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This study examined the effect of danger on consolidation of neutral information in two regions of the rat (male and female) medial temporal lobe: the perirhinal cortex (PRh) and basolateral amygdala complex (BLA). The neutral information was the association that forms between an auditory stimulus and a visual stimulus (labeled S2 and S1) across their pairings in sensory preconditioning. We show that, when the sensory preconditioning session is followed by a shocked context exposure, the danger shifts consolidation of the S2-S1 association from the PRh to the BLA; and does so by interacting with processes involved in encoding of the S2-S1 pairings. Specifically, we show that the initial S2-S1 pairing in sensory preconditioning is encoded in the BLA and not the PRh; whereas the later S2-S1 pairings are encoded in the PRh and not the BLA. When the sensory preconditioning session is followed by a context alone exposure, the BLA-dependent trace of the early S2-S1 pairings decays and the PRhdependent trace of the later S2-S1 pairings is consolidated in memory. However, when the sensory preconditioning session is followed by a shocked context exposure, the PRh-dependent trace of the later S2-S1 pairings is suppressed and the BLAdependent trace of the initial S2-S1 pairing is consolidated in memory. These findings are discussed with respect to mutually inhibitory interactions between the PRh and BLA, and the way that these regions support memory in other protocols, including recognition memory in people. [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.

We report findings from two sensory preconditioning experiments in which rats consumed two flavoured solutions, each with two gustatory components (AX and BY), composed of sweet, bitter, salt, and acid elements. After this pre-exposure, rats were conditioned to X by pairing with lithium chloride. Standard sensory preconditioning was observed: Consumption of flavour A was less than that of B. We found that sensory preconditioning was maintained when X was added to A and B. Both experiments included one group of rats with lesions of the perirhinal cortex, which did not influence sensory preconditioning. We discuss our findings in the light of other sensory preconditioning procedures that involve the perirhinal cortex and conclude that differences in experimental variables invoke different mechanisms of sensory preconditioning, which vary in their requirement of the perirhinal cortex. [ABSTRACT FROM AUTHOR]

Learning and memory storage is a complex process that has proven challenging to tackle. It is likely that, in nature, the instructive value of reinforcing experiences is acquired rather than innate. The association between seemingly neutral stimuli increases the gamut of possibilities to create meaningful associations and the predictive power of moment-by-moment experiences. Here, we report physiological and behavioral evidence of olfactory unimodal sensory preconditioning in fruit flies. We show that the presentation of a pair of odors (S1 and S2) before one of them (S1) is associated with electric shocks elicits a conditional response not only to the trained odor (S1) but to the odor previously paired with it (S2). This occurs even if the S2 odor was never presented in contiguity with the aversive stimulus. In addition, we show that inhibition of the small G protein Rac1, a known forgetting regulator, facilitates the association between S1/S2 odors. These results indicate that flies can infer value to olfactory stimuli based on the previous associative structure between odors, and that inhibition of Rac1 lengthens the time window of the olfactory ‘sensory buffer’, allowing the establishment of associations between odors presented in sequence.

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.

