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Pavlovian conditioning is a ubiquitous form of associative learning that enables animals to remember appetitive and aversive experiences. Animals possess appetitive and aversive conditioning systems that memorize and retrieve appetitive and aversive experiences. Here, we addressed a question of whether integration of competing appetitive and aversive information takes place during the encoding of the experience or during memory retrieval. We developed novel experimental procedures to address this question using crickets (Gryllus bimaculatus), which allowed selective blockade of the expression of appetitive and aversive memories by injecting octopamine and dopamine receptor antagonists. We conditioned an odour (conditioned stimulus 1, CS1) with water and then with sodium chloride solution. At 24 h after conditioning, crickets retained both appetitive and aversive memories, and the memories were integrated to produce a conditioned response (CR). Importantly, when a visual pattern (CS2) was conditioned with CS1, appetitive and aversive memories formed simultaneously. This indicates that appetitive and aversive second-order conditionings are achieved at the same time. The memories were integrated for producing a conditioned response. We conclude that appetitive and aversive conditioning systems operate independently to form parallel appetitive and aversive memories, which compete to produce learned behaviour in crickets. [ABSTRACT FROM AUTHOR]

In well-established first-order conditioning experiments, the concurrence of a sensory cue with reinforcement forms an association, allowing the cue to predict future reinforcement. In the insect mushroom body, a brain region central to learning and memory, such associations are encoded in the synapses between its intrinsic and output neurons. This process is mediated by the activity of dopaminergic neurons that encode reinforcement signals. In second-order conditioning, a new sensory cue is paired with an already established one that presumably activates dopaminergic neurons due to its predictive power of the reinforcement. We explored minimal circuit motifs in the mushroom body for their ability to support second-order conditioning using mechanistic models. We found that dopaminergic neurons can either be activated directly by the mushroom body’s intrinsic neurons or via feedback from the output neurons via several pathways. We demonstrated that the circuit motifs differ in their computational efficiency and robustness. Beyond previous research, we suggest an additional motif that relies on feedforward input of the mushroom body intrinsic neurons to dopaminergic neurons as a promising candidate for experimental evaluation. It differentiates well between trained and novel stimuli, demonstrating robust performance across a range of model parameters. [ABSTRACT FROM AUTHOR]

Activity in the basolateral amygdala complex (BLA) is needed to encode fears acquired through contact with both innate sources of danger (i.e., things that are painful) and learned sources of danger (e.g., being threatened with a gun). However, within the BLA, the molecular processes required to consolidate the two types of fear are not the same: protein synthesis is needed to consolidate the first type of fear (so-called first-order fear) but not the latter (so-called second-order fear). The present study examined why first- and second-order fears differ in this respect. Specifically, it used a range of conditioning protocols in male and female rats, and assessed the effects of a BLA infusion of the protein synthesis inhibitor, cycloheximide, on first- and second-order conditioned fear. The results revealed that the differential protein synthesis requirements for consolidation of first- and second-order fears reflect differences in what is learned in each case. Protein synthesis in the BLA is needed to consolidate fears that result from encoding of relations between stimuli in the environment (stimulus--stimulus associations, typical for first-order fear) but is not needed to consolidate fears that form when environmental stimuli associate directly with fear responses emitted by the animal (stimulus-- response associations, typical for second-order fear). Thus, the substrates of Pavlovian fear conditioning in the BLA depend on the way that the environment impinges upon the animal. This is discussed with respect to theories of amygdala function in Pavlovian fear conditioning, and ways in which stimulus--response associations might be consolidated in the brain. [ABSTRACT FROM AUTHOR]

In well-established first-order conditioning experiments, the concurrence of a sensory cue with reinforcement forms an association, allowing the cue to predict future reinforcement. In the insect mushroom body, a brain region central to learning and memory, such associations are encoded in the synapses between its intrinsic and output neurons. This process is mediated by the activity of dopaminergic neurons that encode reinforcement signals. In second-order conditioning, a new sensory cue is paired with an already established one that presumably activates dopaminergic neurons due to its predictive power of the reinforcement. We explored minimal circuit motifs in the mushroom body for their ability to support second-order conditioning using mechanistic models. We found that dopaminergic neurons can either be activated directly by the mushroom body’s intrinsic neurons or via feedback from the output neurons via several pathways. We demonstrated that the circuit motifs differ in their computational efficiency and robustness. Beyond previous research, we suggest an additional motif that relies on feedforward input of the mushroom body intrinsic neurons to dopaminergic neurons as a promising candidate for experimental evaluation. It differentiates well between trained and novel stimuli, demonstrating robust performance across a range of model parameters.

