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Phenylacetaldehyde (PAH), an aromatic compound, is present in a diverse range of fruits including overripe bananas and prickly pear cactus, the two major host fruits for Drosophila melanogaster. PAH acts as a potent ligand for the ionotropic receptor 84a (IR84a) in the adult fruit fly and it is detected by the IR84a/IR8a heterotetrameric complex. Its role in the male courtship behavior through IR84a as an environmental aphrodisiac is of additional importance. In D. melanogaster, two distinct kinds of olfactory receptors, that is, odorant receptors (ORs) and ionotropic receptors (IRs), perceive the odorant stimuli. They display unique structural, molecular, and functional characteristics in addition to having different evolutionary origins. Traditionally, olfactory cues detected by the ORs such as ethyl acetate, 1‐butanol, isoamyl acetate, 1‐octanol, 4‐methylcyclohexanol, etc. classified as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit flies. This underlines the participation of OR‐activated olfactory pathways in learning and memory formation. Our study elucidates that likewise ethyl acetate (EA) (an OR‐responsive odorant), PAH (an IR‐responsive aromatic compound) too can form learning and memory when associated with an appetitive gustatory reinforcer. The association of PAH with sucrose (PAH/SUC) led to learning and formation of the long‐term memory (LTM). Additionally, the Orco1, Ir84aMI00501, and Ir8a1 mutant flies were used to confirm the exclusive participation of the IR84a/IR8a complex in PAH/SUC olfactory associative conditioning. These results highlight the involvement of IRs via an IR‐activated pathway in facilitating robust olfactory behavior. [ABSTRACT FROM AUTHOR]

Introduction: Anorexia nervosa (AN) is a debilitating and potentially chronic eating disorder, characterized by low hedonic drive toward food, which has been linked with perturbations in both reward processing and dopaminergic activity. Neuromelanin‐sensitive magnetic resonance imaging (MRI) is an emerging method to index midbrain neuromelanin—a by‐product of dopaminergic synthesis. The assessment of midbrain neuromelanin, and its association with AN psychopathology and reward‐related processes, may provide critical insights into reward circuit function in AN. Methods: This study will incorporate neuromelanin‐sensitive MRI into an existing study of appetitive conditioning in those with AN. Specifically, those with acute and underweight AN (N = 30), those with weight‐restored AN (N = 30), and age‐matched healthy controls (N = 30) will undergo clinical assessment of current and previous psychopathology, in addition to structural neuromelanin‐sensitive MRI, diffusion MRI, and functional MRI (fMRI) during appetitive conditioning. Conclusion: This study will be among the first to interrogate midbrain neuromelanin in AN—a disorder characterized by altered dopaminergic activity. Results will help establish whether abnormalities in the midbrain synthesis of dopamine are evident in those with AN and are associated with symptomatic behavior and reduced ability to experience pleasure and reward. [ABSTRACT FROM AUTHOR]

Appetitive conditioning plays an important role in the development and maintenance of pornography‐use and gaming disorders. It is assumed that primary and secondary reinforcers are involved in these processes. Despite the common use of pornography and gaming in the general population appetitive conditioning processes in this context are still not well studied. This study aims to compare appetitive conditioning processes using primary (pornographic) and secondary (monetary and gaming‐related) rewards as unconditioned stimuli (UCS) in the general population. Additionally, it investigates the conditioning processes with gaming‐related stimuli as this type of UCS was not used in previous studies. Thirty‐one subjects participated in a differential conditioning procedure in which four geometric symbols were paired with either pornographic, monetary, or gaming‐related rewards or with nothing to become conditioned stimuli (CS + porn, CS + game, CS + money, and CS−) in an functional magnetic resonance imaging study. We observed elevated arousal and valence ratings as well as skin conductance responses for each CS+ condition compared to the CS−. On the neural level, we found activations during the presentation of the CS + porn in the bilateral nucleus accumbens, right medial orbitofrontal cortex, and the right ventral anterior cingulate cortex compared to the CS−, but no significant activations during CS + money and CS + game compared to the CS−. These results indicate that different processes emerge depending on whether primary and secondary rewards are presented separately or together in the same experimental paradigm. Additionally, monetary and gaming‐related stimuli seem to have a lower appetitive value than pornographic rewards. [ABSTRACT FROM AUTHOR]

Associating a neutral conditioned stimulus (CS) with the absence of a biologically significant unconditioned stimulus (US) confers conditioned inhibitory properties upon the CS, referred to as conditioned inhibition. Conditioned inhibition and conditioned excitation, an association of a CS with the presence of the US, are fundamental components of associative learning. While the neural substrates of conditioned excitation are well established, those of conditioned inhibition remain poorly understood. Recent research has shed light on the lateral habenula (LHb) engagement in conditioned inhibition, along with the midbrain dopaminergic neurons. This article reviews behavioral tasks conducted to assess conditioned inhibition and how experimental LHb manipulations affect performance in these tasks. These results underscore the critical role of the LHb in conditioned inhibition. Intriguingly, stress increases LHb reactivity and impairs performances in tasks consisting of a component of conditioned inhibition in animals. Dysfunction of the LHb is observed in patients with depression. The ability of an organism to perform conditioned inhibition is closely linked to altered neuronal activity in the LHb, which has implications for mental disorders. [ABSTRACT FROM AUTHOR]

BackgroundAnorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations-a critical component of hedonic responding-has never been studied in AN.MethodsThis multi-modal study will employ a 2-day Pavlovian appetitive conditioning paradigm to interrogate the (1) acquisition, (2) extinction, (3) spontaneous recovery and (4) reinstatement of appetitive learning in adolescents and young adults with AN. Participants will be 30 currently ill, underweight individuals with AN; 30 weight-restored individuals with AN; and 30 age-matched healthy controls, all aged 12-22 years. All subjects will undergo clinical assessment, followed by the 2-day appetitive conditioning task during which fMRI, pupillometry, heart rate deceleration, and subjective ratings will be acquired.DiscussionThis study will be the first to interrogate appetitive conditioning in AN-a disorder characterized by altered hedonic responding to food. Results will help establish objective biomarkers of appetitive conditioning in AN and lay the groundwork for developing novel lines of treatment for AN and other psychiatric disorders involving diminished ability to experience pleasure and reward.Trial registrationPending.Intended registryClinicaltrials.gov.

