Stimulus Preexposure Research Articles

A test of pre-exposure spacing and multiple context pre-exposure on the mechanisms of latent inhibition of dental fear: A study protocol

BackgroundLatent inhibition occurs when exposure to a stimulus prior its direct associative conditioning impairs learning. Results from naturalistic studies suggest that latent inhibition disrupts the learning of dental fear from aversive associative conditioning and thereby reduces the development of dental phobia. Although theory suggests latent inhibition occurs because pre-exposure changes the expected relevance and attention directed to the pre-exposed stimulus, evidence supporting these mechanisms in humans is limited. The aim of this study is to determine if two variables, pre-exposure session spacing and multiple context pre-exposure, potentiate the hypothesized mechanisms of expected relevance and attention and, in turn, increase latent inhibition of dental fear.MethodsIn a virtual reality simulation, child and adult community members (ages 6 to 35) will take part in pre-exposure and conditioning trials, followed by short- and long-term tests of learning. A 100ms puff of 60 psi air to a maxillary anterior tooth will serve as the unconditioned stimulus. Pre-exposure session spacing (no spacing vs. sessions spaced) and multiple context pre-exposure (single context vs. multiple contexts) will be between-subject factors. Stimulus type (pre-exposed to-be conditioned stimulus, a non-pre-exposed conditioned stimulus, and an unpaired control stimulus) and trial will serve as within-subject factors. Baseline pain sensitivity will also be measured as a potential moderator.DiscussionIt is hypothesized that spaced pre-exposure and pre-exposure in multiple contexts will increase the engagement of the mechanisms of expected relevance and attention and increase the latent inhibition of dental fear. It is expected that the findings will add to theory on fear learning and provide information to aid the design of future interventions that leverage latent inhibition to reduce dental phobia.

A study protocol testing pre-exposure dose and compound pre-exposure on the mechanisms of latent inhibition of dental fear

BackgroundDental stimuli can evoke fear after being paired - or conditioned - with aversive outcomes (e.g., pain). Pre-exposing the stimuli before conditioning can impair dental fear learning via a phenomenon known as latent inhibition. Theory suggests changes in expected relevance and attention are two mechanisms responsible for latent inhibition. In the proposed research, we test whether pre-exposure dose and degree of pre-exposure novelty potentiate changes in expected relevance and attention to a pre-exposed stimulus. We also assess if the manipulations alter latent inhibition and explore the possible moderating role of individual differences in pain sensitivity.MethodsParticipants will be healthy individuals across a wide range of ages (6 to 35 years), from two study sites. Participants will undergo pre-exposure and conditioning followed by both a short-term and long-term test of learning, all in a novel virtual reality environment. The unconditioned stimulus will be a brief pressurized puff of air to a maxillary anterior tooth. Pre-exposure dose (low vs. high) and pre-exposure novelty (element stimulus vs. compound stimuli) will be between-subject factors, with stimulus type (pre-exposed to-be conditioned stimulus, a non-pre-exposed conditioned stimulus, and an unpaired control stimulus) and trial as within-subject factors. Pain sensitivity will be measured through self-report and a cold pressor test. It is hypothesized that a larger dose of pre-exposure and compound pre-exposure will potentiate the engagement of the target mechanisms and thereby result in greater latent inhibition in the form of reduced fear learning. Further, it is hypothesized that larger effects will be observed in participants with greater baseline pain sensitivity.DiscussionThe proposed study will test whether pre-exposure dose and compound stimulus presentation change expected relevance and attention to the pre-exposed stimulus, and thereby enhance latent inhibition of dental fear. If found, the results will add to our theoretical understanding of the latent inhibition of dental fear and inform future interventions for dental phobia prevention.

Behavioral and electrophysiological evidence of different processes during a target identification task assessing perceptual learning.