Simple Summary: Threat conditioning is a process by which animals learn about danger. As such, this process has been extensively studied as a model of how humans develop fears and anxiety, and their related disorders such as post-traumatic stress disorder (PTSD), which affects seven to eight percent of adults at some point in their life. Conversely, threat extinction is essentially the reverse of this process, by which animals adaptively learn that something is no longer dangerous. Threat extinction forms the basis of exposure therapy, a cornerstone in the treatment of such disorders, during which patients face their fears in order to overcome them. So-called higher-order forms of learning such as second-order threat conditioning add layers of complexity to threat conditioning and may thus more closely mimic processes underlying the development of such disorders. While the amygdala has long been thought to be at the center of such processes, being activated and suppressed during threat conditioning and extinction, respectively, in reality a complex network of structures governs these forms of learning. While such networks are not proposed to hold all the answers to our understanding of the development and treatment of such disorders, they are an important piece of the puzzle, and are thus reviewed here. Recent advances are presenting new areas of exploration into the brain-based mechanisms of such forms of learning and may ultimately inform the treatment of fear- and anxiety-related disorders. Threat conditioning, extinction, and second-order threat conditioning studied in animal models provide insight into the brain-based mechanisms of fear- and anxiety-related disorders and their treatment. Much attention has been paid to the role of the basolateral amygdala (BLA) in such processes, an overview of which is presented in this review. More recent evidence suggests that the BLA serves as the core of a greater network of structures in these forms of learning, including associative and sensory cortices. The BLA is importantly regulated by hippocampal and prefrontal inputs, as well as by the catecholaminergic neuromodulators, norepinephrine and dopamine, that may provide important prediction-error or learning signals for these forms of learning. The sensory cortices may be required for the long-term storage of threat memories. As such, future research may further investigate the potential of the sensory cortices for the long-term storage of extinction and second-order conditioning memories. [ABSTRACT FROM AUTHOR]

Threat conditioning, extinction, and second-order threat conditioning studied in animal models provide insight into the brain-based mechanisms of fear- and anxiety-related disorders and their treatment. Much attention has been paid to the role of the basolateral amygdala (BLA) in such processes, an overview of which is presented in this review. More recent evidence suggests that the BLA serves as the core of a greater network of structures in these forms of learning, including associative and sensory cortices. The BLA is importantly regulated by hippocampal and prefrontal inputs, as well as by the catecholaminergic neuromodulators, norepinephrine and dopamine, that may provide important prediction-error or learning signals for these forms of learning. The sensory cortices may be required for the long-term storage of threat memories. As such, future research may further investigate the potential of the sensory cortices for the long-term storage of extinction and second-order conditioning memories.

In standard (first-order) Pavlovian conditioning protocols, pairings of an initially neutral conditioned stimulus (CS) and a biologically significant unconditioned stimulus (US) result in the formation of a CS-US association. The strength of this association is theoretically regulated by prediction error: specifically, the difference between the total level of conditioning supported by the US and the degree to which it is predicted by all stimuli present (i.e., a common error term). In higher-order conditioning protocols (e.g., sensory preconditioning and second-order conditioning), a Pavlovian CS is used to condition responses to other stimuli with which it is paired. At present, it is unknown whether error-correction processes regulate associative learning in higher-order conditioning and, if so, whether these processes are the same as those that regulate formation of a CS-US association in first-order conditioning. Here we review studies that have provided findings relevant to this question: specifically, studies that have examined blocking and/or inhibitory learning in sensory preconditioning and second-order conditioning. These studies show that: (1) animals can form inhibitory associations between relatively neutral sensory stimuli; (2) the learning that occurs in sensory preconditioning and second-order conditioning can be blocked; and, finally, (3) a first-order CS can block conditioning to a second-order CS, and vice versa. The findings are taken to imply that a common error term regulates associative learning in higher-order conditioning, just as it regulates associative learning in first-order conditioning. They are discussed with respect to the nature of the error signal that underlies conditioning and future work that is needed to advance our understanding of the rules that govern different types of learning.

