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Navigation ability is particularly sensitive to aging. Evidence of aging patterns is largely restricted to comparing young adults and elderly and limited in the variety of navigation tasks used. Therefore, we designed a novel task battery to assess navigation ability in a very large, representative sample (N = 11,887, 8–100 years). The main aim was to measure navigation ability across the lifespan in a brief, yet comprehensive manner. Tasks included landmark knowledge, egocentric and allocentric location knowledge, and path knowledge for a route and survey perspective. Additionally, factors that potentially contribute to navigation ability were considered; gender, spatial experience and spatial anxiety. Increase in performance with age in children was found for allocentric location knowledge and for route-based path knowledge. Age related decline was found for all five tasks, each with clearly discernible aging patterns, substantiated the claim that each task distinctively contributes to the assessment of navigation ability. This study provides an in depth examination of navigation ability across dissociable functional domains and describes cognitive changes across the lifespan. The outcome supports the use of this task battery for brief assessment of navigation for experimental and clinical purposes.

Placebo and nocebo effects are known to play a key role in treatment effects in a wide variety of conditions. These effects have frequently been investigated with regard to pain and also in other physical sensations, but have hardly been investigated with regard to itch. In addition, neither in pain nor in any other physical sensation, the single and combined contribution of the expectancy mechanisms of conditioning and verbal suggestion have ever been investigated in both placebo and nocebo effects within one design. For the first time, the role of verbal suggestion and conditioning in placebo and nocebo effects on itch was experimentally investigated. Expectations about itch stimuli were induced in healthy subjects by verbal suggestion, conditioning, or a combination of both procedures, and compared with a control group without expectation induction. Itch was induced electrically by means of quantitative sensory testing. Significant placebo and nocebo effects were induced in the group in which combined procedures of conditioning and verbal suggestion were applied in comparison with the control group. The conditioning and verbal suggestion procedures applied individually did not induce significant placebo and nocebo effects when compared with the control group. The results of this study extend existing evidence on different physical sensations, like pain, by showing that also for itch, the combination of conditioning and verbal suggestion is most promising in inducing both placebo and nocebo effects. More research on placebo and nocebo effects at a perceptive and neurobiological level is warranted to further elucidate the common and specific mechanisms underlying placebo and nocebo effects on itch and other physical sensations.

Nocebo effects, i.e., adverse treatment effects which are induced by patients' expectations, are known to contribute to the experience of physical symptoms such as pain and itch. A better understanding of how to minimize nocebo responses might eventually contribute to enhanced treatment effects. However, little is known about how to reduce nocebo effects. In the current randomized controlled study, we tested whether nocebo effects can be minimized by positive expectation induction with respect to electrical and histaminic itch stimuli. First, negative expectations about electrical itch stimuli were induced by verbal suggestion and conditioning (part 1: induction of nocebo effect). Second, participants were randomized to either the experimental group or one of the control groups (part 2: reversing nocebo effect). In the experimental group, positive expectations were induced by conditioning with verbal suggestion. In the control groups either the negative expectation induction was continued or an extinction procedure was applied. Afterwards, a histamine application test was conducted. Positive expectation induction resulted in a significantly smaller nocebo effect in comparison with both control groups. Mean change itch NRS scores showed that the nocebo effect was even reversed, indicating a placebo effect. Comparable effects were also found for histamine application. This study is the first to demonstrate that nocebo effects can be minimized and even reversed by conditioning with verbal suggestion. The results of the current study indicate that learning via counterconditioning and verbal suggestion represents a promising strategy for diminishing nocebo responses.

Background Progression of chronic kidney disease (CKD) may be delayed if patients engage in healthy lifestyle behaviors. However, lifestyle adherence is very difficult and may be influenced by problems in psychosocial functioning. This qualitative study was performed to gain insights into psychosocial barriers and facilitators for lifestyle adherence among patients with CKD not receiving dialysis. Methods Eight semi-structured focus groups were conducted with a purposive sample of 24 patients and 23 health care professionals from four Dutch medical centers. Transcripts were analyzed using thematic analysis. Subsequently, the codes from the inductive analysis were deductively mapped onto the Theoretical Domains Framework (TDF). Results Many psychosocial barriers and facilitators for engagement in a healthy lifestyle were brought forward, such as patients’ knowledge and intrinsic motivation, emotional wellbeing and psychological distress, optimism, and disease acceptance. The findings of the inductive analysis matched all fourteen domains of the TDF. The most prominent domains were ‘social influences’’and ‘environmental context and resources’, reflecting how patients’ environments hinder or support engagement in a healthy lifestyle. Conclusions The results indicate a need for tailored behavioral lifestyle interventions to support disease self-management. The TDF domains can guide development of adequate strategies to identify and target individually experienced psychosocial barriers and facilitators.

