Siyang Luo

Serotonin transporter polymorphism alters citalopram effects on human pain responses to physical pain.

Humans exhibit substantial inter-individual differences in pain perception, which contributes to variability in analgesic efficacy. Individual differences in pain sensitivity have been linked with variation in the serotonin transporter gene (5-HTTLPR), and selective serotonin reuptake inhibitors (SSRIs) such as citalopram have been increasingly used as treatments for multiple pain conditions. We combined genotyping, pharmacological challenge, and neuroimaging during painful electrical stimulation to reveal how serotonin genetics and pharmacology interact to influence pain perception and its underlying neurobiological mechanisms. In a double-blind, placebo-controlled procedure, we acutely administrated citalopram (30mgpo) to short/short (s/s) and long/long (l/l) healthy male 5-HTTLPR homozygotes during functional MRI with painful and non-painful electrical stimulation. 5-HTTLPR genotype modulated citalopram effects on pain-related brain responses in the thalamus, cerebellum, anterior insula, midcingulate cortex and inferior frontal cortex. Specifically, citalopram significantly reduced pain-related brain responses in l/l but not in s/s homozygotes. Moreover, the interaction between 5-HTTLPR genotype and pain-related brain activity was a good predictor of the citalopram-induced reductions in pain reports. The genetic modulations of citalopram effects on brain-wide pain processing were paralleled by significant effects on the Neurological Pain Signature, a multivariate brain pattern validated to be sensitive and specific to physical pain. This work provides neurobiological mechanism by which genetic variation shapes brain responses to pain perception and treatment efficacy. These findings have important implications for the types of individuals for whom serotonergic treatments provide effective pain relief, which is critical for advancing personalized pain treatment.

Influence of ethnic group-membership and gaze direction on the perception of emotions. A cross-cultural study between Germany and China.

Emotional facial expressions provide important nonverbal cues in human interactions. The perception of emotions is not only influenced by a person’s ethnic background but also depends on whether a person is engaged with the emotion-encoder. Although these factors are known to affect emotion perception, their impact has only been studied in isolation before. The aim of the present study was to investigate their combined influence. Thus, in order to study the influence of engagement on emotion perception between persons from different ethnicities, we compared participants from China and Germany. Asian-looking and European-looking virtual agents expressed anger and happiness while gazing at the participant or at another person. Participants had to assess the perceived valence of the emotional expressions. Results indicate that indeed two factors that are known to have a considerable influence on emotion perception interacted in their combined influence: We found that the perceived intensity of an emotion expressed by ethnic in-group members was in most cases independent of gaze direction, whereas gaze direction had an influence on the emotion perception of ethnic out-group members. Additionally, participants from the ethnic out-group tended to perceive emotions as more pronounced than participants from the ethnic in-group when they were directly gazed at. These findings suggest that gaze direction has a differential influence on ethnic in-group and ethnic out-group dynamics during emotion perception.

Embodied neural responses to others’ suffering

To investigate whether and how facial mimicry in observers affects their empathic neural responses to others’ pain expressions, we recorded event-related potentials (ERPs) from Chinese adults while viewing pain and neutral expressions of Asian and Caucasian faces. Facial mimicry was manipulated by allowing participants to freely move their facial muscles (the relaxed condition) or asking them to hold a pen horizontally using both teeth and lips to prevent facial muscle movement and facial mimicry (the blocked condition). We found that the frontal N1 at 100–120 ms was enlarged by pain vs. neutral expressions. The N1 modulation by facial expressions was significantly reduced in the blocked compared to relaxed conditions and this effect was observed for Asian but not Caucasian faces. The findings suggest that facial mimicry plays a causal role in the early empathic neural response and the embodied empathic neural responses are constrained by the racial intergroup relationship.

Empathy in female submissive BDSM practitioners

ABSTRACT The practice of bondage/discipline, dominance/submission, sadism/masochism (BDSM) sometimes is associated with giving and receiving pain. It remains unresolved how BDSM practitioners perceive the pain of other people. This study investigated whether and how the BDSM experience affects human empathy. Experiment 1 measured trait empathy and subjective empathic responses in BDSM practitioners and control respondents. The results revealed lower trait empathy scores and subjective pain intensity ratings in the female submissive group (Subs) compared to controls. Experiment 2 measured participants’ neural responses to others’ suffering by recording event‐related potentials (ERPs) from female Subs and controls while viewing painful and neutral expressions. We found that the differential amplitudes between painful and neutral expressions in the frontal N1 (92–112 ms), frontal P2 (132–172 ms) and central late LPP (700–1000 ms) were reduced in the submissive group versus the control group. These findings suggest that being in the submissive role during BDSM practice weakens female individuals’ empathic responses to others’ suffering at both the behavioral and neural levels. HIGHLIGHTSInvolving in BDSM relationships and practices did not necessarily result in weaken empathy abilities.Female submissives’ empathic responses were weakened at both behavioral/psychological and neural levels.Both early automatic empathic responses and late controlled processes were modulated by BDSM experiences in the female subs.

