Increased pain sensitivity and pain-related anxiety in individuals with autism

Introduction: Individuals with autism spectrum disorder (ASD) often exhibit differences in pain responsivity. This altered responsivity could be related to ASD-related social communication difficulties, sensory differences, or altered processing of pain stimuli. Previous neuroimaging work suggests altered pain evaluation could contribute to pain-related anxiety in ASD. Objectives: We hypothesized that individuals with ASD would report increased pain sensitivity and endorse more pain-related anxiety, compared to typically developing controls. Methods: We recruited 43 adults (ASD, n = 24; typically developing, n = 19) for 3 heat pain tasks (applied to the calf). We measured heat pain thresholds using a method of limits approach, a pain-rating curve (7 temperatures between 40 and 48°C, 5 seconds, 5 trials each), and a sustained heat pain task with alternating low (42°C) and high (46°C) temperatures (21 seconds, 6 trials each). Individual differences in pain-related anxiety, fear of pain, situational pain catastrophizing, depressive symptoms, and autism-related social communication were assessed by self-report. Results: There were no group differences in pain thresholds. For suprathreshold tasks, mean pain ratings were higher in ASD across both the pain-rating curve and the sustained heat pain tasks, but responses in the ASD group were more varied. Pain anxiety (PASS-Total) and pain-related fear (FOP-III-Total) were higher in the ASD group and were positively associated with pain ratings. Conclusions: Our results suggest that both sensory and cognitive experiences of pain are heightened and interact reciprocally in adults with ASD. Future studies are needed to evaluate the impact of pain-related anxiety on treatment-seeking and pain behaviors, given higher levels of pain-related anxiety in ASD

Visuo-tactile integration in autism: atypical temporal binding may underlie greater reliance on proprioceptive information

BackgroundEvidence indicates that social functioning deficits and sensory sensitivities in autism spectrum disorder (ASD) are related to atypical sensory integration. The exact mechanisms underlying these integration difficulties are unknown; however, two leading accounts are (1) an over-reliance on proprioception and (2) atypical visuo-tactile temporal binding. We directly tested these theories by selectively manipulating proprioceptive alignment and visuo-tactile synchrony to assess the extent that these impact upon body ownership.MethodsChildren with ASD and typically developing controls placed their hand into a multisensory illusion apparatus, which presented two, identical live video images of their own hand in the same plane as their actual hand. One virtual hand was aligned proprioceptively with the actual hand (the veridical hand), and the other was displaced to the left or right. While a brushstroke was applied to the participants’ actual (hidden) hand, they observed the two virtual images of their hand also being stroked and were asked to identify their real hand. During brushing, one of three different temporal delays was applied to either the displaced hand or the veridical hand. Thus, only one virtual hand had synchronous visuo-tactile inputs.ResultsResults showed that visuo-tactile synchrony overrides incongruent proprioceptive inputs in typically developing children but not in autistic children. Evidence for both temporally extended visuo-tactile binding and a greater reliance on proprioception are discussed.ConclusionsThis is the first study to provide definitive evidence for temporally extended visuo-tactile binding in ASD. This may result in reduced processing of amodal inputs (i.e. temporal synchrony) over modal-specific information (i.e. proprioception). This would likely lead to failures in appropriately binding information from related events, which would impact upon sensitivity to sensory stimuli, body representation and social processes such as empathy and imitation

Reward processing in autism: a thematic series

This thematic series presents theoretical and empirical papers focused on understanding autism from the perspective of reward processing deficits. Although the core symptoms of autism have not traditionally been conceptualized with respect to altered reward-based processes, it is clear that brain reward circuitry plays a critical role in guiding social and nonsocial learning and behavior throughout development. Additionally, brain reward circuitry may respond to social sources of information in ways that are similar to responses to primary rewards, and recent clinical data consistently suggest abnormal behavioral and neurobiologic responses to rewards in autism. This thematic series presents empirical data and review papers that highlight the utility of considering autism from the perspective of reward processing deficits. Our hope is that this novel framework may further elucidate autism pathophysiology, with the ultimate goal of yielding novel insights with potential therapeutic implications

