, alcohol to a non-alcoholic solution. These results provide evidence that alcohol-related stimuli can elicit craving for specific types of alcohol (as revealed by specific PIT), but that this effect is sensitive to extinction. This paradigm of contrasting two distinctly flavored alcohols may be an especially useful animal model of alcohol addiction.

Project description:Threat conditioning is a common associative learning model with translational relevance. How threat-conditioned cues impact on formally unrelated instrumental behavior in humans is not well known. Such an effect is known as Pavlovian-to-instrumental transfer (PIT). While PIT with aversive primary Pavlovian reinforcers is established in nonhuman animals, this is less clear in humans, where secondary reinforcers or instructed instrumental responses are most often investigated. We modified an existing human PIT procedure to include primary reinforcers. Participants first learned to obtain (or avoid losing) appetitive instrumental reinforcement (chocolate) by appropriate approach or avoidance actions. They either had to act (Go) or to withhold an action (NoGo), and in the Go condition either to approach a reward target to collect it or to withdraw from the reward target to avoid losing it. Then they learned to associate screen color (CS) with aversive Pavlovian reinforcement (electric shock US). In the transfer phase, we conducted the instrumental task during the presence of Pavlovian CS. In a first experiment, we show that the aversive Pavlovian CS+, compared to CS-, increased response rate in Go-Withdraw trials, i.e., induce conditioned facilitation of avoidance responses. This finding was confirmed in a second and independent experiment with an increased number of Go-Withdraw trials. Notably, we observed no appreciable conditioned suppression of approach responses. Effect size to distinguish CS+/CS- in Go-Withdraw trials was d = 0.42 in the confirmation sample. This would require n = 37 participants to demonstrate threat learning with 80% power. Thus, the effect size is on a practically useful scale although smaller than for model-based analysis of autonomic measures. In summary, our results indicate conditioned facilitation of formally unrelated instrumental avoidance behavior in humans and provide a novel behavioral threat learning measure that requires only key presses.

Project description:Individual differences in Pavlovian approach predict differences in devaluation sensitivity. Recent studies indicate goal-tracking (GT) rats are sensitive to outcome devaluation while sign-tracking (ST) rats are not. With extended training in Pavlovian lever autoshaping (PLA), GT rats display more lever-directed behavior, typical of ST rats, suggesting they may become insensitive to devaluation with more Pavlovian training experience. Here, we use a within-subject satiety-induced outcome devaluation procedure to test devaluation sensitivity after limited and extended PLA training in GT and ST rats. We trained rats in PLA to determine GT and ST groups. Then, we sated rats on either the training pellets (devalued condition) or homecage chow (valued condition) prior to brief non-reinforced test sessions after limited (sessions 5/6) and extended (sessions 17/18) PLA training. GT rats decreased conditioned responding under devalued relative to valued conditions after both limited and extended training, demonstrating they are sensitive to satiety devaluation regardless of the amount of PLA training. While ST rats were insensitive to satiety devaluation after limited training, their lever directed behavior became devaluation sensitive after extended training. To determine whether sign-tracking rats also displayed sensitivity to illness-induced outcome devaluation after extended training, we trained a separate cohort of rats in extended PLA and devalued the outcome with lithium chloride injections after pellet consumption in the homecage. ST rats failed to decrease conditioned responding after illness-induced outcome devaluation, while Non-ST rats (GT and intermediates) were sensitive to illness-induced outcome devaluation after extended training. Together, our results confirm devaluation sensitivity is stable in GT rats across training and devaluation approaches. Extended training unmasks devaluation sensitivity in ST rats after satiety, but not illness-induced devaluation, suggesting ST rats respond appropriately by decreasing responding to cues during state-dependent but not inference-based devaluation. The differences in behavioral flexibility across tracking groups and devaluation paradigms have translational relevance for the understanding state- vs. inference-based reward devaluation as it pertains to drug addiction vulnerability.

Project description: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.

Dataset Information

Intact corticostriatal control of goal-directed action in Alcohol Use Disorder: a Pavlovian-to-instrumental transfer and outcome-devaluation study.

Publications

Intact corticostriatal control of goal-directed action in Alcohol Use Disorder: a Pavlovian-to-instrumental transfer and outcome-devaluation study.

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