The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study.

Rodent research delineates how the basolateral amygdala (BLA) and central amygdala (CeA) control defensive behaviors, but translation of these findings to humans is needed. Here, we compare humans with natural-selective bilateral BLA lesions to rats with a chemogenetically silenced BLA. We find, across species, an essential role for the BLA in the selection of active escape over passive freezing during exposure to imminent yet escapable threat (Timm). In response to Timm, BLA-damaged humans showed increased startle potentiation and BLA-silenced rats demonstrated increased startle potentiation, freezing, and reduced escape behavior as compared to controls. Neuroimaging in humans suggested that the BLA reduces passive defensive responses by inhibiting the brainstem via the CeA. Indeed, Timm conditioning potentiated BLA projections onto an inhibitory CeA pathway, and pharmacological activation of this pathway rescued deficient Timm responses in BLA-silenced rats. Our data reveal how the BLA, via the CeA, adaptively regulates escape behavior from imminent threat and that this mechanism is evolutionary conserved across rodents and humans.

Facing infant cuteness: How nurturing care motivation and oxytocin system gene methylation are associated with responses to baby schema features.

Baby schema features are a specific set of physical features-including chubby cheeks, large, low-set eyes, and a large, round head-that have evolutionary adaptive value in their ability to trigger nurturant care. In this study among nulliparous women (N = 81; M age = 23.60, SD = 0.44), we examined how sensitivity to these baby schema features differs based on individual variations in nurturant care motivation and oxytocin system gene methylation. We integrated subjective ratings with measures of facial expressions and electroencephalography (EEG) in response to infant faces that were manipulated to contain more or less pronounced baby schema features. Linear mixed effects analyses demonstrated that infants with more pronounced baby schema features were rated as cuter and participants indicated greater motivation to take care of them. Furthermore, infants with more pronounced baby schema features elicited stronger smiling responses and enhanced P2 and LPP amplitudes compared to infants with less pronounced baby schema features. Importantly, individual differences significantly predicted baby schema effects. Specifically, women with low OXTR methylation and high nurturance motivation showed enhanced differentiation in automatic neurophysiological responses to infants with high and low levels of baby schema features. These findings highlight the importance of considering individual differences in continued research to further understand the complexities of sensitivity to child cues, including facial features, which will improve our understanding of the intricate neurobiological system that forms the basis of caregiving behavior.

Reciprocal self-disclosure makes children feel more loved by their parents in the moment: A proof-of-concept experiment.

Feeling loved by one's parents is critical for children's health and well-being. How can such feelings be fostered? A vital feature of loving interactions is reciprocal self-disclosure, where individuals disclose intimate information about themselves. In a proof-of-concept experiment, we examined whether encouraging reciprocal self-disclosure in parent-child dyads would make children feel more loved during the conversation. Participants were 218 children (ages 8-13, 50% girls, 94% Dutch) and one of their parents (ages 28-56, 62% women, 90% Dutch). Parent-child dyads received a list of 14 questions and took turns asking them each other for 9 min. Dyads were assigned randomly to engage in self-disclosure (questions invoking escalated intimacy) or small talk (questions invoking minimal intimacy). Before and after, children reported how loved they felt by their parent during the conversation. Self-disclosure made children feel more loved during the conversation than did small talk. Compared to small talk, self-disclosure did not instigate conversations that were lengthier or more positive; rather, it instigated conversations that were more emotionally charged (reflecting anger, anxiety, and sadness), social (discussing family and friends), reflective (creating insight), and meaningful (addressing deeply personal topics, including the passing of loved ones). The dyad's gender composition did not significantly moderate these effects. Our research suggests that reciprocal self-disclosure can make children feel more loved in the moment, uncovers linguistic signatures of reciprocal self-disclosure, and offers developmental scientists a tool to examine causal effects of reciprocal self-disclosure in parent-child dyads. Future work should examine long-term effects in everyday parent-child interactions. RESEARCH HIGHLIGHTS: How can parents make children feel more loved by them in the moment? We theorize that these feelings can be cultivated through reciprocal self-disclosure. In a proof-of-concept experiment, we examined effects of reciprocal self-disclosure versus small talk in 218 parent-child dyads, with children aged 8-13. Self-disclosure (vs. small talk) made children feel more loved during the conversation. Linguistically, self-disclosure instigated conversations that were more emotionally charged, social, reflective, and meaningful. This research provides an experimental method to study self-disclosure in parent-child dyads and suggests that self-disclosure can make children feel more loved in the moment.