S-ketamine and midazolam are frequently used to provide sedation while maintaining spontaneous respiration. However, the effects of these agents on respiratory variability, which reflects the adaptability of the respiratory system, have not been thoroughly explored. We evaluated these effects in a randomized controlled pilot trial. This study was conducted as part of a randomized controlled trial originally designed to assess the effects of s-ketamine conditioning on pain sensitivity in patients with fibromyalgia syndrome. Participants were randomly assigned to receive an infusion of either s-ketamine (0.3 mg kg -1 h -1 ), midazolam (0.05 mg kg -1 h -1 ), or saline in a blinded fashion. Mean respiratory rate, variability of respiratory rate (VRR), and variability of tidal volume (VTV) were measured continuously and non-invasively with a bio-impedance method. Changes during drug infusion were compared in a linear mixed model to assess the effects of s-ketamine and midazolam compared to saline. Data were analyzed for 57 experiments in 28 participants. Their median baseline variabilities of respiratory rate and tidal volume were 0.19 (IQR: 0.16–0.25) and 0.23 (0.19–0.34), respectively. While mean respiratory rate was not affected, midazolam resulted in a significant decrease in both VRR (ß = −0.071, 95% CI: −0.120 to −0.021) and VTV (ß = −0.117, 95% CI: −0.170 to −0.062). In contrast, s-ketamine appeared to produce a smaller decrease in VTV (ß = −0.062, 95% CI: −0.118 to −0.003) with VRR remaining unaffected (ß = −0.036, 95% CI: −0.092 to 0.019). In conclusion, our study demonstrates that midazolam reduces respiratory variability, potentially impairing the adaptability of the respiratory system. In contrast, s-ketamine largely preserved respiratory variability, suggesting it may be a safer alternative for sedation in patients with impaired spontaneous breathing. Further studies are needed to assess the clinical implications of these observations in patients undergoing sedation.

Despite the increasing knowledge about placebo effects and their beneficial impact on treatment outcomes, strategies that explicitly employ these mechanisms remain scarce. To benefit from placebo effects, it is important to gain better understanding in how individuals want to be informed about placebo effects (for example about the underlying mechanisms that steer placebo effects). The main aim of this study was to investigate placebo information strategies in a general population sample by assessing current placebo knowledge, preferences for different placebo explanations (built around well-known mechanisms involved in placebo effects), and attitudes and acceptability towards the use of placebo effects in treatment. Online survey. Leiden, The Netherlands. 444 participants (377 completers), aged 16-78 years. Current placebo knowledge, placebo explanation preferences, and placebo attitudes and acceptability. Participants scored high on current placebo knowledge (correct answers: M = 81.15%, SD = 12.75). Comparisons of 8 different placebo explanations revealed that participants preferred explanations based on brain mechanisms and positive expectations more than all other explanations (F(7, 368) = 3.618, p = .001). Furthermore, attitudes and acceptability for placebos in treatment varied for the type of the condition (i.e. more acceptant for psychological complaints) and participants indicated that physicians do not always have to be honest while making use of placebo effects for therapeutic benefit. Our results brought forth new evidence in placebo information strategies, and indicated that explanations based on brain mechanisms and positive expectations were most preferred. These results can be insightful to construct placebo information strategies for both clinical context and research practices.

Rapidly attending towards potentially harmful stimuli to prevent possible damage to the body is a critical component of adaptive behavior. Research suggests that individuals display an attentional bias, i.e., preferential allocation of attention, for consciously perceived bodily sensations that signal potential threat, like itch or pain. Evidence is not yet clear whether an attentional bias also exists for stimuli that have been presented for such a short duration that they do not enter the stream of consciousness. This study investigated whether a preconscious attentional bias towards itch-related pictures exists in 127 healthy participants and whether this can be influenced by priming with mild itch-related stimuli compared to control stimuli. Mild itch was induced with von Frey monofilaments and scratching sounds, while control stimuli where of matched modalities but neutral. Attentional bias was measured with a subliminal pictorial dot-probe task. Moreover, we investigated how attentional inhibition of irrelevant information and the ability to switch between different tasks, i.e., cognitive flexibility, contribute to the emergence of an attentional bias. Attentional inhibition was measured with a Flanker paradigm and cognitive flexibility was measured with a cued-switching paradigm. Contrary to our expectations, results showed that participants attention was not biased towards the itch-related pictures, in facts, attention was significantly drawn towards the neutral pictures. In addition, no effect of the itch-related priming was observed. Finally, this effect was not influenced by participants’ attentional inhibition and cognitive flexibility. Therefore, we have no evidence for a preconscious attentional bias towards itch stimuli. The role of preconscious attentional bias in patients with chronic itch should be investigated in future studies.

