Reciprocal gaze, the mutual exchange of eye contact, plays a key role in human communication and bonding, yet it is often experienced as challenging for individuals with autism. In recent years, administration of the neuropeptide oxytocin is increasingly considered a novel approach for supporting social experiences in children with autism, but insights regarding its effects on mutual gaze or pupil dynamics remain limited—particularly regarding how chronic, repeated dosing impacts these processes.This double-blind, randomized, placebo-controlled trial examined the effects of four weeks of chronic intranasal oxytocin administration on gaze behavior and pupil dynamics during live dyadic interactions in school-aged children with autism (aged 8-12 years, 15 oxytocin, 20 placebo).While the overall duration of fixations toward the face remained unchanged, oxytocin altered the distribution of gaze, resulting in a more balanced pattern of looking toward and away from the face of a live interaction partner, an effect observed only in the oxytocin group and not in the placebo group. In addition, the four-week oxytocin administration period induced a relative increase in pupil dilation, an index of sympathetic arousal and attentional engagement, with this heightened autonomic responsivity showing a moderate association with children’s self-reported feelings of secure attachment.Together, these findings indicate that repeated oxytocin administration may modulate gaze parameters in live social interactions in children with autism. While cautiously encouraging, future work will be needed to further delineate whether these changes meaningfully reflect ameliorated experience and comfort in social settings.

Autism is frequently associated with sensory processing differences that affect daily functioning, yet the neural mechanisms underlying these differences remain insufficiently understood. Interoception-the perception of internal bodily signals-has received less attention than exteroception, despite its relevance for arousal regulation and emotional functioning in autism. The heartbeat evoked potential (HEP), a neural response time-locked to the cardiac cycle, increases when individuals attend to their heartbeat, making it a useful marker of bodily sensing. In this study, we characterized the neural dynamics of interoceptive and exteroceptive processing in autistic individuals using HEPs and compared these responses with those of non-autistic individuals. We examined HEPs in 38 autistic and 22 non-autistic participants during interoceptive (tapping to one’s heartbeat) and exteroceptive (tapping to external heartbeat audio) tasks, using cluster-based Monte Carlo permutation testing for all contrasts. Significant cluster amplitudes were modelled using linear regressions with IQ and sensitivity scores, and nonlinear models incorporating a sensitivity component (task-derived d’ and mean distance) and heart rate. Early interoceptive HEP modulation was reduced in autistic participants. In non-autistic participants, modulation was predicted only by the sensitivity component, whereas in autistic participants, heart rate -but not sensitivity- predicted neural responses. Modulation differences between interoception and exteroception were robust in the non-autistic group but absent in the autistic group. Linear models indicated that IQ predicted modulation in the only significant interoceptive intergroup cluster in non-autistic participants, while BPQ predicted modulation in a small exteroceptive cluster. These findings provide neural evidence of altered interoceptive processing in autism, suggesting reduced differentiation between internal and external signals, with implications for interventions targeting autonomic and interoceptive awareness. Keywords: Autism; cardiac interoception; cluster-based Monte Carlo permutations; electroencephalography; heartbeat evoked potentials; interoception; sensitivity.

Atypical oxytocinergic functioning and altered microbiome compositions have both been implicated in autism, with growing evidence of interactions between these systems. However, how exogenous oxytocin influences the oral microbiome remains largely unexplored. This exploratory study examined for the first time how oral microbiome alterations link to oxytocinergic signalling in school-aged autistic (n = 80) and non-autistic children (n = 40). Additionally, we investigated the effect of four-weeks of intranasal oxytocin administration in autistic children on oral microbiome compositions immediately post-treatment (T1) and at four-weeks follow-up (T2). At baseline, lower endogenous salivary oxytocin levels were linked to greater microbial evenness and diversity, with twelve genera showing significant associations with oxytocin levels. In autistic children, four weeks of oxytocin administration was associated with significant increases in the abundances of Centipeda immediately post-treatment (T0-T1), alongside decreases in Moraxella (T0-T1), and subsequent reductions in Rothia observed at the four-week follow-up (T1-T2). Particularly, the genus Moraxella emerged as relevant, as lower baseline abundance was associated with higher endogenous oxytocin levels, and a stronger oxytocin-induced downregulation of its abundance correlated with greater increases in endogenous oxytocin levels, accompanied by hypomethylation of the oxytocin receptor gene. All results persisted after adjusting for nutrition and dental care. This exploratory study provides initial evidence for a role of the oxytocinergic system in shaping the oral microbiome in autistic children. These results may facilitate the integration of oral microbiome profiling into autism diagnostic criteria and stimulate future studies on the use of oxytocin as a therapeutic option targeting oral microbiome alterations.

