Attention and Nocebo Hyperalgesia: Testing a Novel Virtual Reality Attention Bias Modification Paradigm.

Nocebo effects in pain (nocebo hyperalgesia) have received significant attention recently, with negative expectancies and anxiety proposed to be explanatory factors. While both expectancy and anxiety can bias attention, attention has been rarely explored as a potential mechanism involved in nocebo hyperalgesia. The present study aimed to explore whether attention bias modification (ABM) using an immersive, ecologically valid VR paradigm successfully induced attention biases (AB) and subsequently influenced nocebo hyperalgesia. One-hundred and two healthy participants were randomised in a 2 (AB training: towards vs. away from pain) x 2 (nocebo condition: nocebo vs. control) design. Pain-related AB was successfully changed by the VR paradigm as measured by reaction time and gaze, with moderate to large effects. Participants then completed either a nocebo instruction and conditioning procedure (nocebo paradigm) or a matched control procedure. The primary outcome was self-reported pain intensity. Secondary outcomes were attention bias and self-reports of expectancy, anticipatory anxiety, and state anxiety. The nocebo paradigm induced significantly greater pain expectancy, anticipatory anxiety and pain intensity during the test phase for the nocebo group compared to control. Pain expectancy also fully mediated the effect of the nocebo group on nocebo hyperalgesia and anticipatory anxiety in separate models. ABM did not, however, affect nocebo hyperalgesia or pain expectancy, casting doubt on the potential for ABM to inoculate against nocebo hyperalgesia. Unexpected effects of ABM were observed for state anxiety and anticipatory anxiety, whereby training away from pain exacerbated each, which necessitates further exploration. PERSPECTIVE: This article tests the efficacy of a novel attention bias modification paradigm, designed in virtual reality, for inducing pain-related biases, and whether these biases exacerbate or inoculate against nocebo hyperalgesia. While pain-related biases were successfully induced, there was no relationship with the strength of induced nocebo hyperalgesia.

Interpersonal physiological and psychological synchrony predict the social transmission of nocebo hyperalgesia between individuals.

Witnessing another's pain can heighten pain in the observer. However, research has focused on the observer's intrapersonal experience. Here, a social transmission-chain explored the spread of socially-acquired nocebo hyperalgesia. Dyads of genuine participants were randomised to 'Generations' (G1-G3). G1-Demonstrators, observed by G2-Observers, experienced high/low thermal pain contingent on supposed activity/inactivity of a sham-treatment. G2 became Demonstrators, witnessed by G3-Observers. They experienced fixed low-temperature stimuli irrespective of sham-treatment 'activity'. G3 then Demonstrated for G4-Observers (a confederate), also experiencing low-temperature stimuli only. Pain ratings, electrodermal activity, and facial action units were measured. G1's treatment-related pain propagated throughout the chain. G2 and G3 participants showed heightened subjective and physiological response to sham-treatment, despite equivalent stimulus temperatures, and G3 never witnessing the initial pain-event. Dyadic interpersonal physiological synchrony (electrodermal activity) and psychological synchrony (Observer's ability to predict the Demonstrator's pain), predicted subsequent socially-acquired pain. Implications relate to the interpersonal spread of maladaptive pain experiences.

The effect of social learning on the nocebo effect: a systematic review and meta-analysis with recommendations for the future.

ABSTRACTIndividuals frequently update their beliefs and behaviours based on observation of others' experience. While often adaptive, social learning can contribute to the development of negative health expectations, leading to worsened health outcomes, a phenomenon known as the nocebo effect. This systematic review and meta-analysis examined: whether social learning is sufficient to induce the nocebo effect, how it compares to other forms of induction (classical conditioning and explicit instruction), and factors that influence these effects. The meta-analysis included twenty studies (n = 1388). Social learning showed a medium-large effect size (Hedges' g = .74) relative to no treatment and a to small-medium effect (g = .42) when compared to neutral modelling. The effect of social learning was similar in magnitude to classical conditioning but greater than explicit instruction with a small-medium effect (g = .46). Face-to-face social modelling, longer exposure, higher proportions of female participants and models, and greater observer empathy led to stronger socially-induced nocebo effects. However, further research is essential as only a minority of studies measured important constructs like negative expectancies and state anxiety. Nonetheless, the study highlights social learning as a key pathway for nocebo effects, suggesting it as a target for interventions to reduce the substantial personal and societal burden caused by nocebo effects.

