BackgroundShifts 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.MethodsWithin 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).ResultsCompared 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).ConclusionsChronic 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.

中文翻译：

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慢性催产素可改善自闭症儿童静息时的神经解耦：一项探索性随机对照试验

背景振荡神经节律峰值频率的变化被认为是在大脑中实现交叉频率耦合/解耦的主要机制。在主动神经处理过程中，通过“谐波”跨频耦合的短暂形成促进功能整合，而神经振荡节律之间的“非谐波”解耦则被假定为表征大脑的静息默认状态，从而最大限度地减少虚假、噪声的发生。方法在这项探索性、随机、安慰剂对照试验中，我们评估了 α (8-14 Hz) 和 theta (4-8 Hz) 频段峰值频率之间的非谐波和谐波关系的瞬时发生是否受到影响通过鼻内施用催产素，一种神经调节剂，与改善体内平衡和减轻压力/焦虑有关。为此，对患有自闭症谱系障碍的儿童（8-12 岁，n= 33 催产素；n= 34 安慰剂）。在基线时，将自闭症儿童的神经评估与匹配的非自闭症儿童群体的神经评估进行了比较（n= 40）。结果与非自闭症同龄人相比，自闭症儿童表现出非谐波 α-θ 交叉频率解耦的发生率较低，这表明他们静息大脑中虚假“噪音”耦合的发生率较高（p= .001)。从维度来看，神经耦合的增加与更多的社交困难相关（p= .002）以及自主神经系统副交感神经“休息和消化”分支的活动降低（p= .018），以高频心率变异性为索引。值得注意的是，在施用催产素后，自闭症儿童队列中非谐波交叉频率配置的瞬时形成增加了（p< .001），表明催产素对减少虚假交叉频率相互作用具有有益作用。此外，催产素受体基因的平行表观遗传学变化表明，神经效应可能是由内源性催产素信号的变化介导的。p=.006）。结论慢性催产素引起静息态内在神经频率结构的重要稳态变化，反映了噪声振荡耦合的减少和信噪比特性的改善。