Unreinforced Exposure Research Articles

Vagus nerve stimulation as a tool for enhancing extinction in exposure-based therapies.

Emotionally traumatic experiences can lead to maladaptive memories that are enduring and intrusive. The goal of exposure-based therapies is to extinguish conditioned fears through repeated, unreinforced exposures to reminders of traumatic events. The extinction of conditioned fear depends upon the consolidation of new memories made during exposure to reminders. An impairment in extinction recall, observed in certain patient populations, can interfere with progress in exposure-based therapies, and the drive to avoid thoughts and reminders of the trauma can undermine compliance and increase dropout rate. Effective adjuncts to exposure-based therapies should improve the consolidation and maintenance of the extinction memory or improve the tolerability of the therapy. Under stressful conditions, the vagus nerve responds to elevations in epinephrine and signals the brain to facilitate the storage of new memories while, as part of the parasympathetic nervous system, it slows the sympathetic response. Here, we review studies relevant to fear extinction, describing the anatomical and functional characteristics of the vagus nerve and mechanisms of vagus nerve stimulation (VNS)-induced memory enhancement and plasticity. We propose that stimulation of the left cervical vagus nerve during exposure to conditioned cues signals the brain to store new memories just as epinephrine or emotional arousal would do, but bypasses the peripheral sympathetic "fight-or-flight" response. In support of this hypothesis, we have found that VNS accelerates extinction and prevents reinstatement of conditioned fear in rats. Finally, we propose future studies targeting the optimization of stimulation parameters and the search for biomarkers of VNS effectiveness that may improve exposure therapy outcomes.

Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction

Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40μl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0±0.2months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction using extinction therapy.

Extinction in multiple virtual reality contexts diminishes fear reinstatement in humans

Although conditioned fear can be effectively extinguished by unreinforced exposure to a threat cue, fear responses tend to return when the cue is encountered some time after extinction (spontaneous recovery), in a novel environment (renewal), or following presentation of an aversive stimulus (reinstatement). As extinction represents a context-dependent form of new learning, one possible strategy to circumvent the return of fear is to conduct extinction across several environments. Here, we tested the effectiveness of multiple context extinction in a two-day fear conditioning experiment using 3-D virtual reality technology to create immersive, ecologically-valid context changes. Fear-potentiated startle served as the dependent measure. All three experimental groups initially acquired fear in a single context. A multiple extinction group then underwent extinction in three contexts, while a second group underwent extinction in the acquisition context and a third group underwent extinction in a single different context. All groups returned 24h later to test for return of fear in the extinction context (spontaneous recovery) and a novel context (renewal and reinstatement/test). Extinction in multiple contexts attenuated reinstatement of fear but did not reduce spontaneous recovery. Results from fear renewal were tendential. Our findings suggest that multi-context extinction can reduce fear relapse following an aversive event – an event that often induces return of fear in real-world settings – and provides empirical support for conducting exposure-based clinical treatments across a variety of environments.

Nonassociative plasticity alters competitive interactions among mixture components in early olfactory processing

Experience-related plasticity is an essential component of networks involved in early olfactory processing. However, the mechanisms and functions of plasticity in these neural networks are not well understood. We studied nonassociative plasticity by evaluating responses to two pure odors (A and X) and their binary mixture using calcium imaging of odor-elicited activity in output neurons of the honey bee antennal lobe. Unreinforced exposure to A or X produced no change in the neural response elicited by the pure odors. However, exposure to one odor (e.g. A) caused the response to the mixture to become more similar to that of the other component (X). We also show in behavioral analyses that unreinforced exposure to A caused the mixture to become perceptually more similar to X. These results suggest that nonassociative plasticity modifies neural networks in such a way that it affects local competitive interactions among mixture components. We used a computational model to evaluate the most likely targets for modification. Hebbian modification of synapses from inhibitory local interneurons to projection neurons most reliably produced the observed shift in response to the mixture. These results are consistent with a model in which the antennal lobe acts to filter olfactory information according to its relevance for performing a particular task.

