Embodied Precision : Intranasal Oxytocin Modulates Multisensory Integration

© 2018 Massachusetts Institute of Technology.Multisensory integration processes are fundamental to our sense of self as embodied beings. Bodily illusions, such as the rubber hand illusion (RHI) and the size-weight illusion (SWI), allow us to investigate how the brain resolves conflicting multisensory evidence during perceptual inference in relation to different facets of body representation. In the RHI, synchronous tactile stimulation of a participant's hidden hand and a visible rubber hand creates illusory body ownership; in the SWI, the perceived size of the body can modulate the estimated weight of external objects. According to Bayesian models, such illusions arise as an attempt to explain the causes of multisensory perception and may reflect the attenuation of somatosensory precision, which is required to resolve perceptual hypotheses about conflicting multisensory input. Recent hypotheses propose that the precision of sensorimotor representations is determined by modulators of synaptic gain, like dopamine, acetylcholine, and oxytocin. However, these neuromodulatory hypotheses have not been tested in the context of embodied multisensory integration. The present, double-blind, placebo-controlled, crossover study ( N = 41 healthy volunteers) aimed to investigate the effect of intranasal oxytocin (IN-OT) on multisensory integration processes, tested by means of the RHI and the SWI. Results showed that IN-OT enhanced the subjective feeling of ownership in the RHI, only when synchronous tactile stimulation was involved. Furthermore, IN-OT increased an embodied version of the SWI (quantified as estimation error during a weight estimation task). These findings suggest that oxytocin might modulate processes of visuotactile multisensory integration by increasing the precision of top-down signals against bottom-up sensory input.Peer reviewedFinal Accepted Versio

Partners' Empathy Increases Pain Ratings: Effects of Perceived Empathy and Attachment Style on Pain Report and Display

Pain can be influenced by its social context. We aimed to examine under controlled experimental conditions how empathy from a partner and personal attachment style affect pain report, tolerance, and facial expressions of pain. Fifty-four participants, divided into secure, anxious, and avoidant attachment style groups, underwent a cold pressor task with their partners present. We manipulated how much empathy the participants perceived that their partners had for them. We observed a significant main effect of perceived empathy on pain report, with greater pain reported in the high perceived empathy condition. No such effects were found for pain tolerance or facial display. We also found a significant interaction of empathy with attachment style group, with the avoidant group reporting and displaying less pain than the secure and the anxious groups in the high perceived empathy condition. No such findings were observed in the low empathy condition. These results suggest that empathy from one's partner may influence pain report beyond behavioral reactions. In addition, the amount of pain report and expression that people show in high empathy conditions depends on their attachment style. Perspective: Believing that one's partner feels high empathy for one's pain may lead individuals to rate the intensity of pain as higher. Individual differences in attachment style moderate this empathy effect

A Pilot Study Investigating the Influence of Oxytocin on Attentional Bias to Food Images in Women with Bulimia Nervosa or Binge Eating Disorder