Attentional Processes in Pain: The Importance of Context and Attentional Alignment.

The attentional bias literature has consistently failed to take context into account. We developed a novel paradigm in immersive virtual reality (VR) with pain stimuli where it would be adaptive or nonadaptive to attend to the stimuli. Participants had to indicate the location of the stimuli. Seventy participants were recruited. The VR-attention task assessed overall attentional bias (the tendency to prioritize pain compared with nonpain stimuli) and attentional alignment (the tendency to attend to pain more in adaptive than nonadaptive situations). Pain tolerance and threshold were measured using electrocutaneous stimulation and thermal pain. We conducted 2 (context: adaptive vs nonadaptive) × 2 (congruence: congruent vs incongruent) Analysis of Covariance, controlling for threat. Participants responded to pain probes more quickly in adaptive than nonadaptive contexts. There was an overall bias away from pain-related stimuli (avoidance) in reaction time to the target. There was also an interaction where avoidance was greater in nonadaptive contexts, indicative of attentional alignment. For gaze behavior, both attentional alignment and attentional bias were observed for latency to first fixation on the target, such that participants showed vigilance for pain particularly in the adaptive context. Attentional alignment was correlated with threshold and tolerance from electrocutaneous stimulation but not thermal pain. In conclusion, we found overall attentional biases indicating vigilance (latency to first fixation) and avoidance (response to target). We also found that participants evidenced a pattern of attention favoring adaptive over nonadaptive contexts (attentional alignment). It was attentional alignment, but not overall attentional bias, that predicted pain tolerance and threshold. PERSPECTIVE: The study explored attentional processes in pain through a novel paradigm designed in VR. The results found that positive attentional alignment, or the tendency to attend to pain more in adaptive contexts rather than nonadaptive contexts, predicted pain outcomes.

Instruction on the Scientific Method Provides (Some) Protection Against Illusions of Causality.

People tend to overestimate the efficacy of an ineffective treatment when they experience the treatment and its supposed outcome co-occurring frequently. This is referred to as the outcome density effect. Here, we attempted to improve the accuracy of participants' assessments of an ineffective treatment by instructing them about the scientific practice of comparing treatment effects against a relevant base-rate, i.e., when no treatment is delivered. The effect of these instructions was assessed in both a trial-by-trial contingency learning task, where cue administration was either decided by the participant (Experiments 1 & 2) or pre-determined by the experimenter (Experiment 3), as well as in summary format where all information was presented on a single screen (Experiment 4). Overall, we found two means by which base-rate instructions influence efficacy ratings for the ineffective treatment: 1) When information was presented sequentially, the benefit of base-rate instructions on illusory belief was mediated by reduced sampling of cue-present trials, and 2) When information was presented in summary format, we found a direct effect of base-rate instruction on reducing causal illusion. Together, these findings suggest that simple instructions on the scientific method were able to decrease participants' (over-)weighting of cue-outcome coincidences when making causal judgements, as well as decrease their tendency to over-sample cue-present events. However, the effect of base-rate instructions on correcting illusory beliefs was incomplete, and participants still showed illusory causal judgements when the probability of the outcome occurring was high. Thus, simple textual information about assessing causal relationships is partially effective in influencing people's judgements of treatment efficacy, suggesting an important role of scientific instruction in debiasing cognitive errors.

The downside to choice: instrumental control increases conditioned nocebo hyperalgesia.