This paper is organized in three sections. In the first section, we discuss the relevance of comparative psychology to clinical issues by relating resistance to extinction to psychological disorders involving anxiety, addiction, and fetishism. In the second section, we review areas of comparative psychology that deal in one way or another with the general problem of treating an insignificant event as it were significant. We describe research on supernormal stimuli, evaluative conditioning, acquired drives, incentive sensitization, and consummatory response theory. In the third section of the paper, we present new research on second-order sexual conditioning of male Japanese quail related to the consummatory response theory. First-order conditioning was conducted by pairing the presentation of a terrycloth object (CS1 or conditioned stimulus 1) with copulation with a female (the US or unconditioned stimulus). The male quail came to approach the terrycloth object during the first-order conditioning phase. In addition, about half of the quail also showed conditioned consummatory responses directed towards the terrycloth object. During the second-order conditioning phase, the terrycloth object was used to condition responding to a light (CS2) in the absence of further exposures to the unconditioned stimulus. Birds that showed conditioned consummatory behavior towards CS1 persisted in this behavior during the second-order phase and showed successful second-order conditioning of the light. In contrast, birds that failed to develop conditioned consummatory responses to CS1 showed rapid extinction and minimal second-order conditioning. The implications of these finding for learning theory and for psychopathology are discussed.

Associative learning is often considered to require the physical presence of stimuli in the environment in order for them to be linked. This, however, is not a necessary condition for learning. Indeed, associative relationships can form between events that are never directly paired. That is, associative learning can occur by integrating information across different phases of training. Higher-order conditioning provides evidence for such learning through two deceptively similar designs – sensory preconditioning and second-order conditioning. In this review, we detail the procedures and factors that influence learning in these designs, describe the associative relationships that can be acquired, and argue for the importance of this knowledge in studying brain function. [ABSTRACT FROM AUTHOR]

Associative learning is often considered to require the physical presence of stimuli in the environment in order for them to be linked. This, however, is not a necessary condition for learning. Indeed, associative relationships can form between events that are never directly paired. That is, associative learning can occur by integrating information across different phases of training. Higher-order conditioning provides evidence for such learning through two deceptively similar designs – sensory preconditioning and second-order conditioning. In this review, we detail the procedures and factors that influence learning in these designs, describe the associative relationships that can be acquired, and argue for the importance of this knowledge in studying brain function.

Stimuli in reality rarely co-occur with primary reward or punishment to allow direct associative learning of value. Instead, value is thought to be inferred through complex higher-order associations. Rodent research has demonstrated that the formation and maintenance of first-order and higher-order associations are supported by distinct neural substrates. In this study, we explored whether this pattern of findings held true for humans. Participants underwent first-order and subsequent higher-order conditioning using an aversive burst of white noise or neutral tone as the unconditioned stimuli. Four distinct tones, initially neutral, served as first-order and higher-order conditioned stimuli. Autonomic and neural responses were indexed by pupillometry and evoked response potentials (ERPs) respectively. Conditioned aversive values of first-order and higher-order stimuli led to increased autonomic responses, as indexed by pupil dilation. Distinct temporo-spatial auditory evoked response potentials were elicited by first-order and high-order conditioned stimuli. Conditioned first-order responses peaked around 260 ms and source estimation suggested a primary medial prefrontal and amygdala source. Conversely, conditioned higher-order responses peaked around 120 ms with an estimated source in the medial temporal lobe. Interestingly, pupillometry responses to first-order conditioned stimuli were diminished after higher order training, possibly signifying concomitant incidental extinction, while responses to higher-order stimuli remained. This suggests that once formed, higher order associations are at least partially independent of first order conditioned representations. This experiment demonstrates that first-order and higher-order conditioned associations have distinct neural signatures, and like rodents, the medial temporal lobe may be specifically involved with higher-order conditioning. [ABSTRACT FROM AUTHOR]

Stimuli in reality rarely co-occur with primary reward or punishment to allow direct associative learning of value. Instead, value is thought to be inferred through complex higher-order associations. Rodent research has demonstrated that the formation and maintenance of first-order and higher-order associations are supported by distinct neural substrates. In this study, we explored whether this pattern of findings held true for humans. Participants underwent first-order and subsequent higher-order conditioning using an aversive burst of white noise or neutral tone as the unconditioned stimuli. Four distinct tones, initially neutral, served as first-order and higher-order conditioned stimuli. Autonomic and neural responses were indexed by pupillometry and evoked response potentials (ERPs) respectively. Conditioned aversive values of first-order and higher-order stimuli led to increased autonomic responses, as indexed by pupil dilation. Distinct temporo-spatial auditory evoked response potentials were elicited by first-order and high-order conditioned stimuli. Conditioned first-order responses peaked around 260 ms and source estimation suggested a primary medial prefrontal and amygdala source. Conversely, conditioned higher-order responses peaked around 120 ms with an estimated source in the medial temporal lobe. Interestingly, pupillometry responses to first-order conditioned stimuli were diminished after higher order training, possibly signifying concomitant incidental extinction, while responses to higher-order stimuli remained. This suggests that once formed, higher order associations are at least partially independent of first order conditioned representations. This experiment demonstrates that first-order and higher-order conditioned associations have distinct neural signatures, and like rodents, the medial temporal lobe may be specifically involved with higher-order conditioning.

In contrast to the large body of work demonstrating second-order conditioning (SOC) in non-human animals, the evidence for SOC in humans is scant. In this review, I examine the existing literature and suggest theoretical and procedural explanations for why SOC has been so elusive in humans. In particular, I discuss potential interactions with conditioned inhibition, whether SOC is rational, and propose critical parameters needed to obtain the effect. I conclude that SOC is a real but difficult phenomenon to obtain in humans, and suggest directions for future research.

In contrast to the large body of work demonstrating second-order conditioning (SOC) in non-human animals, the evidence for SOC in humans is scant. In this review, I examine the existing literature and suggest theoretical and procedural explanations for why SOC has been so elusive in humans. In particular, I discuss potential interactions with conditioned inhibition, whether SOC is rational, and propose critical parameters needed to obtain the effect. I conclude that SOC is a real but difficult phenomenon to obtain in humans, and suggest directions for future research. [ABSTRACT FROM AUTHOR]

In higher-order conditioning paradigms, such as sensory preconditioning or second-order conditioning, discrete (e.g., phasic) or contextual (e.g., static) stimuli can gain the ability to elicit learned responses despite never being directly paired with reinforcement. The purpose of this mini-review is to examine the neuroanatomical basis of high-order conditioning, by selectively reviewing research that has examined the role of the retrosplenial cortex (RSC) in sensory preconditioning and second-order conditioning. For both forms of higher-order conditioning, we first discuss the types of associations that may occur and then review findings from RSC lesion/inactivation experiments. These experiments demonstrate a role for the RSC in sensory preconditioning, suggesting that this cortical region might contribute to higher-order conditioning via the encoding of neutral stimulus-stimulus associations. In addition, we address knowledge gaps, avenues for future research, and consider the contribution of the RSC to higher-order conditioning in relation to related brain structures.

The feature negative discrimination (A+/AX−) can result in X gaining excitatory properties (second-order conditioning, SOC) or in X gaining inhibitory properties (conditioned inhibition, CI), a challenging finding for most current associative learning theories. Research on the variables that modulate which of these phenomena would occur is scarce but has clearly identified the trial number as an important variable. In the set of experiments presented here, the effect of trial number was assessed in a magazine training task with rats as a function of both the conditioning sessions and the number of A+ and AX− trials per session, holding constant the total number of trials per session. The results indicated that SOC is most likely to be found at the beginning of training when there are many A+ and few AX− trials, and CI (as assessed by a retardation test) is most likely to be found at the end of training when there are few A+ and many AX− trials. Both phenomena were also found at different moments of training when the number of A+ trials was equal to the number of AX− trials. These results cannot be predicted by acquisition-focused associative models but can be predicted by theories that distinguish between learning and performance.

