Reward-associated Cues Research Articles

Implementations of sign- and goal-tracking behavior in humans: A scoping review.

Animal research has identified two major phenotypes in the tendency to attribute incentive salience to a reward-associated cue. Individuals called "sign-trackers" (STs) preferentially approach the cue, assigning both predictive and incentive values to it. In contrast, individuals called "goal-trackers" (GTs) preferentially approach the location of the upcoming reward, assigning only a predictive value to the cue. The ST/GT model has been shown to be relevant to understanding addiction vulnerability and other pathological behaviors in animals. Therefore, recent studies tried to implement this animal model in the human population. This scoping review aimed to identify and map evidence of human sign- and goal-tracking. Studies that explicitly measured human sign- and goal-tracking or related phenomena (e.g., attentional bias induced by reward-related cues), using paradigms in line with the animal model, were eligible for this review. We searched for published, unpublished, and gray literature (PhD theses, posters, conference papers) through the following databases: MEDLINE, Scopus, PsycINFO, Embase, OSF, and Google Scholar. The JBI scoping review methodology was adopted. Screening and extraction were carried out by three reviewers, in pairs. A total of 48 studies were identified. These studies used various experimental paradigms and used the term "sign-tracking" inconsistently, sometimes implicitly or not at all. We conclude that the literature on human sign-tracking is very heterogeneous on many levels. Overall, evidence supports the existence of sign- and goal-tracking behaviors in humans, although further validated research is crucially needed.

Role of dopamine in reward expectation and predictability during execution of action sequences.

Reward-associated cues serve different functions depending on whether they precede or terminate action sequences. Cues that precede action sequences and signal opportunity for reward could serve as GO signals to initiate the sequence, whereas sequence termination cues could serve as response feedback by signaling reward delivery. Reward expectation during sequence execution depends on these cues and might condition whether behavior is habitual or goal-directed. However, it remains unknown how sequence initiation and termination cues differentially affect reward expectation and contribute to habit learning. Further, while mesolimbic dopamine plays a key role in cue-induced reward expectation and sequence learning, how dynamic changes in dopamine signals differ depending on the response strategy is unclear. Here, we determined how mesolimbic DA signals change over training during cue-mediated sequence learning, depending on the type of cue and the nature of behavioral control. We found sequence initiation and termination cues differentially affect reward expectation during action sequences, with the termination cue contributing to habit and automaticity. Distinct response strategies induced by sequence initiation and termination cues induced differential changes in mesolimbic DA signals that captured variations in reward expectation along sequence execution. Notably, habit-like behavior induced by the sequence termination cue was associated with a rapid shift in DA signals from reward retrieval to the cue. This habit-like behavior was reflected in behavioral inflexibility and attenuated DA reward prediction error signals. Finally, using optogenetics, we provide evidence that phasic DA activity elicited by the sequence termination cue is critical for the development of habit-like behavior.

Neural activity ramps in frontal cortex signal extended motivation during learning

Learning requires the ability to link actions to outcomes. How motivation facilitates learning is not well understood. We designed a behavioral task in which mice self-initiate trials to learn cue-reward contingencies and found that the anterior cingulate region of the prefrontal cortex (ACC) contains motivation-related signals to maximize rewards. In particular, we found that ACC neural activity was consistently tied to trial initiations where mice seek to leave unrewarded cues to reach reward-associated cues. Notably, this neural signal persisted over consecutive unrewarded cues until reward-associated cues were reached, and was required for learning. To determine how ACC inherits this motivational signal we performed projection-specific photometry recordings from several inputs to ACC during learning. In doing so, we identified a ramp in bulk neural activity in orbitofrontal cortex (OFC)-to-ACC projections as mice received unrewarded cues, which continued ramping across consecutive unrewarded cues, and finally peaked upon reaching a reward-associated cue, thus maintaining an extended motivational state. Cellular resolution imaging of OFC confirmed these neural correlates of motivation, and further delineated separate ensembles of neurons that sequentially tiled the ramp. Together, these results identify a mechanism by which OFC maps out task structure to convey an extended motivational state to ACC to facilitate goal-directed learning.

