Oxytocin’s role on the central and autonomic neurophysiological correlates of salience attribution

807 

Abstract Submission 

Gonçalo Cosme¹, Diana Prata²

¹Instituto de Biofísica e Engenharia Biomédica, Lisbon, AK, ²Instituto de Biofísica e Engenharia Biomédica, Lisboa, AK

Gonçalo Cosme  
Instituto de Biofísica e Engenharia Biomédica
Lisbon, AK

Diana Prata  
Instituto de Biofísica e Engenharia Biomédica
Lisboa, AK

Well-adapted cooperative behaviours are crucial for our species survival. Behaviours like resource sharing, group defense, social bonding, and support between peers have been associated with the neuropeptide oxytocin which is now known to be a key neuromodulator of social cognition in humans. Evidence suggests the involvement of the oxytocinergic system in the etiology of mental disorders, particularly those characterized by social deficits, for which intranasal oxytocin administration may represent a promising therapeutic solution. However, a large body of evidence have failed to converge in support of oxytocin's foremost hypothesis that oxytocin acts as a pure facilitator of pro-social behaviour. Currently, one leading hypothesis posits oxytocin to increase salience towards social relevant/rewarding stimuli (Shamay-Tsoory and Abu-Akel, 2016), yet the social specificity of the hypothesis has been questioned by others (Quintana and Guastella, 2020). In this study we tested this hypothesis by recording central (eye-gaze) and autonomic (pupil size) neurophysiological correlates of salience attribution during two paradigms: free-video watching of social interactions, to probe oxytocin's salience attribution in varying levels of arousal and valence; and the social salience attribution test, where the social and reward value of stimuli were orthogonalized, to probe the social specificity of oxytocin's salience attribution.

We carried the study with 62 healthy male participants in a double-blind, placebo-controlled, between-subjects design with intranasal administration of oxytocin. In the first paradigm participants free viewed 16 short clips of social interactions varying in arousal (high vs. low) and valence (positive vs. negative). Four short clips of landscapes were used as a non-social and neutral condition. From participants' eye gaze we computed a spatio-temporal salience score (Traver et al., 2021) across each clip, for each drug group. On the other hand, the social salience attribution test (Roiser et al., 2009) was reinforcement learning paradigm where stimuli varied in social (faces or fruits; task-irrelevant) and color (red or blue; task-relevant) dimensions, and participants were monetarily incentivized to learn which type of stimuli were more rewarding.

During video watching, intranasal oxytocin increased, compared to placebo, the spatio-temporal salience score for 19 out of 20 clips. On average, the high arousing negative clips elicited the highest mean scores and as expected, the neutral condition, the lowest. Salience scores did not differ between drug groups for high vs. low arousing clips. During the social salience attribution test, we found a significant drug by socialness interaction on pupil size where oxytocin increased pupil dilation for social vs non-social stimuli, during stimuli onset. We also found a significant drug by reinforcement probability interaction where oxytocin increased pupil dilation for rewarding vs non-rewarding stimuli, but close to feedback. Crucially, there was no socialness by reinforcement probability interaction effect on pupil size, validating our orthogonalization.

Taken together, these results support the social salience hypothesis of oxytocin given we found evidence, from two distinct paradigms, that oxytocin increased the salience towards social stimuli, measured by neurophysiological correlates of central and autonomic activity in eye gaze and pupil size. Specifically, from the free viewing paradigm, we found specificity of salience attribution to negatively valenced stimuli in line with previous studies indicating consistently that oxytocin reduces amygdala activation to fearful stimuli (Labuschagne et al., 2010). From the social salience attribution test we found specificity of salience attribution to both rewarding and social, but in different moments of the task, nonetheless supporting a suggested oxytocin and dopamine interplay (Shamay-Tsoory and Abu-Akel, 2016). This work was supported by: FCT UIDB/00645/2020.

Reward and Punishment

Social Cognition ¹

Learning and Memory Other

Pharmacology and Neurotransmission ²

Physiology, Metabolism and Neurotransmission Other

Cognition

ELECTROPHYSIOLOGY

Neurotransmitter

Other - Oxytocin; Eye-tracking; Social cognition; Reward; Reinforcement learning