Pavlovian-to-instrumental Transfer Research Articles

Pavlovian-to-instrumental transfer in intertemporal choice

Abstract We often forego a larger future reward in order to obtain a smaller reward immediately, known as impatient intertemporal choice. The current study investigated the role of Pavlovian-to-instrumental transfer (PIT) as a mechanism contributing to impatient intertemporal choice, following a theoretical framework proposing that cues associated with immediate gratification trigger a Pavlovian approach response, interfering with goal-directed (instrumental) inhibitory behavior. We developed a paradigm in which participants first learned to make instrumental go/no-go responses in order to win rewards and avoid punishments. Next, they learned the associations between Pavlovian cues and rewards varying in amount and delay. Finally, we tested whether these (task-irrelevant) cues exerted transfer effects by influencing instrumental actions while participants again completed the go/no-go task. Across two experiments, Pavlovian cues associated with larger (versus smaller) and immediate (versus delayed) rewards were evaluated more positively, reflecting the successful acquisition of Pavlovian cue–outcome associations. These findings replicated the previously reported classical transfer effect of reward amount on instrumental behavior, as large (versus smaller) cues increased instrumental approach. In contrast, we found no evidence for the hypothesized transfer effects for reward delay, contrary to the proposed role of PIT in impatient intertemporal choice. These results suggest that although both reward amount and delay were important in the evaluation of cues, only the amount associated with cues influenced instrumental choice. We provide concrete suggestions for future studies, addressing instrumental outcome identity, competition between cue–amount and cue–delay associations, and individual differences in response to Pavlovian cues.

Enhanced Pavlovian-to-instrumental transfer in internet gaming disorder

The Pavlovian-to-instrumental transfer (PIT) effect is a phenomenon that Pavlovian conditioned cues that could influence one's instrumental behavior. In several substance and behavioral addictions, such as tobacco use disorder and gambling disorder, addiction-related cues could promote independently trained instrumental drug-seeking/drug-taking behaviors, indicating a specific PIT effect. However, it is unclear whether Internet gaming disorder (IGD) would show a similar change in PIT effects as other addictions. The study aimed to explore the specific PIT effects in IGD. We administrated a PIT task to individuals with IGD (n = 40) and matched health controls (HCs, n=50), and compared the magnitude of specific PIT effects between the two groups. The severity of the IGD symptoms was assessed by the Chinese version 9-item Internet Gaming Disorder Scale (IGDS) and the Internet Addiction Test (IAT). We found that: (1) related to the HCs group, the IGD group showed enhanced specific PITgame effects, where gaming-related cues lead to an increased choice rate of gaming-related responses; (2) in the IGD group, the magnitude of specific PITgame effects were positively correlated with IAT scores (rho = 0.39, p = 0.014). Individualswith IGD showed enhanced specific PIT effects related to HCs, which were associated with the severity of addictive symptoms. Our results highlighted the incentive salience of gaming-related cues in IGD.

Effect of striatal dopamine on Pavlovian bias. A large [¹⁸F]-DOPA PET study.

Interaction between Pavlovian and instrumental control systems is key for adaptive motivated behavior, but also plays an important role in various neuropsychiatric disorders, including depression, addiction, and anxiety. Here, we employed the flouorodopa positron emission tomography ([¹⁸F]-DOPA PET) in healthy participants (N = 100) to assess whether dopamine synthesis capacity (Ki), specifically in the ventral striatum, accounts for individual variation in Pavlovian-to-instrumental transfer (PIT). Surprisingly, this was not the case. Rather, the relationship of ventral striatal Ki with PIT depended on working memory (WM) capacity. Ventral striatal dopamine boosted the effects of Pavlovian cues on instrumental responding to a greater degree in participants with higher WM capacity. Caution is warranted to interpret this post hoc four-way interaction given the modest sample size. Nonetheless, these results chime with prior findings demonstrating that dopaminergic drugs boost Pavlovian biases to a greater degree in participants with greater WM capacity and highlight the importance of interactions between striatal dopamine and WM capacity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effects of a brief mindfulness meditation practice on Pavlovian-to-instrumental transfer in alcohol use disorder - a pilot study.

