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.

Breakdown of utilitarian moral judgement after basolateral amygdala damage.

Most of us would regard killing another person as morally wrong, but when the death of one saves multiple others, it can be morally permitted. According to a prominent computational dual-systems framework, in these life-and-death dilemmas, deontological (nonsacrificial) moral judgments stem from a model-free algorithm that emphasizes the intrinsic value of the sacrificial action, while utilitarian (sacrificial) moral judgments are derived from a model-based algorithm that emphasizes the outcome of the sacrificial action. Rodent decision-making research suggests that the model-based algorithm depends on the basolateral amygdala (BLA), but these findings have not yet been translated to human moral decision-making. Here, in five humans with selective, bilateral BLA damage, we show a breakdown of utilitarian sacrificial moral judgments, pointing at deficient model-based moral decision-making. Across an established set of moral dilemmas, healthy controls frequently sacrifice one person to save numerous others, but BLA-damaged humans withhold such sacrificial judgments even at the cost of thousands of lives. Our translational research confirms a neurocomputational hypothesis drawn from rodent decision-making research by indicating that the model-based algorithm which underlies outcome-based, utilitarian moral judgements in humans critically depends on the BLA.

Pattern classification based on the amygdala does not predict an individual's response to emotional stimuli.

Functional magnetic resonance imaging (fMRI) studies have often recorded robust univariate group effects in the amygdala of subjects exposed to emotional stimuli. Yet it is unclear to what extent this effect also holds true when multi-voxel pattern analysis (MVPA) is applied at the level of the individual participant. Here we sought to answer this question. To this end, we combined fMRI data from two prior studies (N = 112). For each participant, a linear support vector machine was trained to decode the valence of emotional pictures (negative, neutral, positive) based on brain activity patterns in either the amygdala (primary region-of-interest analysis) or the whole-brain (secondary exploratory analysis). The accuracy score of the amygdala-based pattern classifications was statistically significant for only a handful of participants (4.5%) with a mean and standard deviation of 37% ± 5% across all subjects (range: 28-58%; chance-level: 33%). In contrast, the accuracy score of the whole-brain pattern classifications was statistically significant in roughly half of the participants (50.9%), and had an across-subjects mean and standard deviation of 49% ± 6% (range: 33-62%). The current results suggest that the information conveyed by the emotional pictures was encoded by spatially distributed parts of the brain, rather than by the amygdala alone, and may be of particular relevance to studies that seek to target the amygdala in the treatment of emotion regulation problems, for example via real-time fMRI neurofeedback training.

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.

Effects of Multisession Transcranial Direct Current Stimulation on Stress Regulation and Emotional Working Memory: A Randomized Controlled Trial in Healthy Military Personnel.

OBJECTIVES: Top-down stress regulation, important for military operational performance and mental health, involves emotional working memory and the dorsolateral prefrontal cortex (DLPFC). Multisession transcranial direct current stimulation (tDCS) applied over the DLPFC during working memory training has been shown to improve working memory performance. This study tested the hypothesis that combined tDCS with working memory training also improves top-down stress regulation. However, tDCS response differs between individuals. Resting-state electrophysiological brain activity was post hoc explored as a possible predictor of tDCS response. The predictive value of the ratio between slow-wave theta oscillations and fast-wave beta oscillations (theta/beta ratio) was examined, together with the previously identified tDCS response predictors age, education, and baseline working memory performance. MATERIALS AND METHODS: Healthy military service members (n = 79) underwent three sessions of real or sham tDCS over the right DLPFC (anode: F4, cathode: behind C2) at 2 mA for 20 minutes during emotional working memory training (N-back task). At baseline and within a week after the tDCS training sessions, stress regulation was assessed by fear-potentiated startle responses and subjective fear in a threat-of-shock paradigm with instructed emotional downregulation. Results were analyzed in generalized linear mixed-effects models. RESULTS: Threat-of-shock responses and emotional working memory performance showed no significant group-level effects of the real vs sham tDCS training intervention (p > 0.07). In contrast, when considering baseline theta/beta ratios or the other tDCS response predictors, exploratory results showed a trait-dependent beneficial effect of tDCS on emotional working memory training performance during the first session (p < 0.01). CONCLUSIONS: No evidence was found for effectivity of the tDCS training intervention to improve stress regulation in healthy military personnel. The emotional working memory training results emphasize the importance of studying the effects of tDCS in relation to individual differences. CLINICAL TRIAL REGISTRATION: This study was preregistered on September 16, 2019, at the Netherlands Trial Register (www.trialregister.nl) with ID: NL8028.

Voxel-based morphometry and cortical thickness in combat veterans suffering from impulsive aggression.