• Sensory and emotional memories can be integrated in two ways. First, when the two memories share common content, the retrieval of one memory may call to mind the other, thereby allowing the sensory stimuli encoded as part of memory 1 to elicit responses that are appropriate to the emotional content of memory 2 ("memory chaining" at choice points). Second, as new emotional memories are encoded, past sensory memories can be activated and integrated with the emotional memory content ("online" integration), essentially resulting in formation of a false memory (or false memory content). • Here, we review studies of sensory preconditioning that have examined how sensory and emotional memories are integrated in the brain. We find that the two forms of integration are not mutually exclusive. That is, rather than the sensory and emotional memories that form in a preconditioning protocol being integrated in just one way or another, both forms of integration operate concurrently, with different protocols/parameters or training/test conditions increasing the likelihood of observing one form or another. • Chaining was observed in studies where the sensory stimuli presented in stage 1 of preconditioning were perceptually distinct, the emotional memory formed in stage 2 was very strong, and the context used for memory testing was highly familiar. • Online integration was observed in studies where the sensory stimuli presented in stage 1 of preconditioning were perceptually overlapping, the emotional memory formed in stage 2 was not over-trained, and the context used for memory testing was less familiar. Sensory preconditioning protocols can be used to assess how the brain integrates memories that share common features. In these protocols, animals are first exposed to pairings of two relatively innocuous stimuli, S2 and S1 (stage 1), and then to pairings of one of these stimuli, S1, with an event of motivational significance (stage 2). Following this training, test presentations of S2 elicit responses appropriate to the motivationally significant event, and these responses are taken to indicate formation of distinct S2-S1 and S1-event memories that are integrated in some way to generate that responding. This paper reviews studies of sensory preconditioning in rats, mice, rabbits and people to determine whether S2-S1 and S1-event memories are integrated through a chaining process at the time of their retrieval (i.e., test presentations of S2 trigger retrieval of S1, and thereby, responses appropriate to the event); or "online" at the time of memory formation (i.e., in stage 2, S1 activates a representation of S2 such that both stimuli associate with the motivationally significant event). It finds that the type of integration is determined by the manner in which stimuli are presented in preconditioning as well as their familiarity. When the stimuli in preconditioning are presented repeatedly and/or serially (i.e., one after the other), the S2-S1 and S1-event memories are chained at the time of retrieval/testing. In contrast, when the stimuli in preconditioning are relatively novel and/or presented simultaneously , the S2-S1 and S1-event memories are integrated online. These statements are related to prior claims regarding the circumstances that promote different types of memory integration and, more generally, mechanisms of information processing in the mammalian brain. [ABSTRACT FROM AUTHOR]

Neurobiological theories of memory posit that the neocortex is a storage site of declarative memories, a hallmark of which is the association of two arbitrary neutral stimuli. Early sensory cortices, once assumed uninvolved in memory storage, recently have been implicated in associations between neutral stimuli and reward or punishment. We asked whether links between neutral stimuli also could be formed in early visual or auditory cortices. Rats were presented with a tone paired with a light using a sensory preconditioning paradigm that enabled later evaluation of successful association. Subjects that acquired this association developed enhanced sound evoked potentials in their primary and secondary visual cortices. Laminar recordings localized this potential to cortical Layers 5 and 6. A similar pattern of activation was elicited by microstimulation of primary auditory cortex in the same subjects, consistent with a cortico-cortical substrate of association. Thus, early sensory cortex has the capability to form neutral stimulus associations. This plasticity may constitute a declarative memory trace between sensory cortices.

The opioid receptor antagonist naloxone enhances Pavlovian fear conditioning when rats are exposed to pairings of an initially neutral stimulus, such as a tone, and a painful foot shock unconditioned stimulus (US; so-called first-order fear conditioning; Pavlov, 1927). The present series of experiments examined whether naloxone has the same effect when conditioning occurs in the absence of US exposure. In Experiments 1a and 1b, rats were exposed to tone-shock pairings in stage 1 (one trial per day for 4 days) and then to pairings of an initially neutral light with the already conditioned tone in stage 2 (one trial per day for 4 days). Experiment 1a confirmed that this training results in second-order fear of the light; and Experiment 1b showed that naloxone enhances this conditioning: rats injected with naloxone in stage 2 froze more than vehicle-injected controls when tested with the light alone (drug-free). In Experiments 2a and 2b, rats were exposed to light-tone pairings in stage 1 (one trial per day for 4 days) and then to tone-shock pairings in stage 2 (one trial per day for 2 days). Experiment 2a confirmed that this training results in sensory preconditioned fear of the light; and Experiment 2b showed that naloxone enhances sensory preconditioning when injected prior to each of the light-tone pairings: rats injected with naloxone in stage 1 froze more than vehicle-injected controls when tested with the light alone (drug-free). These results were taken to mean that naloxone enhances fear conditioning independently of its effect on US processing; and more generally, that opioids regulate the error-correction mechanisms that underlie associative formation.