Pavlovian conditioned contextual cues have been suggested to modulate instrumental action and might explain maladaptive behavior such as relapse in participants suffering from alcohol use disorder (AUD). Pavlovian-to-Instrumental transfer (PIT) experimentally assesses the magnitude of this context-dependent effect and studies have shown a larger PIT effect in AUD populations. Taken this into account, a reduction of the influence of cues on behavior seems warranted and one approach that could alter such cue reactivity is mindfulness. Mindfulness-based interventions have been shown to be efficient in the treatment of AUD, but underlying mechanisms are yet to be elucidated. Therefore, we aim at investigating the effect of a brief mindful body scan meditation on the magnitude of the PIT effect in AUD subjects and matched controls. Using a randomized within-subjects design, we compared the effect of a short audio guided body scan meditation against a control condition (audio of nature sounds) on PIT in healthy (n = 35) and AUD (n = 27) participants. We found no differences in PIT effect between healthy and AUD participants as well as between conditions. However, a significant interaction effect points to a decreased PIT effect after body scan meditation in AUD subjects only. These pilot results suggest that AUD might be susceptible to mindfulness-induced changes in PIT, with these findings contributing to entangling the underlying mechanisms of the efficacy of mindfulness-based interventions in AUD. However, further investigation should confirm these preliminary results and the efficacy of mindfulness meditation practice in decreasing the PIT effect.

Mechanisms underlying performance in a cued go/no-go Pavlovian-to-instrumental transfer paradigm

Environmental cues that remind us of rewarding outcomes (drugs, food) play a significant role in addiction relapse. In the lab the Pavlovian-to-instrumental transfer (PIT) task has been used to formally examine how cues associated with reward or punishment can bias ongoing instrumental responding. Using a version of this paradigm that integrates PIT with a go/no-go task many studies have related stronger PIT effects (with non-drug rewards) to problematic alcohol use including risky alcohol users relative to non-risky drinkers, individuals with alcohol dependence versus healthy controls and individuals in recovery from alcohol use disorder who are more likely to relapse. However the theoretical importance of these findings and the implications for models of addiction was previously not clear. Understanding if this task indexes the general motivating effects of reward cues on instrumental responding (and whether this is sensitive to shifts in motivation for those outcomes) is critical for understanding these previous results within the context of addiction. Thus, in the current study we aimed to delineate the associative mechanisms that drive the stimulus effects observed in this PIT task. Specifically, we wished to examine whether the cueing effects observed in the cued-go/no-go task were selective in their effect on action, insofar as Pavlovian cues specifically invigorated (or suppressed) responding only if they were associated with congruent outcomes. We conclude that the PIT measured with this task is general in nature. Surprisingly however, the biasing effects of Pavlovian cues on instrumental responding did not appear to be sensitive to outcome devaluation.

Susceptibility to interference between Pavlovian and instrumental control predisposes risky alcohol use developmental trajectory from ages 18 to 24.

Pavlovian cues can influence ongoing instrumental behaviour via Pavlovian-to-instrumental transfer (PIT) processes. While appetitive Pavlovian cues tend to promote instrumental approach, they are detrimental when avoidance behaviour is required, and vice versa for aversive cues. We recently reported that susceptibility to interference between Pavlovian and instrumental control assessed via a PIT task was associated with risky alcohol use at age 18. We now investigated whether such susceptibility also predicts drinking trajectories until age 24, based on AUDIT (Alcohol Use Disorders Identification Test) consumption and binge drinking (gramme alcohol/drinking occasion) scores. The interference PIT effect, assessed at ages 18 and 21 during fMRI, was characterized by increased error rates (ER) and enhanced neural responses in the ventral striatum (VS), the lateral and dorsomedial prefrontal cortices (dmPFC) during conflict, that is, when an instrumental approach was required in the presence of an aversive Pavlovian cue or vice versa. We found that a stronger VS response during conflict at age 18 was associated with a higher starting point of both drinking trajectories but predicted a decrease in binge drinking. At age 21, high ER and enhanced neural responses in the dmPFC were associated with increasing AUDIT-C scores over the next 3 years until age 24. Overall, susceptibility to interference between Pavlovian and instrumental control might be viewed as a predisposing mechanism towards hazardous alcohol use during young adulthood, and the identified high-risk group may profit from targeted interventions.

Environmental control of social goals: using Pavlovian-to-instrumental transfer to test cue-based pro-self and pro-social outcome responses.

