Comparison of clear and narrow outcomes on testosterone levels in social competition.

This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.yhbeh.2016.05.016A contribution to a special issue on Hormones and Human Competition. Social competition is associated with marked emotional, behavioral and hormonal responses, including changes in testosterone levels. The strength and direction of these responses is often modulated by levels of other hormones (e.g. cortisol) and depends on psychological factors - classically, the objective outcome of a competition (win vs. loss) but also, hypothetically, the closeness of that outcome (e.g. decisive victory vs. close victory). We manipulated these two aspects of a social contest among male participants (N=166), to investigate how testosterone and affect fluctuated as a function of clear vs. narrow wins and clear vs. narrow losses. We found that losing a competition by a small margin (a narrow loss) was experienced as more pleasant than a clear loss. Among individuals with higher levels of basal cortisol, winning the competition by a narrow margin was associated with a decrease in testosterone levels. These findings are discussed within the framework of the status instability hypothesis and the growing literature on how situational and physiological factors modulate testosterone reactivity to social contests

Blocking D2/D3 dopamine receptors in male participants increases volatility of beliefs when learning to trust others

The ability to learn about other people is crucial for human social functioning. Dopamine has been proposed to regulate the precision of beliefs, but direct behavioural evidence of this is lacking. In this study, we investigate how a high dose of the D2/D3 dopamine receptor antagonist sulpiride impacts learning about other people’s prosocial attitudes in a repeated Trust game. Using a Bayesian model of belief updating, we show that in a sample of 76 male participants sulpiride increases the volatility of beliefs, which leads to higher precision weights on prediction errors. This effect is driven by participants with genetically conferred higher dopamine availability (Taq1a polymorphism) and remains even after controlling for working memory performance. Higher precision weights are reflected in higher reciprocal behaviour in the repeated Trust game but not in single-round Trust games. Our data provide evidence that the D2 receptors are pivotal in regulating prediction error-driven belief updating in a social context

Studying the Neurobiology of Social Interaction with Transcranial Direct Current Stimulation—The Example of Punishing Unfairness

Studying social behavior often requires the simultaneous interaction of many subjects. As yet, however, no painless, noninvasive brain stimulation tool existed that allowed the simultaneous affection of brain processes in many interacting subjects. Here we show that transcranial direct current stimulation (tDCS) can overcome these limits. We apply right prefrontal cathodal tDCS and show that subjects' propensity to punish unfair behavior is reduced significantl

The Human Basolateral Amygdala Is Indispensable for Social Experiential Learning

Trust and betrayal are central to our social world, and adaptive responses to generous and selfish behavior are crucial to our economic and social well-being [1]. We learn about others’ trustworthiness through trial and error during repeated interactions [2]. By reinforcing and suppressing behavior during positive and negative interactions with conspecifics, rodent research has established a crucial role for the basolateral amygdala (BLA) in social experiential learning [3, 4]. The human BLA has undergone a reorganization with massive expansion relative to other amygdala nuclei [5], and there is no translational research on its role in experiential learning. The human amygdala is traditionally researched as a single structure [6], neglecting the sub-nuclei's structural und functional differences [7], which might explain inconsistent findings in research on social interactions [8, 9]. Here, we study whether the human BLA is necessary for social and non-social experiential learning by testing a group of five humans with selective bilateral damage to the BLA. We compared their learning behavior in a repeated trust game, and a non-social control task, to healthy, matched controls. Crucially, BLA-damaged subjects, unlike control subjects, completely failed to adapt their investments when interacting with a trustworthy and an untrustworthy partner. In the non-social task, BLA-damaged subjects learned from positive outcomes but differed from the controls by not learning from negative outcomes. Our data extend findings in rodent research by showing that the human BLA is essential for social experiential learning and provide confirmatory evidence of divergent mechanisms for differentially valenced outcomes in non-social learning

Dopaminergic stimulation increases selfish behavior in the absence of punishment threat

Rationale: People often face decisions that pit self-interested behavior aimed at maximizing personal reward against normative behavior such as acting cooperatively, which benefits others. The threat of social sanctions for defying the fairness norm prevents people from behaving overly selfish. Thus, normative behavior is influenced by both seeking rewards and avoiding punishment. However, the neurochemical processes mediating the impact of these influences remain unknown. Several lines of evidence link the dopaminergic system to reward and punishment processing, respectively, but this evidence stems from studies in non-social contexts. Objectives: The present study investigates dopaminergic drug effects on individuals' reward seeking and punishment avoidance in social interaction. Methods: Two-hundred one healthy male participants were randomly assigned to receive 300mg of l-3,4-dihydroxyphenylalanine (L-DOPA) or a placebo before playing an economic bargaining game. This game involved two conditions, one in which unfair behavior could be punished and one in which unfair behavior could not be punished. Results: In the absence of punishment threats, L-DOPA administration led to more selfish behavior, likely mediated through an increase in reward seeking. In contrast, L-DOPA administration had no significant effect on behavior when faced with punishment threats. Conclusions: The results of this study broaden the role of the dopaminergic system in reward seeking to human social interactions. We could show that even a single dose of a dopaminergic drug may bring selfish behavior to the fore, which in turn may shed new light on potential causal relationships between the dopaminergic system and norm abiding behaviors in certain clinical subpopulations

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

Role of Dopamine D2 Receptors in Human Reinforcement Learning

Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, while loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically-determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.Neuropsychopharmacology accepted article peview online, 09 April 2014; doi:10.1038/npp.2014.84

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