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Fear over-generalization as a core symptom of anxiety disorders is manifested by fear responses even to safe stimuli that are very dissimilar to the original dangerous stimulus. The present study investigated the effects of two separate conditioned stimuli–unconditioned stimuli (CS–US) pairing procedures on fear acquisition and generalization using a perceptual discrimination fear-conditioning paradigm, with US expectancy ratings and skin conductance response (SCR) as indicators. One group accepted continuous followed by partial CS–US pairings (C–P group); the other group accepted partial followed by continuous CS–US pairings (P–C group). It was found that compared to the P–C group, the C–P group showed stronger perceptual discrimination of CS+ and CS− in the fear acquisition and showed weaker SCRs and stronger extinction of US expectancy in the generalization. These findings emphasize that CS–US pairings significantly influence fear acquisition and generalization and suggest that continuous-following partial CS–US pairings promote individual discrimination of threat and safety signals and inhibit the generalization of conditioned fear. The results of this study have implications for clinical interventions for patients experiencing negative events. [ABSTRACT FROM AUTHOR]

Prior attempts at forming theoretical predictions regarding the quality of binary odor mixtures have failed to find any consistent predictor for overshadowing of one component in a binary mixture by the other. We test here the hypothesis that trigeminality contributes to overshadowing effects in binary mixture perception. Most odorants stimulate the trigeminal nerve in the nasal sensory epithelium. In the current study we test rats' ability to detect component odorants in four binary odor sets chosen for their relative trigeminality. We predicted that the difference in trigeminal intensity would predict the degree of overshadowing by boosting or suppressing perceptual intensity of these odorants during learning or during mixture perception. We used a two-alternative choice (TAC) task in which rats were trained to recognize the two components of each mixture and tested on a range of mixtures of the two without reinforcement. We found that even though odorant concentrations were adjusted to balance volatility, all odor sets produced asymmetric psychometric curves. Odor pairs with the greatest difference in trigeminality showed overshadowing by the odorant with weaker trigeminal properties. Odor sets with more evenly matched trigeminal properties also showed asymmetry that was not predicted by either small differences in volatility or trigeminality. Thus, trigeminal properties may influence overshadowing in odor mixtures, but other factors are also likely involved. These mixed results further support the need to test each odor mixture to determine its odor quality and underscore recent results at the level of olfactory receptor neurons that show massive and unpredictable inhibition among odorants in complex mixtures. [ABSTRACT FROM AUTHOR]

Cu–Al–Ni shape memory alloys (SMAs) have high thermal stability and various potential applications. The most significant factors limiting their application are their relatively low elastic strain and poor shape memory effect known as recoverable strain. In addition, the incorporation of new elements for reinforcement usually results in a polycrystalline structure with a larger grain size, which is not suitable for shape memory applications. To overcome these drawbacks, a new method is introduced in this study to increase the shape memory effect and its stability in Cu–Al–Ni SMAs through partial reinforcement with alumina (Al2O3) by selective laser melting. In this approach, the reinforcing lines are deposited in-plane at the mid-height of the printed part, i.e., in the neutral plane. To characterize the effect of partial reinforcement, partially reinforced parts with 0.3 wt% and 0.9 wt% Al2O3 are compared to fully reinforced parts. The results show that the accumulation of localized residual compressive stresses above the reinforcing lines in the neutral plane, induced during selective laser melting, increases the shape memory effect as a result of the increase in mechanical anisotropy in the building direction. Moreover, a new phenomenon named the “waistband effect” is observed in cyclic compressive operation, which results in incremental penetration of the reinforcing particles into the neutral plane during compression. This facilitates a higher strain recovery in the partially reinforced part. These results clearly confirm that partial reinforcement with Al2O3 significantly enhances the shape memory effect of Cu–Al–Ni SMAs.

We sought to provide evidence for a combined effect of two attentional mechanisms during associative learning. Participants' eye movements were recorded as they predicted the outcomes following different pairs of cues. Across the trials of an initial stage, a relevant cue in each pair was consistently followed by one of two outcomes, while an irrelevant cue was equally followed by either of them. Thus, the relevant cue should have been associated with small relative prediction errors, compared to the irrelevant cue. In a later stage, each pair came to be followed by one outcome on a random half of the trials and by the other outcome on the remaining half, and thus there should have been a rise in the overall prediction error. Consistent with an attentional mechanism based on relative prediction error, an attentional advantage for the relevant cue was evident in the first stage. However, in accordance with a mechanism linked to overall prediction error, the attention paid to both types of cues increased at the beginning of the second stage. These results showed up in both dwell times and within-trial patterns of fixations, and they were predicted by a hybrid model of attention. [ABSTRACT FROM AUTHOR]

Background: Previous research has shown that after one month of full dose nightly treatment with zolpidem (priming), subjects with chronic insomnia (CI) switched to intermittent dosing with medication and placebos were able to maintain their treatment responses. This approach to maintenance therapy is referred to as partial reinforcement. The present study sought to assess whether priming is required for partial reinforcement or whether intermittent dosing with placebos (50% placebos and 50% active medication) can, by itself, be used for both acute and extended treatment.Method: 55 CI subjects underwent a baseline evaluation (Phase-1) and then were randomized to one of two conditions in Phase-2 of the study: one month of (1) nightly medication use with standard-dose zolpidem (QHS [n = 39]) or (2) intermittent dosing with standard-dose zolpidem and placebos (IDwP [n = 16]). In Phase-3 (three months), the QHS group was re-randomized to either continued QHS full dose treatment (FD/FD) or to IDwP dose treatment (FD/VD). Treatment response rates and Total Wake Time (TWT = [SL + WASO + EMA]) were assessed during each phase of the study.Results: In Phase-2, 77% (QHS) and 50% (IDwP) subjects exhibited treatment responses (p = 0.09) where the average change in TWT was similar. In Phase-3, 73% (FD/FD), 57% (FD/VD), and 88% (VD/VD) of subjects exhibited continued treatment responses (p = 0.22) where the average improvement in TWT continued with FD/FD and remained stable for FD/VD and VD/VD (p < 0.01).Conclusion: These results suggest that intermittent dosing with placebos can maintain effects but do not allow for the additional clinical gains afforded by continuous treatment. [ABSTRACT FROM AUTHOR]