A large amount of literature demonstrates that social behaviour can be triggered by environmental cues. A long-standing debate involves the question of whether such stimuli trigger behaviour directly (i.e. habits) or whether these effects mediate goals. As studies on automatic goal pursuit typically use real-world cues that are already associated with the behaviour and potentially the goal, it is impossible to make strong claims about the nature of the effects. In the present paper, we use a paradigm inspired by the Pavlovian-to-instrumental transfer (PIT) literature to examine how the environment can trigger goal-directed behaviour. Building on the essence of pro-self and pro-social motives in humans, two experiments explored the PIT effect when the outcomes were framed in terms of self- versus other-interest. Participants performed actions to earn money for themselves or a charity. Each outcome was linked to a different cue. The results showed that a cue predictive of self-interest outcomes facilitated responses instrumental in gaining the outcome, while such specific PIT effect for other-interest outcomes only emerged when participants were free to donate the money. We briefly discuss these findings reflecting on whether the PIT effect in our paradigm is indeed sensitive to the value of social goals.

Automatic Approach Behaviors in Alcohol Dependence: Does a Cognitive Bias Modification Training Affect Pavlovian-to-Instrumental Transfer Effects?

Introduction: Positively conditioned Pavlovian cues tend to promote approach and negative cues promote withdrawal in a Pavlovian-to-instrumental transfer (PIT) paradigm, and the strength of this PIT effect was associated with the subsequent relapse risk in alcohol-dependent (AD) patients. When investigating the effect of alcohol-related background cues, instrumental approach behavior was inhibited in subsequent abstainers but not relapsers. An automatic approach bias towards alcohol can be modified using a cognitive bias modification (CBM) intervention, which has previously been shown to reduce the relapse risk in AD patients. Here we examined the effects of such CBM training on PIT effects and explored its effect on the relapse risk in detoxified AD patients. Methods: N = 81 recently detoxified AD patients performed non-drug-related and drug-related PIT tasks before and after CBM versus placebo training. In addition, an alcohol approach/avoidance task (aAAT) was performed before and after the training to assess the alcohol approach bias. Patients were followed up for 6 months. Results: A stronger alcohol approach bias as well as a stronger non-drug-related PIT effect predicted relapse status in AD patients. No significant difference regarding relapse status or the number of heavy drinking days was found when comparing the CBM training group versus the placebo group. Moreover, there was no significant modulation effect of CBM training on any PIT effect or the aAAT. Conclusion: A higher alcohol approach bias in the aAAT and a stronger non-drug-related PIT effect both predicted relapse in AD patients, while treatment outcome was not associated with the drug-related PIT effect. Unlike expected, CBM training did not significantly interact with the non-drug-related or the drug-related PIT effects or the alcohol approach bias.

Development of Novel Tasks to Assess Outcome-Specific and General Pavlovian-to-Instrumental Transfer in Humans

Introduction: The emergence of Pavlovian-to-instrumental transfer (PIT) research in the human neurobehavioral domain has been met with increased interest over the past two decades. A variety of PIT tasks were developed during this time; while successful in demonstrating transfer phenomena, existing tasks have limitations that should be addressed. Herein, we introduce two PIT paradigms designed to assess outcome-specific and general PIT within the context of addiction. Materials and Methods: The single-lever PIT task, based on an established paradigm, replaced button presses with joystick motion to better assess avoidance behavior. The full transfer task uses alcohol and nonalcohol rewards associated with Pavlovian cues and instrumental responses, along with other gustatory and monetary rewards. We constructed mixed-effects models with the addition of other statistical analyses as needed to interpret various behavioral measures. Results: Single-lever PIT: both versions were successful in eliciting a PIT effect (joystick: p < 0.001, η_p² = 0.36, button-box: p < 0.001, η_p² = 0.30). Full transfer task: it was determined that the alcohol and nonalcoholic reward cues selectively primed their respective reward-associated responses (gustatory version: p < 0.001, r = 0.59, and monetary version: p < 0.001, r = 0.84). The appetitive/aversive cues resulted in a general transfer effect (gustatory: p < 0.001, η_p² = 0.09, and monetary: p < 0.001, η_p² = 0.17). Discussion/Conclusion: Single-lever PIT: PIT was observed in both task versions. We posit that the use of a joystick is more advantageous for the analysis of avoidance behavior. It evenly distributes movement between approach and avoid trials, which is relevant to analyzing fMRI data. Full transfer task: While gustatory conditioning has been used in the past to elicit transfer effects, we present the first paradigm that successfully elicits both specific and general transfers in humans with gustatory alcohol rewards.