Neural activity ramps in frontal cortex signal extended motivation during learning.

Learning requires the ability to link actions to outcomes. How motivation facilitates learning is not well understood. We designed a behavioral task in which mice self-initiate trials to learn cue-reward contingencies and found that the anterior cingulate region of the prefrontal cortex (ACC) contains motivation-related signals to maximize rewards. In particular, we found that ACC neural activity was consistently tied to trial initiations where mice seek to leave unrewarded cues to reach reward-associated cues. Notably, this neural signal persisted over consecutive unrewarded cues until reward-associated cues were reached, and was required for learning. To determine how ACC inherits this motivational signal we performed projection-specific photometry recordings from several inputs to ACC during learning. In doing so, we identified a ramp in bulk neural activity in orbitofrontal cortex (OFC)-to-ACC projections as mice received unrewarded cues, which continued ramping across consecutive unrewarded cues, and finally peaked upon reaching a reward-associated cue, thus maintaining an extended motivational state. Cellular resolution imaging of OFC confirmed these neural correlates of motivation, and further delineated separate ensembles of neurons that sequentially tiled the ramp. Together, these results identify a mechanism by which OFC maps out task structure to convey an extended motivational state to ACC to facilitate goal-directed learning.

Distinct Patterns of Connectivity between Brain Regions Underlie the Intra-Modal and Cross-Modal Value-Driven Modulations of the Visual Cortex.

Past reward associations may be signaled from different sensory modalities; however, it remains unclear how different types of reward-associated stimuli modulate sensory perception. In this human fMRI study (female and male participants), a visual target was simultaneously presented with either an intra- (visual) or a cross-modal (auditory) cue that was previously associated with rewards. We hypothesized that, depending on the sensory modality of the cues, distinct neural mechanisms underlie the value-driven modulation of visual processing. Using a multivariate approach, we confirmed that reward-associated cues enhanced the target representation in early visual areas and identified the brain valuation regions. Then, using an effective connectivity analysis, we tested three possible patterns of connectivity that could underlie the modulation of the visual cortex: a direct pathway from the frontal valuation areas to the visual areas, a mediated pathway through the attention-related areas, and a mediated pathway that additionally involved sensory association areas. We found evidence for the third model demonstrating that the reward-related information in both sensory modalities is communicated across the valuation and attention-related brain regions. Additionally, the superior temporal areas were recruited when reward was cued cross-modally. The strongest dissociation between the intra- and cross-modal reward-driven effects was observed at the level of the feedforward and feedback connections of the visual cortex estimated from the winning model. These results suggest that, in the presence of previously rewarded stimuli from different sensory modalities, a combination of domain-general and domain-specific mechanisms are recruited across the brain to adjust the visual perception.SIGNIFICANCE STATEMENT Reward has a profound effect on perception, but it is not known whether shared or disparate mechanisms underlie the reward-driven effects across sensory modalities. In this human fMRI study, we examined the reward-driven modulation of the visual cortex by visual (intra-modal) and auditory (cross-modal) reward-associated cues. Using a model-based approach to identify the most plausible pattern of inter-regional effective connectivity, we found that higher-order areas involved in the valuation and attentional processing were recruited by both types of rewards. However, the pattern of connectivity between these areas and the early visual cortex was distinct between the intra- and cross-modal rewards. This evidence suggests that, to effectively adapt to the environment, reward signals may recruit both domain-general and domain-specific mechanisms.

β2* nicotinic acetylcholine receptor subtypes mediate nicotine-induced enhancement of Pavlovian conditioned responding to an alcohol cue.