This is the peer reviewed version of the following article: Leslie, M., Leppanen, J., Paloyelis, Y., Treasure, J. (2020). A pilot study investigating the influence of oxytocin on attentional bias to food images in women with bulimia nervosa or binge eating disorder. Journal of Neuroendocrinology, 32(5), e12843, which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1111/jne.12843. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Background: Previous research has found that exogenous oxytocin administration has the potential to modulate attentional biases in women with anorexia nervosa. Recent work has indicated that attentional biases to food may reinforce the recurrent binge eating behaviour which characterises bulimia nervosa and binge eating disorder. To date, however, no study has yet investigated the effect of oxytocin on attentional biases to palatable food in women with bulimia nervosa and binge eating disorder. Methods: This study employed a single-session crossover design to test the hypothesis that a divided dose of 64IU intranasal oxytocin, administered as one intranasal dose of 40IU oxytocin followed by a top-up of 24IU oxytocin 80 minutes later, versus placebo administration administered in the same dosing schedule, would reduce attentional biases towards food images in a dot probe task. We hypothesised that oxytocin administration would reduce vigilance towards food to a greater degree in women with bulimia nervosa or binge eating disorder, versus healthy comparison women. Twenty-five women with bulimia nervosa or binge eating disorder and 27 comparison women without history of an eating disorder were recruited to take part in the study. Results: Contrary to our hypothesis, there was no main effect of diagnosis on attentional bias to food (fixed effect = 5.70, p = .363), nor a significant interaction between diagnosis and drug condition (fixed effect = -14.80, p = .645). There was a main effect of drug condition, such that oxytocin increased vigilance towards food, versus neutral, images in the dot probe task (fixed effect = 10.42, p = .044). A correlation analysis revealed that this effect was moderated by attentional bias in the placebo condition, such that greater avoidance of food stimuli in the placebo condition was associated with a greater increase in vigilance induced by oxytocin. Conclusion: The current findings add to a mixed body of literature investigating the therapeutic effects of oxytocin in women. Future research would benefit from dose-response studies investigating the optimal dose of oxytocin for modulating the attentional processing of palatable food in populations with eating disorders

The Influence of Oxytocin on Risk-Taking in the Balloon Analogue Risk Task Among Women with Bulimia Nervosa and Binge Eating Disorder

This is the peer reviewed version of the following article: Leslie, M., Leppanen, J., Paloyelis, Y., & Treasure, J. (2019). The influence of oxytocin on risk-taking in the balloon analogue risk task among women with bulimia nervosa and binge eating disorder. Journal of Neuroendocrinology, 31(8), e12771. doi:10.1111/jne.12771, which has been published in final form at https://onlinelibrary.wiley.com/doi/abs/10.1111/jne.12771. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Previous theoretical models of bulimia nervosa (BN) and binge eating disorder (BED) have implicated cross-domain risk-taking behaviour as a significant maintenance factor in both disorders. The current study sought to test this hypothesis by administering the Balloon Analogue Risk Task (BART) to 25 women with BN or BED and 27 healthy comparison women without history of an eating disorder. Furthermore, we tested the effect of a divided dose of 64IU oxytocin on risk-taking behaviour in the BART. Contrary to our hypothesis, women with BN or BED did not exhibit baseline differences in performance on the BART in the placebo condition (t = 1.42, df = 50, p = .161, d = 0.39). Oxytocin did not have a main effect on performance in the BART (F = 0.01, df = 1, p = .907, η2partial < .001); however, there was an interaction such that participants in the BN/BED participant group, compared to the healthy comparison group, demonstrated safer behaviour on the BART specifically in the oxytocin condition, but not in the placebo condition (F = 4.29, df = 1, p = .044, η2partial = .082). These findings cast doubt on the common assumption that individuals with BN and BED exhibit greater risk-taking behaviour in all domains and add to evidence that oxytocin plays a functional role in modulating behaviours which entail trade-offs between reward approach and risk in humans. We recommend that future dose-response studies further investigate the effect of oxytocin on reward approach behaviour in women with recurrent binge eating behaviour and the clinical significance of this effect

The Influence of Oxytocin on Eating Behaviours and Stress in Women with Bulimia Nervosa and Binge Eating Disorder