Outcome devaluation by specific satiety disrupts sensory-specific Pavlovian-to-instrumental transfer.

Reward predictive cues can selectively motivate instrumental behaviors that predict the same rewarding outcomes, an effect known as specific Pavlovian-to-instrumental transfer (PIT). This selective effect is thought to be mediated by a representation of the sensory specific properties of an outcome, that has become associated with both the Pavlovian cue and the instrumental response during initial learning. Specific satiety is a common method of outcome devaluation that reduces an outcome's value but might also lead to the habituation of the outcome's sensory properties. Previous research has demonstrated that specific PIT is insensitive to changes in specific outcome value following taste aversion devaluation, as well as general satiety manipulations, and therefore specific satiety should not disrupt specific PIT by reducing outcome value. The present rodent experiments used a specific satiety devaluation procedure immediately prior to a specific PIT test to show that habituation of these outcome specific sensory representations can disrupt its efficacy as a stimulus and abolish the specific PIT effect. Experiment 1 employed a two-lever choice test to show that a non-devalued stimulus supports specific PIT, whereas a devalued stimulus abolished the specific PIT effect. Experiment 2 replicated this procedure while controlling for response competition by using a single-lever test to confirm that a devalued stimulus abolishes the specific PIT effect. These findings demonstrate that specific satiety can disrupt the ability of an outcome specific representation to support specific PIT. Given previous findings that specific PIT is insensitive to changes in outcome value by general satiety and taste aversion devaluation, this suggests that specific satiety devaluation might disrupt the use of sensory specific outcome representations to guide behavior via a mechanism that is independent of the outcome's current value.

Persistent effects of acute trauma on Pavlovian-to-instrumental transfer.

In humans, an acutely traumatic experience can lead to post-traumatic stress disorder (PTSD), which is often characterized by changes in anxiety and motivation months after trauma. There are few demonstrations of the persistent motivational effects of an acute stressor in rodent approaches to PTSD. In two experiments, we evaluated the persistent effects of a battery of footshocks in one context on appetitive Pavlovian conditioning, instrumental learning, and Pavlovian-to-instrumental transfer (PIT) in a different context. In Experiment 1, a battery of footshocks before appetitive training caused deficits in single-outcome PIT (SO-PIT) in male Long Evans rats. The same battery of footshocks after appetitive training, but before testing had little effect on SO-PIT overall, but there were some deficits in within-stimulus expression of SO-PIT. In Experiment 2, the battery of footshocks had no effect on sensory-specific PIT in male or female rats, but two sex differences emerged: males showed more generalized fear from the aversive to the appetitive context compared to females, and females showed less evidence for sensory-specific PIT compared to males. Males showed robust sensory-specific PIT, with clear extinction and spontaneous recovery of the sensory-specific PIT effect across test sessions. These findings show that (a) an acute trauma can have persistent effects on general motivational processes and (b) in sensory-specific PIT, females may show transfer through generalized motivational processes, whereas males may rely on specific features of the cues and outcomes to augment instrumental responding selectively. We discuss implications for current approaches to stress and motivation in preclinical approaches to PTSD.

No significant effect of frequent online sexual behaviour on Pavlovian-to-instrumental transfer (PIT): Implications for compulsive sexual behaviour disorder.

Reward based learning is broadly acknowledged to underpin the development and maintenance of addictive behaviour although the mechanism in sexual compulsivity is less understood. Using a Pavlovian-to-Instrumental Transfer (PIT) task we tested whether the motivational aspect of conditioned Pavlovian conditioned stimulus invigorated instrumental responding in relation to specific compatible monetary rewards. Performance on the task was analysed between two groups of males based on Low (N = 38) and High (N = 41) self-report online sexual behaviour (OSB). Psychometric tests including sexual compulsivity scale and behavioural activation/behavioural inhibition (BIS/BAS) were also administered to determine the relationship between OSB and general reward sensitivity. We show clear evidence of acquisition in the Pavlovian and instrumental conditioning phases. Specific transfer effect was greater in the High-OSB group although the difference compared to the Low-OSB group was non-significant. OSB negatively correlated with both BIS and BAS indicative of introversion and low reward sensitivity. OSB positively correlated with sexual compulsivity although it is unclear whether individuals in the High-OSB group considered their behaviour either excessive or problematic. These findings contribute to the ongoing debate regarding the nature of problematic OSB. Fundamental differences in motivational characteristics and mechanism contributing to compulsive behaviour in relation to high-OSB might indicate incompatibility with behavioural addiction models. PIT was not enhanced in high-OSB by appetitive conditioning, although problematic OSB could stem from failure to inhibit actions. Further research should investigate whether aversive conditioning differentially affects responding in high-OSB individuals, potentially explaining perseverant behaviour despite negative consequences.