This study aimed to test whether a target identification task involving same and different judgments to assess the ability to differentiate between similar pre-exposed stimuli-i.e., perceptual learning-could actually be assessing two different cognitive processes. Specifically, the hypothesis was that while "different" trials might be truly assessing the ability to differentiate between the pre-exposed stimuli, "same" trials might be assessing the ability to recognize one of these stimuli as the target. To test this hypothesis, accuracy on judgments as well as reaction times and event-related potentials for same/different trials were recorded after concurrent pre-exposure to similar stimuli. If same/different trials were assessing cognitive processes with different time courses, distinct outcomes for such trials would be expected at the behavioral and neural level. Results showed that participants were very accurate both in same and different judgments, indicating that they were perfectly able to differentiate between the stimuli after their concurrent presentations. However, larger P3 latencies and slower reaction times for different trials than for same trials were found. These results seem to support the idea that cognitive processes activated in same and different trials are different due to their distinct time courses. The importance of these findings for the theoretical approaches to perceptual learning is discussed.

Context specificity of latent inhibition in the snail Cornu aspersum

The present study was conducted to assess the context specificity of latent inhibition (LI) in the snail Cornu aspersum, using the appetitive Pavlovian Conditioning procedure of tentacle lowering. Snails experienced an odorous conditioned stimulus (CS) without any consequence before being conditioned with food. The conditioned stimulus preexposure occurred in the same context than the conditioning and the test context or in the different context. The study was performed in two replicas in which the photoperiod was defined by level of illumination and time of day (circadian replica) or was defined only by light (light replica). Both replicas showed that the CS preexposure in the same context as conditioning produced a delay in the acquisition of the conditioned response (CR). However, when the CS preexposure took place in a different context than the conditioning context, an equivalent level of CR as that observed in controls without preexposition to CS was shown. These results are congruent with context specificity of LI and they provide the first evidence of this phenomenon in terrestrial mollusks. Learning processes and theories involved in this phenomenon are also debated in the paper.

Supplemental Material for The Effects of Stimulus Pre-Exposure and Conditioning on Overt Visual Attention

Supplemental Material for The Effects of Stimulus Pre-Exposure and Conditioning on Overt Visual Attention

Latent inhibition in young children: A developmental effect?

Previous research by Kaniel & Lubow in 1986 found that young children (aged 4-5 years) exhibited poorer learning (latent inhibition) to preexposed stimuli than older children (aged 7-10 years). The aim of our research was to develop a computer-based, child-friendly study that would replicate and extend the work of Kaniel & Lubow in a way that ruled out other, attention-based explanations of their effect. One hundred and four children and 32 undergraduate students took part in our experiment. This consisted of a preexposure/study phase in which participants were asked to press computer keys in response to clipart pictures of animals and dinosaurs. Each animal or dinosaur picture was preceded by one of 2 "warning signals" that acted as the preexposed stimuli (to which no response was required). In the test phase that followed, the participants had to either press the spacebar or withhold their response to each preexposed stimulus and two novel stimuli. They learned which response was correct by trial and error using the feedback provided. The accuracy and reaction time (RT) of the responses during the test phase were analyzed and indicated that the youngest children showed significantly lower mean accuracy and longer mean response times to the preexposed stimuli than to stimuli they had not been preexposed to. In contrast, the older children showed no significant differences in their responses to preexposed and novel stimuli. These results are consistent with those found by Kaniel & Lubow and as such provide additional evidence for latent inhibition in young children. We discuss the implications for theories of perceptual learning in humans. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Age, sex and pre-exposure effects on acquisition and generalization of conditioned taste aversion in rats