Contact Force and Scanning Velocity during Active Roughness Perception

Haptic perception is bidirectionally related to exploratory movements, which means that exploration influences perception, but perception also influences exploration. We can optimize or change exploratory movements according to the perception and/or the task, consciously or unconsciously. This paper presents a psychophysical experiment on active roughness perception to investigate movement changes as the haptic task changes. Exerted normal force and scanning velocity are measured in different perceptual tasks (discrimination or identification) using rough and smooth stimuli. The results show that humans use a greater variation in contact force for the smooth stimuli than for the rough stimuli. Moreover, they use higher scanning velocities and shorter break times between stimuli in the discrimination task than in the identification task. Thus, in roughness perception humans spontaneously use different strategies that seem effective for the perceptual task and the stimuli. A control task, in which the participants just explore the stimuli without any perceptual objective, shows that humans use a smaller contact force and a lower scanning velocity for the rough stimuli than for the smooth stimuli. Possibly, these strategies are related to aversiveness while exploring stimuli

The infuence of skin colour on the experience of ownership in the rubber hand illusion

Racial prejudice is associated with a fundamental distinction between "us" and "them"-a distinction linked to the perceived overlap between representations of the self and others. Implicit prejudice has been shown to reduce the intensity of White individuals' hand ownership sensation as induced by the Rubber Hand Illusion (RHI) with dark rubber hands. However, evidence for this link to implicit prejudice comes from self-report questionnaire data regarding the RHI. As an alternative, we assessed the onset time of the RHI. We hypothesized that onset time of the RHI would be higher for the black compared to the white RH, acting as the mediator between implicit prejudice and magnitude of the RH illusion and proprioceptive drift. As expected, participants took longer to incorporate the black RH and presented lower RH illusion magnitude and a smaller proprioceptive drift for the black RH. Mediation analysis revealed a significant indirect effect of implicit racial bias on proprioceptive drift and magnitude of illusion through onset time to illusion only for the black RH. These findings further illuminate the connection between implicit prejudice and embodied perception, suggesting new perspectives on how implicit biases operate.This work was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; grant numbers: 466922/2014-0 and 401143/2014-7).info:eu-repo/semantics/publishedVersio

Developmental perspectives on interpersonal affective touch

In the last decade, philosophy, neuroscience and psychology alike have paid increasing attention to the study of interpersonal affective touch, which refers to the emotional and motivational facets of tactile sensation. Some aspects of affective touch have been linked to a neurophysiologically specialised system, namely the C tactile (CT) system. While the role of this sys-tem for affiliation, social bonding and communication of emotions have been widely investigated, only recently researchers have started to focus on the potential role of interpersonal affective touch in acquiring awareness of the body as our own, i.e. as belonging to our psychological ‘self’. We review and discuss recent developmental and adult findings, pointing to the central role of interpersonal affective touch in body awareness and social cognition in health and disorders. We propose that interpersonal affective touch, as an interoceptive modality invested of a social nature, can uniquely contribute to the ongoing debate in philosophy about the primacy of the relational nature of the minimal self