Autistic children often experience behavioral difficulties alongside nutritional and gastro-intestinal (GI) problems, including gut dysbiosis. Recent research has highlighted important interactions between the oxytocinergic system and gut microbiome compositions, however, insights into how exogenous administration of oxytocin may influence GI health remain largely unexplored.Here, we first examined whether nutrition, GI symptoms and microbiome compositions vary in autistic versus non-autistic children, and how alterations link to clinical-behavioral difficulties and oxytocinergic signaling. Next, we examined the effect of a four-week intranasal oxytocin administration regimen on GI health/dysbiosis in autistic children enrolled in a randomized placebo-controlled trial.Compared to non-autistic children, autistic children consumed more soft drinks, and fewer vegetables and experienced abdominal pain more frequently over the past three months. Notably, epigenetic variations in the oxytocin receptor gene (OXTR) were associated with stool consistency, indicating that children with looser stools exhibited lower OXTR methylation levels, indicative of increased receptor expression. Additionally, a higher abundance of Romboutsia was associated with OXTR hypo-methylation and more anxiety-like behavior. In autistic children, the four-week oxytocin regimen had no effect on bacterial diversity but did modify stool consistency, leading to less dense stools with an overall more normal stool consistency, and an increased abundance of the potentially anti-inflammatory genus Fusicatenibacter.To conclude, this study provides novel insights into the role of the oxytocinergic system in GI symptoms and gut microbiome compositions in autistic children, and preliminary evidence suggesting a modulatory effect of exogenously administered oxytocin on these parameters.

Integrating the menstrual cycle into heart-brain research is a crucial step toward advancing sex-specific medicine and improving outcomes for female brain and body health.

Understanding and interpreting non-verbal actions are critical components of social cognition, which are often challenging for autistic individuals. Oxytocin, a neuropeptide known to modulate social behavior and enhance the salience of social stimuli, is being explored as a therapeutic option for improving social mirroring. However, its effects are mediated by context- and person-dependent factors. This study examines the impact of a single intranasal dose of oxytocin (24 IU) on interpersonal motor resonance in young adult men with and without autism. Neurophysiological assessments of corticomotor excitability were performed using transcranial magnetic stimulation while participants observed real-time hand movements displayed by an experimenter demonstrating varying social intent (i.e. showing direct vs averted gaze). While no overall effect of oxytocin on interpersonal motor resonance was observed across groups, person-specific factors significantly influenced outcomes. In the autism group, individuals with higher endogenous oxytocin levels exhibited greater motor resonance during action observation. Autistic individuals with heightened social difficulties or avoidant attachment styles showed enhanced motor resonance following oxytocin administration. These findings highlight the nuanced role of both endogenous and exogenous oxytocin in shaping neurophysiological motor resonance and emphasize the importance of individual variability in assessing oxytocin's therapeutic potential for addressing social challenges in autism.Lay abstractThis study explores how oxytocin, a hormone that influences social behaviors, affects the ability to interpret and respond to non-verbal cues, particularly in autistic adults. Understanding others' actions and intentions, often guided by observing body language and eye contact, is a critical part of social interaction. Autistic individuals frequently face challenges in these areas. Using a safe, non-invasive brain stimulation technique, the study measured participants' brain responses as they observed real-time hand movements paired with the interaction partner's direct eye contact or averted gaze. Participants included young autistic and non-autistic adult men who received a placebo and a single dose of oxytocin via nasal spray. Results showed no overall differences between the two groups in their brain responses to these movements. However, in the autism group, several factors significantly influenced the effects of oxytocin. Participants with higher natural oxytocin levels or those who reported greater social challenges showed stronger responses after oxytocin administration, particularly when observing hand movements combined with direct gaze. These findings suggest that oxytocin may enhance social understanding in autistic individuals, especially for those experiencing greater difficulties. This highlights the potential of personalized approaches when considering oxytocin as a therapeutic option to improve social interactions.

