Effects of dopamine and opioid receptor antagonism on the neural processing of social and nonsocial rewards.

Rewards are a broad category of stimuli inducing approach behavior to aid survival. Extensive evidence from animal research has shown that wanting (the motivation to pursue a reward) and liking (the pleasure associated with its consumption) are mostly regulated by dopaminergic and opioidergic activity in dedicated brain areas. However, less is known about the neuroanatomy of dopaminergic and opioidergic regulation of reward processing in humans, especially when considering different types of rewards (i.e., social and nonsocial). To fill this gap of knowledge, we combined dopaminergic and opioidergic antagonism (via amisulpride and naltrexone administration) with functional neuroimaging to investigate the neurochemical and neuroanatomical bases of wanting and liking of matched nonsocial (food) and social (interpersonal touch) rewards, using a randomized, between-subject, placebo-controlled, double-blind design. While no drug effect was observed at the behavioral level, brain activity was modulated by the administered compounds. In particular, opioid antagonism, compared to placebo, reduced activity in the medial orbitofrontal cortex during consumption of the most valued social and nonsocial rewards. Dopamine antagonism, however, had no clear effects on brain activity in response to reward anticipation. These findings provide insights into the neurobiology of human reward processing and suggest a similar opioidergic regulation of the neural responses to social and nonsocial reward consumption.

Homeostatic Regulation of Energetic Arousal During Acute Social Isolation: Evidence From the Lab and the Field.

Recent evidence suggests that social contact is a basic need governed by a social homeostatic system. Little is known, however, about how conditions of altered social homeostasis affect human psychology and physiology. Here, we investigated the effects of 8 hr of social isolation on psychological and physiological variables and compared this with 8 hr of food deprivation in a lab experiment (N = 30 adult women). Social isolation led to lowered self-reported energetic arousal and heightened fatigue, comparable with food deprivation. To test whether these findings would extend to a real-life setting, we conducted a preregistered field study during a COVID-19 lockdown (N = 87 adults; 47 women). The drop in energetic arousal after social isolation observed in the lab replicated in the field study for participants who lived alone or reported high sociability, suggesting that lowered energy could be part of a homeostatic response to the lack of social contact.

Diurnal dynamics of stress and mood during COVID-19 lockdown: a large multinational ecological momentary assessment study.

The COVID-19 pandemic resulted in severe disruption to people's lives as governments imposed national 'lockdowns'. Several large surveys have underlined the detrimental short- and long-term mental health consequences resulting from this disruption, but survey findings are only informative of individuals' retrospectively reported psychological states. Furthermore, knowledge on psychobiological responses to lockdown restrictions is scarce. We used smartphone-based real-time assessments in 731 participants for 7 days and investigated how individuals' self-reported stress and mood fluctuated diurnally during lockdown in spring 2020. We found that age, gender, financial security, depressive symptoms and trait loneliness modulated the diurnal dynamics of participants' momentary stress and mood. For example, younger and less financially secure individuals showed an attenuated decline in stress as the day progressed, and similarly, more lonely individuals showed a diminished increase in calmness throughout the day. Hair collected from a subsample (n = 140) indicated a decrease in cortisol concentrations following lockdown, but these changes were not related to any of the assessed person-related characteristics. Our findings provide novel insights into the psychobiological impact of lockdown and have implications for how, when and which individuals might benefit most from interventions during psychologically demanding periods.

Beyond Sharing Unpleasant Affect-Evidence for Pain-Specific Opioidergic Modulation of Empathy for Pain.

It is not known how specific the neural mechanisms underpinning empathy for different domains are. In the present study, we set out to test whether shared neural representations between first-hand pain and empathy for pain are pain-specific or extend to empathy for unpleasant affective touch as well. Using functional magnetic resonance imaging and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them with the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiates the role of shared representations in empathy.

Neural Correlates of Interpersonal Space Permeability and Flexibility in Autism Spectrum Disorder.

