Dissecting the Role of Estradiol in Mediating Gender-specific Anxiolytic and Prosocial Effects of Oxytocin

In Study 1, electrodermal responses will be measured during the fear conditioning and fear extinction tasks. The paradigm is an adapted version of a validated fear-conditioning procedure. Before the start of the paradigm a baseline of electrodermal activity is recorded for 60 seconds. During the conditioning session four neutral conditioned stimuli (two CS+ A and two CS+ B) are paired with an aversive US (electric shock) in 75 % contingency, whereas two other neutral stimuli are never paired with the US (non-fear-associated stimulus [CS-]). In CS+ trials electric shocks are administered during the last 500 milliseconds of the trial. In the fear extinction session all CS+ and CS- are presented in the absence of electric shocks. Oxytocin and estradiol baseline concentrations will be tested as moderator variables.

In Study 1, emotion recognition will be measured. During the emotion recognition task, emotional faces are presented and participants are required to indicate the perceived emotion ("neutral", "fearful", "happy", "disgusted", "angry", "not sure") in a following self-paced phase. A Bayesian adaptive procedure ("QUEST") will be used to determine the stimulus presentation and to estimate individual emotion thresholds. Oxytocin and estradiol baseline concentrations will be tested as moderator variables.

In Study 2, resting state functional connectivity will be measured. The resting state fMRI analysis will focus on functional connectivity between regions-of-interest (ROIs) associated with emotional processing (i.e. amygdala, cingulate and prefrontal cortex, insula, striatal areas). Oxytocin and estradiol baseline concentrations will be tested as moderator variables.

In Study 2, neural responses to emotional faces will be measured. Functional magnetic resonance imaging will be performed to measure the blood-oxygen-level dependent signal in response to emotional faces. Analyses will focus on regions-of-interest associated with emotional processing (i.e. amygdala, cingulate and prefrontal cortex, insula, striatal areas). Oxytocin and estradiol baseline concentrations will be tested as moderator variables.

In Study 2, neural responses to an emotional subsequent memory task will be measured. Functional magnetic resonance imaging will be performed to measure the blood-oxygen-level dependent signal in response to emotional scenes. The investigators plan to analyze scenes depending on valence (positive, negative, neural) and sociality (social, non-social). Furthermore, remembered and non-remembered emotional pictures will be compared. To classify pictures as remembered and non-remembered, participants will perform a memory recognition task three days after the MRI scan. The recognition task will include pictures shown in the scanner and distractors. Analyses will focus on regions-of-interest associated with emotional processing and memory (i.e. amygdala, hippocampus, cingulate and prefrontal cortex, insula, striatal areas). Oxytocin and estradiol baseline concentrations will be tested as moderator variables.

In both studies, blood samples will be collected 5 minutes before gel administration and 5 minutes after the last task.

In both studies, blood samples will be collected 5 minutes before gel administration and 5 minutes after the last task.

In Study 1, during the first 3500 ms of a trial in the fear conditioning and fear extinction tasks participants will be required to indicate via button press whether they expect to receive an electric shock (yes, no, not sure). Oxytocin and estradiol baseline concentrations will be tested as moderator variables.

In Study 1, bargaining behavior will be measured in three different versions of the Ultimatum Game (restricted, unrestricted and computer ultimatum game). All participants will play as responders in the three versions. As a cover story, participants will be told that they play against real partners, who took part in previous experiments. In the restricted version of the Ultimatum Game, the proposer can only decide between two given options. As such, chosen offers are either framed as fair or unfair depending on the alternative option. In the unrestricted Ultimatum Game, the proposer can freely decide how to split 10 Euro. In addition, participants will complete 24 trials of a computer version of the unrestricted Ultimatum Game, in which the word "computer" will be shown instead of a picture of the proposer. Estradiol baseline concentrations will be tested as moderator variables.

In Study 1, subjects will perform a delayed discounting task in order to assess their control of impulsive preferences. Participants will be asked to choose between small immediate rewards and larger later rewards. Estradiol baseline concentrations will be tested as moderator variables.

In Study 2, participants' empathy will be assessed with the Multifaceted Empathy Test (MET) which includes photographs showing people in emotionally charged situations. Participants will be asked to infer the mental states of the individuals shown (cognitive empathy) and to rate their emotional response to the picture (emotional empathy). Participants will perform the MET twice: 1. before the fMRI in the second session and and 2. three days following the fMRI. Estradiol baseline concentrations will be tested as moderator variables.

In Study 2, the investigators will use an iterated version of the prisoner's dilemma to evaluate the participant's cooperative behavior. The participants will have to decide multiple times whether they want to betray their opponent or whether they choose to cooperate. Participants will perform the Prisoner's Dilemma twice: 1. before the fMRI in the second session and and 2. three days following the fMRI.Estradiol baseline concentrations will be tested as moderator variables.