The current study aimed to test the influence of oxytocin on palatable food intake, 24-hour caloric consumption, and stress in women with bulimia nervosa and binge eating disorder. We recruited 25 women with DSM-5 bulimia nervosa or binge eating disorder, and 27 weight-matched comparison women without history of an eating disorder. We employed a double-blind, placebo-controlled crossover design in which each participant attended the lab for two experimental sessions, receiving a divided dose of 64IU intranasal oxytocin in one session and equivalent volume of placebo nasal spray in the opposite session. The order of administration was pseudo-randomised across participants. We hypothesised that a divided dose of 64IU intranasal oxytocin administration would reduce subjective hunger, the immediate consumption of palatable food, 24-hour calorie consumption, and the incidence of binge eating when compared to placebo. We also hypothesised that oxytocin administration would be associated with lower levels of stress and salivary cortisol, and that there would be an interaction with participant group such that oxytocin would reduce eating behaviour and stress to a greater degree in women with bulimia nervosa or binge eating disorder, compared to women without history of an eating disorder. We did not find a significant effect of oxytocin on any of the measurements of eating behaviour, subjective stress, or salivary cortisol. We recommend that future studies test the dose-response effect of oxytocin on eating behaviours and stress in human populations with eating disorders to further clarify the moderating factors for oxytocin’s effect on eating

Brain perfusion alterations in bulimia/binge-eating

Advances in the treatment of bulimia nervosa and binge eating disorder (BN/BED) have been marred by our limited understanding of the underpinning neurobiology. Here we measured regional cerebral blood flow (rCBF) to map resting perfusion abnormalities in women with BN/BED compared to healthy controls and investigate if intranasal oxytocin (OT), proposed as a potential treatment, can restore perfusion in disorder-related brain circuits. Twenty-four women with BN/BED and 23 healthy women participated in a randomised, double-blind, crossover, placebo-controlled study. We used arterial spin labelling MRI to measure rCBF and the effects of an acute dose of intranasal OT (40IU) or placebo over 18-26 minutes post-dosing, as we have previously shown robust OT-induced changes in resting rCBF in men in a similar time-window (15-36 min post-dosing). We tested for effects of treatment, diagnosis and their interaction on extracted rCBF values in anatomical regions-of-interest previously implicated in BN/BED by other neuroimaging modalities, and conducted exploratory whole-brain analyses to investigate previously unidentified brain regions. We demonstrated that women with BN/BED presented increased resting rCBF in the medial prefrontal and orbitofrontal cortices, anterior cingulate gyrus, posterior insula and middle/inferior temporal gyri bilaterally. Hyperperfusion in these areas specifically correlated with eating symptoms severity in patients. Our data did not support a normalizing effect of intranasal OT on perfusion abnormalities in these patients, at least for the specific dose (40 IU) and post-dosing interval (18-26 minutes) examined. Our findings enhance our understanding of resting brain abnormalities in BN/BED and identify resting rCBF as a non-invasive potential biomarker for disease-related changes and treatment monitoring. They also highlight the need for a comprehensive investigation of intranasal OT pharmacodynamics in women before we can fully ascertain its therapeutic value in disorders affecting predominantly this gender, such as BN/BED

The Analgesic Effect of Oxytocin in Humans: A Double-Blind, Placebo-Controlled Cross-Over Study Using Laser-Evoked Potentials

Oxytocin is a neuropeptide regulating social‐affiliative and reproductive behaviour in mammals. Despite robust preclinical evidence for the antinociceptive effects and mechanisms of action of exogenous oxytocin, human studies have produced mixed results regarding the analgesic role of oxytocin and are yet to show a specific modulation of neural processes involved in pain perception. In the present study, we investigated the analgesic effects of 40 IU of intranasal oxytocin in 13 healthy male volunteers using a double‐blind, placebo‐controlled, cross‐over design and brief radiant heat pulses generated by an infrared laser that selectively activate Aδ‐ and C‐fibre nerve endings in the epidermis, at the same time as recording the ensuing laser‐evoked potentials (LEPs). We predicted that oxytocin would reduce subjective pain ratings and attenuate the amplitude of the N1, N2 and P2 components. We observed that oxytocin attenuated perceived pain intensity and the local peak amplitude of the N1 and N2 (but not of P2) LEPs, and increased the latency of the N2 component. Importantly, for the first time, the present study reports an association between the analgesic effect of oxytocin (reduction in subjective pain ratings) and the oxytocin‐induced modulation of cortical activity after noxious stimulation (attenuation of the N2 LEP). These effects indicate that oxytocin modulates neural processes contributing to pain perception. The present study reports preliminary evidence that is consistent with electrophysiological studies in rodents showing that oxytocin specifically modulates Aδ/C‐fibre nociceptive afferent signalling at the spinal level and provides further specificity to evidence obtained in humans indicating that oxytocin may be modulating pain experience by modulating activity in the cortical areas involved in pain processing

