Computational Modeling of Oxytocin in the Regulation of Trust

The purpose of the study is to understand how oxytocin affects brain and behavior. The study will compare Syntocinon Nasal Spray to placebo. The specific aims are to: Determine the default circuitry of oxytocin (OT). Determine time-course and gender differences for default neural response to OT. Using an iterative version of the classical neuroeconomic game (Trust Study), behaviorally test whether OT down-regulates reward learning, thereby enhancing the effects of kinship bias, to account for the polarizing effects (in which OT increases trust for 'in-groups' and increases aggression for 'out-groups'). Identify the down-regulation of reward learning neurobiologically, via data-driven control systems modeling of the reward circuit using MRI (fMRI: time-series analysis of the orbitofrontal cortex, amygdala, anterior and posterior cingulate, and nucleus accumbens, and magnetic resonance spectroscopy: focusing on gamma-Aminobutyric acid neurotransmitters within the nucleus accumbens) and magnetoencephalography (focusing on the dynamics within the prefrontal cortex). FMRI and MRS will be conducted during the same MRI scan, while MEG will be conducted separately. STUDY PROCEDURES: Nasal Obstruction/Anosmia Screening: All potential subjects will be screened for total or partial anosmia and nasal congestion using the University of Pennsylvania Smell Identification Test (Psychological Assessment Resources, Lutz FL). Pregnancy and Lactation Screening: Oxytocin is often used clinically to trigger labor in late-stage pregnancy. Although none of our subjects will be in late-stage pregnancy and subjects will be receiving dosages far smaller that those used to trigger labor, to be safe all potential female subjects will be urine screened for pregnancy immediately during the history and physical. Lactation screening will be performed via self-report, and is conducted to avoid confounds due to endogenously produced OT during the milk-ejection reflex. Oxytocin/Placebo Procedures: Oxytocin intranasal spray is manufactured as the Syntocinon Nasal Spray. The typical dose oxytocin of for short-term intranasal use is 40IU, and has an expected half-life of 20 minutes. Placebos, identical in preparation except for the oxytocin component, will be administered in the same manner in a double blind procedure. To avoid bleed-through between conditions while controlling for order effects, sessions will not be mixed between drug and placebo conditions: each session, conducted on separate days, will be either 'drug' or 'placebo.' Scanning Procedures: Scanning procedure for MRI will include: structural scan (6 minutes), fMRI or MRS resting state (10 minutes), and a neuroeconomic task scan (10 minutes). Scanning procedure for MEG will include: resting state (10 minutes), and a neuroeconomic task scan (20 minutes). Behavioral Task: During scans, subjects will participate in an interactive neuroeconomic game, an iterative version of the classical "Trust Study". During this game, the subject ('investor') is first provided a sum of money. He then has the choice in terms of how much to invest in a fictional computer-generated trustee or, in forced-choice versions, to choose between different trustees. The trustee then sends some percentage back to the subject ('investor'), and the game iterates over many trials. Previous research has shown that OT disrupts participant's use of the optimal solution, eliciting greater "trust" in the trustee than would be expected by Nash Equilibrium. To modulate reward learning, algorithms for trustee behavior will be modulated towards greater and lesser generosity. To modulate kinship bias, trustees will be represented on the screen using faces of greater and lesser similarity to that of the subject, created using MorphMan video-editing software (STOIK Imaging, Moscow Russia).