The main aim of the present study was to assess the effect of sex and aging in two pre-exposure learning effects, latent inhibition (LI) and perceptual learning (PL), with a conditioned taste aversion paradigm. Young adult (90 days) and aged (more than 18 months) males and females received 8 pre-exposure trials either with stimulus AX (LI conditions) or BX (PL conditions). Then, all animals received a conditioning trial with AX and two test trials, one with AX and other with BX. The level of generalization between AX and BX was assessed by means of the absolute level of consumption of BX and by the difference in consumption between both stimuli. The results showed an attenuation of latent inhibition as well a stronger generalization of conditioned taste aversion in females when generalization is inferred from the BX consumption. A facilitation of conditioning for the aged animals was also found regardless of the pre-exposed stimulus. Pre-exposures to BX resulted in little generalization, but pre-exposures to AX resulted in a very similar consumption of both compounds, indicating a strong generalization between them. Overall, the study provided novel evidence about the effect of sex and aging on taste aversion, raising at the same time some relevant questions about perceptual learning and how such pre-exposure effect has been typically assessed.

Anterior thalamic nuclei, but not retrosplenial cortex, lesions abolish latent inhibition in rats.

The present study examined the effects of excitotoxic lesions in 2 closely related structures, the anterior thalamic nuclei and the retrosplenial cortex, on latent inhibition. Latent inhibition occurs when nonreinforced preexposure to a stimulus retards the subsequent acquisition of conditioned responding to that stimulus. Latent inhibition was assessed in a within-subject procedure with auditory stimuli and food reinforcement. As expected, sham-operated animals were slower to acquire conditioned responding to a stimulus that had previously been experienced without consequence, relative to a non-preexposed stimulus. This latent inhibition effect was absent in rats with excitotoxic lesions in the anterior thalamic nuclei, as these animals conditioned to both stimuli at equivalent rates. The retrosplenial lesions appeared to spare latent inhibition, as these animals displayed a robust stimulus preexposure effect. The demonstration here that anterior thalamic nuclei lesions abolish latent inhibition is consistent with emerging evidence of the importance of these thalamic nuclei for attentional control.

First sexual experiences determine the development of conditioned ejaculatory preference in male rats.

We have shown previously that male rats develop a conditioned ejaculatory preference (CEP) for females scented with a neutral odor like almond or lemon that is paired with the male's post-ejaculatory reward state during their first and subsequent early sexual experiences. However, preexposing males to the neutral odor alone prior to its pairing with sexual reward results in latent inhibition. Here, we examined the phenomenon of unconditioned stimulus (US) preexposure, in which male rats were preexposed to the ejaculatory reward state either one or five times with scented (ScF) versus unscented (UnScF) females prior to multiple ejaculatory trials with females in the opposite condition (e.g., ScF preexposure received 10 subsequent ejaculatory trials with UnScF, whereas UnScF preexposure received 10 subsequent ejaculatory trials with ScF). As before, mate and partner preference was evaluated in an open field where each male had access to two females, one ScF and the other UnScF. Males that underwent five trials of preexposure did not display a CEP for either female. Conversely, males preexposed once to a ScF, and later trained with UnScF developed a preference for the latter, whereas males preexposed once to the UnScF, and then trained with ScF did not show a preference for any of the females. Subsequent exposure to the odor cue alone revealed different patterns of brain activation in areas related to sexual behavior that depended on the animal's group membership. Altogether, these findings demonstrate the pivotal role of first sexual experiences in the establishment of future sexual partner preference in the male rat, and suggest an innate preference for estrous odors over neutral odors that can become conditioned subsequently as predictors of sexual reward.

The infralimbic cortex encodes inhibition irrespective of motivational significance.

Evidence indicates that the infralimbic cortex (IL) encodes and retrieves the inhibitory memory produced by fear extinction. Recently, we have shown that the IL is also involved in the inhibitory memory generated by stimulus pre-exposure that causes latent inhibition. These results are surprising because a stimulus undergoing fear extinction carries aversive motivational value, whereas a pre-exposed stimulus is neutral. The present experiments tested the hypothesis that the IL encodes inhibition irrespective of the motivational information about the stimulus. Using rats, we first confirmed that IL activity during stimulus pre-exposure is required for latent inhibition. Then, we found that pharmacological stimulation of the IL facilitated aversive extinction to a stimulus that had been trained and extinguished as an appetitive stimulus. This facilitation was stimulus specific and required appetitive extinction. The same facilitation was found when appetitive extinction was replaced with random presentations of the stimulus and an appetitive outcome. Together, these findings indicate that non-reinforced stimulus presentations establish an inhibitory memory that is reactivated and strengthened in the IL during subsequent aversive extinction. This is consistent with the view that the IL encodes inhibition irrespective of motivational value, suggesting that this brain region plays a general role in inhibitory learning.