Memories of the past can guide humans to avoid harm. The logical consequence of this is if memories are changed, avoidance behavior should be affected. More than 80 years of false memory research has shown that people’s memory can be re-constructed or distorted by receiving suggestive false feedback. The current study examined whether manipulating people’s memories of learned associations would impact fear related behavior. A modified sensory preconditioning paradigm of fear learning was used. Critically, in a memory test after fear learning, participants received verbal false feedback to change their memory associations. After receiving the false feedback, participants’ beliefs and memories ratings for learned associations decreased significantly compared to the no feedback condition. Furthermore, in the false feedback condition, participants no longer showed avoidance to fear conditioned stimuli and relevant subjective fear ratings dropped significantly. Our results suggest that manipulating memory associations might minimize avoidance behavior in fear conditioning. These data also highlight the role of memory in higher order conditioning.

Higher-order conditioning involves learning causal links between multiple events, which then allows one to make novel inferences. For example, observing a correlation between two events (e.g., a neighbor wearing a particular sports jersey), later helps one make new predictions based on this knowledge (e.g., the neighbor’s wife’s favorite sports team). This type of learning is important because it allows one to benefit maximally from previous experiences and perform adaptively in complex environments where many things are ambiguous or uncertain. Two procedures in the lab are often used to probe this kind of learning, second-order conditioning (SOC) and sensory preconditioning (SPC). In second-order conditioning (SOC), we first teach subjects that there is a relationship between a stimulus and an outcome (e.g., a tone that predicts food). Then, an additional stimulus is taught to precede the predictive stimulus (e.g., a light leads to the food-predictive tone). In sensory preconditioning (SPC), this order of training is reversed. Specifically, the two neutral stimuli (i.e., light and tone) are first paired together and then the tone is paired separately with food. Interestingly, in both SPC and SOC, humans, rodents, and even insects, and other invertebrates will later predict that both the light and tone are likely to lead to food, even though they only experienced the tone directly paired with food. While these processes are procedurally similar, a wealth of research suggests they are associatively and neurobiologically distinct. However, midbrain dopamine, a neurotransmitter long thought to facilitate basic Pavlovian conditioning in a relatively simplistic manner, appears critical for both SOC and SPC. These findings suggest dopamine may contribute to learning in ways that transcend differences in associative and neurological structure. We discuss how research demonstrating that dopamine is critical to both SOC and SPC places it at the center of more complex forms of cognition (e.g., spatial navigation and causal reasoning). Further, we suggest that these more sophisticated learning procedures, coupled with recent advances in recording and manipulating dopamine neurons, represent a new path forward in understanding dopamine’s contribution to learning and cognition.

The opioid receptor antagonist naloxone enhances Pavlovian fear conditioning when rats are exposed to pairings of an initially neutral stimulus, such as a tone, and a painful foot shock unconditioned stimulus (US; so-called first-order fear conditioning; Pavlov, 1927). The present series of experiments examined whether naloxone has the same effect when conditioning occurs in the absence of US exposure. In Experiments 1a and 1b, rats were exposed to tone-shock pairings in stage 1 (one trial per day for 4 days) and then to pairings of an initially neutral light with the already conditioned tone in stage 2 (one trial per day for 4 days). Experiment 1a confirmed that this training results in second-order fear of the light; and Experiment 1b showed that naloxone enhances this conditioning: rats injected with naloxone in stage 2 froze more than vehicle-injected controls when tested with the light alone (drug-free). In Experiments 2a and 2b, rats were exposed to light-tone pairings in stage 1 (one trial per day for 4 days) and then to tone-shock pairings in stage 2 (one trial per day for 2 days). Experiment 2a confirmed that this training results in sensory preconditioned fear of the light; and Experiment 2b showed that naloxone enhances sensory preconditioning when injected prior to each of the light-tone pairings: rats injected with naloxone in stage 1 froze more than vehicle-injected controls when tested with the light alone (drug-free). These results were taken to mean that naloxone enhances fear conditioning independently of its effect on US processing; and more generally, that opioids regulate the error-correction mechanisms that underlie associative formation. [ABSTRACT FROM AUTHOR]