Previous research indicates that the size of interpersonal space at which the other is perceived as intrusive (permeability) and the ability to adapt interpersonal distance based on contextual factors (flexibility) are altered in Autism Spectrum Disorder (ASD). However, the neurophysiological basis of these alterations remains poorly understood. To fill this gap, we used fMRI and assessed interpersonal space preferences of individuals with ASD before and after engaging in cooperative and non-cooperative social interactions. Compared to matched controls, ASDs showed lower comfort in response to an approaching confederate, indicating preference for larger interpersonal space in autism (altered permeability). This preference was accompanied by reduced activity in bilateral dorsal intraparietal sulcus (dIPS) and left fusiform face area (FFA), regions previously shown to be involved in interpersonal space regulation. Furthermore, we observed differences in effective connectivity among dIPS, FFA, and amygdala in ASDs compared to controls, depending on the level of experienced comfort. No differences between groups were observed in interpersonal space regulation after an experienced social interaction (flexibility). Taken together, the present findings suggest that a dysregulation of the activity and connectivity of brain areas involved in interpersonal space processing may contribute to avoidance of physical proximity and social impairments in ASD.

Reduced shared emotional representations toward women revealing more skin.

Extensive experimental research has been conducted to investigate how individuals empathise with others depending on contextual and motivational factors. However, the effect of sexual objectification (i.e. focus on the individual's physical appearance over his/her mental state) on empathy is scarce at best thus far. The aim of this work is to shed light on whether objectification modulates empathic responses toward humans and human-like objects. In Experiment 1, participants either underwent visuo-tactile stimulation or witnessed another person (a mannequin, a sexualized or a non-sexualized female confederate) being stimulated with pleasant or unpleasant objects. Participants were then asked to report either their own or the other's emotional experience. Results showed that shared representations (i.e. similarity between self-other emotional ratings) are significantly lower for the mannequin, intermediate for the sexualized woman, and reach the highest values for the non-sexualized woman. In Experiment 2, shared representations were assessed during a ball-tossing game in which the participants or one of the two confederates (sexualized or non-sexualized woman) were excluded from the game. Again, results showed reduced similarity between self-other emotional ratings toward sexualized as compared to non-sexualized women. The findings suggest that interacting with sexually objectified women reduces empathic responses typically observed within human relations.

Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain.

Empathy for pain activates brain areas partially overlapping with those underpinning the first-hand experience of pain. It remains unclear, however, whether such shared activations imply that pain empathy engages similar neural functions as first-hand pain experiences. To overcome the limitations of previous neuroimaging research, we pursued a conceptually novel approach: we used the phenomenon of placebo analgesia to experimentally reduce the first-hand experience of pain, and assessed whether this results in a concomitant reduction of empathy for pain. We first carried out a functional MRI experiment (n = 102) that yielded results in the expected direction: participants experiencing placebo analgesia also reported decreased empathy for pain, and this was associated with reduced engagement of anterior insular and midcingulate cortex: that is, areas previously associated with shared activations in pain and empathy for pain. In a second step, we used a psychopharmacological manipulation (n = 50) to determine whether these effects can be blocked via an opioid antagonist. The administration of the opioid antagonist naltrexone blocked placebo analgesia and also resulted in a corresponding "normalization" of empathy for pain. Taken together, these findings suggest that pain empathy may be associated with neural responses and neurotransmitter activity engaged during first-hand pain, and thus might indeed be grounded in our own pain experiences.

Selective disruption of sociocognitive structural brain networks in autism and alexithymia.

Autism spectrum conditions (ASC) are neurodevelopmental disorders characterized by abnormal social cognition. A core feature of ASC is disrupted Theory of Mind (ToM), our ability to take the mental perspective of others. ASC is also associated with alexithymia, a trait characterized by altered emotional interoception and empathy. Here, we applied structural MRI covariance analysis to assess whether ASC and alexithymia differentially affect structural brain networks associated with sociocognitive and socioaffective functions. Based on previous functional MRI findings, we expected disrupted ToM networks (centered on dorsomedial prefontal cortex [dmPFC], and temporo-parietal junction [TPJ]) in ASC, while alexithymia would affect networks centered on fronto-insular cortex (FI), regions associated with interoception of emotion and empathy. Relative to controls, ASC indeed showed reduced covariance in networks centered on dmPFC and TPJ, but not within FI networks. Irrespective of ASC, covariance was negatively modulated by alexithymia in networks extending from FI to posterior regions. Network findings were complemented by self-reports, indicating decreased perspective taking but normal empathic concern in ASC. Our results show divergent effects of ASC and alexithymia on inter-regional structural networks, suggesting that networks mediating socioaffective processes may be separable from networks mediating sociocognitive processing.

Right supramarginal gyrus is crucial to overcome emotional egocentricity bias in social judgments.