Repeated recall of learned immunosuppression: Evidence from rats and men

Akin to other physiological responses, the immune system can be modified, via Pavlovian or behavioral conditioning. It is unknown, however, whether and to what extent learned immune responses can be repeatedly recalled over time. Here we demonstrate in both rats and humans that repeated contingent pairing of a novel taste (conditioned stimulus, CS) together with the immunosuppressive drug cyclosporine A as unconditioned stimulus (US) leads to the acquisition of a learned immunosuppression. Sole presentation of the CS caused a significant inhibition of interleukin (IL)-2 and interferon (IFN)-γ production by rat splenic T cells and human peripheral T lymphocytes, closely mimicking the effect of the drug. More importantly, a comparable suppression of cytokine production was also observed after a second, unreinforced exposure to the CS that was separated from the first evocation by an interval of 6 (rats) or 11 (humans)days, respectively. Together, our findings demonstrate that a learned immunosuppression can be repeatedly recalled in both animals and humans, which is an important prerequisite for the implementation of conditioning paradigms as supportive therapy.

Does extinction of responses to cigarette cues occur during smoking cessation?

This study investigated whether Pavlovian extinction occurs during smoking cessation by determining whether experience abstaining from smoking in the presence of cigarette cues leads to decreased probability of lapsing and whether this effect is mediated by craving. Secondary analyses were carried out with data sets from two studies with correlational/observational designs. Data were collected in smokers' natural environments using ecological momentary assessment techniques. Sixty-one and 207 smokers who were attempting cessation participated. Multi-level path models were used to examine effects of prior experience abstaining in the presence of available cigarettes and while others were smoking on subsequent craving intensity and the probability of lapsing. Control variables included current cigarette availability, current exposure to others smoking, number of prior lapses and time in the study. Both currently available cigarettes [odds ratios (OR) = 36.60, 11.59] and the current presence of other smoking (OR = 5.00, 1.52) were powerful predictors of smoking lapse. Repeated exposure to available cigarettes without smoking was associated with a significantly lower probability of lapse in subsequent episodes (OR = 0.44, 0.52). However, exposure to others smoking was not a reliable predictor, being significant only in the smaller study (OR = 0.30). Craving functioned as a mediator between extinction of available cigarettes and lapsing only in the smaller study and was not a mediator for extinction of others smoking in either study. This study showed that exposure to available cigarettes is a large risk factor for lapsing, but that this risk can also be reduced over time by repeated exposures without smoking. Smoking cessation interventions should attempt to reduce cigarette exposure (by training cigarette avoidance) but recognize the potential advantage of unreinforced exposure to available cigarettes.

Varieties of perceptual learning

Although most studies of perceptual learning in human participants have concentrated on the changes in perception assumed to be occurring, studies of nonhuman animals necessarily measure discrimination learning and generalization and remain agnostic on the question of whether changes in behavior reflect changes in perception. On the other hand, animal studies do make it easier to draw a distinction between supervised and unsupervised learning. Differential reinforcement will surely teach animals to attend to some features of a stimulus array rather than to others. But it is an open question as to whether such changes in attention underlie the enhanced discrimination seen after unreinforced exposure to such an array. I argue that most instances of unsupervised perceptual learning observed in animals (and at least some in human animals) are better explained by appeal to well-established principles and phenomena of associative learning theory: excitatory and inhibitory associations between stimulus elements, latent inhibition, and habituation.

Repeated cue exposure effects on subjective and physiological indices of chocolate craving

The aim of this study is to investigate the effects of repeated unreinforced exposure to chocolate cues in persons reporting chocolate craving. Participants in the experimental group ( n=40) received 10 consecutive brief exposures to chocolate cues in each of two sessions, separated by 1–3 days. Control participants ( n=18) received two exposures at the start and end of each session. Chocolate craving was measured (alternately) through subjective report and the amount of saliva secretion to chocolate cues. Results showed a between-sessions decrease in both craving measures in the experimental group, whereas no differences in craving between sessions were observed in the control group. These results provide evidence for the effects of cue exposure treatment in chocolate craving.

Determinants of Preference: When do we like What we Know?

Repeated mere or unreinforced exposure positively affects the aesthetic response to various types of stimuli. Studies using artworks in laboratory experiments in which familiarity was experimentally manipulated revealed little or no effects of repeated exposure. The lack of mere exposure effects with artworks might be due to factors such as knowledge, stimulus complexity, or level of liking. In the present article, five studies are reported in which the relationship between familiarity and liking for 54 reproductions of van Gogh paintings was investigated under different conditions of evaluation and information about the paintings. Studies 1 and 2 revealed that positive correlations existed for liking and familiarity ratings even when it was possible that some of the stimuli seen were not original paintings. The correlations were significantly reduced when the beholder was told that all stimuli were fakes of van Gogh paintings (Study 3) and that they were fakes or non-van Goghs (Study 4). In Study 5, the correlation was reduced when inspection time was increased, thus, simple familiarity-liking relations are weakened by knowledge and are greater in spontaneous judgments.