Effects of central amygdala chemogenetic manipulation and prior chronic alcohol exposure on Pavlovian-to-instrumental transfer.

Recent work suggests that a history of chronic alcohol exposure can enhance the influence of nondrug reward cues on ongoing actions. This is often modeled in Pavlovian-to-instrumental transfer (PIT) tasks that examine the interaction between Pavlovian and instrumental learning processes, usually reflected as an increase in action vigor during the presentation of a reward-associated cue. Though prior chronic alcohol exposure strengthens this type of cue-guided behavior, the neural mechanisms underlying such enhancements are not known. In the present work, we examined the contribution of the central amygdala (CeA), a region strongly implicated in PIT behaviors and functionally altered by chronic alcohol exposure. We utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to examine the impact of inhibitory and excitatory CeA manipulation on PIT behaviors in alcohol-naïve mice and mice with a history of chronic intermittent ethano vapor exposure and withdrawal (CIE). Replicating previous work, we found that a history of CIE strengthened baseline PIT, in the absence of any CeA manipulation. We also found that activation of both inhibitory and excitatory DREADDs expressed in CeA enhanced PIT in alcohol-naïve mice, though the latter markedly reduced response rates. However, in mice exposed to CIE, activation of excitatory DREADD receptors expressed in CeA appeared to weaken PIT. These results suggest that alcohol-induced disruptions in amygdala function may contribute to changes in appetitive behaviors, such as cue-guided responding, following chronic exposure to alcohol. Better elucidating the neural mechanisms that underlie disrupted cue-guided behavior following chronic alcohol exposure may help to understand and treat deficits in adaptive behavior associated with chronic alcohol use in humans.

The Association of Non–Drug-Related Pavlovian-to-Instrumental Transfer Effect in Nucleus Accumbens With Relapse in Alcohol Dependence: A Replication

BackgroundThe Pavlovian-to-instrumental transfer (PIT) paradigm measures the effects of Pavlovian conditioned cues on instrumental behavior in the laboratory. A previous study conducted by our research group observed activity in the left nucleus accumbens (NAcc) elicited by a non–drug-related PIT task across patients with alcohol dependence (AD) and healthy control subjects, and the left NAcc PIT effect differentiated patients who subsequently relapsed from those who remained abstinent. In this study, we aimed to examine whether such effects were present in a larger sample collected at a later date. MethodsA total of 129 recently detoxified patients with AD (21 females) and 74 healthy, age- and gender-matched control subjects (12 females) performing a PIT task during functional magnetic resonance imaging were examined. After task assessments, patients were followed for 6 months. Forty-seven patients relapsed and 37 remained abstinent. ResultsWe found a significant behavioral non–drug-related PIT effect and PIT-related activity in the NAcc across all participants. Moreover, subsequent relapsers showed stronger behavioral and left NAcc PIT effects than abstainers. These findings are consistent with our previous findings. ConclusionsBehavioral non–drug-related PIT and neural PIT correlates are associated with prospective relapse risk in AD. This study replicated previous findings and provides evidence for the clinical relevance of PIT mechanisms to treatment outcome in AD. The observed difference between prospective relapsers and abstainers in the NAcc PIT effect in our study is small overall. Future studies are needed to further elucidate the mechanisms and the possible modulators of neural PIT in relapse in AD.

Amygdala response predicts clinical symptom reduction in patients with borderline personality disorder: A pilot fMRI study.

