Development of a computerized 2D rating scale for continuous and simultaneous evaluation of two dimensions of a sensory stimulus

INTRODUCTION One-dimensional rating scales are widely used in research and in the clinic to assess individuals' perceptions of sensory stimuli. Although these scales provide essential knowledge of stimulus perception, their limitation to one dimension hinders our understanding of complex stimuli. METHODS To allow improved investigation of complex stimuli, a two-dimensional scale based on the one-dimensional Gracely Box Scale was developed and tested in healthy participants on a visual and an auditory task (rating changes in brightness and size of circles and rating changes in frequency and sound pressure of sounds, which was compared to ratings on one-dimensional scales). Before performing these tasks, participants were familiarized with the intensity descriptors of the two-dimensional scale by completing two tasks. First, participants sorted the descriptors based on their judgment of the intensity of the descriptors. Second, participants evaluated the intensity of the descriptors by pressing a button for the duration they considered matching the intensity of the descriptors or squeezing a hand grip dynamometer as strong as they considered matching the intensity of the descriptors. RESULTS Results from these tasks confirmed the order of the descriptors as displayed on the original rating scale. Results from the visual and auditory tasks showed that participants were able to rate changes in the physical attributes of visual or auditory stimuli on the two-dimensional scale as accurately as on one-dimensional scales. DISCUSSION These results support the use of a two-dimensional scale to simultaneously report multiple dimensions of complex stimuli

Endogenous opioids contribute to the feeling of pain relief in humans

Endogenous opioids mediate the pleasurable responses to positively reinforcing stimuli such as palatable food. Yet, the reduction or omission of a negative experience can also be rewarding (negative reinforcement). As such, pain relief leads to negative reinforcement and evokes a pleasant feeling in humans. Although it has been shown that the feeling of pleasure associated with positive reinforcement is at least partly mediated through endogenous opioids, it is currently unknown whether similar neurochemical mechanisms are involved in the pleasant feeling evoked by pain relief. In this study, 27 healthy participants completed 2 identical experimental sessions, 1 with placebo and 1 with naltrexone, an endogenous opioid antagonist. Pain relief was induced by superficial cooling after heat stimulation of capsaicin-sensitized skin. Participants rated the relief and pleasantness in response to the cooling. Endogenous opioid blockade by naltrexone decreased relief and pleasantness ratings compared with placebo (P 5 0.0027). This study provides evidence that endogenous opioids play a role in mediating the pleasant feeling of pain relief in humans. Clinically, the rewarding nature of pain relief and its underlying mechanisms require consideration because of their potential reinforcing effects on behaviors that might be beneficial short-term but maladaptive long-term

Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain

INTRODUCTION: Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline. This will facilitate risk stratification in adolescent patients with chronic MSK pain and more resourceful allocation of patients to costly and potentially burdensome multidisciplinary pain treatment approaches. METHODS AND ANALYSIS: Here we describe a multi-institutional effort to collect, curate and analyse a high dimensional data set including epidemiological, psychometric, quantitative sensory, brain imaging and biological information collected over the course of 12 months. The aim of this effort is to derive a multivariate model with strong prognostic power regarding the clinical course of adolescent MSK pain and function. ETHICS AND DISSEMINATION: The study complies with the National Institutes of Health policy on the use of a single internal review board (sIRB) for multisite research, with Cincinnati Children's Hospital Medical Center Review Board as the reviewing IRB. Stanford's IRB is a relying IRB within the sIRB. As foreign institutions, the University of Toronto and The Hospital for Sick Children (SickKids) are overseen by their respective ethics boards. All participants provide signed informed consent. We are committed to open-access publication, so that patients, clinicians and scientists have access to the study data and the signature(s) derived. After findings are published, we will upload a limited data set for sharing with other investigators on applicable repositories. TRIAL REGISTRATION NUMBER: NCT04285112

Le trouble de la personnalité borderline et ses facteurs environnementaux, génétiques et épigénétiques: possible effet des abus sexuels sur la méthylation du brain-derived neurotrophic factor dans une population borderline