The role of stimulus comparison in animal perceptual learning: Effects of a distractor placement.

Research on perceptual learning shows that the way stimuli are presented leads to different outcomes. The intermixed/blocked (I/B) effect is one of these outcomes, and different mechanisms have been proposed to explain it. In human research, it seems that comparison between stimuli is important, and the placement of a distractor between the pre-exposed stimuli interferes with the effect. Results from animal research are usually interpreted in different terms because the type of procedure normally used in animal perceptual learning does not favour comparison. In our experiments, we explore the possibility that a distractor placed between the to-be-discriminated stimuli may interfere with the perceptual learning process in rats. In Experiment 1, two flavoured solutions are presented in an I/B fashion, with a short time lapse between them to favour comparison, showing the typical I/B effect. In Experiment 2, we introduced a distractor in between the solutions, abolishing this effect. Experiment 3 further replicates this by comparing two intermixed groups with or without distractor. The results replicate the findings from human research, suggesting that comparison also plays an important role in animal perceptual learning.

Augmentation’s boundary conditions? Investigation of spatial contiguity, temporal contiguity, and target flavor familiarity

When a preconditioned flavor (A) is conditioned in compound with a novel target flavor (X), the aversion to the target X is increased; this enhanced aversion to X is called augmentation. In 6 experiments with rat subjects, we manipulated the spatial contiguity of cues during compound conditioning (AX+), the temporal contiguity of cues during compound conditioning (AX+), and the familiarity of the target. In all 6 studies, augmentation was recorded with spatially separated flavors. In Experiments 2–4, augmentation was not detected if the two flavors were temporally discontiguous, but augmentation still occurred if the cues were partially contiguous (i.e., the flavors co-occurred for 2 min of a 4-min exposure). Even though stimulus preexposure can often weaken subsequent conditioning, augmentation was observed following 1 or 4 preexposures to the target taste (Experiment 5A) or target odor (Experiment 5B). In sum, manipulations that should weaken, but not eliminate, the within-compound association formed during AX+ conditioning did not prevent augmentation, suggesting the robustness of the within-compound association when one of the elements is a preconditioned flavor.

Morphofunctional experience-dependent plasticity in the honeybee brain.

Repeated or prolonged exposure to an odorant without any positive or negative reinforcement produces experience-dependent plasticity, which results in habituation and latent inhibition. In the honeybee (Apis mellifera), it has been demonstrated that, even if the absolute neural representation of an odor in the primary olfactory center, the antennal lobe (AL), is not changed by repeated presentations, its relative representation with respect to unfamiliar stimuli is modified. In particular, the representation of a stimulus composed of a 50:50 mixture of a familiar and a novel odorant becomes more similar to that of the novel stimulus after repeated stimulus preexposure. In a calcium-imaging study, we found that the same functional effect develops following prolonged odor exposure. By analyzing the brains of the animals subjected to this procedure, we found that such functional changes are accompanied by morphological changes in the AL (i.e., a decrease in volume in specific glomeruli). The AL glomeruli that exhibited structural plasticity also modified their functional responses to the three stimuli (familiar odor, novel odor, binary mixture). We suggest a model in which rebalancing inhibition within the AL glomeruli may be sufficient to elicit structural and functional correlates of experience-dependent plasticity.

Stimulus preexposure speeds or slows subsequent acquisition of associative learning depending on learning test procedures and response measure.