Sensory preconditioning in honeybees.

Sensory preconditioning means that reinforcement of stimulus A after unreinforced exposure to a compound AB also leads to responses to stimulus B. Here, we describe and analyze sensory preconditioning in an insect, the honeybee Apis mellifera. Using two-element odorant compounds in classical conditioning of the proboscis extension reflex, we found (i) that sensory preconditioning is not due to stimulus generalization, (ii) that paired, but not unpaired, presentation of elements supports sensory preconditioning, (iii) that simultaneous, but not sequential, exposure to the elements of the compound supports sensory preconditioning and (iv) that a single presentation of the compound yields maximal sensory preconditioning. The results are discussed with respect to configural and chain-like associative explanations for sensory preconditioning. We suggest an experience-dependent step of compound processing, establishing configural units, as an additional explanation for sensory preconditioning.

Appetite Changes Under Free-living Conditions During Ramadan Fasting

During the fasting month of Ramadan, Muslims abstain from food and drink from sunrise until sunset. This change of eating pattern provides an opportunity to investigate factors controlling hunger and thirst. A group of healthy Muslims (15 men and 26 women) living in Reading, U.K. made hourly ratings of their hunger, mood and thirst, and recorded their food and drink intake on specified days before, during and after Ramadan between January and March 1996. There were no significant changes in body weight over Ramadan. Rated hunger increased substantially during the daily fast, and hunger was higher for the women than the men during the earlier days of Ramadan, whereas later, on average, fasting levels of hunger were very similar for both sexes (significant gender × day interaction,p<0·001). During Ramadan, the men tended to spend much of their time away from home, and may therefore have largely avoided eating-related cues during the daily fast. The women, however, were frequently involved in preparing food to be eaten later after sunset, which suggests an explanation for the results based on the external cue control of hunger. That is, unreinforced exposure to food cues in this context may have led to a decrease in the capacity of these cues to stimulate hunger.

Conditioning processes and cue exposure in the modification of excessive eating

Excessive eating is one of the principal characteristics of bulimia. Eating more than intended is also a prominent feature both of obese people who are trying to lose weight and normal weight women who are attempting to restrict their food intake. Overeating tends to be triggered by a specific set of cues, which commonly involve either mood disturbances or exposure to “forbidden” food, but may include other environmental cues. It is argued that conditioning processes are relevant both to the establishment of meal patterns in normal subjects and in the maintenance of excessive eating. Treatment procedures have typically followed the general approach of “Self Management” which emphasises reducing exposure to the cues associated with eating. An alternative approach derives from the idea that the association between eating responses (or urges to eat) and external cues may be learned, and therefore should in principle be ameanable to extinction through systematic unreinforced exposure. In this article the possible mechanisms of cue-induced overeating are discussed and the potential utility of cue exposure techniques for the management of excessive eating evaluated.

The ontogeny of the pecking response of herring gull chicks

The ontogeny of the pecking response of herring gull chicks, Larus argentatus, was investigated in an attempt to resolve potential contributions of maturation, habituation, conditioned inhibitioned, classical conditioning and imprinting. Previous studies had shown strong innate preferences for certain stimuli,but no significant preference for herring gulls over laughing gulls, Larus atricilla, either at birth or among older chicks whether wild-rearedorr laboratory trained. In the tests reported here, naive herring gull chicks, both at 18 h and 5–6 days, showed no preference between a model of their species and one of a laughing gull. High response rates to several scrambled models indicated chicks have no inmate configuration image variable. Older naive chicks lost much of their response specificity. Unreinforced exposure to a model herring gull had no effect. Unreinforced exposure to a laughing gull model, on the other hand, specifically reduced the response to laughing gulls, showing that conditioned inhibition can be strong. Reinforcement to laughing gull models resulted in a species preference. However, chicks did not learn to prefer herring gulls or white circles when reinforced by these models, and showed no conditioned inhibition to herring gulls. Wild-reared herring gulls show a weak preference for their own species.