BACKGROUND: Problems with impulsive aggression occur in many forms of psychiatric dysfunction, and are a common complaint among combat veterans. The present study sought to examine the neuroanatomical correlates of combat-related impulsive aggression. METHODS: T1-weighted magnetic resonance images were acquired from 29 male veterans with impulsive aggression and 30 non-aggressive combat controls. Subcortical volumetry was conducted with the amygdala and hippocampus and their main constituent subdivisions as regions-of-interest (ROIs) (basolateral, centromedial amygdala; head, body, tail of hippocampus). Cortical thickness measurements were extracted for the dorsolateral prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex. Within-group correlations with psychometric measures were also explored. RESULTS: No significant group differences in cortical thickness or subcortical grey matter volumes were observed for any of the ROIs. Also, no significant correlations with any of the psychometric measures were recorded. Exploratory whole-brain analysis of cortical thickness revealed a significant group × anxiety interaction effect in a cluster located in the left lingual gyrus. CONCLUSIONS: The current findings indicate that problems with impulsive aggression may not be directly associated with alterations in cortical thickness or amygdalar/hippocampal (sub)volumes. The observed interplay between impulsive aggression problems and anxiety-related symptoms is consistent with prior work showing the two phenomena may share the same underlying (neural) mechanisms.

Effects of tDCS during inhibitory control training on performance and PTSD, aggression and anxiety symptoms: a randomized-controlled trial in a military sample.

BACKGROUND: Post-traumatic stress disorder (PTSD), anxiety, and impulsive aggression are linked to transdiagnostic neurocognitive deficits. This includes impaired inhibitory control over inappropriate responses. Prior studies showed that inhibitory control can be improved by modulating the right inferior frontal gyrus (IFG) with transcranial direct current stimulation (tDCS) in combination with inhibitory control training. However, its clinical potential remains unclear. We therefore aimed to replicate a tDCS-enhanced inhibitory control training in a clinical sample and test whether this reduces stress-related mental health symptoms. METHODS: In a preregistered double-blind randomized-controlled trial, 100 active-duty military personnel and post-active veterans with PTSD, anxiety, or impulsive aggression symptoms underwent a 5-session intervention where a stop-signal response inhibition training was combined with anodal tDCS over the right IFG for 20 min at 1.25 mA. Inhibitory control was evaluated with the emotional go/no-go task and implicit association test. Stress-related symptoms were assessed by self-report at baseline, post-intervention, and after 3-months and 1-year follow-ups. RESULTS: Active relative to sham tDCS neither influenced performance during inhibitory control training nor on assessment tasks, and did also not significantly influence self-reported symptoms of PTSD, anxiety, impulsive aggression, or depression at post-assessment or follow-up. CONCLUSIONS: Our results do not support the idea that anodal tDCS over the right IFG at 1.25 mA enhances response inhibition training in a clinical sample, or that this tDCS-training combination can reduce stress-related symptoms. Applying different tDCS parameters or combining tDCS with more challenging tasks might provide better conditions to modulate cognitive functioning and stress-related symptoms.

Testosterone administration in women increases the size of their peripersonal space.

Peripersonal space (PPS) is the space immediately surrounding the body, conceptualised as a sensory-motor interface between body and environment. PPS size differs between individuals and contexts, with intrapersonal traits and states, as well as social factors having a determining role on the size of PPS. Testosterone plays an important role in regulating social-motivational behaviour and is known to enhance dominance motivation in an implicit and unconscious manner. We investigated whether the dominance-enhancing effects of testosterone reflect as changes in the representation of PPS in a within-subjects testosterone administration study in women (N = 19). Participants performed a visuo-tactile integration task in a mixed-reality setup. Results indicated that the administration of testosterone caused a significant enlargement of participants' PPS, suggesting that testosterone caused participants to implicitly appropriate a larger space as their own. These findings suggest that the dominance-enhancing effects of testosterone reflect at the level of sensory-motor processing in PPS.

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.

Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials.

BACKGROUND: In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available. AIM: To investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups. METHODS: 497 women (21-70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg). OUTCOMES: The primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure. RESULTS: In women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57-2.84, P = .004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44-3.45, P = .012; T: Δ = 1.69, 95% CI = 0.58-2.80, P = .003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (Δ = 0.99, 95% CI = 0.17-1.82, P = .019) and monotherapies (B: Δ = 1.52, 95% CI = 0.57-2.46, P = .002; T: Δ = 0.98, 95% CI = 0.17-1.78, P = .018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (T + S treatment, 3%; T + B treatment, 2%), headache (placebo treatment, 2%; T + S treatment, 9%), dizziness (T + B treatment, 3%), and nausea (T + S treatment, 3%; T + B treatment, 2%). CLINICAL IMPLICATIONS: T + S and T + B are promising treatments for women with FSIAD. STRENGTHS AND LIMITATIONS: The data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of T + S and T + B on distress and the potentially sustained improvements after medication cessation were not investigated. CONCLUSIONS: T + S and T + B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups. Tuiten A, van Rooij K, Bloemers J, et al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials. J Sex Med 2018;15:201-216.