Evidence regarding unaware differential fear conditioning in humans is mixed and even less is known about the effects of contingency awareness on appetitive conditioning. Phasic pupil dilation responses (PDR) might be more sensitive for capturing implicit learning than other measures, such as skin conductance responses (SCR). Here, we report data from two delay conditioning experiments utilizing PDR (alongside SCR and subjective assessments) to investigate the role of contingency awareness in aversive and appetitive conditioning. In both experiments, valence of unconditioned stimuli (UCS) was varied within participants by administering aversive (mild electric shocks) and appetitive UCSs (monetary rewards). Preceding visual stimuli (CSs) predicted either the reward, the shock (65% reinforcement), or neither UCS. In Exp. 1, participants were fully instructed about CS‐UCS contingencies, whereas in Exp. 2, no such information was given. PDR and SCR demonstrated successful differential conditioning in Exp. 1 and in (learned) aware participants in Exp. 2. In non‐instructed participants who remained fully unaware of contingencies (Exp. 2), differential modulation of early PDR (immediately after CS onset) by appetitive cues emerged. Associations with model‐derived learning parameters further suggest that early PDR in unaware participants mainly reflect implicit learning of expected outcome value, whereas early PDR in aware (instructed/learned‐aware) participants presumably index attentional processes (related to uncertainty/prediction error processing). Similar, but less clear results emerged for later PDR (preceding UCS onset). Our data argue in favor of a dual‐process account of associative learning, suggesting that value‐related processing can take place irrespective of mechanisms involved in conscious memory formation. While the existence of unaware associative learning is contested, the present study supports a dual‐process model of conditioning, suggesting that the processing of expected outcome value during acquisition is independent of mechanisms involved in conscious memory formation. The results provide the first evidence that such implicit learning processes may be tracked by conditioned pupil dilation responses, which otherwise rather reflect attentional processes in individuals aware of stimulus–outcome contingencies. [ABSTRACT FROM AUTHOR]

Pollinators, such as bees, develop flexible memories of colors, patterns, and shapes, for efficient flower recognition. Here we tested whether other flower-foraging insects have evolved similar cognitive abilities underpinning flexible visual learning. We trained wild hornets from two species commonly found in Europe, the invasive yellow-legged hornet (Vespa velutina nigrithorax) and the European hornet (Vespa crabro), to associate sucrose solution rewards to color stimuli in a Y-maze. Hornets from both species succeeded in differential and reversal learning and developed short-term memories of the learnt associations. Thus, just like bees, hornets can learn various visual cue-reward associations and remember them for at least 1 h for selecting flowers. Our study in non-model species illustrates how standard conditioning approaches can be used to explore and compare the cognitive abilities of animals sharing similar foraging ecologies. Significance statement: Bees can learn an impressive diversity of visual cues to recognize the best rewarding flowers. This can be studied using Y-maze in which individual insects must learn to associate visual stimuli to the presence or absence of nectar rewards. Here, using the same approach, we show that hornets are also capable of these associations. We compared the learning abilities of hornets from two common species in Europe and found that they could similarly learn to discriminate two colors and keep this information in memory for at least 1 h. Hornets thus evolved visual cognition facilitating robust flower foraging, like bees and many other pollinators. [ABSTRACT FROM AUTHOR]

A previous study reported lateral habenula (LHb) lesions decelerated appetitive extinction. Therefore, we examined whether LHb activation accelerated appetitive extinction. In this study, rats received appetitive Pavlovian conditioning, pairing a conditioned stimulus (CS, light) with an unconditioned stimulus (food pellets), followed by CS-alone presentations. Chemogenetic LHb activation accelerated the decline in conditioned food-cup responses during extinction. The present results and the reports of previous LHb lesion studies suggest that LHb mediates appetitive extinction. [ABSTRACT FROM AUTHOR]

Abstract Background Anorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations—a critical component of hedonic responding—has never been studied in AN. Methods This multi-modal study will employ a 2-day Pavlovian appetitive conditioning paradigm to interrogate the (1) acquisition, (2) extinction, (3) spontaneous recovery and (4) reinstatement of appetitive learning in adolescents and young adults with AN. Participants will be 30 currently ill, underweight individuals with AN; 30 weight-restored individuals with AN; and 30 age-matched healthy controls, all aged 12–22 years. All subjects will undergo clinical assessment, followed by the 2-day appetitive conditioning task during which fMRI, pupillometry, heart rate deceleration, and subjective ratings will be acquired. Discussion This study will be the first to interrogate appetitive conditioning in AN—a disorder characterized by altered hedonic responding to food. Results will help establish objective biomarkers of appetitive conditioning in AN and lay the groundwork for developing novel lines of treatment for AN and other psychiatric disorders involving diminished ability to experience pleasure and reward. Trial registration: Pending. Intended registry Clinicaltrials.gov.

