Non-invasive, transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) via the ear is used therapeutically in epilepsy, pain, and depression, and may also have beneficial effects on social cognition. However, the underlying mechanisms of taVNS are unclear and evidence regarding its role in social cognition improvement is limited. To investigate the impact of taVNS on social cognition we have studied its effects on gaze toward emotional faces in combination with eye-tracking and on the release of the neuropeptide oxytocin which plays a key role in influencing social cognition and motivation. A total of 54 subjects were enrolled (49 were included in the final analysis) in a shamcontrolled, participant-blind, crossover experiment, consisting of two treatment Zhu https://orcid

Background: Social touch constitutes a key component of human social relationships although in some conditions with social dysfunction, such as autism, it can be perceived as unpleasant. We have previously shown that intranasal administration of oxytocin facilitates the pleasantness of social touch and activation of brain reward and social processing regions, although it is unclear if it influences responses to gentle stroking touch mediated by cutaneous C-touch fibers or pressure touch mediated by other types of fibers. Additionally, it is unclear whether endogenous oxytocin acts via direct entry into the brain or by increased peripheral blood concentrations.Methods: In a randomized controlled design, we compared effects of intranasal (direct entry into the brain and increased peripheral concentrations) and oral (only peripheral increases) oxytocin on behavioral and neural responses to social touch targeting C-touch (gentle-stroking) or other (medium pressure without stroking) cutaneous receptors.Results: Although both types of touch were perceived as pleasant, intranasal and oral oxytocin equivalently enhanced pleasantness ratings and responses of reward, orbitofrontal cortex, and social processing, superior temporal sulcus, regions only to gentle-stroking not medium pressure touch. Furthermore, increased blood oxytocin concentrations predicted the pleasantness of gentle stroking touch. The specificity of neural effects of oxytocin on C-touch targeted gentle stroking touch were confirmed by time-course extraction and classification analysis.Conclusions: Increased peripheral concentrations of oxytocin primarily modulate its behavioral and neural responses to gentle social touch mediated by C-touch fibers. Findings have potential implications for using oxytocin therapeutically in conditions where social touch is unpleasant.Funding: Key Technological Projects of Guangdong Province grant 2018B030335001.Clinical trial number: NCT05265806.

Social touch is pleasurable and thus constitutes a key component of human social relationships. Intranasal administration of the neuropeptide oxytocin can facilitate the pleasantness of social touch although it is unclear whether it acts specifically on responses to C-touch or other types of cutaneous afferent fibers. Additionally, it is unclear whether effects of intranasal oxytocin are mediated via its direct entry into the brain or indirectly by increased peripheral concentrations. In a randomized controlled design, we therefore investigated effects of intranasally and orally (only increases peripheral concentrations) administered oxytocin on behavioral and neural responses to social touch targeting either C-touch (gentle-stroking touch) or other- (medium pressure massage) types of cutaneous receptors. Although both types of touch were perceived as pleasant, intranasal and oral oxytocin only, and equivalently, enhanced pleasantness ratings and neural responses in reward and touch processing regions to gentle-stroking touch. Plasma oxytocin concentrations also significantly predicted pleasantness ratings and were associated with brain reward responses. Together, our findings provide evidence that exogenously administered oxytocin primarily modulates behavioral and neural responses to C-touch fiber mediated social touch and suggest that it acts via peripheral-mediated routes. Clinical Trial Registration ID #:NCT05265806.

No abstract

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique with promising therapeutic potential in the context of epilepsy, pain, and depression and which may also have beneficial effects on social cognition. However, the underlying mechanisms of taVNS are unclear and evidence regarding its role in social cognition improvement is limited. Objective: In order to investigate the impact of taVNS on social cognition we have studied its effects on gaze towards emotional faces using an eye-tracking task and also on release of the neuropeptide oxytocin which plays a key role in influencing social cognition and motivation. Methods: A total of fifty-four subjects were enrolled in a sham-controlled, participant-blind crossover experiment, consisting of two treatment sessions, separated by one week. In one session participants received 30-min taVNS (tragus), and in the other, they received 30-min sham (earlobe) stimulation with the treatment order counterbalanced across participants. Gaze duration towards the faces and facial features (eyes, nose, and mouth) were measured together with resting pupil size. Additionally, saliva samples were taken for the measurement of oxytocin concentrations by enzyme-linked immunoassay. Results: Saliva oxytocin concentrations increased significantly after taVNS compared to sham stimulation, while resting pupil size did not. In addition, taVNS increased fixation time on the nose region irrespective of face emotion, and this was positively correlated with increased saliva oxytocin concentrations. Conclusion: Our findings suggest that taVNS biases visual attention towards socially salient facial features across different emotions and this is associated with its effects on increasing endogenous oxytocin release.