Preliminary data on oxytocin modulation of neural reactivity in women to emotional stimuli of children depending on childhood emotional neglect.

Sensitivity for rewarding cues and distress signals from children is fundamental to human caregiving and modulated by the neuropeptide oxytocin. In a functional magnetic resonance imaging study, we investigated whether oxytocin regulates neural responses to reward or distress cues form children. In a placebo-controlled, within-subject design, we measured neural responses to positive, negative, and neutral cues from children in 22 healthy female subjects who received oxytocin (24 IU) versus placebo. Further, based on current literature, we hypothesized that oxytocin effects are modulated by experiences of childhood trauma. The task elicited valence-specific effects-positive images activated the ventromedial prefrontal cortex, left anterior cingulate cortex, and right putamen, and images of children in distress activated the bilateral amygdala, hippocampus, and right medial superior frontal cortex. The effects of oxytocin depended on subjective reports of childhood emotional neglect. Self-reported neglect interacted with oxytocin administration in the amygdala, hippocampus, and prefrontal areas. In individuals with higher scores of emotional neglect, oxytocin increased neural reactivity of limbic structures to positive and neutral images. Our findings need replication in larger samples and can therefore be considered preliminary but are in line with the recent literature on the modulating effect of childhood adversity on the sensitivity to oxytocin administration.

Climbing up or falling down: Narcissism predicts physiological sensitivity to social status in children and their parents.

Children's narcissism may be rooted in sensitivity to social status (i.e., prominence, respect, and influence in a social group), and this sensitivity might be shared with parents. Testing this idea, a randomized experiment examined how children with high narcissism levels and their parents respond to gains and losses of social status. On a simulated social media platform, children (N = 123, ages 8-13) competed with fictitious peers for status and were randomly assigned to gain or lose status. Unbeknownst to children, parents viewed the course of the task. Children's and parents' affective reactions during the task were measured with facial electromyography, which detects spontaneous facial muscle activity linked to positive affect (i.e., zygomaticus major activity, involved in smiling) and negative affect (i.e., corrugator supercilii activity, involved in frowning). Children with higher narcissism levels showed steeper increases in negative affect during status loss and steeper increases in both positive and negative affect during status gain. Their parents mirrored the steeper increase in positive affect during their child's status gain, but they did not mirror the increase in negative affect. These results suggest that children with high narcissism levels and their parents show intensified affective-motivational responses to children's status-relevant experiences. These responses may be transmitted from one generation to the other (e.g., genetically or through parent-child socialization).

Neural correlates of self- and other-referential processing in young adolescents and the effects of testosterone and peer similarity.

During adolescence, self-concept develops profoundly, accompanied by major changes in hormone levels. Self-evaluations become more complex, and peers and their opinions increasingly salient. Neuroimaging studies have investigated self- and other-related processing in adolescents, however, the influence of similarity of peers on these processes is still unclear, as well as functional connectivity underlying such processes. We investigated the effect of peer similarity on neural activity and connectivity underlying self- and other-referential processing, by distinguishing between a similar and dissimilar peer when making other-evaluations. Moreover, we explored the association between testosterone and brain activity during self-evaluations. Sixty-six young adolescents underwent functional MRI while performing a trait judgement task in which they indicated whether an adjective described themselves, a similar or a dissimilar classmate. The ventral medial prefrontal cortex (MPFC) showed increased engagement in self-referential processing, and the posterior cingulate cortex and right temporal parietal junction during other-evaluations. However, activity did not differ between the similar and dissimilar other conditions. Functional connectivity of the ventral MPFC included the striatum when evaluating the similar peer and frontoparietal regions when evaluating the dissimilar peer. Furthermore, inter-individual differences in testosterone levels were positively associated with dorsal MPFC activity in males. This study provides insight into the influence of peer similarity on activity and connectivity underlying other-referential processing in young adolescents, and suggests that testosterone affects neural correlates of self-referential processing.

Neural responses in the pain matrix when observing pain of others are unaffected by testosterone administration in women.