Nicotine enhances Pavlovian conditioned responses to reward-associated cues. We investigated through which nicotinic acetylcholine receptor (nAChR) subtypes nicotine acts to produce this behavioral effect to an alcohol-associated cue. Male Long-Evans rats with freely available food and water were first accustomed to drinking 15% ethanol in their home cages using an intermittent access, two-bottle choice procedure. Then the rats were given 15 Pavlovian conditioning sessions in which a 15-s audiovisual conditioned stimulus (CS) predicted the delivery of 0.2 ml of ethanol, the unconditioned stimulus (US). Each session contained 12 CS-US trials. A control group received explicitly unpaired presentations of the CS and US. We measured Pavlovian conditioned approach to the site of US delivery during presentations of the CS, accounting for pre-CS baseline activity. Before each conditioning session, rats were injected subcutaneously with nicotine (0.4 mg/kg) or saline (1 ml/kg). During nAChR antagonist test sessions, rats were first injected systemically with the β2*-selective nAChR antagonist dihydro-beta-erythroidine (DHβE; 3 mg/kg) or the α7-selective nAChR antagonist methyllycaconitine (MLA; 6 mg/kg), followed by their assigned nicotine or saline injection before assessing their conditioned response to the alcohol-associated cue. Consistent with previous reports, nicotine enhanced the Pavlovian conditioned response to the alcohol-paired cue. DHβE attenuated this enhancement, whereas MLA did not. These results suggest that nicotine acts via β2*, but not α7, nAChRs to amplify Pavlovian conditioned responding to an alcohol cue. These findings contribute to a growing literature that identifies nAChRs as potential targets for pharmacological treatment of co-morbid alcohol and tobacco use disorders.

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.

Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies

Sprague Dawley (SD) rats are among the most widely used outbred laboratory rat populations. Despite this, the genetic characteristics of SD rats have not been clearly described, and SD rats are rarely used for experiments aimed at exploring genotype-phenotype relationships. In order to use SD rats to perform a genome-wide association study (GWAS), we collected behavioral data from 4,625 SD rats that were predominantly obtained from two commercial vendors, Charles River Laboratories and Harlan Sprague Dawley Inc. Using double-digest genotyping-by-sequencing (ddGBS), we obtained dense, high-quality genotypes at 291,438 SNPs across 4,061 rats. This genetic data allowed us to characterize the variation present in Charles River vs. Harlan SD rats. We found that the two populations are highly diverged (FST > 0.4). Furthermore, even for rats obtained from the same vendor, there was strong population structure across breeding facilities and even between rooms at the same facility. We performed multiple separate GWAS by fitting a linear mixed model that accounted for population structure and using meta-analysis to jointly analyze all cohorts. Our study examined Pavlovian conditioned approach (PavCA) behavior, which assesses the propensity for rats to attribute incentive salience to reward-associated cues. We identified 46 significant associations for the various metrics used to define PavCA. The surprising degree of population structure among SD rats from different sources has important implications for their use in both genetic and non-genetic studies.

Diurnal rhythms in cholinergic modulation of rapid dopamine signals and associative learning in the striatum.

SUMMARYDysregulation of biological rhythms plays a role in a wide range of psychiatric disorders. We report mechanistic insights into the rhythms of rapid dopamine signals and cholinergic interneurons (CINs) working in concert in the rodent striatum. These rhythms mediate diurnal variation in conditioned responses to reward-associated cues. We report that the dopamine signal-to-noise ratio varies according to the time of day and that phasic signals are magnified during the middle of the dark cycle in rats. We show that CINs provide the mechanism for diurnal variation in rapid dopamine signals by serving as a gain of function to the dopamine signal-to-noise ratio that adjusts across time of day. We also show that conditioned responses to reward-associated cues exhibit diurnal rhythms, with cue-directed behaviors observed exclusively midway through the dark cycle. We conclude that the rapid dopamine signaling rhythm is mediated by a diurnal rhythm in CIN activity, which influences learning and motivated behaviors across the time of day.

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.

Medial orbitofrontal cortex and nucleus accumbens mediation in risk assessment behaviors in adolescents and adults.