Inbred rats from the Roman low-avoidance strain (RLA-I), but not from the Roman high-avoidance strain (RHA-I) increased preference for ethanol after being exposed to sessions of appetitive extinction (Manzo et al. Physiol Behav 2014 123:86-92). RLA-I rats have shown greater sensitivity than RHA-I rats to a variety of anxiogenic situations, including those involving reward loss. Such increased fluid preference did not occur after acquisition (reinforced) sessions or in control groups with postsession access to water, rather than ethanol. Because ethanol has anxiolytic properties in tasks involving reward loss, oral consumption after extinction sessions was interpreted as anti-anxiety or emotional self-medication (ESM). The present research was an attempt to reduce or eliminate the ESM effect in RLA-I rats by giving them 50% partial reinforcement training during the acquisition of an instrumental response, a treatment known to induce resilience to loss-induced anxiety. As expected, partially reinforced RLA-I rats showed a higher resistance to extinction in comparison to continuously reinforced animals, displaying lower ethanol consumption than continuously reinforced rats during the postsession preference test. Partial and continuous control groups receiving water during the preference tests showed no changes in preference. These results suggest that exposure to reward uncertainty typical of partial reinforcement training can reduce ESM in rats genetically selected for high levels of anxiety.

The reinforcement of shield tunnels with secondary linings is a widely used method to enhance the overall rigidity of tunnels; therefore, ensuring tunnel safety during construction and operational periods. According to a new composite curved Euler beam theory, an analytical method will be proposed to analyze a shield tunnel that is reinforced by a secondary lining, in which the radial joints and the interaction between the segmental lining and the surrounding soil will be simulated by a series of concentrated and distributed springs, respectively. In contrast to the radial rigid connection that was assumed in previous studies, radial detachment and tangential slippage between the segmental and secondary linings will be allowed. The solutions for the internal forces and deformations will be derived using the state-space method with arbitrary loads and joint distributions. In addition, the proposed method will be extended to cases with partial reinforcement that have a segment of secondary lining and a reinforcement connected by bolts. The proposed method will be validated using finite element numerical simulations. In addition, the variations in the internal forces and deformation for the soil reaction stiffness under different joint and interfacial stiffnesses will be examined. The results indicate that the internal forces and deformations of the linings decreased with the increase of soil reaction spring stiffness, and the interfacial radial spring stiffness had a more significant influence on the axial force transfer between the linings. [ABSTRACT FROM AUTHOR]

Rats exposed to a downshift in the concentration of a sucrose solution from 32% to 4% exhibit a transient suppression of consummatory behavior relative to an unshifted control always exposed to 4% sucrose. One explanation of this effect, known as consummatory successive negative contrast (cSNC), explains consummatory suppression as arising from an emotional state of frustration that redirects behavior away from the source of the devalued solution. A preliminary selective breeding protocol consisting of three experiments was performed. Experiment 1 reports results from 5 generations of selected breeding for either high (H) or low (L) recovery rates from cSNC. A control line of randomly (R) mated rats was included. cSNC was reduced in H rats, but L and R rats did not differ across generations. H rats also provided no evidence of behavioral activation in acquisition or increased persistence in extinction after partial reinforcement, rather than continuous reinforcement. L and R rats, by contrast, showed both of these effects. H rats were also significantly smaller in body size than R rats, but did not differ in terms of water intake, sucrose sensitivity, open-field activity, or responding to sucrose solutions before the downshift. In Experiment 2, H infants from the sixth selected generation showed increased bandwidth in vocalizations induced by mother-infant separation relative to L and R rats. Experiment 3 showed that H rats failed to show increased response to incentive downshift after treatment with the nonselective opioid antagonist naloxone, as done by L and R rats. The results, if replicated, may provide support for the interpretation of a significant role of frustration in cSNC.

Reward loss experiences are among the main sources of emotional stress that humans face throughout their lives. In the animal laboratory, it has been repeatedly shown that the unexpected omission or devaluation of a reinforcer triggers a physiological, cognitive, and behavioral state called frustration. This state involves emotional mechanisms that resemble those unleashed by the presentation of other aversive stimuli, inducing similar stress responses through the activation of brain circuits involved in fear and anxiety. Although this hypothesis has been supported by behavioral, pharmacological, hormonal, and neurobiological evidence, only a few studies have focused on the neurogenetic basis of frustration in animals. This review focuses on the gene-environment interactions that determine the emotional response under conditions of reward loss. Behavioral and genetic correlates of frustration are reviewed in two strains of animals selected on the basis of extreme differences in active avoidance learning: inbred Roman High- (RHA-I) and Roman Low-Avoidance (RLA-I) rats. The review shows the usefulness of Roman strains for neurogenetic research and sets out unsolved questions regarding gene-environment interactions underlying behavior induced by incentive loss.