There is evidence of testosterone having deteriorating effects on cognitive and affective empathic behaviour in men and women under varying conditions. However, whether testosterone influences empathy for pain has not yet been investigated. Therefore, we tested neural responses to witnessing others in pain in a within-subject placebo-controlled testosterone administration study in healthy young women. Using functional magnetic resonance imaging, we provide affirming evidence that an empathy-inducing paradigm causes changes in the activity throughout the pain circuitry, including the bilateral insula and anterior cingulate cortex. Administration of testosterone, however, did not influence these activation patterns in the pain matrix. Testosterone has thus downregulating effects on aspects of empathic behaviour, but based on these data does not seem to influence neural responses during empathy for others' pain. This finding gives more insight into the role of testosterone in human empathy.

Mothers' neural responses to infant faces are associated with activation of the maternal care system and observed intrusiveness with their own child.

Certain infant facial characteristics, referred to as baby schema, are thought to automatically trigger parenting behavior and affective orientation toward infants. Electroencephalography (EEG) is well suited to assessing the intuitive nature and temporal dynamics of parenting responses, due to its millisecond temporal resolution. Little is known, however, about the relations between neural processing of infant cues and actual parenting behavior in a naturalistic setting. In the present study we examined the event-related potentials (ERPs) of mothers (N = 33) watching infant faces of varying attractiveness, in relation to activation of the maternal care system and the mothers' observed parenting behavior (sensitivity, nonintrusiveness) with their own child (2-6 years old). The results revealed that, irrespective of the cuteness of the infant face, mothers' neural processing of infant faces involved both early P1 and P2 components (related to orienting/detecting processes) and late positive potentials (LPPs; related to more controlled cognitive evaluation/attentional engagement). Increased early detection and processing of infant faces (reflected by P1 and P2 activity) was related to increased activation of the parental care system. In later stages of face processing, increased attentional engagement with infant faces (as reflected by LPP activity) was associated with more intrusiveness of a mother with her own child during interaction. These findings suggest that individual variations in responses to infant stimuli are associated with individual differences in parental care system activation and parenting quality. Furthermore, the parental care system might be activated relatively automatically, but actual parenting and caregiving behavior requires more conscious control.

The endocrinology of human caregiving and its intergenerational transmission.

Variation in the quality of parental care has a tremendous impact on a child's social-emotional development. Research investigating the predictors of this variability in human caregiving behavior has mostly focused on learning mechanisms. Evidence is currently accumulating for the complementary underlying role of steroid hormones and neuropeptides. An overview is provided of the hormones and neuropeptides relevant for human caregiving behavior. Then the developmental factors are described that stimulate variability in sensitivity to these hormones and neuropeptides, which may result in variability in the behavioral repertoire of caregiving. The role of genetic variation in neuropeptide and steroid receptors, the role of testosterone and oxytocin during fetal development and parturition, and the impact of experienced caregiving in childhood on functioning of the neuroendocrine stress and oxytocin system are discussed. Besides providing a heuristic framework for further research on the ontogenetic development of human caregiving, a neuroendocrine model is also presented for the intergenerational transmission of caregiving practices. Insight into the underlying biological mechanisms that bring about maladaptive caregiving behavior, such as neglect and insensitive parenting, will hopefully result in more efficient approaches to reduce the high prevalence of such behavior and to minimize the impact on those affected.

Oxytocin reduces neural activity in the pain circuitry when seeing pain in others.

Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have repeatedly been shown to improve cognitive empathy (e.g. mind reading and emotion recognition). However, OXT has not yet been shown to increase neural empathic responses to pain in others, a core aspect of affective empathy. Effects of OXT on empathy for pain are difficult to predict, because OXT evidently has pain-reducing properties. Accordingly, OXT might paradoxically decrease empathy for pain. Here, using functional neuroimaging we show robust activation in the neural circuitry of pain (insula and sensorimotor regions) when subjects observe pain in others. Crucially, this empathy-related activation in the neural circuitry of pain is strongly reduced after intranasal OXT, specifically in the left insula. OXT on the basis of our neuroimaging data thus remarkably decreases empathy for pain, but further research including behavioral measures is necessary to draw definite conclusions.

Dissociated neural effects of cortisol depending on threat escapability.

