Oxytocin's Effects on Emotional Processing and Its Acting Routes

In recent years ample studies have reported that intranasally administered oxytocin (OT) can facilitate social motivation and cognition in healthy and clinical populations. However, it is still unclear how effects are mediated since intranasally administered OT can both directly enter the brain (nose to brain) and increase peripheral vascular concentrations (nose to blood). The relative functional contributions of these routes are not established and have received insufficient attention in the field. Therefore, the investigators use the vasoconstrictor (VC) pretreatment to prevent intranasal OT (24 IU) from increasing peripheral concentrations and combine fMRI, behavioral measures, with physiological recording to examine the modulatory effects of OT on implicit emotional processing and its acting routes. In total 120 male participants are recruited for this double-blind, between-subject, placebo-controlled study. After arriving at the laboratory, participants first completed questionnaires for about 30 minutes, and were then randomly assigned into 3 groups receiving intranasal administration of "VC + OT", "placebo (PLC) + OT", or "VC + PLC". Then, they complete a resting-state scan and two task-based scans lasting approximately 65 minutes in total. There is a sencond resting-state scan between two task-based scans, which is mainly used as a break between the two tasks. Blood samples are collected twice (after finishing questionnaires and 30 minutes post-treatment) for subsequent analyses of plasma OT concentrations. The two task-based scans consist of an implicit face-emotion processing task (gender judgments of faces) and an emotional scene processing task (judging whether a child/old people/building/dog is present in the picture). After scanning, there is a 40-minute picture rating task (emotional valence, intensity, and arousal). Questionnaires include State-Trait Anxiety Inventory, Beck Depression Inventory II, Liebowitz Social Anxiety Scale, Autism Spectrum Quotient, Social Responsiveness Scale-2, Interpersonal Reactivity Index, Childhood Trauma Questionnaire, Toronto Alexithymia Scale and Positive and Negative Affect Schedule.

• placebo (compared to vasoconstrictor) (Drug): intranasal administration of placebo (4 sprays of 0.9% saline and glycerin)
• vasoconstrictor (Otrivin) (Drug): intranasal administration of vasoconstrictor (4 sprays of 0.9% Otrivin)
• placebo (compared to oxytocin) (Drug): intranasal administration of placebo (24 IU)
• oxytocin (Drug): intranasal administration of oxytocin (24IU)

Primary outcomes

• Brain activity in response to emotional stimuli during task-based fMRI scanning [1 hour]: Subjects receive task fMRI scanning after treatment. The investigators will compare the activation differences in the brain, specifically focusing on the amygdala, among three groups.
• Changes in plasma oxytocin concentrations [After finishing questionnaires and 30-minute post-treatment]: Blood samples will be collected two times, with one sample collected after finishing questionnaires and the other one 30-minute post-treatment.

Secondary outcomes

• The valence rating in response to different emotional stimuli [40 minutes]: The valence rating scores (1\~9) were collected in response to neutral, positive or negative emotional pictures. The higher the score (5\~9), the more positive the participants consider the picture to be; the lower the score (1\~5), the more negative the participants consider the picture to be. The rating scores will be collected after fMRI scanning.
• The intensity rating in response to different emotional stimuli [40 minutes]: The intensity rating scores (1\~9) were collected in response to neutral, positive or negative emotional pictures. The higher the score, the stronger the intensity level. The rating scores will be collected after fMRI scanning.
• The arousal rating in response to different emotional stimuli [40 minutes]: The arousal rating scores (1\~9) were collected in response to neutral, positive or negative emotional pictures. The higher the score, the stronger the arousal level. The rating scores will be collected after fMRI scanning.
• Resting-state fMRI [17 minutes in total with each lasting around 8.5 minutes.]: Subjects receive resting-state fMRI scanning before and after first task, with the sencond resting-state scan being mainly used as a break between the two tasks. The investigators will compare the resting-state functional connectivity (the amygdala as the seed region) among three groups.

Sex: Male, ages: 18 Years to 30 Years, accepts healthy volunteers

Inclusion Criteria:

* Healthy subjects without past or current psychiatric or neurological disorders

Exclusion Criteria:

* History of head injury.
* Medical or psychiatric illness.
* Subjects take a certain drug for a long period of time.
* Subjects have metal implants in their bodies.

• Shuxia Yao, Dr, Principal investigator, University of Electronic Science and Technology of China