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Background: Interoception represents perception of the internal bodily state, which is closely associated with social/emotional processing and physical health in humans. Understanding the mechanism that underlies interoceptive processing, particularly its modulation, is therefore of great importance. Given the overlap between oxytocinergic pathways and interoceptive signaling substrates in both peripheral visceral organs and the brain, intranasal oxytocin administration is a promising approach for modulating interoceptive processing., Methods: Using a double-blind, placebo-controlled, between-participant design, we recruited 72 healthy male participants who performed a cardiac interoceptive task during electroencephalograph and electrocardiograph recording to examine whether intranasal administration of the neuropeptide oxytocin could modulate interoceptive processing. We also collected data in a resting state to examine whether we could replicate previous findings., Results: The results showed that in the interoceptive task, oxytocin increased interoceptive accuracy at the behavioral level, which was paralleled by larger heartbeat-evoked potential amplitudes in frontocentral and central regions on the neural level. However, there were no significant effects of oxytocin on electroencephalograph or electrocardiograph during resting state., Conclusions: These findings suggest that oxytocin may only have a facilitatory effect on interoceptive processing under task-based conditions. Our findings not only provide new insights into the modulation of interoceptive processing via targeting the oxytocinergic system but also provide proof-of-concept evidence for the therapeutic potential of intranasal oxytocin in mental disorders with dysfunctional interoception., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Over the last decade, a number of clinical trials have reported effects of chronic treatment with intranasal oxytocin on autistic symptoms but with inconsistent findings. Autism is a heterogeneous disorder and one factor which may influence treatment outcome is whether a subtype of individuals is more sensitive to oxytocin. In a recent cross-over trial on 41 young autistic children we reported that 44% showed a reliable improvement in clinical symptoms (Autism Diagnostic Observation Schedule, ADOS-2) after a placebo-controlled, 6-week intranasal oxytocin intervention where treatment was given every other day followed by a period of positive social interaction. In the current re-assessment of the data, we used an unsupervised data-driven cluster analysis approach to identify autism subtypes using 23 different demographic, social subtype, endocrine, eye-tracking and clinical symptom measures taken before treatment and this revealed an optimum of two different subtypes. We then assessed the proportion of identified responders to oxytocin and found that while 61.5% of one subtype included responders only 13.3% of the other did so. During the placebo phase there was no difference between the two subtypes for the small proportion of responders (19.2% vs 6.7%). This oxytocin-sensitive subtype also showed overall significant post-treatment clinical and eye-tracking measure changes. The oxytocin-sensitive subtype was primarily characterized at baseline by lower initial clinical severity (ADOS-2) and greater interest in the eye-region of emotional faces. These features alone were nearly as efficient in identifying the two subtypes as all 23 baseline measures and this easy-to-conduct approach may help rapidly and objectively screen for oxytocin responders. Future clinical trials using oxytocin interventions may therefore achieve greater success by focusing on children with this specific autism subtype and help develop individualized oxytocin intervention., (© 2024. The Author(s).)

Outcomes of past decisions profoundly shape our behavior. However, choice-outcome associations can become volatile and adaption to such changes is of importance. The present study combines pharmaco-electroencephalography with computational modeling to examine whether intranasal oxytocin can modulate reinforcement learning under a volatile vs. a stable association. Results show that oxytocin increases choice accuracy independent of learning context, which is paralleled by a larger N2pc and a smaller P300. Model-based analyses reveal that while oxytocin promotes learning by accelerating value update of outcomes in the volatile context, in the stable context it does so by improving choice consistency. These findings suggest that oxytocin's facilitatory effects on learning may be exerted via improving early attentional selection and late neural processing efficiency, although at the computational level oxytocin's actions are highly adaptive between learning contexts. Our findings provide proof of concept for oxytocin's therapeutic potential in mental disorders with adaptive learning dysfunction., (© 2024. The Author(s).)

In recent years ample studies have reported that intranasal administration of the neuropeptide oxytocin can facilitate social motivation and cognition in healthy and clinical populations. However, it is still unclear how effects are mediated since intranasally administered oxytocin can both directly enter the brain (nose to brain) and increase peripheral vascular concentrations (nose to blood). The relative functional contributions of these routes are not established and have received insufficient attention in the field. The current study used vasoconstrictor pretreatment to prevent intranasal oxytocin (24 IU) from increasing peripheral concentrations and measured effects on both resting-state neural (electroencephalography) and physiological responses (electrocardiogram, electrogastrogram and skin conductance). Results demonstrated that intranasal oxytocin alone produced robust and widespread increases of delta-beta cross-frequency coupling (CFC) from 30 min post-treatment but did not influence peripheral physiological measures. As predicted, vasoconstrictor pretreatment greatly reduced the normal increase in peripheral oxytocin concentrations and, importantly, abolished the majority of intranasal oxytocin effects on delta-beta CFC. Furthermore, time-dependent positive correlations were found between increases in plasma oxytocin concentrations and corresponding increases in delta-beta CFC following oxytocin treatment alone. Our findings suggest a critical role of peripheral vasculature-mediated routes on neural effects of exogenous oxytocin administration with important translational implications for its use as an intervention in psychiatric disorders., (© 2023. The Author(s).)