Evolution has provided us with a highly flexible neuroendocrine threat system which, depending on threat imminence, switches between active escape and passive freezing. Cortisol, the "stress-hormone", is thought to play an important role in both fear behaviors, but the exact mechanisms are not understood. Using pharmacological functional magnetic resonance imaging we investigated how cortisol modulates the brain's fear systems when humans are under virtual-predator attack. We show dissociated neural effects of cortisol depending on whether escape from threat is possible. During inescapable threat cortisol reduces fear-related midbrain activity, whereas in anticipation of active escape cortisol boosts activity in the frontal salience network (insula and anterior cingulate cortex), which is involved in autonomic control, visceral perception and motivated action. Our findings suggest that cortisol adjusts the human neural threat system from passive fear to active escape, which illuminates the hormone's crucial role in the adaptive flexibility of fear behaviors.

Cognition as the tip of the emotional iceberg: A neuro-evolutionary perspective.

We emphasize the importance of a neuroevolutionary perspective in moving beyond the cognition-emotion dichotomy. Cognitive behavior depends on cortical structures firmly rooted in the emotional brain from which they have evolved. As such, there cannot be cognition without emotion. Endocrine regulation of amygdala connectivity, a neural "switch" between impulsivity and deliberation, further underscores the phylogenetic impossibility of a cognition-emotion dichotomy.

Cortisol administration increases hippocampal activation to infant crying in males depending on childhood neglect.

Animal studies show that exposure to parental neglect alters stress regulation and can lead to neural hyposensitivity or hypersensitivity in response to cortisol, most pronounced in the hippocampus. Cortisol, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, has also been related to parenting more directly, for example, in both sexes, cortisol levels increase when listening to infants crying, possibly to activate and facilitate effective care behavior. Severe trauma is known to negatively affect the HPA-axis in humans; however, it is unknown whether normal variation in parental care in the healthy population can alter sensitivity of the hippocampus to cortisol. Here, we investigate whether variation in experienced neglect changes neural sensitivity to cortisol when humans listen to infant crying, which is an unequivocal signal relevant for care behavior. In a placebo-controlled, within-subject neuroimaging study, we administered 40 mg cortisol to 21 healthy young males without children and used a validated task for measuring neural responses to infant crying. The Dutch version of the Childhood Trauma Questionnaire was used to index participants' early exposure to abuse and neglect. The data show that cortisol markedly increased hippocampal activation toward crying infants, and this effect varied significantly with parental neglect, even in our nonclinical subject sample. Without exposure to severe trauma or neglect, reduced self-experienced quality of parental care in the normal range already substantially increased hippocampal responsivity to cortisol. Altered hippocampal sensitivity to cortisol might be a cross-species marker for the risk of developing later life psychopathology.

Testosterone administration impairs cognitive empathy in women depending on second-to-fourth digit ratio.

During social interactions we automatically infer motives, intentions, and feelings from bodily cues of others, especially from the eye region of their faces. This cognitive empathic ability is one of the most important components of social intelligence, and is essential for effective social interaction. Females on average outperform males in this cognitive empathy, and the male sex hormone testosterone is thought to be involved. Testosterone may not only down-regulate social intelligence organizationally, by affecting fetal brain development, but also activationally, by its current effects on the brain. Here, we show that administration of testosterone in 16 young women led to a significant impairment in their cognitive empathy, and that this effect is powerfully predicted by a proxy of fetal testosterone: the right-hand second digit-to-fourth digit ratio. Our data thus not only demonstrate down-regulatory effects of current testosterone on cognitive empathy, but also suggest these are preprogrammed by the very same hormone prenatally. These findings have importance for our understanding of the psychobiology of human social intelligence.

Revealed masks: Facial mimicry after oxytocin administration in forensic psychopathic patients.

Facial mimicry serves as an evolutionarily rooted important interpersonal communication process that touches on the concepts of socialization and empathy. Facial electromyography (EMG) of the corrugator muscle and the zygomaticus muscle was recorded while male forensic psychopathic patients and controls watched morphed angry or happy facial expressions. We tested the hypothesis that psychopathic patients would show weaker short latency facial mimicry (that is, within 600 ms after stimulus onset) than controls. Exclusively in the group of 20 psychopathic patients, we tested in a placebo-controlled crossover within-subject design the hypothesis that oxytocin would enhance short-latency facial mimicry. Compared with placebo, we found no oxytocin-related significant short-latency responses of the corrugator and the zygomaticus. However, compared with 19 normal controls, psychopathic patients in the placebo condition showed significantly weaker short-latency zygomaticus responses to happy faces, while there was a trend toward significantly weaker short-latency corrugator responses to angry faces. These results are consistent with a recent study of facial EMG responses in adolescents with psychopathic traits. We therefore posit a lifetime developmental deficit in psychopathy pertaining short-latency mimicry of emotional facial expressions. Ultimately, this deficit in mimicking angry and happy expressions may hinder the elicitation of empathy, which is known to be impaired in psychopathy.