Individual differences or vulnerabilities must exist which bias some individuals toward psychopathology while others remain resilient in the face of trauma. Recent work has studied the effects of uncertainty on individuals expressing behavioral inhibition (BI). The current study extended this work with uncertainty to Wistar Kyoto (WKY) rats which are a behaviorally inhibited inbred strain that models learning vulnerabilities for anxiety disorders and posttraumatic stress disorder (PTSD). WKY rats exhibit superior avoidance performance in a signaled bar press avoidance task in which a tone conditioned stimulus (CS) signals a foot shock unconditional stimulus (US) when compared with non-inhibited Sprague-Dawley (SD) rats. In addition, WKY rats express enhanced eyeblink conditioning. Recent work with behaviorally inhibited humans has indicated that this enhanced eyeblink conditioning is more evident in conditions that insert CS- or US-alone trials into CS-US paired training, resulting in uncertain and suboptimal learning conditions. The current study examined the effects of partial predictability training, in which the CS signaled the US only one-half of the time, on the acquisition and expression of avoidance. Standard training with a fixed 60-s CS which predicted shock on 100% of trials was compared with training in which the CS predicted shock on 50% of trials (partial predictability) using a pseudorandom schedule. As expected, WKY rats acquired avoidance responses faster and to a greater degree than SD rats. Partial predictability of the US essentially reduced SD rats to escape responding. Partial predictability also reduced avoidance in WKY rats; however, adjusting avoidance rates for the number of potential pairings of the CS and US early in training suggested a similar degree of avoidance expression late in the last session of training. Enhanced active avoidance expression, even in uncertain learning conditions, can be interpreted as behaviorally inhibited WKY rats responding to the expectancy of the shock by avoiding, whereas non-inhibited SD rats were responding to the presence of the shock by escaping. Future work should explore how WKY and SD rats as well as behaviorally inhibited humans acquire and extinguish avoidance responses in uncertain learning situations.

This paper investigates the effect of reinforcement schedules on biofeedback games for stress self-regulation. In particular, it examines whether partial reinforcement can improve resistance to extinction of relaxation behaviors, i.e., once biofeedback is removed. Namely, we compare two types of reinforcement schedules (partial and continuous) in a mobile biofeedback game that encourages players to slow their breathing during gameplay. The game uses a negative-reinforcement instrumental conditioning paradigm, removing an aversive stimulus (random actions in the game) if players slows down their breathing. We conducted an experimental trial with 24 participants to compare the two reinforcement schedules against a control condition. Our results indicate that partial reinforcement improves resistance to extinction, as measured by breathing rate and skin conductance post-treatment. In addition, based on linear regression and correlation analysis we found that participants in the partial reinforcement learned to slow their breathing at the same pace as those under continuous reinforcement. The article discusses the implications of these results and directions for future work. [ABSTRACT FROM AUTHOR]

Individual differences or vulnerabilities must exist which bias some individuals toward psychopathology while others remain resilient in the face of trauma. Recent work has studied the effects of uncertainty on individuals expressing behavioral inhibition (BI). The current study extended this work with uncertainty to Wistar Kyoto (WKY) rats which are a behaviorally inhibited inbred strain that models learning vulnerabilities for anxiety disorders and posttraumatic stress disorder (PTSD). WKY rats exhibit superior avoidance performance in a signaled bar press avoidance task in which a tone conditioned stimulus (CS) signals a foot shock unconditional stimulus (US) when compared with non-inhibited Sprague-Dawley (SD) rats. In addition, WKY rats express enhanced eyeblink conditioning. Recent work with behaviorally inhibited humans has indicated that this enhanced eyeblink conditioning is more evident in conditions that insert CS- or US-alone trials into CS-US paired training, resulting in uncertain and suboptimal learning conditions. The current study examined the effects of partial predictability training, in which the CS signaled the US only one-half of the time, on the acquisition and expression of avoidance. Standard training with a fixed 60-s CS which predicted shock on 100% of trials was compared with training in which the CS predicted shock on 50% of trials (partial predictability) using a pseudorandom schedule. As expected, WKY rats acquired avoidance responses faster and to a greater degree than SD rats. Partial predictability of the US essentially reduced SD rats to escape responding. Partial predictability also reduced avoidance in WKY rats; however, adjusting avoidance rates for the number of potential pairings of the CS and US early in training suggested a similar degree of avoidance expression late in the last session of training. Enhanced active avoidance expression, even in uncertain learning conditions, can be interpreted as behaviorally inhibited WKY rats responding to the expectancy of the shock by avoiding, whereas non-inhibited SD rats were responding to the presence of the shock by escaping. Future work should explore how WKY and SD rats as well as behaviorally inhibited humans acquire and extinguish avoidance responses in uncertain learning situations. [ABSTRACT FROM AUTHOR]

Highlights • Prediction errors are computed within the brain during drug administrations. • CNS responses towards a given substance can be shaped through implicit UCS revaluation. • Neuropharmacological and immunosuppressive drugs effectiveness can be strongly enhanced. • Pain perception can be strongly reduced exploiting dose varying administration schedules. • Immunosuppression in psoriasis treatment can be increased of an eight factor. Abstract The human brain can be conceptualized as an inference machine that actively predicts and explains its sensations and perceptions: it makes predictions through a probabilistic model. Such a model is continuously and implicitly updated by the computation and minimization of weighted prediction errors, as shown by numerous studies and experimental results. Nevertheless, such an algorithmic functioning of the brain has not been exploited in the neuropharmacological practice. In this manuscript, we show by theoretical analysis and model fitting of previously published data in two different contexts, how it is possible to increase the effectiveness of neuropharmacological and immunosuppressive drugs, through the modulation of the weighted prediction errors. Moreover, on the basis of the proposed model, we derive an optimized drug administration schedule able to increase the drug effectiveness of one order of magnitude, in psoriasis treatment. We make important testable predictions, evidencing the impact and the potential benefit of prediction errors modulation within the brain, in the pharmacotherapeutic practice. Finally, our results lead to a novel formal theory of implicit learning, and shed lights on the actual roles of classical conditioning and UCS revaluation in behavioral and pharmacological conditioning experiments. The potential practical implications of our results are many: the reduction of drugs side effects; the maximization of the therapeutic outcome; a more effective treatment for chronic pain, certain neuropsychiatric diseases, autoimmune diseases and allergic diseases. [ABSTRACT FROM AUTHOR]