Humans tend to use the self as a reference point to perceive the world and gain information about other people's mental states. However, applying such a self-referential projection mechanism in situations where it is inappropriate can result in egocentrically biased judgments. To assess egocentricity bias in the emotional domain (EEB), we developed a novel visuo-tactile paradigm assessing the degree to which empathic judgments are biased by one's own emotions if they are incongruent to those of the person we empathize with. A first behavioral experiment confirmed the existence of such EEB, and two independent fMRI experiments revealed that overcoming biased empathic judgments is associated with increased activation in the right supramarginal gyrus (rSMG), in a location distinct from activations in right temporoparietal junction reported in previous social cognition studies. Using temporary disruption of rSMG with repetitive transcranial magnetic stimulation resulted in a substantial increase of EEB, and so did reducing visuo-tactile stimulation time as shown in an additional behavioral experiment. Our findings provide converging evidence from multiple methods and experiments that rSMG is crucial for overcoming emotional egocentricity. Effective connectivity analyses suggest that this may be achieved by early perceptual regulation processes disambiguating proprioceptive first-person information (touch) from exteroceptive third-person information (vision) during incongruency between self- and other-related affective states. Our study extends previous models of social cognition. It shows that although shared neural networks may underlie emotional understanding in some situations, an additional mechanism subserved by rSMG is needed to avoid biased social judgments in other situations.

Brain activity and prosocial behavior in a simulated life-threatening situation.

To study the neuronal basis of altruistic behavior, we investigated functional connectivity within brain networks of participants who exhibited either a self-benefit behavior or an altruistic one in a life-threatening situation simulated in a virtual environment. In particular, participants were asked to evacuate a virtual building on fire and, without being previously informed, they were faced with a decision on whether to stop and help a trapped virtual human, at the possible cost of losing their own life in the virtual experience. Group independent component analysis (gICA) applied on blood-oxygen-level-dependent (BOLD) functional images revealed significant differences between the group of participants who showed selfish behavior and those who acted prosocially. Specifically, an increased functional connectivity in the salience network, comprising the anterior insula (AI) and the anterior mid cingulate cortex (aMCC), was observed in the selfish group compared to the prosocial one. Conversely, higher ICA weights in the medial prefrontal cortex and temporo-parietal junction (TPJ), were observed in the prosocial group. The findings show that an increased functional connectivity of the salience network, which suggests an enhanced sensitivity to the threatening situation and potential danger for the individual, resulted in more selfish choices, while the engagement of the medial prefrontal and temporo-parietal cortices subserved prosocial behavior, possibly due to their role in perspective-taking. The study provides the first online neurophysiological measurement of prosocial decision-making during threatening situations, opening new avenues to the investigation of neuronal substrates of complex social behaviors.

The relationship between attachment, primary emotions and positive/negative spirituality: a path analysis.

Objective: The present study investigates what may influence individuals to experience their religiosity/spirituality as either subjectively positive [religious or spiritual (r/s) wellbeing] or as negative (r/s struggles). Drawing on existing literature attachment insecurity and the seven primary emotions as outlined by Jaak Panksepp in Affective Neuroscience are identified as likely influences. Methods: The final sample consisted of 340 participants (age: M = 36, SD = 14.2; 68.5% = female), among which 65% self-identified as religious/spiritual. A path analysis was conducted to test a proposed mediation model in which the expected effects of primary emotions (B-ANPS) on r/s wellbeing (MI-RSWB) and r/s struggles (RSSS) were mediated through attachment insecurity (ECR-RD8). Results: The data indicated that attachment insecurity fully mediated the relationships between the primary emotions SADNESS and LUST with r/s struggles. Furthermore, the primary emotions FEAR and ANGER displayed small direct effects on both r/s struggles and r/s wellbeing. Overall, the model, which demonstrated excellent model fit, was able to explain 30% of the variance of r/s struggles, 24% of attachment insecurity and 5% of r/s wellbeing. Conclusions: The findings suggest that primary emotions such as SADNESS and LUST substantially explain r/s struggles and that these relationships seem to be mediated through attachment. Moreover, r/s struggles seem to be qualitatively distinct from r/s wellbeing. Finally, a moderate link between LUST and attachment suggests that sexuality plays a significant role in (adult) attachment processes.

Neural Hyperresponsivity During the Anticipation of Tangible Social and Nonsocial Rewards in Autism Spectrum Disorder: A Concurrent Neuroimaging and Facial Electromyography Study.

