Chronic oxytocin improves neural decoupling at rest in children with autism: an exploratory RCT

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Main Authors: Kaat Alaerts, Matthijs Moerkerke, Nicky Daniels, Qianqian Zhang, Ricchiuti Grazia, Jean Steyaert, Jellina Prinsen, Bart Boets
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Published: Wiley 2024
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author Kaat Alaerts
Matthijs Moerkerke
Nicky Daniels
Qianqian Zhang
Ricchiuti Grazia
Jean Steyaert
Jellina Prinsen
Bart Boets
author_facet Kaat Alaerts
Matthijs Moerkerke
Nicky Daniels
Qianqian Zhang
Ricchiuti Grazia
Jean Steyaert
Jellina Prinsen
Bart Boets
Kaat Alaerts
Matthijs Moerkerke
Nicky Daniels
Qianqian Zhang
Ricchiuti Grazia
Jean Steyaert
Jellina Prinsen
Bart Boets
collection Wiley Open Access
contents Chronic oxytocin improves neural decoupling at rest in children with autism: an exploratory RCT Kaat Alaerts Matthijs Moerkerke Nicky Daniels Qianqian Zhang Ricchiuti Grazia Jean Steyaert Jellina Prinsen Bart Boets Journal of Child Psychology and Psychiatry 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. 10.1111/jcpp.13966 http://onlinelibrary.wiley.com/termsAndConditions#vor
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spellingShingle Chronic oxytocin improves neural decoupling at rest in children with autism: an exploratory RCT
Kaat Alaerts
Matthijs Moerkerke
Nicky Daniels
Qianqian Zhang
Ricchiuti Grazia
Jean Steyaert
Jellina Prinsen
Bart Boets
Journal of Child Psychology and Psychiatry
Chronic oxytocin improves neural decoupling at rest in children with autism: an exploratory RCT Kaat Alaerts Matthijs Moerkerke Nicky Daniels Qianqian Zhang Ricchiuti Grazia Jean Steyaert Jellina Prinsen Bart Boets Journal of Child Psychology and Psychiatry 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. 10.1111/jcpp.13966 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Chronic oxytocin improves neural decoupling at rest in children with autism: an exploratory RCT
topic Journal of Child Psychology and Psychiatry
url https://acamh.onlinelibrary.wiley.com/doi/10.1111/jcpp.13966