There is initial support for the effectiveness of approach-avoidance trainings in altering food-related health behaviors. Furthermore, outcome expectancies induced by verbal suggestions might optimize the effectiveness of these interventions, as shown in placebo research. The present study investigated the effectiveness of a gamified approach-avoidance training on food-related outcomes and whether verbal suggestions could strengthen those effects. A total of 120 participants were randomly assigned to 1 of 4 conditions: serious gaming only, verbal suggestions only, serious gaming combined with verbal suggestions, or a gaming control condition. Virtual food preference and food choice were assessed with a food choice task, with pairs differing in healthiness or in healthiness and attractiveness. Implicit food preference was assessed with an Implicit Association Test and food intake with a bogus taste test. Participants in both serious gaming conditions made healthier food choices for pairs differing in healthiness and attractiveness and had healthier implicit food preferences compared to gaming control. No effects were found on food intake. These findings provide the first preliminary support for the effects of a gamified approach-avoidance training on virtual food choice and implicit food preference. Future studies should further elucidate these effects, also in other health domains such as physical activity.

This study aimed to identify electrophysiological correlates of nocebo-augmented pain. Nocebo hyperalgesia (i.e., increases in perceived pain resulting from negative expectations) has been found to impact how healthy and patient populations experience pain and is a phenomenon that could be better understood in terms of its neurophysiological underpinnings. In this study, nocebo hyperalgesia was induced in 36 healthy participants through classical conditioning and negative suggestions. Electroencephalography was recorded during rest (pre- and post-acquisition) and during pain stimulation (baseline, acquisition, evocation) First, participants received baseline high thermal pain stimulations. During nocebo acquisition, participants learned to associate an inert gel applied to their forearm with administered high pain stimuli, relative to moderate intensity control stimuli administered without gel. During evocation, all stimuli were accompanied by moderate pain, to measure nocebo responses to the inert gel. Pre- to post-acquisition beta-band alterations in long-range temporal correlations (LRTC) were negatively associated with nocebo magnitudes. Individuals with strong resting LRTC showed larger nocebo responses than those with weaker LRTC. Nocebo acquisition trials showed reduced alpha power. Alpha power was higher while LRTC were lower during nocebo-augmented pain, compared to baseline. These findings support nocebo learning theories and highlight a role of nocebo-induced cognitive processing.

Background The effects of many treatments in healthcare are determined by factors other than the treatment itself. Patients’ expectations and the relationship with their healthcare provider can significantly affect treatment outcomes and thereby play a major role in eliciting placebo and nocebo effects. We aim to develop and evaluate an innovative communication training, consisting of an e-learning and virtual reality (VR) training, for healthcare providers across all disciplines, to optimize placebo and minimize nocebo effects through healthcare provider-patient communication. The current paper describes the development, mid-term evaluation, optimization, and final evaluation of the communication training, conducted in The Netherlands. Methods The development of both the e-learning and the VR training consisted of four phases: 1) content and technical development, 2) mid-term evaluation by healthcare providers and placebo/communication researchers, 3) optimization of the training, and 4) final evaluation by healthcare providers. To ensure the success, applicability, authenticity, and user-friendliness of the communication training, there was ongoing structural collaboration with healthcare providers as future end users, experts in the field of placebo/communication research, and educational experts in all phases. Results Placebo/communication researchers and healthcare providers evaluated the e-learning positively (overall 7.9 on 0–10 scale) and the content was perceived as useful, accessible, and interesting. The VR training was assessed with an overall 6.9 (0–10 scale) and was evaluated as user-friendly and a safe method for practicing communication skills. Although there were some concerns regarding the authenticity of the VR training (i.e. to what extent the virtual patient reacts like a real patient), placebo and communication researchers, as well as healthcare providers, recognized the significant potential of the VR training for the future. Conclusions We have developed an innovative and user-friendly communication training, consisting of an e-learning and VR training (2D and 3D), that can be used to teach healthcare providers how to optimize placebo effects and minimize nocebo effects through healthcare provider-patient communication. Future studies can work on improved authenticity, translate the training into other languages and cultures, expand with additional VR cases, and measure the expected effects on providers communication skills and subsequently patient outcomes.