Chenbo Wang

Sociocultural patterning of neural activity during self-reflection

Western cultures encourage self-construals independent of social contexts, whereas East Asian cultures foster interdependent self-construals that rely on how others perceive the self. How are culturally specific self-construals mediated by the human brain? Using functional magnetic resonance imaging, we monitored neural responses from adults in East Asian (Chinese) and Western (Danish) cultural contexts during judgments of social, mental and physical attributes of themselves and public figures to assess cultural influences on self-referential processing of personal attributes in different dimensions. We found that judgments of self vs a public figure elicited greater activation in the medial prefrontal cortex (mPFC) in Danish than in Chinese participants regardless of attribute dimensions for judgments. However, self-judgments of social attributes induced greater activity in the temporoparietal junction (TPJ) in Chinese than in Danish participants. Moreover, the group difference in TPJ activity was mediated by a measure of a cultural value (i.e. interdependence of self-construal). Our findings suggest that individuals in different sociocultural contexts may learn and/or adopt distinct strategies for self-reflection by changing the weight of the mPFC and TPJ in the social brain network.

Neural responses to perceived pain in others predict real-life monetary donations in different socioeconomic contexts.

Empathy has been proposed to be a proximate mechanism underlying altruistic behavior. However, both empathy and altruistic behavior differ between human individuals with low and high socioeconomic status. Here we investigated whether subjective socioeconomic status (SSS) modulates the relationship between neural activity to perceived pain in others and human altruistic behaviors in a real-life situation. After being scanned using functional MRI while observing videos of others in pain, participants were invited to make an anonymous monetary donation to a charitable organization. Painful stimuli increased activity in the inferior frontal, insula and somatosensory cortices compared to non-painful stimuli. A hierarchical regression analysis revealed that neural responses to perceived pain predicted the amount of monetary donations with different patterns in high and low SSS individuals. Stronger neural responses to perceived pain were associated with greater monetary donations in high SSS individuals, whereas a reverse pattern was observed in low SSS individuals. Our results suggest that SSS moderates the functional role of empathy-related neural activity in predicting altruistic behavior. Empathy may follow different mechanisms involved in altruistic behaviors (e.g., donation) depending on the social environment.

5-HTTLPR Polymorphism Modulates Neural Mechanisms of Negative Self-Reflection

Cognitive distortion in depression is characterized by enhanced negative thoughts about both environment and oneself. Carriers of a risk allele for depression, that is, the short (s) allele of the serotonin transporter promoter polymorphism (5-HTTLPR), exhibit amygdala hyperresponsiveness to negative environmental stimuli relative to homozygous long variant (l/l). However, the neural correlates of negative self-schema in s allele carriers remain unknown. Using functional MRI, we scanned individuals with s/s or l/l genotype of the 5-HTTLPR during reflection on their own personality traits or a friends personality traits. We found that relative to l/l carriers, s/s carriers showed stronger distressed feelings and greater activity in the dorsal anterior cingulate (dACC)/dorsal medial prefrontal cortex (dmPFC) and the right anterior insula (AI) during negative self-reflection. The 5-HTTLPR effect on the distressed feelings was mediated by the AI/inferior frontal (IF) activity during negative self-reflection. The dACC/dmPFC activity explained 20% of the variation in harm-avoidance tendency in s/s but not l/l carriers. The genotype effects on distress and brain activity were not observed during reflection on a friends negative traits. Our findings reveal that 5-HTTLPR polymorphism modulates distressed feelings and brain activities associated with negative self-schema and suggest a potential neurogenetic susceptibility mechanism for depression.

Self-construal priming modulates pain perception: Event- related potential evidence

We investigated whether and how temporary shifts in self-construals modulate neural correlates of pain perception. Event-related potentials (ERPs) to painful and non-painful electrical stimulations were recorded from adults after being primed with independent and interdependent self-construals. Electrical stimulations to the left hand elicited two negative components (N60 and N130) over the frontal /central regions and two positive components (P90 and P300) over the central/parietal regions with larger amplitudes over the right rather than the left hemispheres. Painful vs. non-painful stimulations enlarged P90, N130, and P300 amplitudes. Independent vs. interdependent self-construal priming induced larger N130 amplitudes to painful stimulations but did not affect the N130 amplitudes to non-painful stimulations. The self-construal priming effect on the P300 amplitudes to painful stimulation positively correlated with self-reported interdependence. Our ERP results suggest that temporary shifts in self-construals affect pain perception by modulating the neural activities engaged in early somatosensory and late evaluation processing of physical pain.

Does self-construal predict activity in the social brain network? A genetic moderation effect.