The partial reinforcement extinction effect (PREE) is the observation that, following training in which a response is followed by reward on only a subset of trials, the response is more resistant to extinction following the total removal of reward than it is after training in which reward is presented on all trials. The PREE is almost ubiquitous in instrumental conditioning procedures but only inconsistently observed in Pavlovian conditioning. In his classic review of animal learning, Mackintosh attributes the bulk of the PREE to generalisation decrement relating to the fact that partial reinforcement typically ensures that acquisition of responding has taken place in conditions similar to that of extinction (e.g., in the absence of the reinforcer). We report here that extinction of a conditioned taste aversion is not retarded by partial reinforcement in terms of either consumption of the taste or hedonic reactions to it (assessed through the analysis of licking microstructure). These results are consistent with Mackintosh's analysis of the PREE and the way in which it might differ between instrumental and Pavlovian conditioning. [ABSTRACT FROM AUTHOR]

Highlights • Over-selectivity is when behavior becomes controlled by only one aspect of the environment. • Experiments explored whether associability accounts might allow better theoretical understanding. • All experiments established the presence of over-selectivity. • Results suggest that unpredictability reduces over-selectivity. • Attentional mechanisms may play a role in acquisition and remediation of over-selectivity. Abstract Background: The phenomenon whereby behavior becomes controlled by one aspect of the environment at the expense of other equally-salient aspects of the environment (stimulus over-selectivity) is extremely common in many with Autism Spectrum Disorder (ASD). However, the theoretical mechanisms underpinning over-selectivity and its remediation are not well understood. Four experiments explored whether principles derived from associability accounts of learning, notably the concept of uncertainty, might allow better theoretical understanding of the phenomenon. Method: Participants with ASD who had language impairments received simultaneous discrimination training (AB+/CD−), and were tested in extinction regarding the degree to which the separate elements (A and B) of the previously reinforced compound (AB+) controlled behavior. Results: All experiments established the presence of over-selectivity; choosing one stimulus element to a greater-extent than the other. In Experiments 1 and 2, relative to a 100% feedback schedule, over-selectivity reduced when a 50%, but not a 25%, schedule of feedback was used. In Experiment 3, prolonged schedule exposure reduced over-selectivity. In Experiment 4, change from a 100% to a 33% schedule did not reduce over-selectivity. Conclusions: These results suggest that unpredictability, rather than variability per se , or reinforcement reduction and change, reduces over-selectivity. This suggests that attentional mechanisms, especially uncertainty, may play a role in this phenomenon during its acquisition and remediation. [ABSTRACT FROM AUTHOR]

Does recovery from reward devaluation or partial reinforcement (PR) involve the counterconditioning of frustration? Transfer among tasks involving reward loss was used to uncover frustration counterconditioning. In Experiment 1, Phase 1 training in consummatory successive negative contrast (cSNC; 32-to-4% sucrose devaluation) eliminated Phase 2 iSNC in one-way avoidance (40-to-3 s safety-time reduction), but the opposite sequence generated no detectable transfer. In Experiment 2, transfer from Phase 1 cSNC to Phase 2 autoshaping extinction after continuous reinforcement increased lever pressing in previously downshifted animals relative to unshifted controls. However, Phase 1 training in autoshaping under partial reinforcement (PR) had no effect on Phase 2 cSNC. Transfer from PR to cSNC also failed when sucrose pellets were used in autoshaping (Experiment 3), when autoshaping acquisition was extended from 100 to 300 trials (Experiment 4), and when preshift training in cSNC was extended from 10 to 20 sessions (Experiment 5). In Experiment 6, Phase 1 training in PR for licking enhanced Phased 2 cSNC, also involving licking, and in Experiment 7 Phase 1 PR training in autoshaping enhanced Phase 2 cSNC after a 22-to-4% sucrose downshift. Whereas prior exposure to cSNC (consummatory task) increased resistance to extinction in autoshaped lever pressing, prior training in one-way avoidance, PR in autoshaping, or PR in taste conditioning (all anticipatory tasks) either had no effect or they enhanced the cSNC effect. Frustration counterconditioning developed during these tasks, but the type of transfer effect depends on task sequence. [ABSTRACT FROM AUTHOR]

Studies of partial reinforcement in eyeblink conditioning have typically shown slower learning of a CS-US association when paired CS-US trials are interleaved with CS-alone trials. However, recent work has shown that CS-US learning is not slowed by interleaved US-alone trials. This discrepancy is surprising since both partial reinforcement protocols reduce the total number of paired CS-US trials. Previously, Kimble et al. (1955) reported that inserting a block of US-alone trials during CS-US training did not disrupt eyeblink acquisition. Here, we sought to replicate and extend these findings by comparing interleaved vs. blocked US-alone trials during CS-US paired training. Ninety-seven undergraduates volunteered for this experiment for research credit. Participants received 60 acquisition trials, consisting of either 100% CS-US paired trials, 50% US-alone trials intermixed with CS-US paired trials, or a block of 20 US-alone trials inserted between blocks of 20 CS-US trials. We also utilized a previously published computational model of hippocampal and cerebellar learning to test the effects of these US-alone protocols. Both empirical and computational results supported the finding that US-alone trials, either intermixed or inserted as a block of trials, do not disrupt acquisition of conditioned eyeblinks. Possible neural substrates of these US-alone effects are discussed. [ABSTRACT FROM AUTHOR]