ABSTRACT: Nocebo hyperalgesia is a pervasive problem in which the treatment context triggers negative expectations that exacerbate pain. Thus, developing ethical strategies to mitigate nocebo hyperalgesia is crucial. Emerging research suggests that choice has the capacity to reduce nocebo side effects, but choice effects on nocebo hyperalgesia have not been explored. This study investigated the impact of choice on conditioned nocebo hyperalgesia using a well-established electrocutaneous pain paradigm where increases in noxious stimulation were surreptitiously paired with the activation of a sham device. In study 1, healthy volunteers (N = 104) were randomised to choice over (nocebo) treatment administration, nocebo administration without choice, or a natural history control group. Nocebo hyperalgesia was greater for those with choice than no choice, suggesting that choice increased rather than diminished nocebo hyperalgesia. Study 2 tested whether providing positive information about the benefits of choice in coping with pain could counteract heightened nocebo hyperalgesia caused by choice. A different sample of healthy adults (N = 137) were randomised to receive nocebo treatment with choice and positive choice information, choice only, or no choice. The positive choice information failed to attenuate the effect of choice on nocebo hyperalgesia. The current results suggest that, rather than decreasing nocebo hyperalgesia, treatment choice may exacerbate pain outcomes when a painful procedure is repeatedly administered. As such, using choice as a strategy to mitigate nocebo outcomes should be treated with caution.

Beyond the modified dot-probe task: A meta-analysis of the efficacy of alternate attention bias modification tasks across domains.

Attention biases towards disease-relevant cues have been implicated in numerous disorders and health conditions, such as anxiety, cancer, drug-use disorders, and chronic pain. Attention bias modification (ABM) has shown that changing attention biases can change related emotional processes. ABM most commonly uses a modified dot-probe task, which has received increasing criticism regarding its reliability and inconsistent findings. The purpose of the present review was thus to systematically review and meta-analyse alternative tasks used in ABM research. We sought to examine whether alternative tasks significantly changed attention biases and emotional outcomes, and critically examined whether relevant sample, task and intervention characteristics moderated each of these effect sizes. Seventy-four (completer n = 15,294) study level comparisons were included in the meta-analysis. Overall, alternative ABM designs had a medium effect on changing biases (g = 0.488), and a small, but significant effect on improving clinical outcomes (g = 0.117). We found this effect to be significantly larger for studies which successfully changed biases compared to those that did not. Across all tasks, it appeared that targeting engagement biases results in the largest change to attention biases. Importantly, we found tasks incorporating gaze-contingency - encouraging engagement with non-biased stimuli - show the most promise for improving emotional outcomes.

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

BACKGROUND: Latent 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. METHODS: In 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. DISCUSSION: It 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.

BACKGROUND: Dental 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. METHODS: Participants 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. DISCUSSION: The 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.

A synthesis of meta-analyses of mindfulness-based interventions in pain.

ABSTRACT: Mindfulness interventions have become popular in recent decades, with many trials, systematic reviews, and meta-analyses of the impact of mindfulness-based interventions (MBIs) on pain. Although many meta-analyses provide support for MBIs, the results are more mixed than they at first appear. The aim of this umbrella review was to determine the strength of evidence for MBIs by synthesizing available meta-analyses in pain. We conducted a systematic search in 5 databases and extracted data from published meta-analyses as the unit of analysis. For each outcome, we reported the range of effect sizes observed across studies and identified the largest meta-analysis as the "representative" study. We separately analysed effect sizes for different pain conditions, different types of MBIs, different control groups, and different outcomes. We identified 21 meta-analyses that included 127 unique studies. According to Assessment of Multiple Systematic Review ratings, the meta-analyses ranged from very strong to weak. Overall, there was an impact of MBIs on pain severity, anxiety, and depression but not pain interference or disability. When conditions were considered in isolation, only fibromyalgia and headache benefited significantly from MBIs. Mindfulness-based interventions were more efficacious for pain severity than passive control conditions but not active control conditions. Only pain severity and anxiety were affected by MBIs at follow-up. Overall, our results suggest that individual meta-analyses of MBIs may have overestimated the efficacy of MBIs in a range of conditions. Mindfulness-based interventions likely have a role in pain management but should not be considered a panacea.

Choice over placebo administration enhances open-label placebo hypoalgesia.