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, ηp2 = 0.36, button-box: p < 0.001, ηp2 = 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, ηp2 = 0.09, and monetary: p < 0.001, ηp2 = 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. [ABSTRACT FROM AUTHOR]

• Meta-analytic evidence for pupil dilation as a robust marker of Pavlovian learning. • Larger average effects (p =.07) in aversive (g = 0.73) vs. appetitive conditioning (g = 0.39). • (Rapid) increase in differential pupil responses over the course of acquisition. • Substantial effects in both early and late response windows (relative to CS/UCS). • UCS modality as a likely moderator, but role of contingency instruction uncertain. The use of pupillometry to track emotional learning processes in humans is generating an increasing interest. Here, we provide a first systematic review and meta-analysis on the value of pupil dilation as a marker of Pavlovian conditioning, focusing on the roles of UCS valence (aversive vs. appetitive), the time course across trials and response intervals within trials. Based on data from 39 independent samples (total n = 1303), our results revealed strong evidence for the overall validity of conditioned pupil responses, with a trend for larger effects in aversive (average g = 0.73) vs. appetitive conditioning (g = 0.39). Response differentiation increased over the course of acquisition. Substantial differentiation effects were found in both early and late response windows. Moderator analyses revealed a consistent influence of UCS modality on differential conditioning, while evidence for moderation by contingency instructions and length of acquisition phase was mixed. The results highlight pupil dilation as a sensitive and reliable index of Pavlovian conditioning across valence categories and stimulus modalities. Important implications regarding methodological considerations and research goals are discussed. [ABSTRACT FROM AUTHOR]

Appetitive and aversive conditioning are thought to be involved in the development and maintenance of mental disorders including anxiety, mood, eating, and substance use disorders. However, few studies measure the relative strength of appetitive and aversive associations, and their relevance to the risk of mental disorders. This study aims to address this gap. We tested how readily healthy volunteers acquire appetitive vs. aversive associations. 150 participants associated complex 3D objects with either gain or loss and made decisions to gain or avoid losing points. We investigated the relationship of a learning asymmetry with neuroticism, impulsivity, and anhedonia, to test the hypothesis that a stronger learning asymmetry corresponds to more extreme scores on these traits. Impulsivity was positively associated with the learning asymmetry (R2 =.10). This resulted from an inverse relation with the strength of aversive associations, indicating that impulsive individuals are worse at aversive learning. However, appetitive associations did not differ significantly. No correlations with neuroticism or anhedonia were found. Conditioning studies typically use primary reinforcers and a CS-. Lacking these may make these results less comparable to other studies. We demonstrate that the learning asymmetry can measure individual differences linked to personality traits, and that impulsivity, normally linked with appetitive learning, also influences aversive learning. These results enable additional studies of learning asymmetry in relation to mental disorders, which could include measurements of mental health symptoms to provide further insight into how appetitive and aversive learning interacts with mental disorders. • Research on learning and conditioning can provide new insights into mental disorders. • Such research is currently limited to either a positive or negative focus, not both. • We demonstrate a method that measures both appetitive and aversive learning. • Aversive learning is shown to be impaired in highly impulsive individuals. • This enables further research using the learning asymmetry to study mental disorders. [ABSTRACT FROM AUTHOR]

Cardiac responses to appetitive stimuli have been studied as indices of motivational states and attentional processes, the former being associated with cardiac acceleration and latter deceleration. Very few studies have examined heart rate changes in appetitive classical conditioning in humans. The current study describes the development and pilot testing of a classical conditioning task to assess cardiac responses to appetitive stimuli and cues that reliably precede them. Data from 18 adults were examined. They were shown initially neutral visual stimuli (putative CS) on a computer screen followed by pictures of high-caloric food (US). Phasic cardiac deceleration to food images was observed, consistent with an orienting response to motivationally significant stimuli. Similar responses were observed to non-appetitive stimuli when they were preceded by the cue associated with the food images, suggesting that attentional processes were engaged by conditioned stimuli. These autonomic changes provide significant information about classical conditioning effects in humans.

Cardiac responses to appetitive stimuli have been studied as indices of motivational states and attentional processes, the former being associated with cardiac acceleration and latter deceleration. Very few studies have examined heart rate changes in appetitive classical conditioning in humans. The current study describes the development and pilot testing of a classical conditioning task to assess cardiac responses to appetitive stimuli and cues that reliably precede them. Data from 18 adults were examined. They were shown initially neutral visual stimuli (putative CS) on a computer screen followed by pictures of high-caloric food (US). Phasic cardiac deceleration to food images was observed, consistent with an orienting response to motivationally significant stimuli. Similar responses were observed to non-appetitive stimuli when they were preceded by the cue associated with the food images, suggesting that attentional processes were engaged by conditioned stimuli. These autonomic changes provide significant information about classical conditioning effects in humans. [ABSTRACT FROM AUTHOR]

Adult hippocampal neurogenesis (AHN) plays an essential role in hippocampal-dependent memory consolidation. Increased neurogenesis enhances learning, whereas its ablation causes memory impairment. In contrast, few reports suggest that neurogenesis reduces after learning. Although the interest in exploring the role of adult neurogenesis in learning has been growing, the evidence is still limited. The role of the trace- and delay-appetitive-conditioning on AHN and its underlying mechanism are not known. The consolidation of trace-conditioned memory requires the hippocampus, but delay-conditioning does not. Moreover, the dorsal hippocampus (DH) and ventral hippocampus (VH) may have a differential role in these two conditioning paradigms. Here, we have investigated the changes in: (A) hippocampal cell proliferation and their progression towards neuronal lineage; and (B) expression of Arc, Erk1, Erk2, and CREB proteins in the DH and VH after trace- and delay-conditioning in the rat. The number of newly generated cells significantly increased in the trace-conditioned but did not change in the delay-conditioned animals compared to the control group. Similarly, the expression of Arc protein significantly increased in the DH but not in the VH after trace-conditioning. Nonetheless, it remains unaltered in the delay-conditioned group. The expression of pErk1, pErk2, and pCREB also increased in the DH after trace-conditioning. Whereas, the expression of only pErk1 pErk2 and pCREB proteins increased in the VH after delay-conditioning. Our results suggest that appetitive trace-conditioning enhances AHN. The increased DH neuronal activation and pErk1, pErk2, and pCREB in the DH may be playing an essential role in learning-induced cell-proliferation after appetitive trace-conditioning.

