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.

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.

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.

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.

EmoSex: Emotion prevails over sex in implicit judgments of faces and voices.

Appraisals can be influenced by cultural beliefs and stereotypes. In line with this, past research has shown that judgments about the emotional expression of a face are influenced by the face's sex, and vice versa that judgments about the sex of a person somewhat depend on the person's facial expression. For example, participants associate anger with male faces, and female faces with happiness or sadness. However, the strength and the bidirectionality of these effects remain debated. Moreover, the interplay of a stimulus' emotion and sex remains mostly unknown in the auditory domain. To investigate these questions, we created a novel stimulus set of 121 avatar faces and 121 human voices (available at https://bit.ly/2JkXrpy) with matched, fine-scale changes along the emotional (happy to angry) and sexual (male to female) dimensions. In a first experiment (N = 76), we found clear evidence for the mutual influence of facial emotion and sex cues on ratings, and moreover for larger implicit (task-irrelevant) effects of stimulus' emotion than of sex. These findings were replicated and extended in two preregistered studies-one laboratory categorization study using the same face stimuli (N = 108; https://osf.io/ve9an), and one online study with vocalizations (N = 72; https://osf.io/vhc9g). Overall, results show that the associations of maleness-anger and femaleness-happiness exist across sensory modalities, and suggest that emotions expressed in the face and voice cannot be entirely disregarded, even when attention is mainly focused on determining stimulus' sex. We discuss the relevance of these findings for cognitive and neural models of face and voice processing. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

Opioid-blunted cortisol response to stress is associated with increased negative mood and wanting of social reward.

Animal research suggests a central role of the µ-opioid receptor (MOR) system in regulating affiliative behaviors and in mediating the stress-buffering function of social contact. However, the neurochemistry of stress-related social contact seeking in humans is still poorly understood. In a randomized, double-blind, between-subjects design, healthy female volunteers (N = 80) received either 10 mg of the µ-opioid agonist morphine sulfate, or a placebo. Following a standardized psychosocial stress induction, participants engaged in a social reward task, in which the motivation to obtain skin-to-skin social touch and the hedonic reactions elicited by such touch were assessed. Morphine prevented the increase of salivary cortisol typically observed following acute stress exposure. Notably, this altered HPA axis responsivity was associated with increased negative affect in response to psychosocial stress, and with enhanced subjective wanting of highly rewarding social contact. These findings provide novel evidence on the effect of exogenous opioids administration on the reactions to psychosocial stress and point to a state-dependent regulation of social motivation.

Effects of dopamine D2/3 and opioid receptor antagonism on the trade-off between model-based and model-free behaviour in healthy volunteers.

Human behaviour requires flexible arbitration between actions we do out of habit and actions that are directed towards a specific goal. Drugs that target opioid and dopamine receptors are notorious for inducing maladaptive habitual drug consumption; yet, how the opioidergic and dopaminergic neurotransmitter systems contribute to the arbitration between habitual and goal-directed behaviour is poorly understood. By combining pharmacological challenges with a well-established decision-making task and a novel computational model, we show that the administration of the dopamine D2/3 receptor antagonist amisulpride led to an increase in goal-directed or 'model-based' relative to habitual or 'model-free' behaviour, whereas the non-selective opioid receptor antagonist naltrexone had no appreciable effect. The effect of amisulpride on model-based/model-free behaviour did not scale with drug serum levels in the blood. Furthermore, participants with higher amisulpride serum levels showed higher explorative behaviour. These findings highlight the distinct functional contributions of dopamine and opioid receptors to goal-directed and habitual behaviour and support the notion that even small doses of amisulpride promote flexible application of cognitive control.

How culturally unique are pandemic effects? Evaluating cultural similarities and differences in effects of age, biological sex, and political beliefs on COVID impacts.

Despite being bio-epidemiological phenomena, the causes and effects of pandemics are culturally influenced in ways that go beyond national boundaries. However, they are often studied in isolated pockets, and this fact makes it difficult to parse the unique influence of specific cultural psychologies. To help fill in this gap, the present study applies existing cultural theories via linear mixed modeling to test the influence of unique cultural factors in a multi-national sample (that moves beyond Western nations) on the effects of age, biological sex, and political beliefs on pandemic outcomes that include adverse financial impacts, adverse resource impacts, adverse psychological impacts, and the health impacts of COVID. Our study spanned 19 nations (participant N = 14,133) and involved translations into 9 languages. Linear mixed models revealed similarities across cultures, with both young persons and women reporting worse outcomes from COVID across the multi-national sample. However, these effects were generally qualified by culture-specific variance, and overall more evidence emerged for effects unique to each culture than effects similar across cultures. Follow-up analyses suggested this cultural variability was consistent with models of pre-existing inequalities and socioecological stressors exacerbating the effects of the pandemic. Collectively, this evidence highlights the importance of developing culturally flexible models for understanding the cross-cultural nature of pandemic psychology beyond typical WEIRD approaches.