Memories of the past can guide humans to avoid harm. The logical consequence of this is if memories are changed, avoidance behavior should be affected. More than 80 years of false memory research has shown that people's memory can be re-constructed or distorted by receiving suggestive false feedback. The current study examined whether manipulating people's memories of learned associations would impact fear related behavior. A modified sensory preconditioning paradigm of fear learning was used. Critically, in a memory test after fear learning, participants received verbal false feedback to change their memory associations. After receiving the false feedback, participants' beliefs and memories ratings for learned associations decreased significantly compared to the no feedback condition. Furthermore, in the false feedback condition, participants no longer showed avoidance to fear conditioned stimuli and relevant subjective fear ratings dropped significantly. Our results suggest that manipulating memory associations might minimize avoidance behavior in fear conditioning. These data also highlight the role of memory in higher order conditioning. [ABSTRACT FROM AUTHOR]

Higher-order conditioning involves learning causal links between multiple events, which then allows one to make novel inferences. For example, observing a correlation between two events (e.g., a neighbor wearing a particular sports jersey), later helps one make new predictions based on this knowledge (e.g., the neighbor's wife's favorite sports team). This type of learning is important because it allows one to benefit maximally from previous experiences and perform adaptively in complex environments where many things are ambiguous or uncertain. Two procedures in the lab are often used to probe this kind of learning, second-order conditioning (SOC) and sensory preconditioning (SPC). In second-order conditioning (SOC), we first teach subjects that there is a relationship between a stimulus and an outcome (e.g., a tone that predicts food). Then, an additional stimulus is taught to precede the predictive stimulus (e.g., a light leads to the food-predictive tone). In sensory preconditioning (SPC), this order of training is reversed. Specifically, the two neutral stimuli (i.e., light and tone) are first paired together and then the tone is paired separately with food. Interestingly, in both SPC and SOC, humans, rodents, and even insects, and other invertebrates will later predict that both the light and tone are likely to lead to food, even though they only experienced the tone directly paired with food. While these processes are procedurally similar, a wealth of research suggests they are associatively and neurobiologically distinct. However, midbrain dopamine, a neurotransmitter long thought to facilitate basic Pavlovian conditioning in a relatively simplistic manner, appears critical for both SOC and SPC. These findings suggest dopamine may contribute to learning in ways that transcend differences in associative and neurological structure. We discuss how research demonstrating that dopamine is critical to both SOC and SPC places it at the center of more complex forms of cognition (e.g., spatial navigation and causal reasoning). Further, we suggest that these more sophisticated learning procedures, coupled with recent advances in recording and manipulating dopamine neurons, represent a new path forward in understanding dopamine's contribution to learning and cognition. [ABSTRACT FROM AUTHOR]