Learning theorists suggest extinction learning to be a central mechanism in weight loss success; however, empirical studies are scarce. In this pilot study, it was examined whether individual differences in extinction learning predict outcome after weight loss treatment. Overweight and obese individuals first completed a laboratory conditioning task in which individual differences in extinction learning were assessed. Next, they were randomised to one of two weight loss interventions: cue exposure therapy (CET), which is considered the clinical analogue of laboratory extinction, or a control lifestyle intervention. In line with expectations, better extinction learning in the laboratory task was associated with more weight loss at both post‐treatment (CET only) and follow‐up (both interventions) measurements. In contrast, two other indices of treatment success (reduction in overeating expectancies and ad libitum food intake during a laboratory taste test) showed no associations with pre‐treatment extinction learning. It is suggested that extinction learning may be a core mechanism underlying weight loss success, and hence, an important target for new obesity interventions. [ABSTRACT FROM AUTHOR]

Animals must quickly adapt food‐seeking strategies to locate nutrient sources in dynamically changing environments. Learned associations between food and environmental cues that predict its availability promote food‐seeking behaviors. However, when such cues cease to predict food availability, animals undergo "extinction" learning, resulting in the inhibition of food‐seeking responses. Repeatedly activated sets of neurons, or "neuronal ensembles," in the dorsal medial prefrontal cortex (dmPFC) are recruited following appetitive conditioning and undergo physiological adaptations thought to encode cue‐reward associations. However, little is known about how the recruitment and intrinsic excitability of such dmPFC ensembles are modulated by extinction learning. Here, we used in vivo 2‐Photon imaging in male Fos‐GFP mice that express green fluorescent protein (GFP) in recently behaviorally activated neurons to determine the recruitment of activated pyramidal and GABAergic interneuron dmPFC ensembles during extinction. During extinction, we revealed a persistent activation of a subset of interneurons which emerged from a wider population of interneurons activated during the initial extinction session. This activation pattern was not observed in pyramidal cells, and extinction learning did not modulate the excitability properties of activated pyramidal cells. Moreover, extinction learning reduced the likelihood of reactivation of pyramidal cells activated during the initial extinction session. Our findings illuminate novel neuronal activation patterns in the dmPFC underlying extinction of food‐seeking, and in particular, highlight an important role for interneuron ensembles in this inhibitory form of learning. [ABSTRACT FROM AUTHOR]

Recognizing reward-related stimuli is crucial for survival. Neuronal projections from the basolateral amygdala (BLA) to the nucleus accumbens (NAc) play an important role in processing reward-related cues. Previous studies revealed synchronization between distant brain regions in reward-sensitive neurocircuits; however, whether the NAc synchronizes with the BLA is unknown. Here, we recorded local field potentials simultaneously from the BLA and NAc of rats during social preference tests and an appetitive conditioning test in which explicit stimuli were associated with food. BLA-NAc coherence in the theta band (5–8 Hz) increased in response to food-associated cues. Meanwhile, the modulatory strength of theta–high gamma (50–110 Hz) phase-amplitude cross-frequency coupling (PAC) in the NAc decreased. Importantly, both of these neuromodulations disappeared upon extinction. In contrast, both theta and gamma power oscillations in each region increased in the presence of social conspecifics or contexts associated with conspecifics, but coherence did not change. To potentially disrupt behavior and associated neural activity, a subgroup of rats was exposed prenatally to valproic acid (VPA), which has been shown to disrupt transcriptome and excitatory/inhibitory balance in the amygdala. VPA-exposed rats demonstrated impulsive-like behavior, but VPA did not affect BLA-NAc coherence. These findings reveal changes in BLA-NAc coherence in response to select reward-related stimuli (i.e., food-predictive cues); the differences between the tasks used here could shed light onto the functional nature of BLA-NAc coherence and are discussed. [ABSTRACT FROM AUTHOR]

Adult hippocampal neurogenesis (AHN) plays an essential role in hippocampal-dependent memory consolidation. Increased neurogenesis enhances learning, whereas its ablation causes memory impairment. In contrast, few reports suggest that neurogenesis reduces after learning. Although the interest in exploring the role of adult neurogenesis in learning has been growing, the evidence is still limited. The role of the trace- and delay-appetitive-conditioning on AHN and its underlying mechanism are not known. The consolidation of trace-conditioned memory requires the hippocampus, but delay-conditioning does not. Moreover, the dorsal hippocampus (DH) and ventral hippocampus (VH) may have a differential role in these two conditioning paradigms. Here, we have investigated the changes in: (A) hippocampal cell proliferation and their progression towards neuronal lineage; and (B) expression of Arc, Erk1, Erk2, and CREB proteins in the DH and VH after trace- and delay-conditioning in the rat. The number of newly generated cells significantly increased in the trace-conditioned but did not change in the delay-conditioned animals compared to the control group. Similarly, the expression of Arc protein significantly increased in the DH but not in the VH after trace-conditioning. Nonetheless, it remains unaltered in the delay-conditioned group. The expression of pErk1, pErk2, and pCREB also increased in the DH after trace-conditioning. Whereas, the expression of only pErk1 pErk2 and pCREB proteins increased in the VH after delay-conditioning. Our results suggest that appetitive trace-conditioning enhances AHN. The increased DH neuronal activation and pErk1, pErk2, and pCREB in the DH may be playing an essential role in learning-induced cell-proliferation after appetitive trace-conditioning. [ABSTRACT FROM AUTHOR]

Anorexia Nervosa is characterized by persistent restraint eating despite severe negative consequences and often a chronic course of the disease. Recent theoretical models suggest that abnormalities in reward processing and incentive salience of disorder‐compatible stimuli as observed in addictive behaviours contribute to the development and maintenance of Anorexia Nervosa. The aim of the present study was to investigate the process of the acquisition of food‐related conditioned responses and the influence of conditioned low‐calorie and high‐calorie food stimuli on instrumental responding for different foods. A Pavlovian‐to‐instrumental transfer paradigm and questionnaires on eating disorder psychopathology (EDE‐Q, EDI‐2) were administered to patients with Anorexia Nervosa (n = 39) and healthy controls (n = 41). Results indicated that patients with Anorexia Nervosa showed deficits of the acquisition of knowledge of the experimental contingencies. Nevertheless, in patients with Anorexia Nervosa and healthy controls instrumental responding for low‐ and high‐calorie food rewards was affected by stimuli conditioned to these rewards; no group differences were observed. Importantly, in Anorexia Nervosa, instrumental responding for low‐calorie food increased with increasing severity of eating disorder psychopathology suggesting weight‐loss directed behaviour. Future studies are warranted to enhance our understanding of deficits of reward‐associated learning and to replicate and extend findings with regard to the impact of conditioned stimuli on instrumental responding. At present, our findings suggest that cognitive treatment interventions might be warranted that challenge dysfunctional beliefs about weight loss. [ABSTRACT FROM AUTHOR]