Intranasal administration of oxytocin is emerging as a potential pharmacological option for mitigating social difficulties and regulating stress in autism spectrum disorder. However, initial single-dose and multiple-dose trials showed mixed results, with some demonstrating improvements in social and repetitive behavior and others showing no benefit over placebo. This perspective aims to elucidate factors contributing to this variability and to highlight pitfalls and opportunities in the field. We identified two major factors: design-related elements and individual participant characteristics. Pertaining to design-related elements, optimal dosing regimens have yet to be established, but appear to favor moderate intervention durations (i.e., 4-6 weeks) with intermittent and intermediate dosing (i.e., 24-32 IU every other day). Also, the context of the intervention seems crucial, as enhanced outcomes are mainly observed when oxytocin administration is paired with a socially stimulating and supporting environment. In addition, more adequate outcome measures have to be established to effectively assess oxytocin's impact, including behavioral scales and objective biophysiological markers tapping into stress and neurophysiological regulation. Future research should also account for individual participant differences in biological sex, developmental stage and cognitive and adaptive functioning, and incorporate (epi)genetic screening to identify responders. Overall, refining study designs and personalizing intervention protocols are essential for optimizing oxytocin's prosocial and anxiolytic effect in autism.

Background Shifts in peak frequencies of oscillatory neural rhythms are put forward as a principal mechanism by which cross‐frequency coupling/decoupling is implemented in the brain. During active neural processing, functional integration is facilitated through transitory formations of “harmonic” cross‐frequency couplings, whereas “nonharmonic” decoupling among neural oscillatory rhythms is postulated to characterize the resting, default state of the brain, minimizing the occurrence of spurious, noisy, background couplings. Methods Within this exploratory, randomized, placebo‐controlled trial, we assessed whether the transient occurrence of nonharmonic and harmonic relationships between peak‐frequencies in the alpha (8–14 Hz) and theta (4–8 Hz) bands is impacted by intranasal administration of oxytocin, a neuromodulator implicated in improving homeostasis and reducing stress/anxiety. To do so, resting‐state electroencephalography was acquired before and after 4 weeks of oxytocin administration (12 IU twice‐daily) in children with autism spectrum disorder (8–12 years, n = 33 oxytocin; n = 34 placebo). At the baseline, neural assessments of children with autism were compared with those of a matched cohort of children without autism ( n = 40). Results Compared to nonautistic peers, autistic children displayed a lower incidence of nonharmonic alpha‐theta cross‐frequency decoupling, indicating a higher incidence of spurious “noisy” coupling in their resting brain ( p = .001). Dimensionally, increased neural coupling was associated with more social difficulties ( p = .002) and lower activity of the parasympathetic “rest & digest” branch of the autonomic nervous system ( p = .018), indexed with high‐frequency heart‐rate‐variability. Notably, after oxytocin administration, the transient formation of nonharmonic cross‐frequency configurations was increased in the cohort of autistic children ( p < .001), indicating a beneficial effect of oxytocin on reducing spurious cross‐frequency‐interactions. Furthermore, parallel epigenetics changes of the oxytocin receptor gene indicated that the neural effects were likely mediated by changes in endogenous oxytocinergic signaling ( p = .006). Conclusions Chronic oxytocin induced important homeostatic changes in the resting‐state intrinsic neural frequency architecture, reflective of reduced noisy oscillatory couplings and improved signal‐to‐noise properties.

Previous research has robustly demonstrated that eye contact between actor and observer promotes the simulation of perceived actions into the observer's own motor system, which in turn facilitates social perception and communication. The socially relevant connotation embedded in eye contact may however be different for individuals with differing social traits. Here, we examined how "normal" (i.e. non -clinical) variability in selfreported social responsiveness/autistic traits, social anxiety and interpersonal relationship style (secure, avoidant or anxious attachment) influences neural motor simulation during action observation in different gaze conditions. To do so, we analyzed an existing dataset involving 124 adult participants (age range: 18-35 years) who underwent transcranial magnetic stimulation (TMS) while observing an actor performing simple hand actions and simultaneously engaging in eye contact or gazing away from the observer. Motor evoked potential (MEP) amplitudes were adopted as an index of motor resonance. Regression -based analyses highlighted the role of social responsiveness and secure attachment in shaping motor resonance, indicating that socially responsive motor resonance during dyadic gaze (i.e., MEPdirect > MEPaverted) was only observed in participants displaying high levels of these traits. Furthermore, a clustering analysis identified two to three distinct subgroups of participants with unique social trait profiles, showing a clear differentiation in motor resonant patterns upon different gaze cues that is in accordance with a recent neurobiological framework of attachment. Together, results demonstrate that motor resonance within a given social interaction may serve as a sensitive tracker of sociointeractive engagement, which allows to capture subclinical inter -individual variation in relevant social traits.