In higher-order conditioning paradigms, such as sensory preconditioning or second-order conditioning, discrete (e.g., phasic) or contextual (e.g., static) stimuli can gain the ability to elicit learned responses despite never being directly paired with reinforcement. The purpose of this mini-review is to examine the neuroanatomical basis of high-order conditioning, by selectively reviewing research that has examined the role of the retrosplenial cortex (RSC) in sensory preconditioning and second-order conditioning. For both forms of higher-order conditioning, we first discuss the types of associations that may occur and then review findings from RSC lesion/inactivation experiments. These experiments demonstrate a role for the RSC in sensory preconditioning, suggesting that this cortical region might contribute to higher-order conditioning via the encoding of neutral stimulus-stimulus associations. In addition, we address knowledge gaps, avenues for future research, and consider the contribution of the RSC to higher-order conditioning in relation to related brain structures. [ABSTRACT FROM AUTHOR]

The feature negative discrimination (A+/AX −) can result in X gaining excitatory properties (second-order conditioning, SOC) or in X gaining inhibitory properties (conditioned inhibition, CI), a challenging finding for most current associative learning theories. Research on the variables that modulate which of these phenomena would occur is scarce but has clearly identified the trial number as an important variable. In the set of experiments presented here, the effect of trial number was assessed in a magazine training task with rats as a function of both the conditioning sessions and the number of A+ and AX − trials per session, holding constant the total number of trials per session. The results indicated that SOC is most likely to be found at the beginning of training when there are many A+ and few AX − trials, and CI (as assessed by a retardation test) is most likely to be found at the end of training when there are few A+ and many AX − trials. Both phenomena were also found at different moments of training when the number of A+ trials was equal to the number of AX − trials. These results cannot be predicted by acquisition-focused associative models but can be predicted by theories that distinguish between learning and performance. [ABSTRACT FROM AUTHOR]

Despite the controlled testing conditions that are typical of captive environments, many evaluations of animal cognition fail to ensure that all tested individuals participate. This is even more evident under wild conditions, as animals are not restricted in their movement or social interactions and have other activities available. In this study, we aimed to understand variation in cognitive task participation in wild chacma baboons, Papio ursinus. We quantified individual differences in the latency and likelihood to approach and explore two types of stimuli for two cognitive tests: a set of coloured paper bags (in an associative learning test) and a blue cardboard square (in a second-order conditioning test). We evaluated whether participation in each task was predicted by individuals' phenotypic traits/states, as well as by two additional aspects of their behaviour: (1) the availability of competing activities at the time of testing and (2) their propensity to exploit social information. We found consistent results for both types of stimuli regarding the effect of age: juveniles were more likely to contact the stimuli and explore them for longer. Similarly, for both tasks, individuals involved in an activity at the time of testing were less likely to contact the stimuli and had a lower exploration time. Finally, juveniles and females with a high propensity to use social information (i.e. scrounge) were more likely, and had shorter latencies, to contact the paper bags. Our findings not only highlight the potential bias cognitive studies conducted in the wild can have, but also some of the individual attributes and external factors that determine task participation. • Cognitive testing requires animals to engage with tasks, but not all do. • Phenotypic traits/states and current behaviour may affect participation. • We tested participation by wild chacma baboons in two cognitive tasks. • Age, competing activities and social information use determined participation. • Participation rates in cognitive studies should be addressed to avoid sampling bias. [ABSTRACT FROM AUTHOR]

Prével and colleagues reported excitatory learning with a backward conditioned stimulus (CS) in a conditioned reinforcement preparation. Their results add to existing evidence of backward CSs sometimes being excitatory and were viewed as challenging the view that learning is driven by prediction error reduction, which assumes that only predictive (i.e., forward) relationships are learned. The results instead were consistent with the assumptions of both Miller's Temporal Coding Hypothesis and Wagner's Sometimes Opponent Processes (SOP) model. The present experiment extended the conditioned reinforcement preparation developed by Prével et al. to a backward second-order conditioning preparation, with the aim of discriminating between these two accounts. We tested whether a second-order CS can serve as an effective conditioned reinforcer, even when the first-order CS with which it was paired is a backward CS that elicits no responding. Evidence of conditioned reinforcement was found, despite no conditioned response (CR) being elicited by the first-order backward CS. The evidence of second-order conditioning in the absence of excitatory conditioning to the first-order CS is interpreted as a challenge to SOP. In contrast, the present results are consistent with the Temporal Coding Hypothesis and constitute a conceptual replication in humans of previous reports of excitatory second-order conditioning in rodents with a backward CS. The proposal is made that learning is driven by "discrepancy" with prior experience as opposed to " prediction error." [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]