Contextual renewal of reward anticipation may be one potential mechanism underlying relapse in eating and substance use disorders. We therefore tested retrieval cues, a method derived from an inhibitory retrieval-based model of extinction learning to attenuate contextual renewal using an appetitive conditioning paradigm. A pilot study was carried out in Experiment 1 to validate a differential chocolate conditioning paradigm, in which a specific tray was set up as a conditioned stimulus (CS) for eating chocolate (unconditioned stimulus, US). Using an ABA renewal design in Experiment 2, half of the participants were presented with a retrieval cue in the acquisition phase (group AC) and the other half in the extinction phase (group EC). Presentation of the retrieval cue in the EC was associated with reduced renewal of US-expectancy, while there was a clear renewal effect for US-expectancy in the AC. One limitation was the difference in cue presentations between both groups due to the number of trials in acquisition and extinction. Experiment 3 therefore aimed at replicating the results of Experiment 2, but with fewer cue presentations for the EC to match the AC. No significant group differences were observed indicating no effect of the retrieval cue. Theoretical and clinical implications in light of the differing results are discussed. • Contextual renewal of conditioned appetitive responses may pose a threat for long-term abstinence and healthy eating. • Inhibitory retrieval theory offers several possible strategies to optimize long-term extinction of conditioned responses. • Retrieval cues may represent one strategy by bridging the gap between what was learned during treatment and everyday life. • Extinction retrieval cues attenuated renewal of reward anticipation within a differential chocolate conditioning paradigm. • Our results indicate that frequency of retrieval cue presentation during extinction seems to play a role. [ABSTRACT FROM AUTHOR]

Learning and memory related brain disorders represent a large unmet medical need. Laboratory studies with animals may model brain disorders and facilitate uncovering their mechanisms. The zebrafish has been proposed for such studies. However, numerous factors that influence performance in learning tasks have yet to be understood in zebrafish. One such factor is what motivates zebrafish. Here we introduce a novel reinforcer, an ecologically relevant unconditioned stimulus (US). We placed a photograph of gravel underneath quarter of the bottom of an experimental tank on one side and also positioned artificial plants there, the "natural" US. First, we showed that this stimulus was preferred by zebrafish. Next, we investigated whether this stimulus could serve as US for associative learning. We marked the walls of the tank on the side where the US was presented with red paper, the conditioned stimulus (CS+) we found neutral before, and we also marked the walls on the other side of the tank where no US was placed with blue paper (CS-). In addition to fish receiving this "paired" training, we also ran unpaired training with another group of zebrafish, in which the fish saw the US associated with blue and red in a random manner. After having trained the fish in this manner, we tested the performance of the paired and unpaired group of zebrafish in a memory probe trial during which no US was present, and only the CSs (blue and red walls) were shown. We found the paired group of zebrafish to show significant preference for the CS+, as they spent more time and swam closer to the red side compared to the unpaired group and compared to chance. We conclude that ecologically relevant stimuli can serve as efficient US in appetitive conditioning of zebrafish. • Classical reinforcers, like food, often fail in zebrafish learning studies. • Here we show zebrafish exhibit innate preference for "natural stimuli". • Gravel bottom & plastic plants, the natural stimuli, may be used as reinforcer. • Conditioned stimulus paired with natural stimuli leads to association memory. • Memory is established after only 4 pairing trials. [ABSTRACT FROM AUTHOR]

Animals selectively respond to environmental cues associated with food reward to optimize nutrient intake. Such appetitive conditioned stimulus--unconditioned stimulus (CS-US) associations are thought to be encoded in select, stable neuronal populations or neuronal ensembles, which undergo physiological modifications during appetitive conditioning. These ensembles in the medial prefrontal cortex (mPFC) control well-established, cue-evoked food seeking, but the mechanisms involved in the genesis of these ensembles are unclear. Here, we used male Fos-GFP mice that express green fluorescent protein (GFP) in recently behaviorally activated neurons, to reveal how dorsal mPFC neurons are recruited and modified to encode CS-US memory representations using an appetitive conditioning task. In the initial conditioning session, animals did not exhibit discriminated, cue-selective food seeking, but did so in later sessions indicating that a CS-US association was established. Using microprism-based in vivo 2-Photon imaging, we revealed that only a minority of neurons activated during the initial session was consistently activated throughout subsequent conditioning sessions and during cue-evoked memory recall. Notably, using ex vivo electrophysiology, we found that neurons activated following the initial session exhibited transient hyperexcitability. Chemogenetically enhancing the excitability of these neurons throughout subsequent conditioning sessions interfered with the development of reliable cue-selective food seeking, indicated by persistent, nondiscriminated performance. We demonstrate how appetitive learning consistently activates a subset of neurons to form a stable neuronal ensemble during the formation of a CS-US association. This ensemble may arise from a pool of hyperexcitable neurons activated during the initial conditioning session. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate spontaneous recovery of reward-expectancies and a reward-associated response in humans and to assess individual factors affecting spontaneous recovery. We therefore implemented an experimental procedure comprising three separate test-sessions. In the first test-session, participants underwent instrumental discrimination training to acquire a conditioned reward-associated response, in the second test-session, memory of this response was tested followed by extinction training. In the third test-session, extinction memory was assessed. Our results demonstrate spontaneous recovery of extinguished conditioned reward-associated expectancies and indicate that differential expectancies after training and extinction and impulsivity significantly predicted the magnitude of spontaneous recovery. In contrast, limited evidence for spontaneous recovery of instrumental responding was found. Given that reward-expectancies might trigger instrumental responding these findings underline the importance of developing extinction procedures that lead to more complete and less fragile long-term extinction of reward-associated responses. • Spontaneous recovery is the return of conditioned responses due to passage of time. • More research on spontaneous recovery of reward-associated responses is needed. • Our results indicate spontaneous recovery of reward-associated expectancies. • This phenomenon might explain the limited efficacy of cue exposure treatment. • Extinction procedures resulting in long-term extinction are needed. [ABSTRACT FROM AUTHOR]

