Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin

Study Overview
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Brief Summary
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This study investigates the efficacy of a single-dose of exogenous oxytocin administration on socially adaptive mirror-motor mapping in participants with Autism Spectrum Disorders. A placebo-controlled cross-over trial will be conducted: each participant will receive both a single-dose of placebo and oxytocin in two sessions separated by one week. The order of nasal spray will be randomised across participants. Mirror-motor mapping will be assessed by transcranial magnetic stimulation (TMS), a standard technique to investigate mirror system activity.

Detailed Description
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The brain's action observation network or 'mirror system' supports a variety of socio-cognitive functions, as it enables us to internally simulate and understand others' actions, emotions and intentions. Generally, mirror responses are larger upon the observation of actions accompanied by relevant information for the observer, such as direct eye contact from the actor. In other words, 'mirroring' is adaptively modulated according to the social salience of the observed actions (i.e. it is socially adaptive). Individuals with Autism Spectrum Disorders (ASD) are known to endure difficulties with correctly recognizing eye contact as a communicative cue. Instead, they tend to experience eye contact as stressful and arousing. It is therefore hypothesized that, upon the observation of actions combined with salient gaze cues from the actor, these mirroring processes will not be adaptively modulated in participants with ASD. As appropriate processing of eye contact is a key aspect of (non-verbal) communicative behavior, the investigator will investigate the efficacy of a single dose of intranasal oxytocin administration for enhancing socially-adaptive mirroring in ASD. Oxytocin is a neuropeptide that acts as a regulator social brain areas. On a behavioral level, it is known to enhance the saliency of observed social cues and to improve prosocial behavior. As such, it is regarded a promising intervention for alleviating the social and communicative deficits in ASD.

Official Title
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To Mirror or Not to Mirror Upon Perceived Eye Contact? The Effect of Oxytocin on Socially Adaptive Mirror System Functioning in Autism

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Oxytocin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Young adults (between 18 - 35 y/o) Right-handed Official diagnosis of Autism Spectrum Disorders (for ASD participants) Exclusion Criteria: Female Left-handed Any neuro(psycho)logical / psychiatric illness (for healthy controls) Motor dysfunctions of the hands / arms Any contradiction to TMS research as assessed with the TMS screening list: no metal objects in the body (e.g. pacemaker, coronary bypass clips, implants, medication pumps, ...), history of brain trauma in the past (e.g. meningitis, epilepsy, surgery, ...) or history of drug and/or alcohol abuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxytocin (OXT) spray<br>Syntocinon nasal spray (product code RVG 03716) will be used to intranasally administer one single dose (24 IU) of OXT (3 puffs of 4 IU per nostril). | Drug: Oxytocin<br>* A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril) will be administered before the assessment of the neurophysiological measures.<br>* Other names: Syntocinon (product code RVG 03716);|
| Placebo Comparator: Placebo (PL) spray<br>Physiological water (a solution of sodium chloride (NaCl) in water) will be used to intranasally administer one single dose (24 IU) of PL (3 puffs of 4 IU per nostril). | Other: Placebo<br>* A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril) will be administered before the assessment of the neurophysiological measures.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in socially adaptive mirroring as measured by TMS | After a single dose of nasal spray, TMS will be applied to assess mirror-motor mapping during the observation of socially relevant vs. irrelevant visuomotor information. | 30 minutes after spray administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mirroring of others' actions as measured by TMS | After a single dose of nasal spray, TMS will be applied to assess basic mirror-motor mapping of observed actions. | 30 minutes after spray administration | 
| Change from baseline in corticospinal excitability as measured by TMS | After a single dose of nasal spray, TMS will be applied to assess corticospinal excitability when the participant is at rest (without any visuomotor information). | 30 minutes after spray administration | 
| Change from baseline in total fixation duration towards the eye region of the model. | During movement observation, participants' viewing behavior will be monitored by means of head-mounted eye tracking technology. | 30 minutes after spray administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oxytocin, Eye Contact, Mirror System, Transcranial Magnetic Stimulation