Emotional experiences can profoundly impact our conceptual model of the world, modifying how we represent and remember a host of information even indirectly associated with that experienced in the past. Yet, how a new emotional experience infiltrates and spreads across pre-existing semantic knowledge structures (e.g., categories) is unknown. We used a modified aversive sensory preconditioning paradigm in fMRI (n = 35) to investigate whether threat memories integrate with a pre-established category to alter the representation of the entire category. We observed selective but transient changes in the representation of conceptually related items in the amygdala, medial prefrontal cortex, and occipitotemporal cortex following threat conditioning to a simple cue (geometric shape) pre-associated with a different, but related, set of category exemplars. These representational changes persisted beyond 24 h in the hippocampus and perirhinal cortex. Reactivation of the semantic category during threat conditioning, combined with activation of the hippocampus or medial prefrontal cortex, was predictive of subsequent amygdala reactivity toward novel category members at test. This provides evidence for online integration of emotional experiences into semantic categories, which then promotes threat generalization. Behaviorally, threat conditioning by proxy selectively and retroactively enhanced recognition memory and increased the perceived typicality of the semantic category indirectly associated with threat. These findings detail a complex route through which new emotional learning generalizes by modifying semantic structures built up over time and stored in memory as conceptual knowledge. • Mechanisms of indirect threat learning are revealed by MVPA of fMRI • Emotional memory integration promotes generalization across semantic categories • Amygdala and medial prefrontal cortex reinstate indirect threat memory • Durable threat representation changes found in hippocampus and perirhinal cortex How do new emotional experiences integrate with prior knowledge? Using sensory preconditioning to produce "threat learning by proxy," Cooper et al. show that threat memories integrate with and generalize across categories. The amygdala and medial prefrontal cortex show transient generalization, whereas the hippocampus and perirhinal cortex are more durable. [ABSTRACT FROM AUTHOR]

The ability to form associations between different stimuli in the environment to guide adaptive behavior is a central element of learning processes, from perceptual learning in humans to Pavlovian conditioning in animals. Like so, classical conditioning paradigms that test direct associations between low salience sensory stimuli and high salience motivational reinforcers are extremely informative. However, a large part of everyday learning cannot be solely explained by direct conditioning mechanisms – this includes to a great extent associations between individual sensory stimuli, carrying low or null immediate motivational value. This type of associative learning is often described as incidental learning and can be captured in animal models through sensory preconditioning procedures. Here we summarize the evolution of research on incidental and mediated learning, overview the brain systems involved and describe evidence for the role of cannabinoid receptors in such higher-order learning tasks. This evidence favors a number of contemporary hypotheses concerning the participation of the endocannabinoid system in psychosis and psychotic experiences and provides a conceptual framework for understanding how the use of cannabinoid drugs can lead to altered perceptive states.

The ability to form associations between different stimuli in the environment to guide adaptive behavior is a central element of learning processes, from perceptual learning in humans to Pavlovian conditioning in animals. Like so, classical conditioning paradigms that test direct associations between low salience sensory stimuli and high salience motivational reinforcers are extremely informative. However, a large part of everyday learning cannot be solely explained by direct conditioning mechanisms – this includes to a great extent associations between individual sensory stimuli, carrying low or null immediate motivational value. This type of associative learning is often described as incidental learning and can be captured in animal models through sensory preconditioning procedures. Here we summarize the evolution of research on incidental and mediated learning, overview the brain systems involved and describe evidence for the role of cannabinoid receptors in such higher-order learning tasks. This evidence favors a number of contemporary hypotheses concerning the participation of the endocannabinoid system in psychosis and psychotic experiences and provides a conceptual framework for understanding how the use of cannabinoid drugs can lead to altered perceptive states. [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.

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 orbitofrontal cortex (OFC) is necessary for inferring value in tests of model-based reasoning, including in sensory preconditioning. This involvement could be accounted for by representation of value or by representation of broader associative structure. We recently reported neural correlates of such broader associative structure in OFC during the initial phase of sensory preconditioning (Sadacca et al., 2018). Here, we used optogenetic inhibition of OFC to test whether these correlates might be necessary for value inference during later probe testing. We found that inhibition of OFC during cue-cue learning abolished value inference during the probe test, inference subsequently shown in control rats to be sensitive to devaluation of the expected reward. These results demonstrate that OFC must be online during cue-cue learning, consistent with the argument that the correlates previously observed are not simply downstream readouts of sensory processing and instead contribute to building the associative model supporting later behavior.