Borderline personality disorder (BPD) is a prevalent, devastating, and heterogeneous psychiatric disorder. Treatment success is highly variable within this patient group. A cognitive neuroscientific approach to BPD might contribute to precision psychiatry by identifying neurocognitive factors that predict who will benefit from a specific treatment. Here, we build on observations that BPD is accompanied by the enhanced impact of the aversive effect on behavior and abnormal neural signaling in the amygdala. We assessed whether BPD is accompanied by abnormal aversive regulation of instrumental behavior and associated neural signaling, in a manner that is predictive of symptom reduction after therapy. We tested a clinical sample of 15 female patients with BPD, awaiting dialectical behavior therapy (DBT), and 16 matched healthy controls using fMRI and an aversive Pavlovian-to-instrumental transfer (PIT) task that assesses how instrumental behaviors are influenced by aversive Pavlovian stimuli. Patients were assessed 1 year after the start of DBT to quantify changes in BPD symptom severity. At baseline, behavioral aversive PIT and associated neural signaling did not differ between groups. However, the BOLD signal in the amygdala measured during aversive PIT was associated with symptom reduction at 1-year follow-up: higher PIT-related aversive amygdala signaling before treatment was associated with reduced clinical improvement at follow-up. Thus, within the evaluated group of BPD patients, the BOLD signal in the amygdala before treatment was related to clinical symptom reduction 1 year after the start of treatment. The results suggest that less PIT-related responsiveness of the amygdala increases the chances of treatment success. We note that the relatively small sample size is a limitation of this study and that replication is warranted.

General Pavlovian-to-instrumental transfer in humans: Evidence from Bayesian inference.

When repeatedly paired with rewarding outcomes (i.e., Pavlovian conditioning), environmental cues may acquire predictive and motivational significance and later enhance instrumental responding for the same (i.e., outcome-specific transfer) or motivationally similar (i.e., general transfer) outcomes. Although outcome-specific and general Pavlovian-to-Instrumental Transfer (PIT) are characterized by different neural substrates and behavioral mechanisms, general transfer has never been studied in isolation from outcome-specific transfer in humans. The first aim of the present study was to test whether the general transfer effect could emerge in isolation and independently of outcome-specific transfer. Our results showed that general transfer can be elicited without the concurrent presence of outcome-specific transfer, supporting the idea that outcome-specific and general transfer can be studied independently of each other. The second aim of the present study was to clarify whether the affordance-like properties of the outcomes can affect the general transfer. In fact, a critical difference in current studies on general transfer concerns the use of cues associated with outcomes for which an action was previously learned (or not) during the instrumental training. This apparently minor difference affects the affordance-like properties of the outcome and may also be transferred to the cue, in turn impacting general transfer. Results revealed a general transfer of the same magnitude regardless of whether cues were associated with reward earned or not during instrumental conditioning. These findings increase the current knowledge on the incentive motivational mechanism behind general transfer, indicating that it is independent of the motor features of the outcome.

Dopamine errors drive excitatory and inhibitory components of backward conditioning in an outcome-specific manner

For over two decades, phasic activity in midbrain dopamine neurons was considered synonymous with the prediction error in temporal-difference reinforcement learning.1-4 Central to this proposal is the notion that reward-predictive stimuli become endowed with the scalar value of predicted rewards. When these cues are subsequently encountered, their predictive value is compared to the value of the actual reward received, allowing for the calculation of prediction errors.5,6 Phasic firing of dopamine neurons was proposed to reflect this computation,1,2 facilitating the backpropagation of value from the predicted reward to the reward-predictive stimulus, thus reducing future prediction errors. There are two critical assumptions of this proposal: (1) that dopamine errors can only facilitate learning about scalar value and not more complex features of predicted rewards, and (2) that the dopamine signal can only be involved in anticipatory cue-reward learning in which cues or actions precede rewards. Recent work7-15 has challenged the first assumption, demonstrating that phasic dopamine signals across species are involved in learning about more complex features of the predicted outcomes, in a manner that transcends this value computation. Here, we tested the validity of the second assumption. Specifically, we examined whether phasic midbrain dopamine activity would be necessary for backward conditioning-when a neutral cue reliably follows a rewarding outcome.16-20 Using a specific Pavlovian-to-instrumental transfer (PIT) procedure,21-23 we show rats learn both excitatory and inhibitory components of a backward association, and that this association entails knowledge of the specific identity of the reward and cue. We demonstrate that brief optogenetic inhibition of VTADA neurons timed to the transition between the reward and cue reduces both of these components of backward conditioning. These findings suggest VTADA neurons are capable of facilitating associations between contiguously occurring events, regardless of the content of those events. We conclude that these data may be in line with suggestions that the VTADA error acts as a universal teaching signal. This may provide insight into why dopamine function has been implicated in myriad psychological disorders that are characterized by very distinct reinforcement-learning deficits.

Metabotropic group II glutamate receptors mediate cue-triggered increases in reward-seeking behaviour.