ABSTRACT: Many studies indicate that deceptively administered placebos can improve pain outcomes. However, the deception involved presents an ethical barrier to translation because it violates informed consent and patient autonomy. Open-label placebos (OLPs), inert treatments that are openly administered as placebos, have been proposed as an ethically acceptable alternative. Early studies have suggested that OLP can improve pain outcomes, but important questions remain as to how to maximise OLP hypoalgesia to improve treatment outcomes in pain patients. This study investigated whether providing choice over when to administer an OLP treatment has the capacity to enhance OLP hypoalgesia using an electrocutaneous pain paradigm. One hundred thirty-two healthy volunteers were randomised to 3 types of treatment: OLP with choice, OLP without choice, and no treatment (natural history). The OLP groups were further randomised such that half were tested with a consistent pain intensity and the other half were tested with variable pain intensity to mimic day-to-day variability in pain intensity in health settings. The results indicated that treatment provided with choice exhibited greater OLP hypoalgesia than that provided without choice and that greater expectancy mediated this effect. Of interest, there was no evidence for OLP hypoalgesia without choice relative to natural history. Furthermore, variability in pain intensity did not affect OLP hypoalgesia. The current findings present novel evidence that choice over treatment administration may be a cheap and effective strategy for boosting the efficacy of OLPs in the clinical care of pain.

Understanding the Role of Expectancy, Anticipatory Anxiety, and Attention Bias in Nocebo Hyperalgesia: A Gaze-Contingent Attention Bias Modification Study.

Nocebo effects in pain (nocebo hyperalgesia) have been thoroughly researched, and negative expectancies have been proposed as a key factor in causing nocebo hyperalgesia. However, little is known about the psychological mechanisms by which expectations exacerbate the perception of pain. A potential mechanism that has been proposed within wider pain research is pain-related attention. The aim of the present study was thus to explore whether attention bias (AB) to pain influenced nocebo hyperalgesia. One-hundred and thirty-four healthy participants were randomized in a 2 (AB training: towards vs away from pain) × 2 (nocebo condition: nocebo vs control) design. Pain-related AB was manipulated through a novel, partially gaze-contingent dot-probe task. Participants then completed either a nocebo instruction and conditioning paradigm or a matched control condition. Primary outcomes were measures of expectancy, anticipatory anxiety, and pain intensity completed during a nocebo test phase. Results showed that the AB manipulation was unsuccessful in inducing ABs either toward or away from pain. The nocebo paradigm induced significantly greater expectancy, anticipatory anxiety, and pain intensity for the nocebo groups compared to the control groups. In a posthoc analysis of participants with correctly induced ABs, AB towards pain amplified nocebo hyperalgesia, expectancy, and anticipatory anxiety relative to AB away from pain. The results are consistent with the expectancy model of nocebo effects and additionally identify anticipatory anxiety as an additional factor. Regarding AB, research is needed to develop reliable means to change attention sample-wide to corroborate the present findings. PERSPECTIVE: This article explores the role of AB, expectancy, and anticipatory anxiety in nocebo hyperalgesia. The study shows that expectancy can trigger anticipatory anxiety that exacerbates nocebo hyperalgesia. Further, successful AB training towards pain heightens nocebo hyperalgesia. These findings identify candidate psychological factors to target in minimizing nocebo hyperalgesia.

The nocebo effect across health outcomes: A systematic review and meta-analysis.

OBJECTIVE: The nocebo effect represents a growing concern in clinical settings. Nocebo effects occur when the treatment context generates negative expectancies that trigger the experience or worsening of negative symptoms beyond any effects attributable to the treatment itself. Despite being identified in a range of outcomes and conditions, from pain to Parkinson's disease, there has not been an attempt to systematically quantify the nocebo effects across health outcomes. The purpose of the present review was thus to systematically review and meta-analyze the nocebo literature to quantify the size of the nocebo effect across outcomes and examine which factors moderate the size of the nocebo effect, including process of induction, treatment type, or health outcome. METHOD: Systematic searches of PubMed, PychInfo, Medline, and Web of Science identified 130 (n = 8,219) independent eligible studies. To be included, studies had to include both a nocebo and control group/condition, which were compared to isolate the nocebo effect size. RESULTS: Overall, the magnitude of the nocebo effect was medium (g = 0.522) and highly heterogeneous. Two key moderators emerged: health outcome and process of induction. Here, the nocebo effect was medium for most somatic outcomes and affect, with no significant effect on worsening cognitive performance. Further, inducing nocebo effects through instruction in combination with conditioning produced larger nocebo effects. CONCLUSIONS: The present review suggests nocebo effects can be reliably induced across somatic health outcomes, and interventions that target the effect of instructions will be of critical importance to reducing the occurrence of nocebo effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Choice Enhances Placebo Hypoalgesia More in Weaker Placebo Contexts: A Partial Reinforcement Study.