When direct experience is unavailable, animals and humans can imagine or infer the future to guide decisions. Behavior based on direct experience versus inference may recruit partially distinct brain circuits. In rodents, the orbitofrontal cortex (OFC) contains neural signatures of inferred outcomes, and OFC is necessary for behavior that requires inference but not for responding driven by direct experience. In humans, OFC activity is also correlated with inferred outcomes, but it is unclear whether OFC activity is required for inference-based behavior. To test this, we used noninvasive network-based continuous theta burst stimulation (cTBS) in human subjects (male and female) to target lateral OFC networks in the context of a sensory preconditioning task that was designed to isolate inference-based behavior from responding that can be based on direct experience alone. We show that, relative to sham, cTBS targeting this network impairs reward-related behavior in conditions in which outcome expectations have to be mentally inferred. In contrast, OFC-targeted stimulation does not impair behavior that can be based on previously experienced stimulus-outcome associations. These findings suggest that activity in the targeted OFC network supports decision-making when outcomes have to be mentally simulated, providing converging cross-species evidence for a critical role of OFC in model-based but not model-free control of behavior. [ABSTRACT FROM AUTHOR]

In two experiments, rats received sensory preconditioning treatment in which an auditory conditioned stimulus (CS) X was followed by visual CS A in Phase 1, and CS A was followed by an appetitive US (sucrose) in Phase 2. Rats also received presentations of auditory CS Y unpaired with other events. At test, rats looked for sucrose more following CS X than following CS Y on non-reinforced probe test trials only if the light bulb on which CS A had been presented during training was removed from the chamber at the time of testing. With the light bulb present (but unlit), rats showed nodifference in amount of nose poking between CS X and CS Y. These results suggest that rats distinguish between the explicit absence of events and lack of information

The integration of spatial maps in pigeons was investigated using a spatial analog to sensory preconditioning. The pigeons were tested in an open-field arena in which they had to locate hidden food among a 4x4 grid of gravel-filled cups. In phase 1, the pigeons were exposed to a consistent spatial relationship (vector) between landmark L (a red L-shaped block of wood), landmark T (a blue T-shaped block of wood) and the hidden food goal. In phase 2, the pigeons were then exposed to landmark T with a different spatial vector to the hidden food goal. Following phase 2, pigeons were tested with trials on which they were presented with only landmark L to examine the potential integration of the phase 1 and 2 vectors via their shared common elements. When these test trials were preceded by phase I and phase 2 reminder trials, pigeons searched for the goal most often at a location consistent with their integration of the L --> T phase 1 and T --> phase 2 goal vectors. This result indicates that integration of spatial vectors acquired during phases I and 2 allowed the pigeons to compute a novel L --> goal vector. This suggests that spatial maps may be enlarged by successively integrating additional spatial information through the linkage of common elements.

How does a stimulus never associated with danger become frightening? The present study addressed this question using a sensory preconditioning task with rats. In this task, rats integrate a sound-light memory formed in stage 1 with a light-danger memory formed in stage 2, as they show fear when tested with the sound in stage 3. Here we show that this integration occurs ‘online’ during stage 2: when activity in the region that consolidated the sound-light memory (perirhinal cortex) was inhibited during formation of the light-danger memory, rats no longer showed fear when tested with the sound but continued to fear the light. Thus, fear that accrues to a stimulus paired with danger simultaneously spreads to its past associates, thereby roping those associates into a fear memory network.

A conditioned response to a stimulus can be transferred to an associated stimulus, as seen in sensory preconditioning. In this research paper, we aimed to explore this phenomenon using a stimulus-response contingency learning paradigm using voluntary actions as responses. We conducted two preregistered experiments that explored whether a learned response can be indirectly activated by a stimulus (S1) that was never directly paired with the response itself. Importantly, S1 was previously associated with another stimulus (S2) that was then directly and contingently paired with a response (S2-R contingency). In Experiment 1a, an indirect activation of acquired stimulus-response contingencies was present for audiovisual stimulus pairs wherein the stimulus association resembled a vocabulary learning setup. This result was replicated in Experiment 1b. Additionally, we found that the effect is moderated by having conscious awareness of the S1-S2 association and the S2-R contingency. By demonstrating indirect activation effects for voluntary actions, our findings show that principles of Pavlovian conditioning like sensory preconditioning also apply to contingency learning of stimulus-response relations for operant behavior.