Le trouble de la personnalité Borderline (BDL) est un trouble du groupe B des troubles de la personnalité (axe II du DSM-IV). Il est caractérisé notamment par des traits d'impulsivité – agressivité, une instabilité de l'humeur, une difficulté à gérer les émotions négatives, des comportements autodommageables, un trouble de l'identité et de nombreuses comorbidités, telles que des troubles dépressifs, bipolaires, des abus de substance ou des troubles des comportements alimentaires. Récemment des études ont démontré que des facteurs environnementaux, génétiques et épigénétiques peuvent être liés au déclenchement et au maintien du trouble. Nous nous intéresserons ici particulièrement à l'association entre les abus sexuels subis dans l'enfance et la méthylation du Brain-Derived Neurotrophic Factor (BDNF). Notre étude comporte une partie clinique, durant laquelle les données ont été recueillies par quatre autoquestionnaires et un hétéroquestionnaire, et une partie de biologie moléculaire, comprenant des analyses génétiques et épigénétiques de BDNF, incluant quatre SNPs, un microsatellite et 2 îlots CpG. Notre hypothèse génétique suppose que certains génotypes créent une vulnérabilité pour le développement de la maladie. Notre étude a permis de mettre en évidence non seulement des facteurs de risque, mais également des facteurs de protection. Du point de vue épigénétique, nous avons mis en évidence un lien clair entre le taux de méthylation et la présence d'un abus sexuel dans l'enfance, même si ce lien ne va pas dans le sens postulé au départ. De plus, chez les victimes d'abus sexuels dans l'enfance, le taux de méthylation augmente avec l'amélioration des symptômes dépressifs, mesurés au Beck Depression Inventory. Malgré des limitations importantes et le fait qu'il s'agisse ici de résultats préliminaires, notre étude montre clairement que la méthylation est un processus dynamique qui semble jouer un rôle dans le développement et l'évolution de la maladie

Evidence for an encounter expectancy bias in fear of spiders.

Whereas research has demonstrated that phobic or fearful individuals overestimate the likelihood of incurring aversive consequences from an encounter with feared stimuli, it has not yet been systematically investigated whether these individuals also overestimate the likelihood (i.e., the frequency) of such encounters. In the current study, spider-fearful and control participants were presented with background information that allowed them to estimate the overall likelihood that different kinds of animals (spiders, snakes, or birds) would be encountered. Spider-fearful participants systematically overestimated the likelihood of encountering a spider with respect to the likelihood of encountering a snake or a bird. No such expectancy bias was observed in control participants. The results thus strengthen our idea that there indeed exist two different types of expectancy bias in high fear and phobia that can be related to different components of the fear response. A conscientious distinction and examination of these two types of expectancy bias are of potential interest for therapeutic applications

Contributions of diagnostic, cognitive, and somatovisceral information to the prediction of fear ratings in spider phobic and non-spider-fearful individuals.

Background Physiological responding is a key characteristic of fear responses. Yet, it is unknown whether the time-consuming measurement of somatovisceral responses ameliorates the prediction of individual fear responses beyond the accuracy reached by the consideration of diagnostic (e.g., phobic vs. non phobic) and cognitive (e.g., risk estimation) factors, which can be more easily assessed. Method We applied a machine learning approach to data of an experiment, in which spider phobic and non-spider fearful participants (diagnostic factor) faced pictures of spiders. For each experimental trial, participants specified their personal risk of encountering the spider (cognitive factor), as well as their subjective fear (outcome variable) on quasi-continuous scales, while diverse somatovisceral responses were registered (heart rate, electrodermal activity, respiration, facial muscle activity). Results The machine-learning analyses revealed that fear ratings were predominantly predictable by the diagnostic factor. Yet, when allowing for learning of individual patterns in the data, somatovisceral responses contributed additional information on the fear ratings, yielding a prediction accuracy of 81% explained variance. Moreover, heart rate prior to picture onset, but not heart rate reactivity increased predictive power. Limitations Fear was solely assessed by verbal reports, only 27 females were considered, and no generalization to other anxiety disorders is possible. Conclusions After training the algorithm to learn about individual-specific responding, somatovisceral patterns can be successfully exploited. Our findings further point to the possibility that the expectancy-related autonomic state throughout the experiment predisposes an individual to experience specific levels of fear, with less influence of the actual visual stimulations

The Sensitivity of Physiological Measures to Phobic and Nonphobic Fear Intensity

We investigated whether amygdala activation, autonomic responses, respiratory responses, and facial muscle activity (measured over the brow and cheek [fear grin] regions) are all sensitive to phobic versus nonphobic fear and, more importantly, whether effects in these variables vary as a function of both phobic and nonphobic fear intensity. Spider-phobic and comparably low spider-fearful control participants imagined encountering different animals and rated their subjective fear while their central and peripheral nervous system activity was measured. All measures included in our study were sensitive to variations in subjective fear, but were related to different ranges and positions on the subjective fear level continuum. Left amygdala activation, heart rate, and facial muscle activity over the cheek region captured fear intensity variations even within narrowly described regions on the fear level continuum (here within extremely low levels of fear and within considerable phobic fear). Skin conductance and facial muscle activity over the brow region did not capture fear intensity variations within low levels of fear: skin conductance mirrored only extreme levels of fear, and activity over the brow region distinguished phobic from nonphobic fear but also low-to-moderate and high phobic fear. Finally, respiratory measures distinguished phobic from nonphobic fear with no further differentiation within phobic and nonphobic fear. We conclude that a careful consideration of the measures to be used in an investigation and the population to be examined can be critical in order to obtain significant results