Effects of Short Exposures to Phobic Material upon Subsequent Phobic Responses

Two theories have been advanced to explain the paradoxical increase in fear and avoidance seen after short unreinforced exposures to phobic stimuli. Incubation theory (Eysenck, 1968) and sensitization theory (Watts, 1971) are similar with regard to the conditions specified for enhancement of such responses. However, an incubated response is seen as specific to the CS in question, whereas sensitized responsiveness is a more generalized process. Subjects were either exposed or not exposed to a feared stimulus (cockroaches), and were then administered generalization tests to the same stimulus or to a non-feared stimulus (toad). Measures of subjective anxiety, behavioural avoidance and physiological activity were taken. No evidence was found for the enhancement phenomenon to either phobic material or non-feared material. The phenomenon does not appear to be a reliable one.

Extinction of taste aversion does not eliminate taste potentiation of odor aversion in rats or color aversion in pigeons

Rats were exposed to an odor-taste compound prior to being poisoned with lithium chloride on two occasions in Experiment 1 but only once in Experiment 2. Then, in each experiment, one group was given unreinforced exposures to the taste cue until extinction of the conditioned taste aversion occurred. During a later test, taste potentiation of odor aversion was obtained to a similar extent whether or not the taste aversion had been extinguished. An analogous finding was obtained with pigeons in Experiment 3. The present results indicate that taste potentiation does not depend on an underlying conditioned taste aversion, and, therefore, they support the notion that taste strengthened the odor-sickness (or color-sickness) association during the conditioning process.

General transfer across sensory modalities survives reductions in the original conditioned reflex in the rabbit

Two experiments demonstrated that transfer of training between CSs from different sensory modalities survived substantial reductions in responding to the first CS. In both experiments, animals received three stages of training. Stage 1 entailed CS-US training with a CS from one modality (e.g., light), and Stage 3 entailed CS-US training with a CS from another modality (e.g., tone). The experiments differed in treatment during Stage 2. In Experiment 1, animals either remained in their home cages or received unreinforced exposures to the first CS, which extinguished the original CR. In Experiment 2, the animals received either continued CS-US training or exposure to the CS and US but at a long interval (2,800 msec), which eliminated the original CR. As the baseline for detection of transfer effects, each experimental group had a control group that received Stage 1 training with a 2,800-msec CS-US interval, which produced minimal CR acquisition. The results of both experiments revealed substantial positive transfer across CS modalities regardless of the treatment during Stage 2. The transfer did not appear immediately on test presentations of the second CS in Stage 3. Rather, the transfer appeared as an enhancement in the rate of CR acquisition after reinforced training with the second CS had commenced. The results are discussed with respect to stimulus generalization, neutralization of background stimuli, and learning processes superordinate to specific associations.

The maintenance of aversive control of behaviour in the cat, dog and rat by the administration of unreinforced exposure to a punishment

Abstract Four experiments investigated the maintenance of aversive control of behaviour by the administration of unreinforced exposure to a punishment situation. Unreinforced exposure, under appropriate conditions, was shown to strengthen resistance to extinction of passive avoidance responding in cats, dogs and rats. Experiments 1 and 2 demonstrated the effect under two different schedules of administration of exposure to cats. Experiment 3 explored the phenomenon in dogs. Animals receiving unreinforced exposure showed significantly more response suppression than either controls or a group receiving low shock following intense shock. Experiment 4 investigated exposure time effects on the maintenance of passive avoidance responding in rats. The critical nature of the brevity of exposure was shown. It is suggested that unreinforced exposure, under the conditions used, promotes further conditioning of fear to the cues in the situation via second-order conditioning.

Rapid extinction of a conditioned taste aversion following unreinforced intraperitoneal injection of the fluid CS

After drinking a novel, saccharin-cyclamate solution, two groups of rats were poisoned with LiCl injection in order to establish a conditioned taste aversion, while a control group was not poisoned. Eighteen hours later, one of the poisoned groups of rats received differential unreinforced exposure to the sweet solution via an intraperitoneal injection. The group injected with the concentrated form of the saccharin-cyclamate solution showed subsequent rapid extinction of the conditioned taste aversion. An analogy was made to the technique of flooding (response prevention) used to hasten extinction of active, shock-motivated avoidance behavior.