Highlights • We have examined the role of memory associations in a reinforced decision-making task. • False feedback can undermine participants' memory associations. • False feedback on memory associations reduces decision bias. Abstract Memories of past experiences can guide our decisions. Thus, if memories are undermined or distorted, decision making should be affected. Nevertheless, little empirical research has been done to examine the role of memory in reinforcement decision-making. We hypothesized that if memories guide choices in a conditioning decision-making task, then manipulating these memories would result in a change of decision preferences to gain reward. We manipulated participants' memories by providing false feedback that their memory associations were wrong before they made decisions that could lead them to win money. Participants' memory ratings decreased significantly after receiving false feedback. More importantly, we found that false feedback led participants' decision bias to disappear after their memory associations were undermined. Our results suggest that reinforcement decision-making can be altered by false feedback on memories. The results are discussed using memory mechanisms such as spreading activation theories. [ABSTRACT FROM AUTHOR]

Background: Generalizing from past experiences can be adaptive by allowing those experiences to guide behavior in new situations. Generalizing too much, however, can be maladaptive. For example, individuals with pathological anxiety are believed to overgeneralize emotional responses from past threats, broadening their scope of fears. Whether individuals with pathological anxiety overgeneralize in other situations remains unclear.Methods: The present study (N = 57) used a monetary sensory preconditioning paradigm with rewards and losses to address this question in individuals with obsessive-compulsive disorder (OCD) and social anxiety disorder (SAD), comparing them to healthy comparison subjects (HC). In all groups, we tested direct learning of associations between cues and reward vs. loss outcomes, as well as generalization of learning to novel choice options.Results: We found no differences between the three groups in the direct learning of stimuli with their outcomes: all subjects demonstrated intact stimulus-response learning by choosing rewarding options and avoiding negative ones. However, OCD subjects were less likely to generalize from rewards than either the SAD or HC groups, and this impairment was not found for losses. Additionally, greater deficits in reward generalization were correlated with severity of threat estimation, as measured by a subscale of the Obsessive Beliefs Questionnaire, both within OCD and across all groups.Conclusions: These findings suggest that a compromised ability to generalize from rewarding events may impede adaptive behavior in OCD and in those susceptible to high estimation of threat. [ABSTRACT FROM AUTHOR]

The retrosplenial cortex (RSC), which receives visuo-spatial sensory input and interacts with numerous hippocampal memory system structures, has a well-established role in contextual learning and memory. While it has been demonstrated that RSC function is necessary to learn to recognize a single environment that is directly paired with an aversive event, the role of the RSC in discriminating between two different contexts remains largely unknown. To address this, first order (Experiment 1) and higher order (Experiment 2) fear conditioning paradigms were conducted with sham and RSC-lesioned rats. In Experiment 1 rats were exposed to one context in which shock was delivered and to a second, distinct context without shock. Their ability to discriminate between the contexts was assessed during a re-exposure test. In a second experiment, a new cohort of RSC-lesioned rats was exposed to two contexts made distinct through visual, olfactory and auditory stimuli. In a subsequent conditioning phase, the salience of one of the auditory stimuli was paired to an aversive footshock while the other was not. Similar to Experiment 1, freezing behavior was analyzed upon re-exposure to the contexts in the absence of both the auditory cue and the footshock. The results revealed that RSC is not necessary for rats to use contextual information to successfully discriminate between two contexts under the relatively simple demands involved in this first order conditioning paradigm but that context discrimination is impaired when the processing of complex and/or ambiguous contextual stimuli is required to select appropriate behavioral responses. [ABSTRACT FROM AUTHOR]