Different brain circuitries mediating controllable and uncontrollable pain

Uncontrollable, compared with controllable, painful stimulation can lead to increased pain perception and activation in pain-processing brain regions, but it is currently unknown which brain areas mediate this effect. When pain is controllable, the lateral prefrontal cortex (PFC) seems to inhibit pain processing, although it is unclear how this is achieved. Using fMRI in healthy volunteers, we examined brain activation during controllable and uncontrollable stimulation to answer these questions. In the controllable task, participants self-adjusted temperatures applied to their hand of pain or warm intensities to provoke a constant sensation. In the uncontrollable task, the temperature time courses of the controllable task were replayed (yoked control) and participants rated their sensation continuously. During controllable pain trials, participants significantly downregulated the temperature to keep their sensation constant. Despite receiving the identical nociceptive input, intensity ratings increased during the uncontrollable pain trials. This additional sensitization was mirrored in increased activation of pain-processing regions such as insula, anterior cingulate cortex, and thalamus. Further, increased connectivity between the anterior insula and medial PFC (mPFC) in the uncontrollable and increased negative connectivity between dorsolateral PFC (dlPFC) and insula in the controllable task were observed. This suggests a pain-facilitating role of the mPFC during uncontrollable pain and a pain-inhibiting role of the dlPFC during controllable pain, both exerting their respective effects via the anterior insula. These results elucidate neural mechanisms of context-dependent pain modulation and their relation to subjective perception.SIGNIFICANCE STATEMENTPain control is of uttermost importance and stimulus controllability is an important way to achieve endogenous pain modulation. Here, we show differential effects of controllability and uncontrollability on pain perception and cerebral pain processing. When pain was controllable, the dorsolateral prefrontal cortex downregulated pain-evoked activation in important pain-processing regions. In contrast, sensitization during uncontrollable pain was mediated by increased connectivity of the medial prefrontal cortex with the anterior insula and other pain-processing regions. These novel insights into cerebral pain modulation by stimulus controllability have the potential to improve treatment approaches in pain patients.</jats:p

Visual avoidance in phobia: particularities in neural activity, autonomic responding, and cognitive risk evaluations.

We investigated the neural mechanisms and the autonomic and cognitive responses associated with visual avoidance behavior in spider phobia. Spider phobic and control participants imagined visiting different forest locations with the possibility of encountering spiders, snakes, or birds (neutral reference category). In each experimental trial, participants saw a picture of a forest location followed by a picture of a spider, snake, or bird, and then rated their personal risk of encountering these animals in this context, as well as their fear. The greater the visual avoidance of spiders that a phobic participant demonstrated (as measured by eye tracking), the higher were her autonomic arousal and neural activity in the amygdala, orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and precuneus at picture onset. Visual avoidance of spiders in phobics also went hand in hand with subsequently reduced cognitive risk of encounters. Control participants, in contrast, displayed a positive relationship between gaze duration toward spiders, on the one hand, and autonomic responding, as well as OFC, ACC, and precuneus activity, on the other hand. In addition, they showed reduced encounter risk estimates when they looked longer at the animal pictures. Our data are consistent with the idea that one reason for phobics to avoid phobic information may be grounded in heightened activity in the fear circuit, which signals potential threat. Because of the absence of alternative efficient regulation strategies, visual avoidance may then function to down-regulate cognitive risk evaluations for threatening information about the phobic stimuli. Control participants, in contrast, may be characterized by a different coping style, whereby paying visual attention to potentially threatening information may help them to actively down-regulate cognitive evaluations of risk

Brain systems underlying encounter expectancy bias in spider phobia

Spider-phobic individuals are characterized by exaggerated expectancies to be faced with spiders (so-called encounter expectancy bias). Whereas phobic responses have been linked to brain systems mediating fear, little is known about how the recruitment of these systems relates to exaggerated expectancies of threat. We used fMRI to examine spider-phobic and control participants while they imagined visiting different locations in a forest after having received background information about the likelihood of encountering different animals (spiders, snakes, and birds) at these locations. Critically, imagined encounter expectancies modulated brain responses differently in phobics as compared with controls. Phobics displayed stronger negative modulation of activity in the lateral prefrontal cortex, precuneus, and visual cortex by encounter expectancies for spiders, relative to snakes or birds (within-participants analysis); these effects were not seen in controls. Between-participants correlation analyses within the phobic group further corroborated the hypothesis that these phobia-specific modulations may underlie irrationality in encounter expectancies (deviations of encounter expectancies from objective background information) in spider phobia; the greater the negative modulation a phobic participant displayed in the lateral prefrontal cortex, precuneus, and visual cortex, the stronger was her bias in encounter expectancies for spiders. Interestingly, irrationality in expectancies reflected in frontal areas relied on right rather than left hemispheric deactivations. Our data accord with the idea that expectancy biases in spider phobia may reflect deficiencies in cognitive control and contextual integration that are mediated by right frontal and parietal areas