Background: Associative learning undergirds the development of addiction, such that drug-related cues serve as conditioned stimuli to elicit drug-seeking responses. Plausibly, among opioid misusing chronic pain patients, pain-related information may serve as a conditioned stimulus to magnify opioid cue-elicited autonomic and craving responses through a process of second-order conditioning.Methods: We utilized a novel psychophysiological probe of pain-opioid conditioned associations, the Cue-Primed Reactivity (CPR) task. In this task, participants were presented with images as primes (200 ms) and cues (6000 ms) in pairs organized in four task blocks: "control-opioid," "pain-opioid," "control-pain," and "opioid-pain." Opioid-treated chronic pain patients (N = 30) recruited from an Army base in the Western United States were classified as opioid misusers (n = 17) or non-misusers (n = 13) via a validated cutpoint on the Prescription Drug Use Questionnaire (PDUQ; Compton et al., 2008). Opioid misuse status was examined as a predictor of HRV, craving, and mood responses on the CPR task.Results: HRV increased to a greater extent during the pain-opioid block compared to the control-opioid block for non-misusers compared to misusers (p = .003, η2partial = 0.27). In contrast, craving increased to a greater extent from baseline to the pain-opioid block for misusers than for non-misusers (p = .03, η2partial = .16).Conclusions: Findings suggest that opioid-treated chronic pain patients exhibit Pavlovian conditioned responses to opioid cues strengthened by an associative learning process of second-order conditioning when primed by pain-related images. This pain-opioid contingency appears to become disrupted among individuals who engage in opioid misuse, such that opioid-related stimuli elicit motivational responses irrespective of pain-related contextual stimuli. [ABSTRACT FROM AUTHOR]

Second-order conditioning (SOC; i.e., conditioned responding to S2 as a result of S1-US pairings followed by S2-S1 pairings) is generally explained by either a direct S2→US association or by an associative chain (i.e., S2→S1→US). Previous research found that differences in responses to S2 after S1 was extinguished often depended on the nature of the S2-S1 pairings (i.e., sequential or simultaneous). In two experiments with human participants, we examined the possibility that such differences result from S1 evoking S2 during extinction of S1 following simultaneous but not sequential S2-S1 pairings. This evocation of S2 by S1 following simultaneous pairings may have paired the evoked representation of S2 with absence of the outcome, thereby facilitating mediated extinction of S2. Using sequential S2-S1 pairings, both Experiments 1 and 2 failed to support this account of how extinction of S1 reduced responding to S2. Experiment 1 found that extinguishing S1 reduced responding to S2, while extinguishing S2 had little effect on responses to S1, although forward evocation of S1 during extinction of S2 paired the evoked representation of S1 with absence of the outcome. In Experiment 2, evocation of S2 during S1 nonreinforced trials was prevented because S2-S1 pairings followed (rather than proceeded) S1-alone exposures. Nevertheless, responding to S2 at test mimicked S1 responding. Responding to S2 was high in the context in which S1 had been reinforced and low in the context in which S1 had been nonreinforced. Collectively, these experiments provide additional support for the associative-chain account of SOC. [ABSTRACT FROM AUTHOR]

Vicarious fear learning refers to the acquisition of fear via observation of the fearful responses of others. The present study aims to extend current knowledge by exploring whether second-order vicarious fear learning can be demonstrated in children. That is, whether vicariously learnt fear responses for one stimulus can be elicited in a second stimulus associated with that initial stimulus. Results demonstrated that children's (5–11 years) fear responses for marsupials and caterpillars increased when they were seen with fearful faces compared to no faces. Additionally, the results indicated a second-order effect in which fear-related learning occurred for other animals seen together with the fear-paired animal, even though the animals were never observed with fearful faces themselves. Overall, the findings indicate that for children in this age group vicariously learnt fear-related responses for one stimulus can subsequently be observed for a second stimulus without it being experienced in a fear-related vicarious learning event. These findings may help to explain why some individuals do not recall involvement of a traumatic learning episode in the development of their fear of a specific stimulus. [ABSTRACT FROM AUTHOR]