Empathy for pain motivates actions without altruistic effects: evidence of motor dynamics and brain activity

Abstract Empathy has been supposed to be a proximate mechanism of altruistic behavior. We investigated whether empathy for pain drives actions without altruistic effects and how such actions modulate neural responses to others’ pain. In two experiments, we asked healthy adults to press a button for no reason when viewing video clips showing faces with pain expressions receiving needle penetration or faces with neutral expressions receiving a cotton swab touch. Experiment 1 found that participants pressed a button with greater response force when watching painful than non-painful stimuli. Participants who reported greater unpleasant feelings pressed the button harder when viewing painful stimuli. Experiment 2 revealed that passively viewing painful vs non-painful stimuli increased blood-oxygen-level-dependent signals in the middle cingulate cortex, supplementary motor cortex, and bilateral second somatosensory and inferior frontal cortex, which, however, were reduced by the action of button press without altruistic effects. In addition, individuals who reported higher personal distress illustrated greater decrease of the second somatosensory activity induced by button press. Our results indicate that empathy for pain motivates simple actions without altruistic effects that in turn reduce neural responses to others’ pain, suggesting a functional role of action execution in self distress relief when viewing others’ suffering.

The oxytocinergic system modulates sadistic context-dependent empathy in humans

The oxytocinergic system is crucial for sociality and well-being and is associated with empathy. It is suggested that the oxytocinergic system exerts context- and person-dependent effects. We examined how sexual sadistic contexts influenced the effects of the oxytocinergic system on empathic-related behaviors and brain activity in healthy adults. Combining genetic neuroimaging, pharmacological techniques and a psychological paradigm of empathy, we recorded EEG neural responses in female OXTR rs53756 G/G and A/A carriers and measured subjective empathic ratings after intranasal administration of oxytocin/placebo in healthy male adults during the perception of painful facial expressions in sadistic/general social contexts. The results revealed that sadistic contexts modulate oxytocinergic effects on empathy at both behavioral and neural levels. The oxytocinergic system preferentially modulated empathic responses to sadistic contexts. These effects are moderated by individual’s trait empathy. Our combined genetic-pharmacological-imaging results provide a neurochemical mechanism for sadistic context-dependent effects of the oxytocinergic system on empathy.

Functional connectivity pattern underlies individual differences in independent self-construal

Abstract Independent vs interdependent self-construal is a concept that reflects how people perceive the relationship between self and other people, which has been extensively examined across disciplines. However, little evidence on the whole-brain functional connectivity (FC) pattern of independent vs interdependent self-construal has been reported. Here, in a sample of 51 healthy participants, we used resting-state functional magnetic resonance imaging and voxel-based FC analysis (i.e. FC strength and seed-based FC) by measuring the temporal correlation of blood oxygen level-dependent signals between spatially separate brain regions to investigate the neural mechanism of independent vs interdependent self-construal. First, we found that FC strength of bilateral posterior cingulate cortex and precuneus, and left inferior frontal gyrus were positively correlated with the independent vs interdependent score. Seed-based FC analysis with these three regions as seeds revealed that, FC within default mode network and executive control network was positively correlated with the independent vs interdependent score. Negative correlation with independent vs interdependent score was shown in the connections between default mode network and executive control regions. Taking together, our results provide a comprehensive FC architecture of the independent vs interdependent self-construal and advance the understanding of the interplay between culture, mind and brain.

Brain Structural and Functional Substrates of Personal Distress in Empathy

Empathy is the capacity to understand and experience the feeling state of others. While individuals attribute negative empathic responses to their own feelings, they would endure personal distress that can be harmful to social interaction. However, the neural mechanism of personal distress remains unclear. Here, we examined the neural substrates of personal distress by combining structural (Voxel-based morphometry (VBM)) and functional (resting-state functional connectivity (FC) analysis) MRI approaches in 53 college students (aged 19–26). A negative correlation was found between a trait measure of personal distress and gray matter (GM) volume in the dorsal medial prefrontal cortex (dmPFC). FC analyses with the dmPFC as a seed further revealed that the connectivity between the dmPFC and posterior insula was positively correlated with the personal distress, and the connectivities between the dmPFC and the anterior middle cingulate cortex, left lateral frontal cortex, and left inferior parietal gyrus were negatively correlated with the personal distress. Our results suggested that personal distress is underlain by neural substrates associated with both cognitive and affective mechanisms. Taken together, the structural and functional correlates of personal distress revealed in the present findings shed new light into the understanding of empathy.

5-HTTLPR moderates the association between interdependence and brain responses to mortality threats

While behavioral research suggests an association between cultural worldview and decreased anxiety of death, the underlying neurobiological mechanisms remain unclear. Using functional MRI, we investigated whether and how the serotonin transporter promoter polymorphism (5‐HTTLPR), which has been associated with mental disorders such as anxiety and depression, moderates the associations between a cultural trait (i.e., interdependence) and self‐report of death anxiety/depression and between interdependence and brain responses to mortality threats. Long/long and short/short allele carriers of the 5‐HTTLPR were scanned using fMRI while they performed a one‐back task on death‐related, death‐unrelated negative, and neutral words. Participants’ interdependence and death anxiety/depression were assessed using questionnaires after scanning. We found that participants who assessed themselves with greater interdependence reported lower death anxiety/depression and showed decreased neural response to death‐related words in emotion‐related brain regions including the anterior cingulate, putamen, and thalamus. However, these results were evident in long/long allele carriers of the 5‐HTTLPR but not in short/short allele carriers who even showed positive associations between interdependence and neural activities in the anterior cingulate, putamen and thalamus in response to death‐related words. Our findings suggest candidate mechanisms for explaining the complex relationship between genotype, cultural traits, and mental/neural responses to mortality threats. Hum Brain Mapp 38:6157–6171, 2017.