Risk assessment behaviors are necessary for gathering risk information and guiding decision-making. Risky decision-making heightens during adolescence, possibly as a result of low risk awareness and an increase in sensitivity to reward-associated cues and experiences. Higher adolescent engagement in high-risk behaviors may be, in part, due to developing circuits that contribute to risk assessment behaviors. Nucleus accumbens (NAc) activity is linked to risky decision-making and receives inputs carrying sensory and emotional information. Namely, the medial orbitofrontal cortex (MO) contributes to behavior guided by reward probability and sends direct projections to the NAc (MO→NAc), which may permit risk assessment in a mature circuit. Here, we evaluated risk assessment behaviors in adult and adolescent rats during elevated plus maze (EPM) exploration, including stretch and attend postures, head dips, and rears. We found that adolescents exhibited fewer EPM risk assessment behaviors than adults. We also quantified MO→NAc projections using a fluorescent anterograde tracer, Fluoro-Ruby, in both age groups. Labeled MO→NAc pathways exhibited greater total fluorescence in adults than in adolescents, indicating MO→NAc fibers increase over development. Using a disconnection approach to measure the contribution of the MO-NAc pathway in adults, we found that ipsilateral inactivation of the MO-NAc did not alter risk assessment behavior; however, MO-NAc disconnection reduced the number of stretch-and-attend postures. Together, this work suggests that the development of MO-NAc pathways can contribute to age-dependent differences in risk assessment.

Neural correlates and determinants of approach–avoidance conflict in the prelimbic prefrontal cortex

The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic (PL) cortex respond to both threat- and reward-associated cues. However, it remains unknown whether PL regulates threat-avoidance vs. reward-approaching responses when an animals' decision depends on previously associated memories. Using a conflict model in which male Long-Evans rats retrieve memories of shock- and food-paired cues, we observed two distinct phenotypes during conflict: (1) rats that continued to press a lever for food (Pressers) and (2) rats that exhibited a complete suppression in food seeking (Non-pressers). Single-unit recordings revealed that increased risk-taking behavior in Pressers is associated with persistent food-cue responses in PL, and reduced spontaneous activity in PL glutamatergic (PLGLUT) neurons during conflict. Activating PLGLUT neurons in Pressers attenuated food-seeking responses in a neutral context, whereas inhibiting PLGLUT neurons in Non-pressers reduced defensive responses and increased food approaching during conflict. Our results establish a causal role for PLGLUT neurons in mediating individual variability in memory-based risky decision-making by regulating threat-avoidance vs. reward-approach behaviors.

Metabotropic group II glutamate receptors in the basolateral amygdala mediate cue-triggered increases in incentive motivation.

Reward-associated cues can trigger incentive motivation for reward and invigorate reward-seeking behaviour via Pavlovian-to-instrumental transfer (PIT). Glutamate signaling within the basolateral amygdala (BLA) modulates cue-triggered increases in incentive motivation. However, the role of BLA metabotropic group II glutamate (mGlu2/3) receptors is largely unknown. In Experiment 1, we characterized cue-triggered increases in incentive motivation for water reward using the PIT paradigm. In Experiment 2, we assessed the influence of intra-BLA microinjections of the mGlu2/3 receptor agonist LY379268 on this effect. Water-restricted male Sprague-Dawley rats learned to press a lever for water. Separately, they learned to associate one of two auditory cues with free water. On test days, rats could lever press under extinction conditions (no water), with intermittent, non-contingent CS+ and CS- presentations. In Experiment 1, rats were tested under baseline conditions. In Experiment 2, rats received intra-BLA microinjections of LY379268 (0, 3 and 6 [Formula: see text]g/hemisphere) before testing. Across experiments, CS+, but not CS-, presentations increased water-associated lever pressing during testing, even though responding was reinforced neither by water nor the CS+. Intra-BLA LY379268 abolished both CS+ potentiated pressing on the water-associated lever and CS+ evoked conditioned approach to the site of water delivery. LY379268 did not influence locomotion or instrumental and Pavlovian response rates during intervals between CS presentations or during the CS-, indicating no motor effects. mGlu2/3 receptor activity in the BLA mediates cue-triggered potentiation of incentive motivation for reward, suppressing both cue-induced increases in instrumental pursuit of the reward and anticipatory approach behaviour.