Shifts in peak frequencies of oscillatory neural rhythms are put forward as a principal mechanism by which cross-frequency coupling/decoupling is implemented in the brain. During active neural processing, functional integration is facilitated through transitory formations of “harmonic” cross-frequency couplings, whereas “nonharmonic” decoupling among neural oscillatory rhythms is postulated to characterize the resting, default state of the brain, minimizing the occurrence of spurious, noisy, background couplings. Within this exploratory, randomized, placebo-controlled trial, we assessed whether the transient occurrence of nonharmonic and harmonic relationships between peak-frequencies in the alpha (8–14 Hz) and theta (4–8 Hz) bands is impacted by intranasal administration of oxytocin, a neuromodulator implicated in improving homeostasis and reducing stress/anxiety. To do so, resting-state electroencephalography was acquired before and after 4 weeks of oxytocin administration (12 IU twice-daily) in children with autism spectrum disorder (8–12 years, n  = 33 oxytocin; n  = 34 placebo). At the baseline, neural assessments of children with autism were compared with those of a matched cohort of children without autism ( n  = 40). Compared to nonautistic peers, autistic children displayed a lower incidence of nonharmonic alpha-theta cross-frequency decoupling, indicating a higher incidence of spurious “noisy” coupling in their resting brain ( p  = .001). Dimensionally, increased neural coupling was associated with more social difficulties ( p  = .002) and lower activity of the parasympathetic “rest & digest” branch of the autonomic nervous system ( p  = .018), indexed with high-frequency heart-rate-variability. Notably, after oxytocin administration, the transient formation of nonharmonic cross-frequency configurations was increased in the cohort of autistic children ( p  < .001), indicating a beneficial effect of oxytocin on reducing spurious cross-frequency-interactions. Furthermore, parallel epigenetics changes of the oxytocin receptor gene indicated that the neural effects were likely mediated by changes in endogenous oxytocinergic signaling ( p  = .006). Chronic oxytocin induced important homeostatic changes in the resting-state intrinsic neural frequency architecture, reflective of reduced noisy oscillatory couplings and improved signal-to-noise properties.

Adolescents with autism present lower levels of cardiac vagal modulation. It was hypothesized that Heart Rate Variability Biofeedback (HRVB) increases cardiac vagal modulation in adolescents with autism, resulting in positive effects on physiological and psychosocial parameters. It was also hypothesized that home-based HRVB training is feasible. In a single-blind, randomized sham-controlled pilot trial, adolescents with autism performed supervised HRVB (n = 24) or sham training (n = 20). Subsequently, half of the adolescents received HRVB training at home, whereas the other subset did not practice. Physiological, cortisol and behavioral data were collected during stress-provoking assessments before and after each training period. Supervised HRVB resulted in a late increase in cardiac vagal modulation in adolescents with autism. Heart rate increased and cortisol decreased significantly immediately after supervised HRVB, but none of these effects remained after follow-up. Following supervised HRVB, no significant change in psychosocial functioning was found. Home-based HRVB was feasible, adolescents reported lower symptoms of stress, but a significant decrease in compliance rate was found. HRVB is feasible and effective in adolescents with autism given the late-emerging increases in cardiac vagal modulation and decrease in stress symptoms. Replicating this study with a larger sample and further exploration of the working mechanisms of HRVB are recommended. ClinicalTrials.gov , NCT04628715.