Large Gatherings? No, Thank You. Devaluation of Crowded Social Scenes During the COVID-19 Pandemic.

In most European countries, the first wave of the COVID-19 pandemic (spring 2020) led to the imposition of physical distancing rules, resulting in a drastic and sudden reduction of real-life social interactions. Even people not directly affected by the virus itself were impacted in their physical and/or mental health, as well as in their financial security, by governmental lockdown measures. We investigated whether the combination of these events had changed people's appraisal of social scenes by testing 241 participants recruited mainly in Italy, Austria, and Germany in an online, preregistered study conducted about 50 days after the beginning of the COVID-19 outbreak in Europe. Images depicting individuals alone, in small groups (up to four people), and in large groups (more than seven people) were rated in terms of valence, arousal, and perceived physical distance. Pre-pandemic normative ratings were obtained from a validated database (OASIS). Several self-report measures were also taken, and condensed into four factors through factor analysis. All images were rated as more arousing compared to the pre-pandemic period, and the greater the decrease in real-life physical interactions reported by participants, the higher the ratings of arousal. As expected, only images depicting large gatherings of people were rated less positively during, compared to before, the pandemic. These ratings of valence were, however, moderated by a factor that included participants' number of days in isolation, relationship closeness, and perceived COVID-19 threat. Higher scores on this factor were associated with more positive ratings of images of individuals alone and in small groups, suggesting an increased appreciation of safer social situations, such as intimate and small-group contacts. The same factor was inversely related to the perceived physical distance between individuals in images of small and large groups, suggesting an impact of lockdown measures and contagion-related worries on the representation of interpersonal space. These findings point to rapid and compelling psychological and social consequences of the lockdown measures imposed during the COVID-19 pandemic on the perception of social groups. Further studies should assess the long-term impact of such events as typical everyday life is restored.

Effects of Appetitive and Aversive Motivational States on Wanting and Liking of Interpersonal Touch.

Social rewards represent a strong driving force behind decisions and behaviors. Previous research suggests that the processing of a reward depends on the initial state of the individual. However, empirical research in humans on the influence of motivational states on reward processing is scant, especially for rewards of social nature. In the present study, we aimed at investigating how aversive and appetitive motivation affects the processing of social rewards, such as interpersonal touch. Participants (n = 102) were assigned to an appetitive (positive) or aversive (negative) motivational state condition (via modified versions of the Trier Social Stress Test) or to a control condition. After the state induction, their (a) self-reports of wanting and liking, (b) effort, and (c) hedonic facial reactions during anticipation and consumption of interpersonal touch, were measured. Participants in the aversive group showed higher subjective wanting of interpersonal touch, but no changes in subjective liking, compared to the control group. The aversive group also showed stronger positive hedonic facial reactions during reward anticipation, reflecting stronger anticipatory pleasure. No significant effects were found for the appetitive group. The results indicate that, after being exposed to an aversive experience, the motivation to obtain interpersonal touch, as well as the associated anticipatory pleasure, increase, without a corresponding change in liking during or after its consumption. The findings point to differential state-dependent effects on the processing of social rewards, possibly due to the action of different neurobiological systems regulating reward anticipation and consumption.

Dopaminergic and opioidergic regulation during anticipation and consumption of social and nonsocial rewards.

The observation of animal orofacial and behavioral reactions has played a fundamental role in research on reward but is seldom assessed in humans. Healthy volunteers (N = 131) received 400 mg of the dopaminergic antagonist amisulpride, 50 mg of the opioidergic antagonist naltrexone, or placebo. Subjective ratings, physical effort, and facial reactions to matched primary social (affective touch) and nonsocial (food) rewards were assessed. Both drugs resulted in lower physical effort and greater negative facial reactions during reward anticipation, especially of food rewards. Only opioidergic manipulation through naltrexone led to a reduction in positive facial reactions to liked rewards during reward consumption. Subjective ratings of wanting and liking were not modulated by either drug. Results suggest that facial reactions during anticipated and experienced pleasure rely on partly different neurochemical systems, and also that the neurochemical bases for food and touch rewards are not identical.

Studies in rats and other species have shown that two chemical messengers in the brain regulate how much an animal desires a reward, and how pleasant receiving the reward is. In this context, chemicals called opioids control both wanting and enjoying a reward, whereas a chemical called dopamine only regulates how much an animal desires it. However, since these results were obtained from research performed on animals, further studies are needed to determine if these chemicals play the same roles in the human brain. Korb et al. show that the same brain chemicals that control reward anticipation and pleasure in rats are also at work in humans. In the experiment, 131 healthy volunteers received either a drug that blocks opioid signaling in the brain, a drug that blocks dopamine signaling, or a placebo, a pill with no effect. Then, participants were given, on several occasions, either sweet milk with chocolate or a gentle caress on the forearm. Participants rated how much they wanted each of the rewards before receiving it, and how much they liked it after experiencing it. To measure their implicit wanting of the reward, participants also pressed a force-measuring device to increase their chances of receiving the reward. Additionally, small electrodes measured the movement of the volunteer's smiling or frowning muscles to detect changes in facial expressions of pleasure. Volunteers taking either drug pressed on the device less hard than the participants taking the placebo, suggesting they did not want the rewards as much, and they frowned more as they anticipated the reward, indicating less anticipatory pleasure. However, only the volunteers taking the opioid-blocking drug smiled less when they received a reward, indicating that these participants did not get as much pleasure as others out of receiving it. These differences were most pronounced when volunteers looked at or received the sweet milk with chocolate. This experiment helps to shed light on the chemicals in the human brain that are involved in reward-seeking behaviors. In the future, the results may be useful for developing better treatments for addictions.