Genomics of Signaling Crosstalk of Estrogen Receptor α in Breast Cancer Cells

BACKGROUND: The estrogen receptor alpha (ERalpha) is a ligand-regulated transcription factor. However, a wide variety of other extracellular signals can activate ERalpha in the absence of estrogen. The impact of these alternate modes of activation on gene expression profiles has not been characterized. METHODOLOGY/PRINCIPAL FINDINGS: We show that estrogen, growth factors and cAMP elicit surprisingly distinct ERalpha-dependent transcriptional responses in human MCF7 breast cancer cells. In response to growth factors and cAMP, ERalpha primarily activates and represses genes, respectively. The combined treatments with the anti-estrogen tamoxifen and cAMP or growth factors regulate yet other sets of genes. In many cases, tamoxifen is perverted to an agonist, potentially mimicking what is happening in certain tamoxifen-resistant breast tumors and emphasizing the importance of the cellular signaling environment. Using a computational analysis, we predicted that a Hox protein might be involved in mediating such combinatorial effects, and then confirmed it experimentally. Although both tamoxifen and cAMP block the proliferation of MCF7 cells, their combined application stimulates it, and this can be blocked with a dominant-negative Hox mutant. CONCLUSIONS/SIGNIFICANCE: The activating signal dictates both target gene selection and regulation by ERalpha, and this has consequences on global gene expression patterns that may be relevant to understanding the progression of ERalpha-dependent carcinomas

Embodiment and body awareness in meditators

[EN] Mindfulness practice consists of focusing attention in an intentional way on the experience of the present moment, including bodily sensations, thoughts or feelings, and the environment, with an attitude of acceptance and without judging. The body and, especially, body awareness are key elements in mindfulness. Embodiment or the feeling of being located within one's physical body is a related concept, and it is composed of the sense of ownership, location, and agency of the body. The rubber hand illusion (RHI) is an experimental paradigm that has been used to understand the mechanisms of embodiment, and evidence shows that body awareness modulates this illusion. To our knowledge, no studies have analyzed embodiment processes in meditators. The aim of this study is to use the RHI to analyze the mechanisms of embodiment and its relationship with body awareness and mindfulness in meditators and non-meditators. The sample was composed of long-term meditators (n = 15) and non-meditators (n = 15). Objective and self-report measures for embodiment with the RHI and self-report questionnaires of body awareness and mindfulness were administered. One-way ANOVA revealed significant differences between groups in sense of agency in the rubber hand. Meditators experienced less sense of agency in the rubber hand than non-meditators. Pearson's correlations showed that this lower sense of agency in the rubber hand was associated with higher body awareness and mindfulness. Results highlight the role of body awareness and mindfulness in embodiment mechanisms. 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Maternal Undernutrition and Long-term Effects on Hepatic Function

Undernutrition in utero, regardless of the source, can impair proper liver development leading to long-term metabolic dysfunction. Understanding the molecular mechanisms underlying how nutritional deficits during perinatal life lead to permanent alterations in hepatic gene expression will provide better therapeutic strategies to alleviate the undernourished liver in postnatal life. This chapter addresses the different experimental models of undernutrition in utero, and highlights the direct and indirect mechanisms involved leading to metabolic diseases in the liver. These include hypoxia, oxidative stress, epigenetic alterations, and endoplasmic reticulum (ER) stress. In addition, promising perinatal nutritional and pharmaceutical interventions are highlighted which illustrate how the placidity of the developing liver can be exploited to prevent the onset of long-term metabolic disease

Effect of Global Cardiac Ischemia on Human Ventricular Fibrillation: Insights from a Multi-scale Mechanistic Model of the Human Heart

Acute regional ischemia in the heart can lead to cardiac arrhythmias such as ventricular fibrillation (VF), which in turn compromise cardiac output and result in secondary global cardiac ischemia. The secondary ischemia may influence the underlying arrhythmia mechanism. A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global ischemia the dominant frequency of activation decreased, while after reperfusion it increased rapidly. At the same time the complexity of epicardial excitation, measured as the number of epicardical phase singularity points, remained approximately constant during ischemia. Here we perform numerical studies based on these clinical data and propose explanations for the observed dynamics of the period and complexity of activation patterns. In particular, we study the effects on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an anatomically accurate model of human heart ventricles. We demonstrate that the fall of dominant frequency in VF during secondary ischemia can be explained by an increase in extracellular potassium, while the increase during reperfusion is consistent with washout of potassium and continued activation of the ATP-dependent potassium channels. We also suggest that memory effects are responsible for the observed complexity dynamics. In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements