Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin

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

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.

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.

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).

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).

A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril) will be administered before the assessment of the neurophysiological measures.

A single dose (24IU) of nasal spray (3 puffs of 4IU per nostril) will be administered before the assessment of the neurophysiological measures.

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.

After a single dose of nasal spray, TMS will be applied to assess basic mirror-motor mapping of observed actions.

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).

During movement observation, participants' viewing behavior will be monitored by means of head-mounted eye tracking technology.

Saliva samples will be collected before nasal spray administration and after the experimental procedure to be able to monitor the pharmacokinetics of oxytocin.

Informant-based self-report scale to assess public self-awareness in a specific situation as measured by SSAS. Likert scale: I totally agree (1) - I totally disagree (10); lower scores indicate more public self-awareness.

Informant-based scale to assess self-reported arousal and pleasure in a specific situation as measured by SAM. Likert scale: Pleasant / Not aroused (1) - Unpleasant / Aroused (9). Higher scores indicate more arousal and less pleasure.

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.

Prinsen J, Bernaerts S, Wang Y, de Beukelaar TT, Cuypers K, Swinnen SP, Alaerts K. Direct eye contact enhances mirroring of others' movements: A transcranial magnetic stimulation study. Neuropsychologia. 2017 Jan 27;95:111-118. doi: 10.1016/j.neuropsychologia.2016.12.011. Epub 2016 Dec 8.

Prinsen J, Brams S, Alaerts K. To mirror or not to mirror upon mutual gaze, oxytocin can pave the way: A cross-over randomized placebo-controlled trial. Psychoneuroendocrinology. 2018 Apr;90:148-156. doi: 10.1016/j.psyneuen.2018.02.016. Epub 2018 Feb 22.