Reward-associated cues can invigorate reward-seeking actions via Pavlovian-to-instrumental transfer (PIT). Glutamatergic neurotransmission mediates the appetitive effects of reward-associated cues. We characterized the expression of PIT and its mediation by metabotropic group II glutamate (mGlu2/3) receptor activity in female and male rats. Across the sexes, we used PIT procedures to determine (i) cue-triggered increases in instrumental responding for water reward (experiment 1) and (ii) the respective influences of the mGlu2/3 receptor agonist LY379268 and thirst satiation on this effect (experiment 2). Water-restricted female and male Sprague-Dawley rats learned to lever press for water. Separately, they learned that one of two auditory stimuli predicts free water (CS + vs CS -). On PIT test days, the CS + and CS - were presented independent of instrumental responding, and we measured effects on lever pressing under extinction (no water). In experiment 1, we characterized PIT across the sexes. In experiment 2, we measured PIT after systemic LY379268 administration (0, 0.3 and 1mg/kg) and thirst satiation, respectively. Female and male rats showed similar PIT, with CS + but not CS - presentations potentiating water-seeking behaviour. LY379268 (1mg/kg) attenuated CS + evoked increases in both water-associated lever pressing and conditioned approach to the water port. Thirst satiation attenuated both water-seeking and CS + evoked conditioned approach behaviour. The sexes show similar cue-triggered increases in reward seeking, and thirst satiation suppresses both water-seeking and cue-triggered anticipation of water reward. Finally, across the sexes, mGlu2/3 receptor activity mediates cue-triggered increases in reward seeking.

Effective Connectivity during an Avoidance-Based Pavlovian-to-Instrumental Transfer Task.

Pavlovian-to-instrumental transfer (PIT) refers to a phenomenon whereby a classically conditioned stimulus (CS) impacts the motivational salience of instrumental behavior. We examined behavioral response patterns and functional magnetic resonance imaging (fMRI) based effective connectivity during an avoidance-based PIT task. Eleven participants (8 females; Mage = 28.2, SD = 2.8, range = 25–32 years) completed the task. Effective connectivity between a priori brain regions engaged during the task was determined using hemodynamic response function group iterative multiple model estimation (HRF-GIMME). Participants exhibited behavior that was suggestive of specific PIT, a CS previously associated with a reinforcing outcome increased instrumental responding directed at the same outcome. We did not find evidence for general PIT; a CS did not significantly increase instrumental responding towards a different but related outcome. Using HRF-GIMME, we recovered effective connectivity maps among corticostriatal circuits engaged during the task. Group-level paths revealed directional effects from left putamen to right insula and from right putamen to right cingulate. Importantly, a direct effect of specific PIT stimuli on blood–oxygen-level-dependent (BOLD) activity in the left putamen was found. Results provide initial evidence of effective connectivity in key brain regions in an avoidance-based PIT task network. This study adds to the literature studying PIT effects in humans and employing GIMME models to understand how psychological phenomena are supported in the brain.

Prior chronic alcohol exposure enhances Pavlovian-to-instrumental transfer.

Alcohol dependence is associated with aberrant decision-making processes, particularly in the presence of alcohol-related environmental cues. For instance, alcohol cues can trigger alcohol seeking, consumption, and even relapse behavior. Recently, works have suggested that alcohol dependence may induce more general alterations in cued processes that support adaptive behavior, including enhanced cue control of volitional behavior unrelated to alcohol use. Here we examine this hypothesis by combining prior exposure to chronic intermittent ethanol and repeated withdrawal (CIE) procedures with a Pavlovian-to-instrumental transfer (PIT) task in mice. The PIT task entails training a Pavlovian association, separately training an instrumental contingency, and a final test during which the Pavlovian cue and instrumental action are combined for the first time. We first tested two variants of the PIT procedure in ethanol-naïve mice, differing in part in the duration of Pavlovian conditioned cues (short or long). We found in the PIT test that the short cue procedure produced negative transfer, whereas the long cue procedure produced positive transfer. We then used the long cue variant to examine PIT behavior in mice previously exposed to either CIE or air vapor. We found that prior CIE exposure strengthened PIT behavior, with enhanced instrumental responding during presentation of the food-associated cue. We further found that this enhancement in CIE mice persisted even after devaluation of the food outcome. Our findings suggest that ethanol dependence can enhance the influence of reward-predictive cues on ongoing behavior. Greater non-alcohol cue control of behavior may reflect the effect of chronic ethanol exposure on neural circuitry critical for cue-guided behavior in general.