Similar to the gut microbiome, oral microbiome compositions have been suggested to play an important role in the etiology of autism. However, empirical research on how variations in the oral microbiome relate to clinical-behavioral difficulties associated with autism remains sparse. Furthermore, it is largely unknown how potentially confounding lifestyle variables, such as oral health and nutrition, may impact these associations. To fill this gap, the current study examined diagnosis-related differences in oral microbiome composition between 80 school-aged autistic children (8-12 years; 64 boys, 16 girls) versus 40 age-matched typically developing peers (32 boys, 8 girls). In addition, associations with individual differences in social functioning (SRS-2), repetitive behavior (RBS-R) and anxiety (SCARED) were explored, as well as the impact of several lifestyle variables regarding nutrition and oral health. Results provide important indications that the bacterial genera Solobacterium, Stomatobaculum, Ruminococcaceae UCG.014, Tannerella and Campylobacter were significantly more abundant in autistic compared to non-autistic children. Furthermore, the former four bacteria that were significantly more abundant in the autistic children showed significant associations with parent-reported social difficulties, repetitive and restrictive behavior and with parent-reported anxiety-like behavior. Importantly, associations among oral microbiome and quantitative diagnostic characteristics were not significantly driven by differences in lifestyle variables. This exploratory study reveals significant differences in oral microbiome composition between autistic and non-autistic children, even while controlling for potential confounding lifestyle variables. Furthermore, the significant associations with clinical characteristics suggest that individual differences in microbiome composition might be involved in shaping the clinical phenotype of autism. However, these associations warrant further exploration of the oral microbiome's potential beyond the oral cavity and specifically with respect to neuropsychiatric conditions.

Clinical efficacy of intranasal administration of oxytocin is increasingly explored in autism spectrum disorder, but to date, the biological effects of chronic administration regimes on endogenous oxytocinergic function are largely unknown. Here exploratory biological assessments from a completed randomized, placebo-controlled trial showed that children with autism (n = 79, 16 females) receiving intranasal oxytocin for four weeks (12 IU, twice daily) displayed significantly higher salivary oxytocin levels 24 hours after the last oxytocin nasal spray administration, but no longer at a four-week follow up session. Regarding salivary oxytocin receptor gene ( OXTR) epigenetics (DNA-methylation), oxytocin-induced reductions in OXTR DNA-methylation were observed, suggesting a facilitation of oxytocin receptor expression in the oxytocin compared to the placebo group. Notably, heightened oxytocin levels post-treatment were significantly associated with reduced OXTR DNA-methylation and improved feelings of secure attachment. These findings indicate that four weeks of chronic oxytocin administration stimulated the endogenous oxytocinergic system in children with autism.

Difficulties with (non-verbal) social communication, including facial expression processing, constitute a hallmark of autism. Intranasal administration of oxytocin has been considered a potential therapeutic option for improving social difficulties in autism, either by enhancing the salience of social cues or by reducing the social stress and anxiety experienced in social encounters. We recorded fMRI brain activity while presenting neutral, fearful and scrambled faces, to compare the neural face processing signature of autistic children (n = 58) with that of matched non-autistic controls (n = 38). Next, in the autistic children group, we implemented this fMRI face processing task in a double-blind, placebo-controlled, multiple-dose oxytocin clinical trial, to evaluate the impact of four-week repeated oxytocin administration (24 IU daily dose) on brain activity in face processing regions. No significant diagnostic-group differences were identified between autistic versus non-autistic children with regard to neural face processing. Furthermore, no significant treatment effects were found in the oxytocin clinical trial. However, exploratory analyses (uncorrected for multiple comparisons) demonstrated decreases in brain activity in the left superior temporal sulcus (STS) and inferior frontal region in the oxytocin compared to the placebo group, and change-from-baseline analyses in the oxytocin group revealed significantly reduced neural activity in the core face-processing network (STS, inferior occipital, and posterior fusiform), as well as in amygdala and inferior frontal region. These findings suggest an attenuating effect of multiple-dose oxytocin administration on neural face processing, potentially supporting the anxiolytic account of oxytocin.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication and interaction. Crucial for efficient social interaction is the ability to quickly and accurately extract information from a person's face. Frequency-tagging electroencephalography (EEG) is a novel tool to quantify face-processing sensitivity in a robust and implicit manner. In terms of intervention approaches, intranasal administration of oxytocin (OT) is increasingly considered as a potential pharmacological approach for improving socio-communicative difficulties in ASD, through enhancing social salience and/or reducing (social) stress and anxiety. In this randomized, double-blind, placebo-controlled, mechanistic pharmaco-neuroimaging clinical trial, we implemented frequency-tagging EEG to conduct an exploratory investigation into the impact of repeated OT administration (4 weeks, 12 IU, twice daily) on neural sensitivity towards happy and fearful facial expressions in children with ASD (8–12 years old; OT: n  = 29; placebo: n  = 32). Neural effects were assessed at baseline, post-nasal spray (24 hr after the last nasal spray) and at a follow-up session, 4 weeks after the OT administration period. At baseline, neural assessments of children with ASD were compared with those of an age- and gender-matched cohort of neurotypical (NT) children ( n  = 39). Children with ASD demonstrated reduced neural sensitivity towards expressive faces, as compared to NT children. Upon nasal spray administration, children with ASD displayed a significant increase in neural sensitivity at the post- and follow-up sessions, but only in the placebo group, likely reflecting an implicit learning effect. Strikingly, in the OT group, neural sensitivity remained unaffected from the baseline to the post-session, likely reflecting a dampening of an otherwise typically occurring implicit learning effect. First, we validated the robustness of the frequency-tagging EEG approach to assess reduced neural sensitivity towards expressive faces in children with ASD. Furthermore, in contrast to social salience effects observed after single-dose administrations, repeated OT administration dampened typically occurring learning effects in neural sensitivity. In line with OT's social anxiolytic account, these observations possibly reflect a predominant (social) stress regulatory effect towards emotionally evocative faces after repeated OT administration.