Highlights • Fish exposure to poor water quality reduces swimming activity and increases shoaling. • Exposure to poor water quality inhibits fish reactivity to a human presence. • Exposure to poor water quality impairs fish food-anticipatory behaviour. • Fish farmers could use these sentience-based tools as sensitive welfare markers. Abstract Recent scientific evidence for fish sentience has stressed the need for novel sentience-based detection tools of fish welfare impairment in commercial farms. In order to mimic a well-characterised stress situation, rainbow trout (Oncorhynchus mykiss) were exposed to poor water quality (hypoxia combined with high ammonia level) for three weeks (stressed group, S) and compared to a non-stressed control group (NS). After a return to water quality standard, emotional responses were assessed in fish subjected to two potentially threatening situations: (i) social isolation in a novel environment and (ii) human presence. In addition, we used an appetitive-conditioning paradigm to determine whether previous chronic deterioration of water quality disturbs cognitive abilities in fish. Spontaneous behaviour in the tanks was also recorded during the environmental challenge as a reference for fish activity. We observed that in S fish, plasma cortisol levels were increased before and after social isolation in a novel environment compared to the plasma cortisol levels in the NS group, despite the absence of a behavioural difference between the two groups. Under deteriorated water quality, fish locomotor activity was globally reduced and this reduction was correlated to increased shoaling behaviour. Farmers can use these first behavioural modifications as a sentinel detector for fish welfare impairment. More importantly, we demonstrated that reactivity to a human presence in a home-environment and food-anticipatory behaviour were both inhibited in the S group. We consider that these two sentience-based tests are highly relevant for fish welfare assessment at the group level and are easy to use in the aquaculture industry. [ABSTRACT FROM AUTHOR]

Theories of functioning in the medial prefrontal cortex are distinct across appetitively and aversively motivated procedures. In the appetitive domain, it is argued that the medial prefrontal cortex is important for producing adaptive behavior when circumstances change. This view advocates a role for this region in using higher-order information to bias performance appropriate to that circumstance. Conversely, literature born out of aversive studies has led to the theory that the prelimbic region of the medial prefrontal cortex is necessary for the expression of conditioned fear, whereas the infralimbic region is necessary for a decrease in responding following extinction. Here, the argument is that these regions are primed to increase or decrease fear responses and that this tendency is gated by subcortical inputs. However, we believe the data from aversive studies can be explained by a supraordinate role for the medial prefrontal cortex in behavioral flexibility, in line with the appetitive literature. Using a dichotomy between the voluntary control of behavior and the execution of well-trained responses, we attempt to reconcile these theories. We argue that the prelimbic region exerts voluntary control over behavior via top-down modulation of stimulus-response pathways according to task demands, contextual cues, and how well a stimulus predicts an outcome. Conversely, the infralimbic region promotes responding based on the strength of stimulusresponse pathways determined by experience with reinforced contingencies. This system resolves the tension between executing voluntary actions sensitive to recent changes in contingencies, and responses that reflect the animal's experience across the long run. [ABSTRACT FROM AUTHOR]

Three experiments examined whether second-order conditioning resulted in the formation of a fully-featured temporal map, as proposed by the temporal coding hypothesis. Experiments 1 and 2 examined second-order conditioning with different first- and second-order relationships. Measures of the strength of second-order conditioning were mostly consistent with the temporal coding hypothesis; second-order conditioning was best with arrangements in which CS2 occurred prior to the time that the US normally occurred during CS1-US presentations. However, there was no evidence of anticipatory timing during CS2 during second-order conditioning. A third experiment directly examined whether a fully-featured temporal map was formed during second-order conditioning by examining the acquisition of anticipatory timing in subsequent reinforced second-order trials. The results of Experiment 3 suggested that the effects obtained in Experiments 1 and 2 were due to learning of the temporal order and coincidence of events that resulted in the formation of an ordinal temporal map, but that precise durations were not encoded. [ABSTRACT FROM AUTHOR]

Abstract: Despite its evolutionary and clinical significance, appetitive conditioning has been rarely investigated in humans. It has been proposed that this discrepancy might stem from the difficulty in finding suitable appetitive stimuli that elicit strong physiological responses. However, this might also be due to a possible lack of sensitivity of the psychophysiological measures commonly used to index human appetitive conditioning. Here, we investigated whether the postauricular reflex—a vestigial muscle microreflex that is potentiated by pleasant stimuli relative to neutral and unpleasant stimuli—may provide a valid psychophysiological indicator of appetitive conditioning in humans. To this end, we used a delay differential appetitive conditioning procedure, in which a neutral stimulus was contingently paired with a pleasant odor (CS+), while another neutral stimulus was not associated with any odor (CS−). We measured the postauricular reflex, the startle eyeblink reflex, and skin conductance response (SCR) as learning indices. Taken together, our results indicate that the postauricular reflex was potentiated in response to the CS+ compared with the CS−, whereas this potentiation extinguished when the pleasant odor was no longer delivered. In contrast, we found no evidence for startle eyeblink reflex attenuation in response to the CS+ relative to the CS−, and no effect of appetitive conditioning was observed on SCR. These findings suggest that the postauricular reflex is a sensitive measure of human appetitive conditioning and constitutes a valuable tool for further shedding light on the basic mechanisms underlying emotional learning in humans. [ABSTRACT FROM AUTHOR]