Prior exposure to a conditioned stimulus (CS) typically results in latent inhibition-slower acquisition of associative learning about that stimulus in subsequent training. Here, we found that CS preexposure had different effects on the appetitive conditioning of rats with a sucrose unconditioned stimulus (US) depending on training test procedures, the similarity of preexposure and training procedures, and the choice of response measure. Preexposure to a visual or an auditory stimulus produced facilitation of acquisition of food-cup-directed responding when both of those cues were (separately) paired with sucrose delivery in the training test (Experiments 1 and 3). By contrast, the same preexposure procedure resulted in latent inhibition of food-cup learning if the second stimulus in the test phase was of the same modality as the preexposed stimulus (Experiment 2). In Experiment 3, latent inhibition was enhanced if both phases included a single CS or both phases included both auditory and visual CSs, compared to treatments in which only one CS was presented in one phase but two CSs were presented in the other phase. In Experiment 4, preexposure of an auditory cue slowed subsequent learning about it if the context was salient but enhanced learning if the context was of weaker salience. Finally, a measure of general activity revealed latent inhibition after preexposure in all conditions in all 4 experiments. We discuss the results within several classes of latent inhibition theories, none of which provides a comprehensive account.

The role of dopamine D2 receptors in the nucleus accumbens during taste-aversive learning and memory extinction after long-term sugar consumption

The nucleus accumbens (NAcc) is a forebrain region that may significantly contribute to the integration of taste and visceral signals during food consumption. Changes in dopamine release in the NAcc have been observed during consumption of a sweet taste and during compulsive consumption of dietary sugars, suggesting that NAcc dopaminergic transmission is strongly correlated with taste familiarity and the hedonic value content. NAcc core and shell nuclei are differentially involved during and after sugar exposure and, particularly, previous evidence suggests that dopamine D2 receptors could be related with the strength of the latent inhibition (LI) of conditioned taste aversion (CTA), which depends on the length of the taste stimulus pre-exposure. Thus, the objective of this work was to evaluate, after long-term exposure to sugar, the function of dopaminergic D2 receptors in the NAcc core during taste memory retrieval preference test, and during CTA. Adult rats were exposed during 14days to 10% sugar solution as a single liquid ad libitum. NAcc core bilateral injections of D2 dopamine receptor antagonist, haloperidol (1μg/μL), were made before third preference test and CTA acquisition. We found that sugar was similarly preferred after 3 acute presentations or 14days of continued sugar consumption and that haloperidol did not disrupt this appetitive memory retrieval. Nevertheless, D2 receptors antagonism differentially affects aversive memory formation after acute or long-term sugar consumption. These results demonstrate that NAcc dopamine D2 receptors have a differential function during CTA depending on the degree of sugar familiarity.

Learning about the CS during latent inhibition: Preexposure enhances temporal control.

In 3 experiments, rats were given nonreinforced preexposure to an auditory stimulus, after which this stimulus and a second, novel cue were paired with food. Lower rates of conditioned responding were observed to the preexposed stimulus across the 3 experiments, indicative of latent inhibition. The degree to which animals used these cues to time the occurrence of food delivery was also examined. Paradoxically, the response slopes—indicating the rate of increase in responding over the course of the conditioned stimulus—were greater for the preexposed than for the novel cues, consistent with the suggestion that the preexposed stimulus exerted greater temporal control. Moreover, this was the case irrespective of whether the duration of the cue during preexposure differed from that during conditioning. These results suggest that although conditioned stimulus preexposure retards conditioning, it may enhance timing. The findings are discussed in terms of current models of conditioning and timing.

Habituation, latent inhibition, and extinction.