Background Clinical efficacy of chronic intranasal administration of oxytocin is increasingly explored in autism spectrum disorder (ASD), but to date, little is known regarding its biological effects and in particular how chronic administration regimes impact endogenous oxytocinergic function. Methods To fill this gap, this double-blind, randomized, placebo-controlled study explored chronic oxytocin administration effects on endogenous salivary oxytocin levels and oxytocin receptor gene ( OXTR ) epigenetics (DNA methylation) in 8-to-12-year-old children with ASD (n = 79, 16 females). Biological sampling was performed at baseline (pre-treatment), immediately (24 hours) after the four-week oxytocin administration period (12 IU, twice daily) and at a follow-up session, four weeks after the last nasal spray administration. Results Compared to placebo, children receiving the oxytocin nasal spray displayed significantly higher salivary oxytocin levels 24 hours after the last oxytocin nasal spray administration, but no longer at the four-week follow up session. Regarding epigenetics, oxytocin-induced reductions in OXTR methylation were observed, reflecting a facilitation of oxytocin receptor expression in the oxytocin, compared to the placebo group. Notably, heightened oxytocin levels post-treatment were significantly associated with reduced OXTR DNA methylation and improved feelings of secure attachment. Conclusion Four weeks of chronic oxytocin administration stimulated the endogenous oxytocinergic system in children with ASD, as evidenced by increased salivary oxytocin levels and reduced OXTR DNA methylation (indicating increased receptor expression).

Introduction: Intranasal administration of oxytocin presents a promising new approach to reduce disability associated with an autism spectrum disorder diagnosis. Previous investigations have emphasized the amygdala as the neural foundation for oxytocin’s acute effects. However, to fully understand oxytocin’s therapeutic potential, it is crucial to gain insight into the neuroplastic changes in amygdala circuitry induced from chronic oxytocin administrations, particularly in pediatric populations. Objective: We aimed to examine the impact of a 4-week course of intranasal oxytocin on amygdala functional connectivity in children with autism, compared to placebo. Additionally, we investigated whether oxytocin improves cardiac autonomic arousal, as indexed by high-frequency heart rate variability. Methods: Fifty-seven children with autism aged 8–12 years (45 boys, 12 girls) participated in a double-blind, randomized pharmaco-neuroimaging trial involving twice-daily administrations of intranasal oxytocin or placebo. Resting-state fMRI scans and simultaneous, in-scanner heart rate recordings were obtained before, immediately after, and 4 weeks after the nasal spray administration period. Results: Significant reductions in intrinsic amygdala-orbitofrontal connectivity were observed, particularly at the 4-week follow-up session. These reductions were correlated with improved social symptoms and lower cardiac autonomic arousal. Further, oxytocin’s neural and cardiac autonomic effects were modulated by epigenetic modifications of the oxytocin receptor gene. The effects were more pronounced in children with reduced epigenetic methylation, signifying heightened expression of the oxytocin receptor. Conclusion: These findings underscore that a 4-week oxytocin administration course decreases amygdala connectivity and improves cardiac autonomic balance. Epigenetic modulators may explain inter-individual variation in responses to oxytocin.