Sign-tracking rats show heightened sensitivity to food- and drug-associated cues, which serve as strong incentives for driving reward seeking. We hypothesized that this enhanced incentive drive is accompanied by an inflexibility when incentive value changes. To examine this we tested rats in Pavlovian outcome devaluation or second-order conditioning prior to the assessment of sign-tracking tendency. To assess behavioral flexibility we trained rats to associate a light with a food outcome. After the food was devalued by pairing with illness, we measured conditioned responding to the light during an outcome devaluation probe test. The level of conditioned responding during outcome devaluation probe test correlated with the rats’ subsequent tracking tendency, with sign-tracking rats failing to suppress conditioned responding to the light after outcome devaluation. To assess Pavlovian incentive learning, we trained rats on first-order (CS+, CS-) and second-order (SOCS+, SOCS-) discriminations. After second-order conditioning, we measured conditioned responding to the second-order cues during a probe test. Second-order conditioning was observed in all rats regardless of tracking tendency. The behavioral inflexibility of sign-trackers has potential relevance for understanding individual variation in vulnerability to drug addiction.

Sensory preconditioned and second-order conditioned responding are each well-documented. The former occurs in subjects (typically rats) exposed to pairings of two relatively neutral stimuli, S2 and S1, and then to pairings of S1 and a motivationally significant event [an unconditioned stimulus (US)]; the latter occurs when the order of these experiences is reversed with rats being exposed to S1-US pairings and then to S2-S1 pairings. In both cases, rats respond when tested with S2 in a manner appropriate to the affective nature of the US, e.g., approach when the US is appetitive and withdrawal when it is aversive. This paper reviews the neural substrates of sensory preconditioning and second-order conditioning. It identifies commonalities and differences in the substrates of these so-called higher-order conditioning protocols and discusses these commonalities/differences in relation to what is learned. In so doing, the review highlights ways in which these types of conditioning enhance our understanding of how the brain encodes and retrieves different types of information to generate appropriate behavior. • This review examines the neural systems involved in the two types of higher-order conditioning, sensory preconditioning and second-order conditioning. • It brings together studies that have focused on different motivational systems (appetitive and aversive) and used stimuli from a variety of sensory modalities (e.g., flavors, contexts, auditory and visual cues). In doing so, it advances our understanding of: 1) the manner in which motivational states alter processing of simple sensory information; 2) how the brain integrates sensory and motivational information; and 3) the mechanisms by which a network of sensory/motivational stimuli expands to include new information. • The review ultimately provides a set of principled statements regarding these aspects of information processing. The statements highlight the importance of higher-order conditioning protocols when trying to understand complex behaviors in simple (laboratory) environments and simple behaviors in complex (everyday) environments. [ABSTRACT FROM AUTHOR]

Background: Cocaine use is often associated with diminished cognitive function, persisting even after abstinence from the drug. Likely targets for these changes are the core and shell of the nucleus accumbens (NAc), which are critical for mediating the rewarding aspects of drugs of abuse as well as supporting associative learning. To understand this deficit, we recorded neural activity in the NAc of rats with a history of cocaine self-administration or control subjects while they learned Pavlovian first- and second-order associations. Methods: Rats were trained for 2 weeks to self-administer intravenous cocaine or water. Later, rats learned a first-order Pavlovian discrimination where a conditioned stimulus (CS)+ predicted food, and a control (CS−) did not. Rats then learned a second-order association where, absent any food reinforcement, a novel cued (SOC+) predicted the CS+ and another (SOC−) predicted the CS−. Electrophysiological recordings were taken during performance of these tasks in the NAc core and shell. Results: Both control subjects and cocaine-experienced rats learned the first-order association, but only control subjects learned the second-order association. Neural recordings indicated that core and shell neurons encoded task-relevant information that correlated with behavioral performance, whereas this type of encoding was abolished in cocaine-experienced rats. Conclusions: The NAc core and shell perform complementary roles in supporting normal associative learning, functions that are impaired after cocaine experience. This impoverished encoding of motivational behavior, even after abstinence from the drug, might provide a key mechanism to understand why addiction remains a chronically relapsing disorder despite repeated attempts at sobriety. [ABSTRACT FROM AUTHOR]