Acute effects of steroid hormones and neuropeptides on human social-emotional behavior: a review of single administration studies.

Steroids and peptides mediate a diverse array of animal social behaviors. Human research is restricted by technical-ethical limitations, and models of the neuroendocrine regulation of social-emotional behavior are therefore mainly limited to non-human species, often under the assumption that human social-emotional behavior is emancipated from hormonal control. Development of acute hormone administration procedures in human research, together with the advent of novel non-invasive neuroimaging techniques, have opened up opportunities to systematically study the neuroendocrinology of human social-emotional behavior. Here, we review all placebo-controlled single hormone administration studies addressing human social-emotional behavior, involving the steroids testosterone and estradiol, and the peptides oxytocin and vasopressin. These studies demonstrate substantial hormonal control over human social-emotional behavior and give insights into the underlying neural mechanisms. Finally, we propose a theoretical model that synthesizes detailed knowledge of the neuroendocrinology of social-emotional behavior in animals with the recently gained data from humans described in our review.

Testosterone decreases trust in socially naive humans.

Trust plays an important role in the formation and maintenance of human social relationships. But trusting others is associated with a cost, given the prevalence of cheaters and deceivers in human society. Recent research has shown that the peptide hormone oxytocin increases trust in humans. However, oxytocin also makes individuals susceptible to betrayal, because under influence of oxytocin, subjects perseverate in giving trust to others they know are untrustworthy. Testosterone, a steroid hormone associated with competition and dominance, is often viewed as an inhibitor of sociality, and may have antagonistic properties with oxytocin. The following experiment tests this possibility in a placebo-controlled, within-subjects design involving the administration of testosterone to 24 female subjects. We show that compared with the placebo, testosterone significantly decreases interpersonal trust, and, as further analyses established, this effect is determined by those who give trust easily. We suggest that testosterone adaptively increases social vigilance in these trusting individuals to better prepare them for competition over status and valued resources. In conclusion, our data provide unique insights into the hormonal regulation of human sociality by showing that testosterone downregulates interpersonal trust in an adaptive manner.

The neural mechanisms by which testosterone acts on interpersonal trust.

Recently, we demonstrated that the steroid-hormone testosterone reduces interpersonal trust in humans. The neural mechanism which underlies this effect is however unknown. It has been proposed that testosterone increases social vigilance via neuropeptide systems in the amygdala, augmenting communication between the amygdala and the brain stem. However, testosterone also affects connectivity between the orbitofrontal cortex (OFC) and the amygdala, which could subsequently lead to increased vigilance by reduced top-down control over the amygdala. Here, in a placebo-controlled testosterone administration study with 16 young women, we use functional magnetic resonance imaging to get more insights into neural mechanisms whereby testosterone acts on trust. Several cortical systems, among others the OFC, are involved in the evaluation of facial trustworthiness. Testosterone administration decreased functional connectivity between amygdala and the OFC during judgments of unfamiliar faces, and also increased amygdala responses specifically to the faces that were rated as untrustworthy. Finally, connectivity between the amygdala and the brain stem was not affected by testosterone administration. Although speculative, a neurobiological explanation for these findings is that in uncertain social situations, testosterone induces sustained decoupling between OFC and amygdala by a prefrontal-dopaminergic mechanism, subsequently resulting in more vigilant responses of the amygdala to signals of untrustworthiness.

Fairness modulates non-conscious facial mimicry in women.

In societies with high cooperation demands, implicit consensus on social norms enables successful human coexistence. Mimicking other people's actions and emotions has been proposed as a means to synchronize behaviour, thereby enhancing affiliation. Mimicry has long been thought to be reflexive, but it has recently been suggested that mimicry might also be motivationally driven. Here, we show during an economic bargaining game that automatic happy mimicry of those making unfair offers disappears. After the bargaining game, when the proposers have acquired either a fair or unfair reputation, we observe increased angry mimicry of proposers with an unfair reputation and decreased angry mimicry of fair proposers. These findings provide direct empirical evidence that non-conscious mimicry is modulated by fairness. We interpret the present results as reflecting that facial mimicry in women functions conditionally, dependent on situational demands.