Facial responses of adult humans during the anticipation and consumption of touch and food rewards.

Whether cognitive, motivational and hedonic aspects of reward anticipation and consumption can be reliably assessed with explicit and implicit measures, and if different motivational (decision utility) and hedonic (experienced utility) processes get recruited by distinct reward types, remain partly unsolved questions that are relevant for theories of social and non-social decision-making. We investigated these topics using a novel experimental paradigm, including carefully matched social and nonsocial rewards, and by focusing on facial responses. Facial expressions are indeed an often-cited implicit measure of rewards' hedonic impact. For example, food rewards elicit powerful facial responses - characterized by lip smacking, tongue protrusion, and relaxation of the middle face - in human newborns, juvenile monkeys, and adult rats. The same stimuli elicit more nuanced facial reactions in adult humans, which can be best captured with facial electromyography (fEMG). However, little is known about facial expressions preceding reward consumption, reflecting the motivation to obtain and possibly the expected pleasantness of a reward, and whether similar facial expressions are elicited by different types of rewards. To investigate these questions, a novel within-subject experimental paradigm was developed. During the anticipation and consumption of social (affective touch) and nonsocial (food) rewards, explicit (ratings of wanting and liking, physical effort) and implicit (fEMG) measures of wanting and liking were taken in 43 healthy adult participants. Reduced activation of the Corrugator Supercilii (CS) muscle (reflecting less frowning and indicating greater positive response) was found in trials with higher wanting and effort during the anticipation of food rewards, as well as in trials with higher liking and effort during the consumption of food rewards. The CS muscle is thus a sensitive measure of wanting and liking of food rewards both during their anticipation and consumption. Crucially, thanks to careful reward matching, these results cannot be explained by differences in subjective wanting, liking, or effort produced to obtain the two types of rewards. No significant modulation of the Zygomaticus Major (ZM) muscle was found for social or food rewards. Explorative analyses however indicated that the ZM may activate during the delivery of the most wanted touch, but not for the most wanted food. The absence of significant effects of social rewards on the activation of CS and ZM muscles are discussed in relation to the specifics of this innovative task comparing two types of matched rewards in the same participants. The present findings contribute to the understanding of the processes underlying motivational and hedonic aspects of rewards, and may therefore inform models of social and non-social decision-making.

Lack of association between celiac disease and dental enamel hypoplasia in a case-control study from an Italian central region.

BACKGROUND: A close correlation between celiac disease (CD) and oral lesions has been reported. The aim of this case-control study was to assess prevalence of enamel hypoplasia, recurrent aphthous stomatitis (RAS), dermatitis herpetiformis and atrophic glossitis in an Italian cohort of patients with CD. METHODS: Fifty patients with CD and fifty healthy subjects (age range: 3-25 years), matched for age, gender and geographical area, were evaluated by a single trained examiner. Diagnosis of oral diseases was based on typical medical history and clinical features. Histopathological analysis was performed when needed. Adequate univariate statistical analysis was performed. RESULTS: Enamel hypoplasia was observed in 26% cases vs 16% in controls (p > 0.2; OR = 1.8446; 95% CI = 0.6886: 4.9414). Frequency of RAS in the CD group was significantly higher (36% vs 12%; p = 0.0091; OR = 4.125; 95% CI = 1.4725: 11.552) in CD group than that in controls (36% vs 12%). Four cases of atrophic glossitis and 1 of dermatitis herpetiformis were found in CD patients vs 1 and none, respectively, among controls. CONCLUSION: The prevalence of enamel hypoplasia was not higher in the study population than in the control group. RAS was significantly more frequent in patients with CD.

Clinical procedures for the immediate reattachment of a tooth fragment.

Uncomplicated crown fractures are frequent dental injuries, especially in young patients. It is beneficial to quickly restore the function and the aesthetics of the traumatized tooth. The immediate fragment reattachment is a therapeutic choice for uncomplicated anterior crown fractures, when the tooth is not luxated and the fragment is correctly stored. The aim of this article is to present the clinical procedures for the immediate fragment reattachment by accurate bonding procedures. The immediate fragment reattachment is a very conservative treatment: it allows the restoration of the original dental anatomy, thus rehabilitating function and aesthetics in a short time, by preserving dental tissues.