The ambiguous-cue task is composed of two-choice simultaneous discriminations involving three stimuli: positive (P), ambiguous (A), and negative (N). Two different trial types are presented: PA and NA. The ambiguous cue (A) served as an S- in PA trials, but as an S+ in NA trials. When using this procedure, it is typical to observe a less accurate performance in PA trials than in NA trials. This is called the ambiguous-cue effect. Recently, it was reported in starlings that the ambiguous-cue effect decreases when the stimuli are presented on an angled (120°) panel. The hypothesis is that the angled panel facilitates that the two cues from each discrimination are perceived as a compound, precluding value transfer via a second-order conditioning mechanism. In this experiment, we used pigeons and a flat panel. Nevertheless, our data were quite similar to the previous data in starlings. We conclude that the form of the panel cannot explain the ambiguous-cue effect. Several alternatives to be explored in future experiments are suggested. The riddle of the ambiguous-cue problem still remains unsolved.

The partial reinforcement extinction effect (PREE) is an experimentally established phenomenon: behavioural response to a given stimulus is more persistent when previously inconsistently rewarded than when consistently rewarded. This phenomenon is, however, controversial in animal/human learning theory. Contradictory findings exist regarding when the PREE occurs. One body of research has found a within-subjects PREE, while another has found a within-subjects reversed PREE (RPREE). These opposing findings constitute what is considered the most important problem of PREE for theoreticians to explain. Here, we provide a neurocomputational account of the PREE, which helps to reconcile these seemingly contradictory findings of within-subjects experimental conditions. The performance of our model demonstrates how omission expectancy, learned according to low probability reward, comes to control response choice following discontinuation of reward presentation (extinction). We find that a PREE will occur when multiple responses become controlled by omission expectation in extinction, but not when only one omission-mediated response is available. Our model exploits the affective states of reward acquisition and reward omission expectancy in order to differentially classify stimuli and differentially mediate response choice. We demonstrate that stimulus-response (retrospective) and stimulus-expectation-response (prospective) routes are required to provide a necessary and sufficient explanation of the PREE versus RPREE data and that Omission representation is key for explaining the nonlinear nature of extinction data. [ABSTRACT FROM AUTHOR]

In anxiety, maladaptive avoidance behavior provides for near-perfect controllability of potential threat. There has been little laboratory-based treatment research conducted on controllability as a contributing factor in the transition from adaptive to maladaptive avoidance. Here, we investigated for the first time whether partial reinforcement rate, or the reliability of avoidance at controlling or preventing contact with an aversive event, influences subsequent extinction of avoidance in humans. Five groups of participants were exposed to different partial reinforcement rates where avoidance cancelled upcoming shock on 100%, 75%, 50%, 25% or 0% of trials. During extinction, all shocks were withheld. Avoidance behavior, online shock expectancy ratings and skin conductance responses (SCRs) were measured throughout. We found that avoidance was a function of relative controllability: higher reinforcement rate groups engaged in significantly more extinction-resistant avoidance than lower reinforcement groups, and shock expectancy was inversely related with reinforcement rate during avoidance acquisition. Partial reinforcement effects were not evident in SCRs. Overall, the current study highlights the clinical relevance of laboratory-based treatment research on partial reinforcement or controllability effects on extinction of avoidance. [ABSTRACT FROM AUTHOR]

Pavlovian conditioning is sensitive to the temporal relationship between the conditioned stimulus (CS) and the unconditioned stimulus (US). This has motivated models that describe learning as a process that continuously updates associative strength during the trial or specifically encodes the CS–US interval. These models predict that extinction of responding is also continuous, such that response loss is proportional to the cumulative duration of exposure to the CS without the US. We review evidence showing that this prediction is incorrect, and that extinction is trial-based rather than time-based. We also present two experiments that test the importance of trials versus time on the Partial Reinforcement Extinction Effect (PREE), in which responding extinguishes more slowly for a CS that was inconsistently reinforced with the US than for a consistently reinforced one. We show that increasing the number of extinction trials of the partially reinforced CS, relative to the consistently reinforced CS, overcomes the PREE. However, increasing the duration of extinction trials by the same amount does not overcome the PREE. We conclude that animals learn about the likelihood of the US per trial during conditioning, and learn trial-by-trial about the absence of the US during extinction. Moreover, what they learn about the likelihood of the US during conditioning affects how sensitive they are to the absence of the US during extinction. [ABSTRACT FROM AUTHOR]

Despite the ubiquitous use of Pavlovian fear conditioning as a model for fear learning, the highly predictable conditions used in the laboratory do not resemble real-world conditions, in which dangerous situations can lead to unpleasant outcomes in unpredictable ways. In the current experiments, we varied the timing of aversive events after predictive cues in rodents and discovered that temporal ambiguity of aversive events greatly enhances fear. During fear conditioning with unpredictably timed aversive events, pharmacological inactivation of the dorsal hippocampus or optogenetic silencing of cornu ammonis 1 cells during aversive negative prediction errors prevented this enhancement of fear without affecting fear learning for predictable events. Dorsal hippocampal inactivation also prevented ambiguity-related enhancement of fear during auditory fear conditioning under a partial-reinforcement schedule. These results reveal that information about the timing and occurrence of aversive events is rapidly acquired and that unexpectedly timed or omitted aversive events generate hippocampal signals to enhance fear learning. [ABSTRACT FROM AUTHOR]