BACKGROUND: Atypical anticipation of social reward has been shown to lie at the core of the social challenges faced by individuals with autism spectrum disorder (ASD). However, previous research has yielded inconsistent results and has often overlooked crucial characteristics of stimuli. Here, we investigated ASD reward processing using social and nonsocial tangible stimuli, carefully matched on several key dimensions. METHODS: We examined the anticipation and consumption of social (interpersonal touch) and nonsocial (flavored milk) rewards in 25 high-functioning individuals with ASD and 25 neurotypical adult individuals. In addition to subjective ratings of wanting and liking, we measured physical energetic expenditure to obtain the rewards, brain activity with neuroimaging, and facial reactions through electromyography on a trial-by-trial basis. RESULTS: Participants with ASD did not exhibit reduced motivation for social or nonsocial rewards; their subjective ratings, motivated efforts, and facial reactions were comparable to those of neurotypical participants. However, anticipation of higher-value rewards increased neural activation in lateral parietal cortices, sensorimotor regions, and the orbitofrontal cortex. Moreover, participants with ASD exhibited hyperconnectivity between frontal medial regions and occipital regions and the thalamus. CONCLUSIONS: Individuals with ASD who experienced rewards with tangible characteristics, whether social or nonsocial, displayed typical subjective and objective motivational and hedonic responses. Notably, the observed hyperactivations in sensory and attentional nodes during anticipation suggest atypical sensory overprocessing of forthcoming rewards rather than decreased reward value. While these atypicalities may not have manifested in observable behavior here, they could impact real-life social interactions that require nuanced predictions, potentially leading to the misperception of reduced interest in rewarding social stimuli in ASD.

The effect of intranasal oxytocin on social reward processing in humans: a systematic review.

Understanding the neurobiology of social reward processing is fundamental, holding promises for reducing maladaptive/dysfunctional social behaviors and boosting the benefits associated with a healthy social life. Current research shows that processing of social (vs. non-social) rewards may be driven by oxytocinergic signaling. However, studies in humans often led to mixed results. This review aimed to systematically summarize available experimental results that assessed the modulation of social reward processing by intranasal oxytocin (IN-OXY) administration in humans. The literature search yielded 385 results, of which 19 studies were included in the qualitative synthesis. The effects of IN-OXY on subjective, behavioral, and (neuro)physiological output variables are discussed in relation to moderating variables-reward phase, reward type, onset and dosage, participants' sex/gender, and clinical condition. Results indicate that IN-OXY is mostly effective during the consumption ("liking") of social rewards. These effects are likely exerted by modulating the activity of the prefrontal cortex, insula, precuneus, anterior cingulate cortex, amygdala, and striatum. Finally, we provide suggestions for designing future oxytocin studies. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021278945, identifier CRD42021278945.

Age-related differences in interference control in the context of a finger-lifting task: an fMRI study.

Humans tend to automatically imitate others and their actions while also being able to control such imitative tendencies. Interference control, necessary to suppress own imitative tendencies, develops rapidly in childhood and adolescence, plateaus in adulthood and slowly declines with advancing age. It remains to be shown though which neural processes underpin these differences across the lifespan. In a cross-sectional functional magnetic resonance imaging study with three age groups (adolescents (ADs) 14-17 years, young adults (YAs) 21-31, older adults (OAs) 56-76, N = 91 healthy female participants), we investigated the behavioral and neural correlates of interference control in the context of automatic imitation using the finger-lifting task. ADs showed the most efficient interference control, while no significant differences emerged between YAs and OAs, despite OAs showing longer reaction times. On the neural level, all age groups showed engagement of the right temporoparietal junction, right supramarginal gyrus and bilateral insula, aligning well with studies previously using this task. However, our analyses did not reveal any age-related differences in brain activation, neither in these nor in other areas. This suggests that ADs might have a more efficient use of the engaged brain networks and, on the other hand, OAs' capacity for interference control and the associated brain functions might be largely preserved.

Facial mimicry is not modulated by dopamine D2/3 and opioid receptor antagonism.