Background: Feedback evaluation of actions and error response detection are critical for optimizing behavioral adaptation. Oxytocin can facilitate learning following social feedback but whether its effects vary as a function of feedback valence remains unclear., Aims: The present study aimed to investigate whether oxytocin would influence responses to positive and negative feedback differentially or equivalently., Methods: The present study employed a randomized, double-blind, placebo controlled within-subject design to investigate whether intranasal oxytocin (24 IU) influenced behavioral and evoked electrophysiological potential responses to positive or negative feedback in a probabilistic learning task., Results: Results showed that oxytocin facilitated learning and this effect was maintained in the absence of feedback. Using novel stimulus pairings, we found that oxytocin abolished bias towards learning more from negative feedback under placebo by increasing accuracy for positively reinforced stimuli. Oxytocin also decreased the feedback-related negativity difference (negative minus positive feedback) during learning, further suggesting that it rendered the evaluation of positive and negative feedback more equivalent. Additionally, post-learning oxytocin attenuated error-related negativity amplitudes but increased the late error positivity, suggesting that it may lower conflict detection between actual errors and expected correct responses at an early stage of processing but at a later stage increase error awareness and motivation for avoiding them., Conclusions: Oxytocin facilitates learning and subsequent performance by rendering the impact of positive relative to negative feedback more equivalent and also by reducing conflict detection and increasing error awareness, which may be beneficial for behavioral adaption.

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 sham‐controlled, participant‐blind, crossover experiment, consisting of two treatment sessions 1 week apart. 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. The proportion of time spent viewing the faces and facial features (eyes, nose, and mouth) was measured together with resting pupil size. Additionally, saliva samples were taken for the measurement of oxytocin concentrations by enzyme‐linked immunoassay. Saliva oxytocin concentrations increased significantly after taVNS compared to sham stimulation, while resting pupil size did not. In addition, taVNS increased time spent viewing the nose region irrespective of face emotion, and this was positively correlated with increased saliva oxytocin concentrations. Our findings suggest that taVNS biases visual attention toward socially salient facial features across different emotions and this is associated with its effects on increasing endogenous oxytocin release. Our findings elucidate the mechanism underlying the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on social cognition. We found that taVNS increased visual attention toward socially salient facial features across different emotions and this is associated with its effects on increasing endogenous oxytocin release, suggesting that taVNS may be a promising therapeutic treatment for disorders with social dysfunctions (i.e., autism spectrum disorder, schizophrenia, depression, and anxiety). [ABSTRACT FROM AUTHOR]

Introduction: There are currently no approved drug interventions for social behavior dysfunction in autism spectrum disorder (ASD). Previous trials investigating effects of daily intranasal oxytocin treatment have reported inconsistent results and have not combined it with positive social interaction. However, in two preclinical studies we established that treatment every other day rather than daily is more efficacious in maintaining neural and behavioral effects by reducing receptor desensitization. Objective: We aimed to establish whether a 6-week intranasal oxytocin compared with placebo treatment, followed by a period of positive social interaction, would produce reliable symptom improvements in children with ASD. Methods: A pilot double-blind, randomized, crossover design trial was completed including 41 children with ASD aged 3–8 years. Primary outcomes were the Autism Diagnostic Observation Schedule-2 (ADOS-2) and social responsivity scale-2 (SRS-2). Secondary measures included cognitive, autism- and caregiver-related questionnaires, and social attention assessed using eye-tracking. Results: Significant improvements were found for oxytocin relative to placebo in primary outcome measures (total ADOS-2 and SRS-2 scores, ps < 0.001) and in behavioral adaptability and repetitive behavior secondary measures. Altered SRS-2 scores were associated with increased saliva oxytocin concentrations. Additionally, oxytocin significantly increased time spent viewing dynamic social compared to geometric stimuli and the eyes of angry, happy, and neutral expression faces. There were no adverse side effects of oxytocin treatment. Conclusions: Overall, results demonstrate that a 6-week intranasal oxytocin treatment administered every other day and followed by positive social interactions can improve clinical, eye tracking, and questionnaire-based assessments of symptoms in young autistic children. [ABSTRACT FROM AUTHOR]