The present study demonstrates the contribution of spatial contiguity in the formation of associations between two neutral stimuli. Using human participants, we used visual conditioned stimuli (CSs) in a sensory preconditioning design in which simultaneous CS2-CS1 pairings and CS4-CS3 pairings were interspersed during Phase 1, followed by sequential CS1-US+ (i.e., CS1-pleasant US) and CS3-US- − (i.e., CS3-unpleasant US) pairings during Phase 2. The conditioned response was a shift in the gaze of the participants to the location where the US+ (i.e., short video clip) appeared. Distances between CS2 and CS1 and between CS4 and CS3 were manipulated. Our results showed a greater response to CS2 when the Phase 1 stimuli were adjacent rather than separated by 100 pixels. Implications for the role of spatial contiguity in associative learning are discussed. [ABSTRACT FROM AUTHOR]

Sensory preconditioning (SPC) is a form of latent learning in which preexposure to co-occurring neutral stimuli (S1-S2) permits subsequent learning to be transferred from one stimulus (S1) to the other (S2). We examined whether human infants exhibit developmental transitions in the temporal parameters of SPC by manipulating the preexposure regimen. Infants received simultaneous or sequential preexposure to puppets S1 and S2 (Days 1-2); saw target actions modeled on S1 (Day 3); and were tested for deferred imitation with S2 (Day 4). Although 6-, 9-, and 12-month-olds associated the puppets, there was a shift in the effective regimen from simultaneous to sequential preexposure-similar to prior findings with rat pups (Experiment 1). Experiment 2 revealed that human infants potentially exhibit another transition in SPC at 15 and 18 months of age. We consider the roles of ontogenetic shifts in infants' ecological niche, selective attention, and unitization in developmental transitions in SPC. [ABSTRACT FROM AUTHOR]

Loss of function of the hippocampus or frontal cortex is associated with reduced performance on memory tasks, in which subjects are incidentally exposed to cues at specific places in the environment and are subsequently asked to recollect the location at which the cue was experienced. Here, we examined the roles of the rodent hippocampus and frontal cortex in cue-directed attention during encoding of memory for the location of a single incidentally experienced cue. During a spatial sensory preconditioning task, rats explored an elevated platform while an auditory cue was incidentally presented at one corner. The opposite corner acted as an unpaired control location. The rats demonstrated recollection of location by avoiding the paired corner after the auditory cue was in turn paired with shock. Damage to either the dorsal hippocampus or the frontal cortex impaired this memory ability. However, we also found that hippocampal lesions enhanced attention directed towards the cue during the encoding phase, while frontal cortical lesions reduced cue-directed attention. These results suggest that the deficit in spatial sensory preconditioning caused by frontal cortical damage may be mediated by inattention to the location of cues during the latent encoding phase, while deficits following hippocampal damage must be related to other mechanisms such as generation of neural plasticity.

is driven by aspects of outcome value. However, animals routinely make associations between contingent stimuli in the world, even if those associations hold no value to the organism. At the neural level, the nucleus accumbens (NAc) is known to encode associative information, but it is not known whether this encoding is specific for value-based information (consistent with reinforcement-based models) or if the NAc additionally plays a more general role in forming predictive associations, independent of outcome value. To test this, we employed a sensory preconditioning (SPC) task where rats initially (Preconditioning) received either contingent pairings of 2 neutral stimuli (e.g., tone [A] and light [X]; "Paired"), or random noncontingent presentations ("Unpaired"). After cue X was subsequently conditioned with food (First-Order Conditioning), the effect of preconditioning was assessed in Phase 3 (Test) by presentations of cue A alone. Electrophysiological recordings from the NAc core showed significant increases in phasic encoding for the stimuli in the Paired (but not Unpaired) condition as well as during test. Further, these effects were only seen in Paired rats that showed successful behavior during test (Good Learners), but not those who did not (Poor Learners) or Unpaired controls. These findings reveal a role for the NAc in the encoding of associative contingencies independent of value, and suggest that this structure also plays a more general role in forming associations necessary for predictive behavior. [ABSTRACT FROM AUTHOR]