Reward produces learning of a consciously inaccessible feature

Reward has a significant impact on behaviour and perception. Most past work in associative reward learning has used perceptually distinct visual cues to associate with different reward values. Thus, it remains unknown to what extent the learned bias towards reward-associated stimuli depends on consciousness of the apparent differences between stimuli. Here, we resolved this issue by using an inter-ocular suppression paradigm with the monetary rewarding and non-rewarding cues identical to each other except for their eye-of-origin information. Thus, the reward coding system cannot rely on consciousness to select the reward-associated cue. Surprisingly, the targets in the rewarded eye broke into awareness faster than those in the non-rewarded eye. We further revealed that producing this effect required both top-down attention and inter-ocular suppression. These findings suggest that the human's reward coding system can produce two different types of reward-based learning. One is independent of consciousness yet fairly consuming attentional resources. The other one results from volitional selection of stimuli of behavioural significance.

Time‐of‐Day Variation in Learning, Reward‐Associated Behaviors, and Rapid Dopamine Release

Research has shown that circadian rhythms in physiology and behavior play a role in a number of psychiatric disorders, like depression and substance use disorder (SUD). For example, time-of-day variation has been observed in craving for nicotine, heroin, and cocaine in abstinent individuals. However, we have yet to fully delineate how these rhythms mediate variations in motivated behavior, learning, and reward seeking. This is critical as aberrant motivation and learning are hallmarks in these disorders. Additionally, the mesolimbic dopamine (DA) system is implicated in the neurobiology of motivation and learning, and research has shown time-of-day variations in DA tone. Less work has focused on rapid DA signals that are critical for motivation and learning. Thus, the purpose of this study was to examine time-of-day variations in incentive motivational properties of reward-associated cues and learning and the degree to which the magnitude of mesolimbic DA release in the nucleus accumbens (NAc) corresponded to dynamic shifts in motivation and learning across time-of-day. Our central hypothesis is that there are critical times within the day that confer increased sensitivity to reward-associated cues, which are mediated by time-of-day variations in the magnitude of phasic DA signaling. Initially, we examined the magnitude of NAc DA signaling to stimulations that mimic both tonic and phasic firing of mesolimbic DA neurons in rats. We used ex vivo fast scan cyclic voltammetry (FSCV) at four different time points across the 12:12 light/dark cycle. Our data demonstrate robust time-of-day differences in DA release magnitude following stimulations that model both phasic (≥20 Hz) and tonic (5 Hz) firing. Given that the phasic/tonic ratio of DA release magnitude was greatest midway through the dark cycle and lowest midway through the light cycle, we examined whether behavioral paradigms sensitive to DA release magnitude would fluctuate consistently with these DA oscillations. We therefore utilized Pavlovian paradigms in rodents to measure incentive motivational aspects and conditioned approach towards a reward-associated cue, during midway through the light cycle and midway through the dark cycle. Furthermore, since DA release and motivated behavior is modulated by striatal cholinergic interneuron (CIN) activity via nicotinic receptors (nAChRs) located on DA axons, we examined whether both DA release and incentive motivation was altered following nicotine exposure. To unmask the circuitry underlying these variations, we utilized ex vivo optogentics. We found a robust increase in DA release magnitude without the contribution of CIN activity midway through the dark cycle. In contrast, DA release was significantly higher in DA release magnitude modulated by CIN activity midway through the light cycle. Lastly, we are currently using in vivo optogenetics to mediate the magnitude of DA release during Pavlovian paradigms at times throughout the light cycles. Collectively, our data suggest that rats midway through their dark cycle exhibit increased sensitivity to reward-associated cues, which may be mediated by rapid DA release that is modulated by oscillations in CIN activity throughout the day.

