At the Head and Heart of Oxytocin’s Stress-Regulatory Neural and Cardiac Effects: A Chronic Administration RCT in Children with Autism

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Objective:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.

Neuroregulatory Effects of Microcone Patch Stimulation on the Auricular Branch of the Vagus Nerve and the Prefrontal Cortex: A Feasibility Study

“…Therefore, it is reasonable to assume that if microcone patch stimulation acts on task-or situation-induced autonomic activity, it will also affect the medial and lateral prefrontal cortices. Recently, the increasing number of reports on the effects of autonomic activity suppression on the central nervous system through various methods can also be seen as further supporting the directionality of this research [34]. Future clinical applications should consider various actual work situations and subjects.…”