In standard (first-order) Pavlovian conditioning protocols, pairings of an initially neutral conditioned stimulus (CS) and a biologically significant unconditioned stimulus (US) result in the formation of a CS-US association. The strength of this association is theoretically regulated by prediction error: specifically, the difference between the total level of conditioning supported by the US and the degree to which it is predicted by all stimuli present (i.e., a common error term). In higher-order conditioning protocols (e.g., sensory preconditioning and second-order conditioning), a Pavlovian CS is used to condition responses to other stimuli with which it is paired. At present, it is unknown whether error-correction processes regulate associative learning in higher-order conditioning and, if so, whether these processes are the same as those that regulate formation of a CS-US association in first-order conditioning. Here we review studies that have provided findings relevant to this question: specifically, studies that have examined blocking and/or inhibitory learning in sensory preconditioning and second-order conditioning. These studies show that: (1) animals can form inhibitory associations between relatively neutral sensory stimuli; (2) the learning that occurs in sensory preconditioning and second-order conditioning can be blocked; and, finally, (3) a first-order CS can block conditioning to a second-order CS, and vice versa. The findings are taken to imply that a common error term regulates associative learning in higher-order conditioning, just as it regulates associative learning in first-order conditioning. They are discussed with respect to the nature of the error signal that underlies conditioning and future work that is needed to advance our understanding of the rules that govern different types of learning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Todd and Holmes.)

Prior research has found that when subjects independently acquire 2 associations with a common element (e.g., S1-S2 and S2-US), each with its own temporal relationship, they behave as if the 2 unique cues (i.e., S1 and US) have a known temporal relationship despite their never having been paired. This is interpreted as indicative of temporal integration of the memories acquired during Phase 1 and Phase 2 of training based on the element common to both experiences (i.e., S2). There are 2 times at which such integration of independent temporal relationships could plausibly occur: at the time of acquisition of the second relationship or at the time of testing. Three lick-suppression experiments with rats were performed to determine when integration occurs. This question of the moment of temporal integration was assessed by extinguishing the mediating element (S2) between learning of the second temporal relationship and testing of SI. Experiment 1 (using sensory preconditioning) and Experiment 2 (using second-order conditioning) found that this manipulation interfered with behavioral control by SI, suggesting that temporal integration occurred at the time of testing. Experiment 3 used spontaneous recovery, a hallmark phenomenon of extinction, to confirm that the S2-alone presentations in Experiments 1 and 2 attenuated integration as a result of extinction of S2. Implications for the temporal coding hypothesis (e.g., Savastano & Miller, 1998) are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of ‘this effect of prenatal ethanol on the sensitivity to ethanol’s reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol’s aversive consequences. The present study assessed ethanol-induced second-order conditioned place preference (CPP) and aversion and ethanol-induced conditioned taste aversion (CTA) in infant rats prenatally exposed to ethanol (2.0g/kg) or vehicle (water) or left untreated. The involvement of the κ opioid receptor system in ethanol-induced CTA was also explored. When place conditioning occurred during the ascending limb of the blood–ethanol curve (Experiment 1), the pups exposed to ethanol in utero exhibited greater CPP than untreated controls, with a shift to the right of the dose–response curve. Conditioning during a later phase of intoxication (30–45min post-administration; Experiment 2) resulted in place aversion in control pups exposed to vehicle during late gestation but not in pups that were exposed to ethanol in utero. Ethanol induced a reliable and similar CTA (Experiment 3) in the pups treated with vehicle or ethanol during gestation, and CTA was insensitive to κ antagonism. These results suggest that brief exposure to a moderate ethanol dose during late gestation promotes ethanol-mediated reinforcement and alters the expression of conditioned aversion by ethanol. This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance. [Copyright &y& Elsevier]