Male Goal-Tracker and Sign-Tracker Rats Do Not Differ in Neuroendocrine or Behavioral Measures of Stress Reactivity.

Environmental cues attain the ability to guide behavior via learned associations. As predictors, cues can elicit adaptive behavior and lead to valuable resources (e.g., food). For some individuals, however, cues are transformed into incentive stimuli and elicit motivational states that can be maladaptive. The goal-tracker (GT)/sign-tracker (ST) animal model captures individual differences in cue-motivated behaviors, with reward-associated cues serving as predictors of reward for both phenotypes but becoming incentive stimuli to a greater degree for STs. While these distinct phenotypes are characterized based on Pavlovian conditioned approach (PavCA) behavior, they exhibit differences on a number of behaviors relevant to psychopathology. To further characterize the neurobehavioral endophenotype associated with individual differences in cue-reward learning, neuroendocrine and behavioral profiles associated with stress and anxiety were investigated in male GT, ST, and intermediate responder (IR) rats. It was revealed that baseline corticosterone (CORT) increases with Pavlovian learning, but to the same degree, regardless of phenotype. No significant differences in behavior were observed between GTs and STs during an elevated plus maze (EPM) or open field test (OFT), nor were there differences in CORT response to the OFT or physiological restraint. Upon examination of central markers associated with stress reactivity, we found that STs have greater glucocorticoid receptor (GR) mRNA expression in the ventral hippocampus, with no phenotypic differences in the dorsal hippocampus or prelimbic cortex (PrL). These findings demonstrate that GTs and STs do not differ on stress-related and anxiety-related behaviors, and suggest that differences in neuroendocrine measures between these phenotypes can be attributed to distinct cue-reward learning styles.

The influence of associative reward learning on motor inhibition

Stimuli that predict a rewarding outcome can cause difficulties to inhibit unfavourable behaviour. Research suggests that this is also the case for stimuli with a history of reward extending these effects on action control to situations, where reward is no longer accessible. We expand this line of research by investigating if previously reward-predictive stimuli promote behavioural activation and impair motor inhibition in a second unrelated task. In two experiments participants were trained to associate colours with a monetary reward or neutral feedback. Afterwards participants performed a cued go/no-go task, where cues appeared in the colours previously associated with feedback during training. In both experiments training resulted in faster responses in rewarded trials providing evidence of a value-driven response bias as long as reward was accessible. However, stimuli with a history of reward did not interfere with goal-directed action and inhibition in a subsequent task after removal of the reward incentives. While the first experiment was not conclusive regarding an impact of reward-associated cues on response inhibition, the second experiment, validated by Bayesian statistics, clearly questioned an effect of reward history on inhibitory control. This stands in contrast to earlier findings suggesting that the effect of reward history on subsequent action control is not as consistent as previously assumed. Our results show that participants are able to overcome influences from Pavlovian learning in a simple inhibition task. We discuss our findings with respect to features of the experimental design which may help or complicate overcoming behavioural biases induced by reward history.

Rat Paraventricular Neurons Encode Predictive and Incentive Information of Reward Cues.