RATIONALE: According to theories of embodied cognition, facial mimicry - the spontaneous, low-intensity imitation of a perceived emotional facial expression - is first an automatic motor response, whose accompanying proprioceptive feedback contributes to emotion recognition. Alternative theoretical accounts, however, view facial mimicry as an emotional response to a rewarding stimulus, and/or an affiliative signal, and thus reject the view of an automatic motor copy. OBJECTIVES: To contribute to this debate and further investigate the neural basis of facial mimicry, as well as its relation to reward processing, we measured facial reactions to dynamic happy and angry faces after pharmacologically manipulating the opioid and dopamine systems - respectively, thought to subserve 'liking' and 'wanting' of rewards. METHODS: In a placebo-controlled, double-blind experiment, 130 volunteers received in a between-subjects design 50 mg of the opioidergic antagonist naltrexone, 400 mg of the dopaminergic antagonist amisulpride, or placebo. RESULTS: Clear occurrence of facial mimicry, measured 4 h after drug intake with electromyography (EMG) of the zygomaticus major and corrugator supercilii muscles, was found. However, facial mimicry was not affected by either compound, as shown with both frequentist statistics, and a Bayesian asymptotic regression model. CONCLUSIONS: This null finding does not support the hypothesis that facial mimicry (of happiness) reflects an emotional response to a rewarding stimulus, leaving open the possibility of facial mimicry being an automatic motor copy. The results are relevant to the discussion about the psychological nature and the neural basis of facial mimicry, although they should be considered preliminary, given the challenges of interpreting null findings when targeting a novel effect of unknown size.

The effects of social interactions on momentary stress and mood during COVID-19 lockdowns.

OBJECTIVE: Social interactions are vital for our well-being, particularly during times of stress. However, previous studies linking social interactions to psychological outcomes during the COVID-19 pandemic have largely been retrospective and/or cross-sectional. Thus, we tested four preregistered hypotheses (H1-H4) concerning the real-time effect of social interactions on momentary changes in stress and mood during two COVID-19 lockdowns. DESIGN: We used an ecological momentary assessment approach in 732 participants in spring 2020 (burst 1) and in a subsample of these participants (n = 281) during a further lockdown in autumn/winter 2020 (burst 2). METHODS: Participants reported their stress and mood in a smartphone app five times per day for 7 days and indicated the nature and frequency of their recent social interactions. RESULTS: Social interactions (H1) and their frequency (H2) improved momentary affect (e.g., social interactions increased mood valence: estimate = 2.605, p < .001 for burst 1). This was particularly the case for face-to-face interactions which, compared with other types of interactions, reduced momentary stress (e.g., estimate = -2.285, p < .001 for burst 1) and boosted mood (e.g., estimate = 1.759, p < .001 for burst 1) across both lockdowns, even when controlling for the pleasantness of the interaction and the closeness of the interaction partner (H3). We also show that individual differences in people's responsiveness to different social rewards modulated the impact of social interactions on momentary mood (H4). CONCLUSIONS: This study extends findings from cross-sectional and retrospective studies by highlighting the real-time affective benefits of social interactions during COVID-19 lockdown. The results have important implications for the (self-) management of stress and mood during psychologically demanding periods.

Perceptions of Stress and Mood Associated With Listening to Music in Daily Life During the COVID-19 Lockdown.

Importance: Music listening is a universal human experience. People of all ages and cultures often use music to reduce stress and improve mood, particularly in times of crisis. However, ecologically valid research examining the real-time association of music listening with stress and mood during the COVID-19 pandemic is scarce. Objective: To explore the associations between listening to music and the perceptions of stress and mood using ecological momentary assessment during the COVID-19 lockdown period. Design, Setting, and Participants: In this cohort study conducted between April 1 and May 8, 2020, adults from the general population residing in Austria and Italy were prompted by an app on their smartphone to report data 5 times per day across 7 consecutive days. Participants provided data on their real-time and real-life experiences in their natural environment while strict lockdown measures were in place. Data analysis was performed from March 2021 to February 2022. Exposures: Data on self-reported music listening were recorded by means of mobile-based assessments. Perceived chronic stress was assessed once at the end of the study. Main Outcomes and Measures: Perceptions of momentary stress and mood were measured using visual analog scales (score range, 0-100, where 0 indicates not at all and 100 indicates very much) by means of mobile app-based assessments. Results: The final sample comprised 711 participants (497 women [69.9%]; median age, 27.0 years [IQR, 24.0-36.0 years]). Participants provided a total of 19 641 data points, including 4677 music listening reports. Music listening was prospectively associated with lower momentary stress levels (ß, -0.92; 95% CI, -1.80 to -0.04; P = .04) and improvements in mood valence (ß, 1.90; 95% CI, 1.17-2.63; P < .001), especially if the music was perceived as happy. Individuals with higher levels of chronic stress reported improved mood valence after music listening (ß, 0.12; 95% CI, 0.02-0.22; P = .02). Conclusions and Relevance: The present findings suggest that music listening may be a means to modulate stress and mood during psychologically demanding periods. Individuals experiencing heightened momentary and/or chronic stress because of the challenges brought about by COVID-19 pandemic-related restrictions might consider music as an easily accessible tool for the management of stress and mood in daily life.