Public concern for farm animal welfare calls for reliable scientific tools to measure it. Measuring cognitive bias, i.e., the influence of affective states on cognitive processing, has gained importance during recent years. The one most often adapted experimental design to test cognitive bias in non-human animals is the spatial judgement task, where animals must judge a goal box/pot based on its location. First, they learn to discriminate between a positively reinforced and a negatively reinforced location, and then they are confronted with ambiguous, intermediate locations. The responses to these so-called probe cues are assumed to be influenced by the animal’s affective state. Current methods for the assessment of cognitive bias in domestic pigs, one of the most intensively housed farm animal species in Europe, still need to be refined and validated. Hence, we developed an improved, reliable design to test pigs repeatedly and induce graded responses to graded probe cues. For this, we used a spatial judgement task in a go/no-go paradigm with partial reinforcement and a mildly aversive negative reinforcer. A total of 16 female juvenile German Landrace pigs underwent discrimination learning of the rewarded vs. punished goal box location; this was then repeatedly tested on three probe locations in between (eight times in four weeks). The subjects learned to discriminate between the two reference locations and showed graded responses (latency to open the goal box) to the probe locations. Analyses of the subjects’ general behaviour implied that additional information on the animals’ state can be derived. The subjects showed no signs of learning with respect to the outcome of probe cues but exhibited stable response levels during test weeks two to four. In conclusion, the design presented in this paper is suitable for spatial judgement tasks in domestic pigs. After successful validation it might be used for testing affective valence based on judgement bias and hence can contribute to our understanding of the welfare of this intensively farmed species. [ABSTRACT FROM AUTHOR]

The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under continuous reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons. [ABSTRACT FROM AUTHOR]

Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22 studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Provided that nondisclosure is preauthorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated. [ABSTRACT FROM AUTHOR]

Avoidance in the face of novel situations or uncertainty is a prime feature of behavioral inhibition which has been put forth as a risk factor for the development of anxiety disorders. Recent work has found that behaviorally inhibited individuals acquire conditioned eyeblinks faster than non-inhibited individuals in omission and yoked paradigms in which the predictive relationship between the conditioned stimulus (CS) and unconditional stimulus (US) is less than optimal as compared to standard training with CS-US paired trials (Holloway et al., 2014). In the current study, we tested explicitly partial schedules in which half the trials were CS alone or US alone trials in addition to the standard CS-US paired trials. One hundred and forty nine college-aged undergraduates participated in the study. All participants completed the Adult Measure of Behavioral Inhibition (i.e., AMBI) which was used to group participants as behaviorally inhibited and non-inhibited. Eyeblink conditioning consisted of 3 US alone trials, 60 acquisition trials, and 20 CS-alone extinction trials presented in one session. Conditioning stimuli were a 500 ms tone conditioned stimulus (CS) and a 50-ms air puff unconditional stimulus (US). Behaviorally inhibited individuals receiving 50% partial reinforcement with CS alone or US alone trials produced facilitated acquisition as compared to non-inhibited individuals. A partial reinforcement extinction effect was evident with CS alone trials in behaviorally inhibited but not non-inhibited individuals. These current findings indicate that avoidance prone individuals self-reporting behavioral inhibition over-learn an association and are slow to extinguish conditioned responses when there is some level of uncertainty between paired trials and CS or US alone presentations.

The ambiguous-cue problem is deceptively simple. It involves two concurrently trained simultaneous discriminations (known as PA and NA trials), but only three stimuli. Stimulus A is common to both discriminations, but serves as non-reinforced stimulus (S-) on PA trials and as reinforced stimulus (S+) on NA trials. Typically, animals’ accuracy is lower on PA trials—the ambiguous-cue effect. We conducted two experiments with European starlings (Sturnus vulgaris) using Urcuioli and Michalek’s [2007, Psychon B Rev 14, 658-662] experimental manipulations as a springboard to test the predictions of two of the most important theoretical accounts of the effect: the interfering cue hypothesis and value transfer theory. Both experiments included two groups of birds, one trained with a regular ambiguous-cue problem (Group Continuous) and another trained with partial reinforcement on PA trials (Group PA-Partial). The experiments differed only in the number of sessions (18 vs. 36) and daily trials (360 vs. 60). As previously observed, we found faster acquisition on NA trials than on PA trials in both experiments, but by the end of training PA performance was surprisingly high, such that no ambiguous-cue effect was present in Group Continuous of either experiment. The effect was still present in both PA-Partial groups, but to a smaller degree than expected. These findings are inconsistent with the literature, in particular with the results of Urcuioli and Michalek with pigeons, and question the aforementioned theoretical accounts as complete explanations of the ambiguous-cue effect. In our view, to achieve such high levels of accuracy on PA trials, starlings must have attended to configural (i.e., contextual) cues, thus differentiating stimulus A when presented on PA trials from stimulus A when presented on NA trials. A post hoc simulation of a reinforcement-based configural model supported our assertion.

Unlabelled: Many studies have found evidence of conditioning-induced nocebo hyperalgesia. However, these studies have exclusively involved continuous reinforcement (CRF) schedules. Thus, it is currently unknown whether nocebo hyperalgesia can result after partial reinforcement (PRF). We tested this using electrodermal pain stimulation in healthy volunteers. Undergraduates (N = 135) received nocebo treatment under the guise of a hyperalgesic. Participants were randomly allocated to CRF, PRF, or control (no conditioning). Conditioning involved surreptitiously increasing pain stimulation on nocebo trials relative to control trials. During training, the CRF group always had the nocebo paired with the surreptitious pain increase, whereas the PRF group experienced the increase on only 62.5% of nocebo trials. In the test phase, pain stimulation was equivalent across nocebo and control trials. PRF was sufficient to induce nocebo hyperalgesia; however, this was weaker than CRF. Nocebo hyperalgesia failed to extinguish irrespective of the training schedule. Additional assessment of expectancies indicated strong concordance between expectancy and nocebo hyperalgesia. Overall, these findings suggest that once established, nocebo hyperalgesia may be difficult to disrupt. PRF may be a novel method of reducing the intensity of nocebo hyperalgesia in the clinic, which may be particularly important given its persistence.Perspective: This study provides novel evidence that partial reinforcement results in weaker nocebo hyperalgesia than continuous reinforcement and that nocebo hyperalgesia fails to extinguish, irrespective of the training schedule. As a result, partial reinforcement may serve as a method for reducing the intensity of nocebo hyperalgesia in the clinic. [ABSTRACT FROM AUTHOR]

Background and aim At present, there is no consensus regarding how to medically manage chronic insomnia in the long term. The unstated standard of practice is for patients to use hypnotics intermittently. The present study aimed to compare a partial reinforcement strategy with nightly and intermittent dosing strategies for its potential as a maintenance therapy. Methods A mixed model was used in the study. One between-subjects factor: group ( n  = 4). One repeated-measures factor: time (12 weekly assessments). A total of 74 subjects with chronic Insomnia were treated with 10 mg zolpidem for 4 weeks. Treatment respondents were randomized to nightly dosing with 10 mg or 5 mg (QHS-10 and QHS-5), intermittent dosing with 10 mg (IDS-10 [3–5 days weekly]), or partial reinforcement dosing with 10 mg (PRS-10 [nightly pill use with 50% active medication and 50% placebos]) for 12 weeks. Results It was found, in compliant subjects ( n  = 55), that all four strategies evaluated maintained treatment response over time (ie, prevented or delayed relapse). For the subjects that remained in remission, the subjects in the intermittent dosing group (IDS-10) group exhibited poorer sleep continuity. Conclusions While best considered a preliminary study, the present findings suggest that the partial reinforcement strategy may be a viable means toward maintaining treatment gains over time with less active medication. [ABSTRACT FROM AUTHOR]

There is a vast literature on the behavioural effects of partial reinforcement in Pavlovian conditioning. Compared with animals receiving continuous reinforcement, partially rewarded animals typically show (a) a slower development of the conditioned response (CR) early in training and (b) a higher asymptotic level of the CR later in training. This phenomenon is known as the partial reinforcement acquisition effect (PRAE). Learning models of Pavlovian conditioning fail to account for it. In accordance with the incentive salience hypothesis, it is here argued that incentive motivation (or ‘wanting’) plays a more direct role in controlling behaviour than does learning, and reward uncertainty is shown to have an excitatory effect on incentive motivation. The psychological origin of that effect is discussed and a computational model integrating this new interpretation is developed. Many features of CRs under partial reinforcement emerge from this model. [ABSTRACT FROM AUTHOR]

Background and Objectives: In anxiety-related disorders, excessive avoidance often coexists with an impaired sense of control over external threats. In contrast, lab studies have shown that avoidance responding increase with higher objective controllability over threat, accompanied with more confidence in the effectiveness of the avoidance response. One reason for this divergence could be that those lab studies are overly simplistic with a single, avoidable threat.Methods: We conducted an experiment that additionally included a completely uncontrollable threat, and we manipulated the reinforcement rate of the avoidance response to the (semi-)controllable threat (75% versus 100%).Results: The 100% group showed increased avoidance to the controllable threat and decreased avoidance to the unavoidable threat over learning. Interestingly, compared to the 100% group, the 75% group displayed less confidence in their avoidance to the controllable threat and they avoided the uncontrollable threat more often.Limitations: Only two reinforcement rates of effective avoidance were included, which may limit the generalizability of the current findings. Perceived control was not directly measured.Conclusions: Lower reinforcement rates create ambiguity between effective and ineffective situations of avoidance, which engenders generalization of unpredictability from effective to ineffective situation, thereby driving up ineffective avoidance rates. Partially reinforced effective avoidance responses and elevated ineffective avoidance responses together lead to more exposure to uncontrollable threat, weakening the sense of control over the threat, which could further increase avoidance behaviors. Controllability is often overlooked in avoidance research but can be key to understanding the development of maladaptive avoidance behaviors. [ABSTRACT FROM AUTHOR]

Animals and humans can easily learn to associate an initially neutral cue with food intake through classical conditioning, but extinction of learned appetitive responses can be more difficult. Intermittent or partial reinforcement of food cues causes especially persistent behaviour in animals: after exposure to such learning schedules, the decline in responding that occurs during extinction is slow. After extinction, increases in responding with renewed reinforcement of food cues (reacquisition) might be less rapid after acquisition with partial reinforcement. In humans, it may be that the eating behaviour of some individuals resembles partial reinforcement schedules to a greater extent, possibly affecting dieting success by interacting with extinction and reacquisition. Furthermore, impulsivity has been associated with less successful dieting, and this association might be explained by impulsivity affecting the learning and extinction of appetitive responses. In the present two studies, the effects of different reinforcement schedules and impulsivity on the acquisition, extinction, and reacquisition of appetitive responses were investigated in a conditioning paradigm involving food rewards in healthy humans. Overall, the results indicate both partial reinforcement schedules and, possibly, impulsivity to be associated with worse extinction performance. A new model of dieting success is proposed: learning histories and, perhaps, certain personality traits (impulsivity) can interfere with the extinction and reacquisition of appetitive responses to food cues and they may be causally related to unsuccessful dieting. [ABSTRACT FROM AUTHOR]