The paraventricular nucleus of the thalamus (PVT) has been implicated in cue-induced motivated behaviors. Although reward-associated cues (conditioned stimuli, CSs) contain different types of information including predictive information of future reward delivery and incentive (motivational) value of the reward, it remains unknown whether PVT neurons represent predictive and incentive information of CSs. It is suggested that neural activity just after the onset of CSs (early activity) and that just before reward delivery (late activity) might more strongly represent predictive and incentive information, respectively. In this study, rats were trained to lick a tube, which was protruded close to their mouth just after a CS, to obtain a reward (sucrose or water) (cue-induced licking task). Auditory and visual CSs were used: each elemental cue (CS) predicted reward or non-reward outcome, while simultaneous presentation of the two elemental cues (configural cues) predicted the opposite reward outcome. We recorded PVT neurons in the cue-induced licking task, and report that half of the CS-responsive PVT neurons responded selectively to the CSs predicting reward outcome regardless of physical property of the cues (CS+-selective). In addition, the early activity of the CS+-selective neurons discriminated reward/non-reward association (predictive information) and was less sensitive to reward value and motivation reflected by lick latency (incentive information), while the late activity of the CS+-selective neurons was correlated with reward value and motivation rather than reward/non-reward association. Early and late population activity of the CS+-selective neurons also represented predictive and incentive information of the CSs, respectively. On the other hand, activity of more than half of the PVT neurons was correlated with individual licking during licking to acquire reward. Taken together, the results suggest that the PVT neurons engage in different neural processes involved in cue-induced motivated behaviors: CS encoding to determine reward availability and form motivation for reward-seeking behavior, and hedonic mouth movements during reward consumption.

The lateral hypothalamus and orexinergic transmission in the paraventricular thalamus promote the attribution of incentive salience to reward-associated cues.

Prior research suggests that the neural pathway from the lateral hypothalamic area (LHA) to the paraventricular nucleus of the thalamus (PVT) mediates the attribution of incentive salience to Pavlovian reward cues. However, a causal role for the LHA and the neurotransmitters involved have not been demonstrated in this regard. To examine (1) the role of LHA in the acquisition of Pavlovian conditioned approach (PavCA) behaviors, and (2) the role of PVT orexin 1 receptors (OX1r) and orexin 2 receptors (OX2r) in the expression of PavCA behaviors and conditioned reinforcement. Rats received excitotoxic lesions of the LHA prior to Pavlovian training. A separate cohort of rats characterized as sign-trackers (STs) or goal-trackers (GTs) received the OX1r antagonist SB-334867, or the OX2r antagonist TCS-OX2-29, into the PVT, to assess their effects on the expression of PavCA behavior and on the conditioned reinforcing properties of a Pavlovian reward cue. LHA lesions attenuated the development of sign-tracking behavior. Administration of either the OX1r or OX2r antagonist into the PVT reduced sign-tracking behavior in STs. Further, OX2r antagonism reduced the conditioned reinforcing properties of a Pavlovian reward cue in STs. The LHA is necessary for the development of sign-tracking behavior; and blockade of orexin signaling in the PVT attenuates the expression of sign-tracking behavior and the conditioned reinforcing properties of a Pavlovian reward cue. Together, these data suggest that LHA orexin inputs to the PVT are a key component of the circuitry that encodes the incentive motivational value of reward cues.

Subliminal determinants of cue-guided choice

By anticipating potential rewards, external cues can guide behavior to achieve a goal. Whether the conscious elaboration of these cues is necessary to elicit cue-guided choices is still unknown. The goal of the present study is to test whether the subliminal presentation of a visual cue previously paired with a reward is sufficient to bias responses that can lead to the same or a similar reward. To this aim, three experiments compared the subliminal and supraliminal presentation of reward-associated cues during a Pavlovian-to-Instrumental Transfer task. In line with previous evidence, results showed that the supraliminal presentation of reward-associated Pavlovian cues biased participant’s choice towards motivationally similar rewards (general transfer) as well as towards rewards sharing the precise sensory-specific properties of the cue (outcome-specific transfer). In striking contrast, subliminal cues biased choice only towards motivationally similar rewards (general transfer). Taken together, these findings suggest that cue-guided choices are modulated by the level of perceptual threshold (i.e., subliminal vs supraliminal) of reward-associated cues. Although conscious elaboration of the cue is necessary to guide choice towards a specific reward, subliminal processing is still sufficient to push towards choices sharing the motivational properties of the cue. Implications for everyday life, clinical conditions, and theoretical accounts of cue-guided choices are discussed.