The effect of intranasal oxytocin on the perception of affective touch and multisensory integration in anorexia nervosa: protocol for a double-blind placebo-controlled crossover study.

INTRODUCTION: Anorexia nervosa (AN) is an eating disorder characterised by restriction of energy intake, fears of gaining weight and related body image disturbances. The oxytocinergic system has been proposed as a pathophysiological candidate for AN. Oxytocin is a neuropeptide involved in bodily processes (eg, breast feeding) and in the onset of social behaviours (eg, bonding). Studies investigating the effect of intranasal oxytocin (IN-OT) in AN showed that it can improve attentional bias for high-calorie food and fat bodies stimuli, and related stress. However, less is known about the effect of IN-OT on bodily awareness and body image distortions, key features of the disorder linked to its development, prognosis and maintenance. Here, we aim to investigate the effect of IN-OT on the perception of affective, C-tactile-optimal touch, known to be impaired in AN and on multisensory integration processes underlying a body ownership illusion (ie, rubber hand illusion). For exploratory purposes, we will also investigate the effect of IN-OT on another interoceptive modality, namely cardiac awareness and its relationship with affective touch. DESIGN, METHODS AND ANALYSIS: Forty women with AN and forty matched healthy controls will be recruited and tested in two separate sessions; self-administering IN-OT (40 IU) or placebo, intranasally, in a pseudo-randomised manner. The data from this double-blind, placebo-controlled, cross-over study will be analysed using linear mixed models that allow the use of both fixed (treatment levels) and random (subjects) effects in the same analysis. To address our main hypotheses, separate analyses will be run for the affective touch task, where the primary outcome dependent variable will be the pleasantness of the touch, and for the rubber hand illusion, where we will investigate multisensory integration quantified as subjective embodiment towards the rubber hand. In the latter, we will manipulate the synchronicity of touch and the size of the hand. ETHICS AND DISSEMINATION: Ethics approval has been obtained by National Research Ethics Service NRES Committee London (Queen's Square Committee, ref number 14/LO/1593). The results will be disseminated through conference presentations and publication in peer-reviewed journals

Impact of intranasal oxytocin on interoceptive accuracy in alcohol users: An attentional mechanism?

Interoception, i.e. the perception and appraisal of internal bodily signals, is related to the phenomenon of craving, and is reportedly disrupted in alcohol use disorders. The hormone oxytocin influences afferent transmission of bodily signals and, through its potential modulation of craving, is proposed as a possible treatment for alcohol use disorders. However, oxytocin’s impact on interoception in alcohol users remains unknown. Healthy alcohol users (N=32) attended two laboratory sessions to perform tests of interoceptive ability (heartbeat tracking: attending to internal signals and, heartbeat discrimination: integrating internal and external signals) after intranasal administration of oxytocin or placebo. Effects of interoceptive accuracy, oxytocin administration and alcohol intake, were tested using mixed-effects models. On the tracking task, oxytocin reduced interoceptive accuracy, but did not interact with alcohol consumption. On the discrimination task, we found an interaction between oxytocin administration and alcohol intake: Oxytocin, compared to placebo, increased interoceptive accuracy in heavy drinkers, but not in light social drinkers. Our study does not suggest a pure interoceptive impairment in alcohol users but instead potentially highlights reduced flexibility of internal and external attentional resource allocation. Importantly, this impairment seems to be mitigated by oxytocin. This attentional hypothesis needs to be explicitly tested in future research