Providing individuals with choice over treatment has been found to enhance placebo hypoalgesia. However, this choice effect is not always present. The current study tested whether the strength of the placebo context influenced the effect of choice on placebo hypoalgesia. Using an established electrocutaneous pain paradigm, the choice effect was compared when placebo hypoalgesia was induced by Continuous Reinforcement (CRF) (strong placebo context) versus partial reinforcement (PRF) (weak placebo context). Healthy volunteers (N = 133) were randomized to receive either choice over treatment administration or no choice and then to placebo conditioning under either CRF (placebo always followed by surreptitious pain reduction during training) or PRF (placebo only followed by surreptitious pain reduction on half of the training trials). At the test, placebo hypoalgesia was greater and more resistant to extinction overall for those with choice. Importantly, however, the choice effect in enhancing the magnitude of placebo hypoalgesia was stronger after PRF than CRF. These results indicate that choice may have greater placebo-enhancing power in weaker placebo contexts. Therefore, choice may be a cheap and effective tool for improving clinical outcomes by facilitating placebo hypoalgesia when the existing treatment context is insufficient to produce placebo hypoalgesia itself. PERSPECTIVE: This study demonstrates that the enhancing effect of choice on placebo hypoalgesia is greater in a weaker placebo context. As such, offering choice could be an ethical way to effectively improve pain outcomes when placebo effects cannot be readily produced by the treatment context.

Socially Acquired Nocebo Effects Generalize but Are Not Attenuated by Choice.

BACKGROUND: Socially observing a negative treatment-related experience has been shown to modulate our own experience with the same intervention, leading to worsened health outcomes. However, whether this social learning generalizes to similar but distinct interventions has not been explored nor what manipulations can reduce these effects. PURPOSE: To determine whether socially acquired nocebo effects can be generated by observing a negative experience with a similar, but distinct intervention, and whether choice can reduce these effects. METHODS: Across three experiments, a community sample of healthy adults (N = 336) either watched a confederate report cybersickness to the same Virtual Reality (VR) activity they were assigned to (Social Modeling: Consistent); a similar, but different VR activity (Social Modeling: Inconsistent); or did not view the confederate (No Social Modeling). Participants were either given choice over the VR (Choice) or assigned by the experimenter (No Choice). RESULTS: Across the experiments, there was significantly greater cybersickness in both Social Modeling groups relative to No Social Modeling, while the two Social Modeling groups did not differ. There was no significant effect of Choice or a Choice by Social Modeling interaction. Social Modeling elicited greater anxiety and expectancies for cybersickness. Furthermore, these mechanisms mediated the association between social modeling and cybersickness. CONCLUSIONS: Socially acquired side-effects were demonstrated to generalize to similar, but distinct interventions, highlighting the diffuse and robust effect social modeling can have on our experiences. However, choice did not attenuate the experience of cybersickness, highlighting the need for alternative methods to counteract the effect of social modeling.

Witnessing someone experience cybersickness during Virtual Reality (VR) generated a nocebo effect in the observer, exacerbating their own symptoms when subsequently encountering VR. The nocebo effect was not specific to the VR activity witnessed, but generalized across different VR experiences, demonstrating that socially acquired nocebo effects are likely to spread rapidly. Choice of VR environment did not reduce the nocebo effect elicited in the observer.

Placebo effects contribute to brief online mindfulness interventions for chronic pain: results from an online randomized sham-controlled trial.

ABSTRACT: Mindfulness apps are becoming popular treatments for chronic pain and mental health, despite mixed evidence supporting their efficacy. Furthermore, it is unclear whether improvements in pain are due to mindfulness-specific effects or placebo effects because no trials have compared mindfulness against a sham control. The objective of this study was to compare mindfulness against 2 sham conditions with differing proximity to mindfulness to characterize the relative contributions of mindfulness-specific and nonspecific processes on chronic pain. We assessed changes in pain intensity and unpleasantness and mindfulness-specific and nonspecific pain-related processes in 169 adults with chronic or recurrent pain randomized to receive a single 20-minute online session of mindfulness, specific sham mindfulness, general sham mindfulness, or audiobook control. Mindfulness was not superior to shams for reducing pain intensity or unpleasantness, and no differential engagement of theorized mindfulness-specific processes was observed. However, mindfulness and both shams reduced pain unpleasantness relative to audiobook control, with expectancy most strongly associated with this effect. Sham specificity had no influence on expectancy or credibility ratings, pain catastrophizing, or pain effects. These findings suggest that improvements in chronic pain unpleasantness following a single session of online-delivered mindfulness meditation may be driven by placebo effects. Nonspecific treatment effects including placebo expectancy and pain catastrophizing may drive immediate pain attenuation rather than theorized mindfulness-specific processes themselves. Further research is needed to understand whether mindfulness-specific effects emerge after longer durations of online training.

Peer-to-peer: The Social Transmission of Symptoms Online.

BACKGROUND: Social learning can be highly adaptive-for example, avoiding a hotplate your friend just burnt themselves on-but it has also been implicated in symptom transmission. Social learning is particularly pertinent given the rapid increase in the use of online mediums for social interaction. Yet, little is known about the social transmission of symptoms online or social chains extending further than a single model-observer interaction. PURPOSE: To explore whether socially induced symptoms could be propagated through a three-generation social transmission chain in an online setting. METHODS: We explored the social transmission of cybersickness following a virtual reality (VR) experience through online webcam interactions. One hundred and seventy-seven adults viewed a VR video in one of four links along a social transmission chain, after: viewing an actor model cybersickness to the VR video (First-Generation); viewing the First-Generation participant undergo VR (Second-Generation); viewing the Second-Generation participant undergo VR (Third-Generation); or naïve (Control). RESULTS: Cybersickness was strongest in First-Generation participants, indicating social transmission from the model. This was mediated by expectancy and anxiety. Whether or not subsequent generations experienced cybersickness depended on what the observed participant verbally reported, which is consistent with social transmission. CONCLUSIONS: Results demonstrate that symptoms can be readily transmitted online, and that expectancy and anxiety are involved. Although it is inconclusive as to whether symptoms can propagate along a social transmission chain, there is some evidence of protection from symptoms when a model who does not report any symptoms is observed. As such, this research highlights the role of social transmission in the modulation of symptoms through virtual mediums.

Social learning is a ubiquitous cognitive process whereby our own behaviors and experiences are influenced by observing others. Occasionally, this can involve the observation of an individual experiencing negative outcomes (e.g., pain or symptoms) following exposure to a treatment or intervention (e.g., consumption of medicine). Previous research has found that individuals may experience an increase in symptoms due to this social learning, even when their treatment has no active components. While research has primarily explored situations in which there is one model and one observer, it was of interest as to whether these socially induced symptoms can be transmitted beyond the first observer. Moreover, with social interaction through online mediums such as social media and video conferencing becoming more common, it was also of interest as to whether these symptoms can be transmitted online. The present findings highlight the significant role of social learning in symptom transmission, even when interactions occur online. With expectancy and anxiety being key features of this social transmission, this study highlights important implications for understanding how individuals can learn about their own future experiences through the observation of others.

Study protocol of an investigation of attention and prediction error as mechanisms of action for latent inhibition of dental fear in humans.

BACKGROUND: Evidence suggests that dental anxiety and phobia are frequently the result of direct associative fear conditioning but that pre-exposure to dental stimuli prior to conditioning results in latent inhibition of fear learning. The mechanisms underlying the pre-exposure effect in humans, however, are poorly understood. Moreover, pain sensitivity has been linked to dental fear conditioning in correlational investigations and theory suggests it may moderate the latent inhibition effect, but this hypothesis has not been directly tested. These gaps in our understanding are a barrier to the development of evidence-based dental phobia prevention efforts. METHODS: Healthy volunteers between the ages of 6 and 35 years will be enrolled across two sites. Participants will complete a conditioning task in a novel virtual reality environment, allowing for control over pre-exposure and the examination of behaviour. A dental startle (a brief, pressurized puff of air to a tooth) will serve as the unconditioned stimulus. Using a within-subjects experimental design, participants will experience a pre-exposed to-be conditioned stimulus, a non-pre-exposed to-be conditioned stimulus, and a neutral control stimulus. Two hypothesized mechanisms, changes in prediction errors and attention, are expected to mediate the association between stimulus condition and fear acquisition, recall, and retention. To ascertain the involvement of pain sensitivity, this construct will be measured through self-report and the cold pressor task. DISCUSSION: Dental phobia negatively affects the dental health and overall health of individuals. This study aims to determine the mechanisms through which pre-exposure retards conditioned dental fear acquisition, recall, and retention. A randomized control trial will be used to identify these mechanisms so that they can be precisely targeted and maximally engaged in preventative efforts.

Replication crisis and placebo studies: rebooting the bioethical debate.

A growing body of cross-cultural survey research shows high percentages of clinicians report using placebos in clinical settings. One motivation for clinicians using placebos is to help patients by capitalising on the placebo effect's reported health benefits. This is not surprising, given that placebo studies are burgeoning, with increasing calls by researchers to ethically harness placebo effects among patients. These calls propose placebos/placebo effects offer clinically significant benefits to patients. In this paper, we argue many findings in this highly cited and 'hot' field have not been independently replicated. Evaluating the ethicality of placebo use in clinical practice involves first understanding whether placebos are efficacious clinically. Therefore, it is crucial to consider placebo research in the context of the replication crisis and what can be learnt to advance evidence-based knowledge of placebos/placebo effects and their clinical relevance (or lack thereof). In doing so, our goal in this paper is to motivate both increased awareness of replication issues and to help pave the way for advances in scientific research in the field of placebo studies to better inform ethical evidence-based practice. We argue that, only by developing a rigorous evidence base can we better understand how, if at all, placebos/placebo effects can be harnessed ethically in clinical settings.

Reduction in caffeine withdrawal after open-label decaffeinated coffee.

BACKGROUND: Withdrawal from addictive drugs can be reduced by administering placebo deceptively, but in the clinic it is unethical to deceive the patient. Open-label placebo effects have been observed across a range of psychophysiological phenomena, and may also apply to drug withdrawal. METHOD: 24-hour abstinent heavy coffee drinkers (N = 61) rated their caffeine withdrawal symptoms before being allocated to one of three groups. The Deceptive group was given decaffeinated coffee (decaf) and told it was caffeinated, the Open-Label group given decaf and told it was decaf and the Control group given water and told it was water. After 45 min, caffeine withdrawal was measured again. All participants rated their expectancies of withdrawal reduction from caffeinated coffee, decaf and water prior to being randomised and the end of the study. RESULTS: There was a significant 9.5-point reduction in caffeine withdrawal in the Open-Label group (95% confidence interval (CI): 4.7, 14.3; p = 0.002), which was 8.6 points less than the Deceptive group (95%CI: 0.4, 16.8; p = 0.014) but 8.9 points greater than the Control group (95%CI: 0.6, 17.2; p = 0.012). Pre-randomisation, participants expected caffeinated coffee to reduce their withdrawal symptoms the most, followed by water and decaf, Pre-randomisation expectancy of withdrawal was only associated with amount of withdrawal reduction in the Deceptive group. CONCLUSION: It appears as if open-label placebo caffeine (i.e. decaf) can reduce caffeine withdrawal symptoms, even when people do not hold a conscious expectancy it will do so. There may be ways to integrate open-label placebo procedures into clinical interventions for drug dependence without violating informed consent.