At present, there is a considerable lack of human studies that investigated the impact of conditioned cues on instrumental responding although these processes are considered as core mechanisms contributing to the development and maintenance of addictive behaviours. No studies are available that assessed these processes with regard to Internet gaming or Internet shopping applications. We thus developed a Pavlovian-to-instrumental transfer (PIT)-Paradigm implementing appetitive stimuli related to Internet gaming and Internet shopping applications and investigated whether an outcome-specific PIT-Effect is observed. In addition, we assessed whether the problematic use of gaming or shopping applications, personality traits and stress would affect the acquisition of knowledge of the experimental contingencies during Pavlovian training and the impact of conditioned stimuli on instrumental responding. A PIT-Paradigm, screenings for Internet gaming disorder and Internet shopping disorder (s-IAT), and questionnaires on personality traits (NEO-FFI, BIS-15) and perceived stress (PSQ20) were administered to sixty-six participants. The PIT-Paradigm demonstrated the effects of stimuli conditioned to rewards related to Internet gaming and Internet shopping applications on instrumental responding to obtain such rewards. Findings also indicated that severity of problematic Internet gaming, but not Internet shopping, contributed to the acquisition of knowledge of the experimental contingencies. Stress, extraversion, neuroticism and gender emerged as further predictors. The strength of expectancy of the different reinforcers affected the ‘gaming PIT’-Effect; however, none of the variables assessed in the present study showed any effect on the ‘shopping PIT’-Effect. Future studies including participants with pathological use patterns that can be classified as internet use disorder are warranted to extend these findings. [ABSTRACT FROM AUTHOR]

Persistent responding to food cues may underlie the difficulty to resist palatable foods and to maintain healthy eating habits. Renewal of responding after extinction is a model of persistent food seeking that can be used to study the underlying neural mechanisms. In context-mediated renewal, a return to the context in which the initial cue-food learning occurred induces robust responding to the cues that were extinguished elsewhere. Previous work found sex differences in context-mediated renewal and in the recruitment of the ventromedial prefrontal cortex (vmPFC) during that behavior. Males exhibited renewal of responding to food cues and had higher Fos induction in the prelimbic area (PL) of the vmPFC, while females failed to exhibit renewal of responding and had lower Fos induction in the PL. The main aim of the current study was to determine key components of the PL circuitry mediating renewal. The focus was on inputs from three areas important in appetitive associative learning and contextual processing: the amygdala, ventral hippocampal formation, and the paraventricular nucleus of the thalamus. The goal was to determine whether neurons from these areas that send direct projections to the PL (identified with a retrograde tracer) are selectively activated (Fos induction) during renewal and whether they are differently recruited in males and females. The Fos induction patterns demonstrated that the PL-projecting neurons in each of these areas were recruited in a sex-specific way that corresponded to the behavioral differences between males and females. These pathways were selectively activated in the male experimental group—the only group that showed renewal behavior. The findings suggest the pathways from the ventral hippocampal formation, paraventricular nucleus of the thalamus, and basolateral amygdala to the PL mediate renewal in males. The lack of recruitment in females suggests that under activation of these pathways may underlie their lack of renewal. [ABSTRACT FROM AUTHOR]

Symposium summary: With the classification of compulsive sexual behavior disorder (CSBD) within the ICD-11 as impulse control disorder, CSBD has been recognized as clinically significant disorder. The problematic and pathological use of pornography (PPU) is listed as one phenotype of CSBD. For a better understanding of the etiology of CSBD and PPU much effort has been put into the understanding of neurobiological and psychological mechanisms underlying CSBD in the last decade. Matthias Brand will give an overview on these advances in research within the first talk. In the second talk, Kseniya Krikova will present recent data on the role of appetitive conditioning and extinction processes in PPU. Comparisons will be made with gaming disorder, a recently classified disorder due to addictive behaviors. One specific mechanism in CSBD and PPU is that the behavior itself is a natural reinforcer and important for the fulfillment of natural sexual needs and functioning. Beáta Bőthe will focus in the third talk on associations between PPU, pornography use and sexual functioning. Within the fourth talk, Stephanie Antons will compare psychological mechanisms of CSBD and PPU aiming to understand specificities of the phenotypes. Collectively, these works present innovative research employing a variety of methods to further elucidate the neurobiological and psychological mechanisms underpinning the development and maintenance of CSBD and PPU. [ABSTRACT FROM AUTHOR]

Wood ants are a model system for studying visual learning and navigation. They can forage for food and navigate to their nests effectively by forming memories of visual features in their surrounding environment. Previous studies of freely behaving ants have revealed many of the behavioural strategies and environmental features necessary for successful navigation. However, little is known about the exact visual properties of the environment that animals learn or the neural mechanisms that allow them to achieve this. As a first step towards addressing this, we developed a classical conditioning paradigm for visual learning in harnessed wood ants that allows us to control precisely the learned visual cues. In this paradigm, ants are fixed and presented with a visual cue paired with an appetitive sugar reward. Using this paradigm, we found that visual cues learnt by wood ants through Pavlovian conditioning are retained for at least 1 h. Furthermore, we found that memory retention is dependent upon the ants' performance during training. Our study provides the first evidence that wood ants can form visual associative memories when restrained. This classical conditioning paradigm has the potential to permit detailed analysis of the dynamics of memory formation and retention, and the neural basis of learning in wood ants. [ABSTRACT FROM AUTHOR]

Wood ants are a model system for studying visual learning and navigation. They can forage for food and navigate to their nests effectively by forming memories of visual features in their surrounding environment. Previous studies of freely behaving ants have revealed many of the behavioural strategies and environmental features necessary for successful navigation. However, little is known about the exact visual properties of the environment that animals learn or the neural mechanisms that allow them to achieve this. As a first step towards addressing this, we developed a classical conditioning paradigm for visual learning in harnessed wood ants that allows us to control precisely the learned visual cues. In this paradigm, ants are fixed and presented with a visual cue paired with an appetitive sugar reward. Using this paradigm, we found that visual cues learnt by wood ants through Pavlovian conditioning are retained for at least one hour. Furthermore, we found that memory retention is dependent upon the ants’ performance during training. Our study provides the first evidence that wood ants can form visual associative memories when restrained. This classical conditioning paradigm has the potential to permit detailed analysis of the dynamics of memory formation and retention, and the neural basis of learning in wood ants. [ABSTRACT FROM AUTHOR]

