Brain Dynamics of Oxytocin
Condition: Brain Dynamics in Healthy Adults
Study type: Interventional
Phase: Phase 1

Summary: 
      Oxytocin is a neuropeptide that is well known for its role in social and affiliative behavior
      in humans. Oxytocin receptors are significantly lowered in autistic individuals and
      administration of oxytocin has shown benefits in enhancing social recognition and behavior in
      autistic children. However, more recent research has refined the behavioral effects of
      oxytocin, moving away from the notion that the neuropeptide blindly induces love and trust,
      towards the view that it actually increases social perception in assessing friend vs. foe:
      supporting cohesion with 'insiders' and distrust and aggression for 'outsiders.' Oxytocin is
      responsible for the selective aggression shown by lactating female mammals protecting their
      young, an effect demonstrated also in humans, and has been shown to strengthen feelings of
      ethnocentrism. However, no neuroimaging study to date has investigated this effect, with the
      consequence that its neurobiological basis is still unknown.

      The general aim of our study is to determine meso-circuit brain dynamics that underlie
      oxytocin's amplification of both trust and aggression; and specifically, using neuroimaging
      (fMRI, magnetoencephalography, and behavioral testing) whether oxytocin amplifies kinship
      bias by attenuating social reward learning.
    

Detailed description: 
      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:

        1. Determine the default circuitry of oxytocin (OT).

        2. Determine time-course and gender differences for default neural response to OT.

        3. 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').

        4. 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).
    

Intervention name(s): Syntocinon Nasal Spray, 40IU; Syntocinon Placebo Formulation, 40IU
Intervention type(s): Drug; Drug
Intervention description(s): Subjects will be scanned twice. Prior to first brain scanning session, they will be randomly assigned to receive either Syntocinon or Placebo. Prior to second scanning session, they will receive what they have not received in the first session; i.e., same subjects will be receiving both Syntocinon and placebo on two different days.; Subjects will be scanned twice. Prior to first brain scanning session, they will be randomly assigned to receive either Syntocinon or Placebo. Prior to second scanning session, they will receive what they have not received in the first session; i.e., same subjects will be receiving both Syntocinon and placebo on two different days.
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: oxytocin; trust; kinship; kin selection