Testosterone facilitates the sense of agency.

Sense of agency (SoA) refers to feelings of being in control of one's actions. Evidence suggests that SoA might contribute towards higher-order feelings of personal control - a key attribute of powerful individuals. Whether testosterone, a steroid hormone linked to power in dominance hierarchies, also influences the SoA is not yet established. In a repeated-measures design, 26 females participated in a double-blind, placebo-controlled trial to test the effects of 0.5 mg testosterone on SoA, using an implicit measure based upon perceived shifts in time between a voluntary action and its outcome. Illusions of control, as operationalized by optimism in affective forecasting, were also assessed. Testosterone increased action binding but there was no significant effect on tone binding. Affective forecasting was found to be significantly more positive on testosterone. SoA and optimistic expectations are basic manifestations of power which may contribute to feelings of infallibility often associated with dominance and testosterone.

A quantitative and qualitative review of the effects of testosterone on the function and structure of the human social-emotional brain.

Social and affective research in humans is increasingly using functional and structural neuroimaging techniques to aid the understanding of how hormones, such as testosterone, modulate a wide range of psychological processes. We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of testosterone administration, and of fMRI studies that measured endogenous levels of the hormone, in relation to social and affective stimuli. Furthermore, we conducted a review of structural MRI i.e. voxel based morphometry (VBM) studies which considered brain volume in relation to testosterone levels in adults and in children. In the included testosterone administration fMRI studies, which consisted of female samples only, bilateral amygdala/parahippocampal regions as well as the right caudate were significantly activated by social-affective stimuli in the testosterone condition. In the studies considering endogenous levels of testosterone, stimuli-invoked activations relating to testosterone levels were noted in the bilateral amygdala/parahippocampal regions and the brainstem. When the endogenous testosterone studies were split by sex, the significant activation of the brain stem was seen in the female samples only. Significant stimuli-invoked deactivations relating to endogenous testosterone levels were also seen in the right and left amygdala/parahippocampal regions studies. The findings of the VBM studies were less consistent. In adults larger volumes in the limbic and temporal regions were associated with higher endogenous testosterone. In children, boys showed a positive correlation between testosterone and brain volume in many regions, including the amygdala, as well as global grey matter volume, while girls showed a neutral or negative association between testosterone levels and many brain volumes. In conclusion, amygdalar and parahippocampal regions appear to be key target regions for the acute actions of testosterone in response to social and affective stimuli, while neurodevelopmentally the volumes of a broader network of brain structures are associated with testosterone levels in a sexually dimorphic manner.

Generous economic investments after basolateral amygdala damage.

Contemporary economic models hold that instrumental and impulsive behaviors underlie human social decision making. The amygdala is assumed to be involved in social-economic behavior, but its role in human behavior is poorly understood. Rodent research suggests that the basolateral amygdala (BLA) subserves instrumental behaviors and regulates the central-medial amygdala, which subserves impulsive behaviors. The human amygdala, however, typically is investigated as a single unit. If these rodent data could be translated to humans, selective dysfunction of the human BLA might constrain instrumental social-economic decisions and result in more impulsive social-economic choice behavior. Here we show that humans with selective BLA damage and a functional central-medial amygdala invest nearly 100% more money in unfamiliar others in a trust game than do healthy controls. We furthermore show that this generosity is not caused by risk-taking deviations in nonsocial contexts. Moreover, these BLA-damaged subjects do not expect higher returns or perceive people as more trustworthy, implying that their generous investments are not instrumental in nature. These findings suggest that the human BLA is essential for instrumental behaviors in social-economic interactions.

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.

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.

Doubling down on dual systems: A cerebellum-amygdala route towards action- and outcome-based social and affective behavior.

The amygdala and cerebellum are both evolutionary preserved brain structures containing cortical as well as subcortical properties. For decades, the amygdala has been considered the fear-center of the brain, but recent advances have shown that the amygdala acts as a critical hub between cortical and subcortical systems and shapes social and affective behaviors beyond fear. Likewise, the cerebellum is a dedicated control unit that fine-tunes motor behavior to fit contextual requirements. There is however increasing evidence that the cerebellum strongly influences subcortical as well as cortical processes beyond the motor domain. These insights broadened the view on the cerebellum's functions to also include social and affective behavior. Here we explore how the amygdala and cerebellum might interact in shaping social and affective behaviors based on their roles in threat reactivity and reinforcement learning. A novel mechanistic neural framework of cerebellum-amygdala interactions will be presented which provides testable hypotheses for future social and affective neuroscientific research in humans.

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.