Overweight and obese individuals show increased psychological and physiological reactivity to food cues and many of them have difficulties in achieving long-term weight loss. The current study tests whether abnormalities in the learning and extinction of appetitive responses to food cues might be responsible for this. Overweight/obese and healthy weight women completed a differential appetitive conditioning task using food as rewards, while eating expectancies, eating desires, conditioned stimulus evaluations, salivation, and electrodermal responses were assessed during an acquisition and extinction phase. Results suggested reduced discriminative conditioning in the overweight/obese group, as reflected by a worse acquisition of differential eating desires and no successful acquisition of differential evaluative responses. Some evidence was also found for impaired contingency learning in overweight and obese individuals. No group differences in conditioned salivation and skin conductance responses were found and no compelling evidence for differences in extinction was found as well. In sum, the current findings indicate that overweight and obesity may be characterized by reduced appetitive conditioning. It is suggested that this could be causally related to overeating via stronger context conditioning or a tendency towards overgeneralization in overweight and obese individuals. [ABSTRACT FROM AUTHOR]

Human laboratory studies have shown that eating desires are easily learned through classical conditioning: after a few pairings of an initially neutral stimulus (e.g., a box) with the intake of palatable food (e.g., chocolate), the stimulus elicits increased eating expectancies and eating desires (acquisition). After repeated non-reinforced presentations of the chocolate-associated stimulus, eating expectancies and desires decrease again (extinction). It is commonly assumed that eating desires in daily life are acquired and extinguished in a similar manner, but to date, this has not been empirically tested. In two studies, we examined whether the repeated consumption of chocolate at a specific time of day elicits increased eating expectancies and eating desires over a period of 5 days (study 1) or 15 days (study 2), and relative to a time of day not paired with chocolate intake. Further, it was tested whether acquired responding diminishes again during extinction (study 1). Ecological momentary assessment was used to carry out the studies in daily life. Results showed that eating expectancies were acquired in both studies. Only in study 2, eating desires were also successfully learned. It is concluded that eating expectancies and eating desires can be conditioned to ecologically valid cues and under real-life circumstances. This highlights the importance of associative learning processes in the experience of eating desires in daily life. [ABSTRACT FROM AUTHOR]

Studies on human appetitive conditioning using food rewards can benefit from including psychophysiological outcome measures. The present study tested whether the skin conductance response can function as a measure of differential responding in an appetitive conditioning paradigm including an acquisition and extinction phase, and examined which time window during a trial is most sensitive to conditioning effects. As a secondary aim, the effects of ambiguous vs. non-ambiguous contingency instructions on conditioned responses (skin conductance responses, US expectancies, chocolate desires, and CS evaluations) were assessed. Results indicated differential skin conductance responses in an anticipatory time window and during unexpected omission of the US in early extinction. Interestingly however, anticipatory responses were only found for participants who received ambiguous contingency instructions – possibly indicating a call for additional processing resources in response to the ambiguous CS +. Further, ambiguous instructions slowed the extinction of US expectancies but did not influence chocolate desires and CS evaluations. It is concluded that skin conductance can function as a sensitive measure of differential responding in appetitive conditioning, though its sensitivity might depend on the specific task context. [ABSTRACT FROM AUTHOR]

Three experiments explored the utility of considering mechanisms of occasion setting for understanding patterning and biconditional discriminations – two more complex conditional discriminations in which the stimulus-outcome relations of occasion setting are embedded. In Experiment 1, rats were trained in an appetitive conditioning task with either a biconditional or a patterning discrimination using relatively brief CSs (10 s) and differential outcomes as USs. In this study, rats learned the positive patterning task before they had learned negative patterning, and the biconditional task was the most difficult. However, a detailed examination of the results suggested that rats trained in the biconditional task responded to the stimulus compounds mainly on the basis of individual stimulus-outcome associations. Different conditioned response (CR) topographies as a function of reinforcer type complicated interpretation of these results. Experiment 2 confirmed that the biconditional task, with the parameters used here, was not learned, regardless of whether training involved differential or non-differential outcomes. In Experiment 3 the CS duration was increased to 30 s and two different USs were used that each supported similar CR topographies. Under these conditions, we observed that whereas the positive patterning task was learned most rapidly, the biconditional discrimination was learned faster than the negative patterning task. Considered in relation to other findings on patterning and biconditional discriminations, the results suggest that elemental, configural, and/or modulatory occasion setting mechanisms may play different roles in these complex conditional discrimination tasks especially as a function of stimulus duration and differential outcome training. [ABSTRACT FROM AUTHOR]

RAB-GDP dissociation inhibitor 1 ( GDI1 ) loss-of-function mutations are responsible for a form of non-specific X-linked Intellectual Disability (XLID) where the only clinical feature is cognitive impairment. GDI1 patients are impaired in specific aspects of executive functions and conditioned response, which are controlled by fronto-striatal circuitries. Previous molecular and behavioral characterization of the Gdi1 -null mouse revealed alterations in the total number/distribution of hippocampal and cortical synaptic vesicles as well as hippocampal short-term synaptic plasticity, and memory deficits. In this study, we employed cognitive protocols with high translational validity to human condition that target the functionality of cortico-striatal circuitry such as attention and stimulus selection ability with progressive degree of complexity. We previously showed that Gdi1 -null mice are impaired in some hippocampus-dependent forms of associative learning assessed by aversive procedures. Here, using appetitive-conditioning procedures we further investigated associative learning deficits sustained by the fronto-striatal system. We report that Gdi1 -null mice are impaired in attention and associative learning processes, which are a key part of the cognitive impairment observed in XLID patients. [ABSTRACT FROM AUTHOR]