Avoidance in the face of novel situations or uncertainty is a prime feature of behavioral inhibition which has been put forth as a risk factor for the development of anxiety disorders. Recent work has found that behaviorally inhibited (BI) individuals acquire conditioned eyeblinks faster than non-inhibited (NI) individuals in omission and yoked paradigms in which the predictive relationship between the conditioned stimulus (CS) and unconditional stimulus (US) is less than optimal as compared to standard training with CS-US paired trials (Holloway et al., 2014). In the current study, we tested explicitly partial schedules in which half the trials were CS alone or US alone trials in addition to the standard CS-US paired trials. One hundred and forty nine college-aged undergraduates participated in the study. All participants completed the Adult Measure of Behavioral Inhibition (i.e., AMBI) which was used to group participants as BI and NI. Eyeblink conditioning consisted of three US alone trials, 60 acquisition trials, and 20 CS-alone extinction trials presented in one session. Conditioning stimuli were a 500 ms tone CS and a 50-ms air puff US. Behaviorally inhibited individuals receiving 50% partial reinforcement with CS alone or US alone trials produced facilitated acquisition as compared to NI individuals. A partial reinforcement extinction effect (PREE) was evident with CS alone trials in BI but not NI individuals. These current findings indicate that avoidance prone individuals self-reporting behavioral inhibition overlearn an association and are slow to extinguish conditioned responses (CRs) when there is some level of uncertainty between paired trials and CS or US alone presentations. [ABSTRACT FROM AUTHOR]

Abstract: Unpredictable stress is known to profoundly enhance susceptibility to fear and anxiety while reducing the ability to extinguish fear when threat is no longer present. Accordingly, partial aversive reinforcement, via random exposure to footshocks, induces fear that is resistant to extinction. Here we sought to determine the hippocampal mechanisms underlying susceptibility versus resistance to context fear extinction as a result of continuous (CR) and partial (PR) reinforcement, respectively. We focused on N-methyl-D-aspartate receptor (NMDAR) subunits 2A and B (NR2A and NR2B) as well as their downstream signaling effector, extracellular signal-regulated kinase (ERK), based on their critical role in the acquisition and extinction of fear. Pharmacological inactivation of NR2A, but not NR2B, blocked extinction after CR, whereas inactivation of NR2A, NR2B, or both subunits facilitated extinction after PR. The latter finding suggests that co-activation of NR2A and NR2B contributes to persistent fear following PR. In contrast to CR, PR increased membrane levels of ERK and NR2 subunits after the conditioning and extinction sessions, respectively. In parallel, nuclear activation of ERK was significantly reduced after the extinction session. Thus, co-activation and increased surface expression of NR2A and NR2B, possibly mediated by ERK, may cause persistent fear. These findings suggest that patients with post-traumatic stress disorder (PTSD) may benefit from antagonism of specific NR2 subunits. [Copyright &y& Elsevier]

The ambiguous-cue problem is deceptively simple. It involves two concurrently trained simultaneous discriminations (known as PA and NA trials), but only three stimuli. Stimulus A is common to both discriminations, but serves as non-reinforced stimulus (S--) on PA trials and as reinforced stimulus (S+) on NA trials. Typically, animals' accuracy is lower on PA trials--the ambiguous-cue effect. We conducted two experiments with European starlings (Sturnus vulgaris) using Urcuioli and Michalek's (2007, Psychon B Rev 14, 658--662) experimental manipulations as a springboard to test the predictions of two of the most important theoretical accounts of the effect: the interfering cue hypothesis and value transfer theory. Both experiments included two groups of birds, one trained with a regular ambiguous-cue problem (Group Continuous) and another trained with partial reinforcement on PA trials (Group PA-Partial).The experiments differed only in the number of sessions (18 vs. 36) and daily trials (360 vs. 60). As previously observed, we found faster acquisition on NA trials than on PA trials in both experiments, but by the end of training PA performance was surprisingly high, such that no ambiguous-cue effect was present in Group Continuous of either experiment. The effect was still present in both PA-Partial groups, but to a smaller degree than expected. These findings are inconsistent with the literature, in particular with the results of Urcuioli and Michalek (2007) with pigeons, and question the aforementioned theoretical accounts as complete explanations of the ambiguous-cue effect. In our view, to achieve such high levels of accuracy on PA trials, starlings must have attended to configural (i.e., contextual) cues, thus differentiating stimulus A when presented on PA trials from stimulus A when presented on NA trials. A post hoc simulation of a reinforcement-based configural model supported our assertion. [ABSTRACT FROM AUTHOR]

Abstract: Numerous studies indicate that placebo analgesia can be established via conditioning procedures. However, these studies have exclusively involved conditioning under continuous reinforcement. Thus, it is currently unknown whether placebo analgesia can be established under partial reinforcement and how durable any such effect would be. We tested this possibility using electrocutaneous pain in healthy volunteers. Sixty undergraduates received placebo treatment (activation of a sham electrode) under the guise of an analgesic trial. The participants were randomly allocated to different conditioning schedules, namely continuous reinforcement (CRF), partial reinforcement (PRF), or control (no conditioning). Conditioning was achieved by surreptitiously reducing pain intensity during training when the placebo was activated compared with when it was inactive. For the CRF group, the placebo was always followed by a surreptitious reduction in pain during training. For the PRF group, the placebo was followed by a reduction in pain stimulation on 62.5% of trials only. In the test phase, pain stimulation was equivalent across placebo and no placebo trials. Both CRF and PRF produced placebo analgesia, with the magnitude of initial analgesia being larger after CRF. However, although the placebo analgesia established under CRF extinguished during test phase, the placebo analgesia established under PRF did not. These findings indicate that PRF can induce placebo analgesia and that these effects are more resistant to extinction than those established via CRF. PRF may therefore reflect a novel way of enhancing clinical outcomes via the placebo effect. [Copyright &y& Elsevier]