Music for autism: a protocol for an international randomized crossover trial on music therapy for children with autism.

The notion of a connection between autism and music is as old as the first reported cases of autism, and music has been used as a therapeutic tool for many decades. Music therapy holds promise as an intervention for individuals with autism, harnessing their strengths in music processing to enhance communication and expression. While previous randomized controlled trials have demonstrated positive outcomes in terms of global improvement and quality of life, their reliance on psychological outcomes restricts our understanding of underlying mechanisms. This paper introduces the protocol for the Music for Autism study, a randomized crossover trial designed to investigate the effects of a 12-week music therapy intervention on a range of psychometric, neuroimaging, and biological outcomes in school-aged children with autism. The protocol builds upon previous research and aims to both replicate and expand upon findings that demonstrated improvements in social communication and functional brain connectivity following a music intervention. The primary objective of this trial is to determine whether music therapy leads to improvements in social communication and functional brain connectivity as compared to play-based therapy. In addition, secondary aims include exploring various relevant psychometric, neuroimaging, and biological outcomes. To achieve these objectives, we will enroll 80 participants aged 6-12 years in this international, assessor-blinded, crossover randomized controlled trial. Each participant will be randomly assigned to receive either music therapy or play-based therapy for a period of 12 weeks, followed by a 12-week washout period, after which they will receive the alternate intervention. Assessments will be conducted four times, before and after each intervention period. The protocol of the Music for Autism trial provides a comprehensive framework for studying the effects of music therapy on a range of multidimensional outcomes in children with autism. The findings from this trial have the potential to contribute to the development of evidence-based interventions that leverage strengths in music processing to address the complex challenges faced by individuals with autism. Clinical Trial Registration: Clinicaltrials.gov identifier NCT04936048.

Anticipatory and Consummatory Responses to Touch and Food Rewards: A Protocol for Human Research.

Understanding the neural basis of reward processing is a major concern, as it holds the key to alleviating symptoms of addiction and poor mental health. However, this goal seems difficult to attain as long as research on reward processing cannot easily be compared across species and reward types, due to methodological differences and the presence of confounding factors. We recently developed an experimental paradigm that allows monitoring anticipatory and consummatory responses to matched social (touch) and nonsocial (food) rewards in adult humans. The following protocol describes in detail the materials and the paradigm, which measures reward wanting and liking with a real effort task and subjective ratings. It can also be used in combination with facial electromyography (EMG), brain imaging (e.g., fMRI), and pharmacological interventions. It is our firm belief that the field will profit greatly from more research being conducted on reward processing using this and similarly controlled paradigms, which allow for cross-species comparison.

Effects of the mu-opioid receptor agonist morphine on facial mimicry and emotion recognition.

Facial mimicry and emotion recognition are two socio-cognitive abilities involved in adaptive socio-emotional behavior, promoting affiliation and the establishment of social bonds. The mu-opioid receptor (MOR) system plays a key role in affiliation and social bonding. However, it remains unclear whether MORs are involved in the categorization and spontaneous mimicry of emotional facial expressions. Using a randomized, placebo-controlled, double-blind, between-subjects design, we investigated in 82 healthy female volunteers the effects of the specific MOR agonist morphine on the recognition accuracy of emotional faces (happiness, anger, fear), and on their facial mimicry (measured with electromyography). Frequentist statistics did not reveal any significant effects of drug administration on facial mimicry or emotion recognition abilities. However, post hoc Bayesian analyses provided support for an effect of morphine on facial mimicry of fearful facial expressions. Specifically, compared to placebo, morphine reduced mimicry of fear, as shown by lower activity of the frontalis muscle. Bayesian analyses also provided support for the absence of a drug effect on mimicry of happy and angry facial expressions, which were assessed with the zygomaticus major and corrugator supercilii muscles, as well as on emotion recognition accuracy. These findings suggest that MOR activity is involved in automatic facial responses to fearful stimuli, but not in their identification. Overall, the current results, together with the previously reported small effects of opioid compounds, suggest a relatively marginal role of the MOR system in emotion simulation and perception.