Oxytocin biases eye-gaze to dynamic and static social images and the eyes of fearful faces: associations with trait autism

Abstract

A key functional effect of intranasal oxytocin with potential therapeutic relevance for autism-spectrum disorder is its reported facilitation of attention towards social stimuli, notably the eye region of faces. In the current randomized placebo-controlled within-subject experiment on 40 healthy males, we investigated the robustness of this facilitation of attention by intranasal oxytocin (24IU) towards social cues. Eye-tracking measures of preference for dynamic and static social vs. non-social stimuli were taken in four different paradigms where autistic individuals tend to exhibit reduced interest in social stimuli. Additionally, we investigated whether oxytocin increases attention towards the eyes relative to other salient face regions in an emotional face paradigm. Results showed that the time spent viewing both dynamic and static social vs. non-social stimuli was negatively associated with trait autism and significantly increased following intranasal oxytocin. For face stimuli, oxytocin primarily increased gaze towards the eyes of fearful expression faces but not for other face emotions. Overall, our findings demonstrate that oxytocin significantly shifts gaze preference towards social vs. non-social stimuli and to the eyes of fearful faces. Importantly, oxytocin appears generally to shift attention more towards salient social stimuli of particular relevance in the context of autism providing further support for its potential therapeutic use in autism-spectrum disorder.

Fig. 1. The effects of oxytocin (OXT) on eye-gaze towards dynamic social and geometric stimuli in the dynamic social attention (DSA) task—Task 1.

a The effects OXT on mean total fixation duration for each type of stimulus in subjects following either OXT or placebo (PLC) treatment. Error bars represent SEM. **p < 0.01, *p < 0.05, OXT vs. PLC and Social vs. Geometric. b, c Correlation (Pearson) between scores on two autistic traits questionnaires and total fixation duration. AQ autism-spectrum quotient, SRS Social Responsiveness Scale.

Fig. 2. The effects of oxytocin (OXT) treatment on eye-gaze towards emotional faces - Task 2 (FE).

Percentage of time viewing the eyes (a), nose (b), mouth (c) regions, and the rest of face (d) during the static face-emotion (angry, fear, happy, and neutral expressions) processing task. Mean percentage total fixation durations on different regions are relative to time spent viewing the screen during the presentation of faces. Error bars represent SEM. ***p<0.001, **p<0.01, *p<0.05, OXT vs. PLC.

Fig. 3. The effects of oxytocin (OXT) treatment on eye-gaze directed towards emotional human or emoticon faces—Task 3.

a Mean total fixation durations for each type of stimulus in subjects following either OXT or placebo (PLC) treatment. Error bars represent SEM. **p < 0.01, *p < 0.05, OXT vs. PLC and Human faces vs. Emoticons. b, c Correlation (Pearson) between scores on autistic traits questionnaires and total fixation duration. AQ autism-spectrum quotient, SRS Social Responsiveness Scale.

Fig. 4. The effects of oxytocin (OXT) treatment on eye-gaze directed towards human with toy/object or toy/object during the static visual attention task—Task 4.

a The effects OXT on mean total fixation duration for each type of stimulus in subjects following either OXT or placebo (PLC) treatment. Error bars represent SEM. **p < 0.01, *p < 0.05, OXT vs. PLC or human with toy/object or toy/object alone. b, c Correlation between scores on two autistic traits questionnaires and total fixation duration. AQ autism-spectrum quotient, SRS Social Responsiveness Scale.

Fig. 5. The effects of oxytocin (OXT) treatment on eye-gaze directed towards social (human walking) or non-social (cat walking) stimuli during the Biological motion task.

a The effects OXT on total fixation duration for each type of stimulus in subjects following either OXT or placebo (PLC) treatment. Error bars represent SEM. **p < 0.01, *p < 0.05 for cat vs. scrambled or human vs. scrambled. b The effects of OXT on the difference in total fixation duration for human minus scrambled (social) and cat minus scrambled (non-social). Error bars represent SEM. **p < 0.01, *p < 0.05, OXT vs. PLC. c Correlation (Pearson) between scores on the autistic spectrum quotient (AQ) and differences in total fixation duration.