Neural activity in the social brain network varies across individuals with different cultural traits and different genetic polymorphisms. It remains unknown whether a specific genetic polymorphism may influence the association between cultural traits and neural activity in the social brain network. We tested whether the serotonin transporter promoter polymorphism (5-HTTLPR) affects the association between self-construals and neural activity involved in reflection of personal attributes of oneself and a significant other (i.e., mother). Using functional MRI, we scanned Chinese adults with short/short (s/s) or long/long (l/l) variants of the 5-HTTLPR during reflection of personal attributes of oneself and ones mother. We found that, while s/s and l/l genotype groups did not differ significantly in self-construals measured by the Self-Construal Scale, the relationship between self-construal scores and neural responses to reflection of oneself and mother was significantly different between the two genotype groups. Specifically, l/l but not s/s genotype group showed significant association between self-construal scores and activity in the medial prefrontal cortex, bilateral middle frontal cortex, temporoparietal junction, insula and hippocampus during reflection on mental attributes of oneself and mother. Our findings suggest that a specific genetic polymorphism may interact with a cultural trait to shape the neural substrates underlying social cognition.

Allelic variation in 5-HTTLPR and the effects of citalopram on the emotional neural network

BACKGROUND Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, which selectively block serotonin transporter (5-HTT) activity, are widely used in the treatment of depression and anxiety disorders. Numerous neuroimaging studies have examined the effects of SSRIs on emotional processes. However, there are considerable inter-individual differences in SSRI effect, and a recent meta-analysis further revealed discrepant effects of acute SSRI administration on neural responses to negative emotions in healthy adults. AIMS We examined how a variant of the serotonin-transporter polymorphism (5-HTTLPR), which affects the expression and function of 5-HTT, influenced the acute effects of an SSRI (citalopram) on emotion-related brain activity in healthy adults. METHOD Combining genetic neuroimaging, pharmacological technique and a psychological paradigm of emotion recognition, we scanned the short/short (s/s) and long/long (l/l) variants of 5-HTTLPR during perception of fearful, happy and neutral facial expressions after the acute administration of an SSRI (i.e. 30 mg citalopram administered orally) or placebo administration. RESULTS We found that 5-HTTLPR modulated the acute effects of citalopram on neural responses to negative emotions. Specifically, relative to placebo, citalopram increased amygdala and insula activity in l/l but not s/s homozygotes during perception of fearful faces. Similar analyses of brain activity in response to happy faces did not show any significant effects. CONCLUSIONS Our combined pharmacogenetic and functional imaging results provide a neurogenetic mechanism for discrepant acute effects of SSRIs.

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.

Distinct oxytocin effects on belief updating in response to desirable and undesirable feedback

Significance People tend to incorporate desirable feedback into their beliefs but discount undesirable ones. Such optimistic updating has evolved as an advantageous mechanism for social adaptation and physical/mental health. Here, in three independent studies, we show that intranasally administered oxytocin (OT), an evolutionary ancient neuropeptide pivotal to social adaptation, augments optimistic belief updating by increasing updates and learning of desirable feedback but impairing updates of undesirable feedback. Moreover, the OT-impaired updating of undesirable feedback is more salient in individuals with high, rather than with low, depression or anxiety traits. OT also increases second-order confidence judgment after desirable feedback. These findings reveal a molecular substrate underlying the formation of optimistic beliefs about the future. Humans update their beliefs upon feedback and, accordingly, modify their behaviors to adapt to the complex, changing social environment. However, people tend to incorporate desirable (better than expected) feedback into their beliefs but to discount undesirable (worse than expected) feedback. Such optimistic updating has evolved as an advantageous mechanism for social adaptation. Here, we examine the role of oxytocin (OT)―an evolutionary ancient neuropeptide pivotal for social adaptation―in belief updating upon desirable and undesirable feedback in three studies (n = 320). Using a double-blind, placebo-controlled between-subjects design, we show that intranasally administered OT (IN-OT) augments optimistic belief updating by facilitating updates of desirable feedback but impairing updates of undesirable feedback. The IN-OT–induced impairment in belief updating upon undesirable feedback is more salient in individuals with high, rather than with low, depression or anxiety traits. IN-OT selectively enhances learning rate (the strength of association between estimation error and subsequent update) of desirable feedback. IN-OT also increases participants’ confidence in their estimates after receiving desirable but not undesirable feedback, and the OT effect on confidence updating upon desirable feedback mediates the effect of IN-OT on optimistic belief updating. Our findings reveal distinct functional roles of OT in updating the first-order estimation and second-order confidence judgment in response to desirable and undesirable feedback, suggesting a molecular substrate for optimistic belief updating.