In two conditioned suppression experiments with a latent inhibition (LI) design, we measured the habituation of rats in preexposure, their LI during conditioning, and then extinction over days. In the first experiment, lick suppression, the preexposed group (PE) showed a significant initial unconditioned response (UR) to the target stimulus and significant long-term habituation (LTH) of that response over days. The significant difference between the PE and nonpreexposed (NPE) groups on the first conditioning trial was due solely to the difference in their URs to the conditioned stimulus (CS)-a habituated response (PE) and an unhabituated response (NPE). In the second experiment, bar-press suppression, little UR to the target stimulus was apparent during preexposure, and no detectable LTH. Thus, there was no difference between the PE and NPE groups on the first conditioning trial. Whether the UR to the CS confounds the interpretation of LI (Exp. 1) or not (Exp. 2) can only be known if the UR is measured. In both experiments, LI was observed in acquisition. Also in both experiments, rats that were preexposed and then conditioned to asymptote were significantly more resistant to extinction than were the rats not preexposed. This result contrasts with the consistently reported finding that preexposure either produces less resistance to extinction or has no effect on extinction. The effect of stimulus preexposure survived conditioning to asymptote and was reflected directly in extinction. These two experiments provide a cautionary procedural note for LI experiments and have shown an unexpected extinction effect that may provide new insights into the interpretation of LI.

Latent inhibition and facilitation of conditioned taste aversion in preweanling rats.

Early in ontogeny, taste preexposure has been found to induce latent inhibition as well as produce a facilitation of conditioned taste aversion (CTA). In this study, the effect of taste preexposure on CTA was investigated in 13-14 day old rats as a function of taste preexposure (0, 1, or 3 trials) and unconditioned stimulus intensity (LiCl: 0, 0.15, or 0.30 M). After one conditioning trial, with the low intensity US, an aversion was only observed after taste preexposure (facilitation). When using the strong US, an aversion was found without preexposure while latent inhibition was observed with 3 preexposure trials. In conclusion, stimulus preexposure can either facilitate conditioning or produce latent inhibition in infant rats, depending on the amount of stimulus preexposure and the intensity of the US.

Is the salience of the distinctive features of similar stimuli affected by stimulus preexposure schedule and length?

Following intermixed or blocked preexposures to two similar stimuli (AX and BX), rats received a single taste aversion conditioning and test trial with a compound composed of the distinctive flavors of the stimuli (AB). AB consumption was lower after intermixed than blocked preexposures (Experiments 1 and 2), regardless of whether rats received few (4) or many (12) stimulus presentations during preexposure, while overall consumption of AB was not affected by the length of preexposure (Experiment 2). Furthermore, consumption of the AB compound in a control group not receiving any preexposure trial was similar to that found for the intermixed preexposure condition but lower than that found for the blocked condition (Experiment 3). Conditioning to the AB compound was always successfully established, but it seemed to be unaffected by the preexposure schedule or its length. These findings are discussed in terms of whether salience is the stimulus property being modified by the preexposure schedule.

Error Correction in Latent Inhibition and its Disruption by Opioid Receptor Blockade with Naloxone

Latent inhibition refers to the retardation in the development of conditioned responding when a pre-exposed stimulus is used to signal an unconditioned stimulus. This effect is described by error-correction models as an attentional deficit and is commonly used as an animal model of schizophrenia. A series of experiments studied the role of error-correction mechanism in latent inhibition and its interaction with the endogenous opioid system. Systemic administration of the competitive opioid receptor antagonist naloxone before rats were pre-exposed to a target stimulus prevented latent inhibition of its subsequent fear conditioning; it was without effect on a non-pre-exposed stimulus and did not produce state-dependent learning (Experiments 1a and 1b). Naloxone did not reverse the latent inhibitory effect already accrued to a pre-exposed target. However, it did prevent the enhancement of latent inhibition by a long retention interval interpolated between its initial exposure and re-exposure (Experiment 2) or by a novel stimulus compounded with the pre-exposed target during re-exposure (Experiment 3). These results provide evidence that attentional loss in latent inhibition is instructed by an opioid-mediated error signal which diminishes with repeated stimulus exposures but recovers with the passage of time or reintroduction of novelty.