Abstract
Oxytocin has recently received remarkable attention for its role as a modulator of human behaviour. Here, we aimed to expand our knowledge of the neural circuits engaged by oxytocin by investigating the effects of intranasal and intravenous oxytocin on the functional connectome at rest in 16 healthy men. Oxytocin modulates the functional connectome within discrete neural systems, but does not affect the global capacity for information transfer. These local effects encompass key hubs of the oxytocin system (e.g. amygdala) but also regions overlooked in previous hypothesis-driven research (i.e. the visual circuits, temporal lobe and cerebellum). Increases in levels of oxytocin in systemic circulation induce broad effects on the functional connectome, yet we provide indirect evidence supporting the involvement of nose-to-brain pathways in at least some of the observed changes after intranasal oxytocin. Together, our results suggest that oxytocin effects on human behaviour entail modulation of multiple levels of brain processing distributed across different systems.
Highlights
Oxytocin has recently received remarkable attention for its role as a modulator of human behaviour
Oxytocin administered with the spray increased the betweenness-centrality of the right orbitofrontal cortex, left lateral occipital cortex, right temporal occipital fusiform cortex and left occipital pole, while it decreased the betweenness-centrality of the precuneus, right posterior supramarginal and middle temporal gyri, the left anterior middle temporal gyrus and the right cerebellum (Fig. 2A and Supplementary Table S1)
Oxytocin increased the betweenness-centrality of the right and left occipital poles, left postcentral gyrus, right supramarginal gyrus and left and right cerebellum, while it decreased the betweenness-centrality of the right amygdala and the anterior parahipoccampal gyrus (Fig. 2C and Supplementary Table S1)
Summary
Oxytocin has recently received remarkable attention for its role as a modulator of human behaviour. Small scale studies aiming to harness the oxytocin system through administration of exogenous oxytocin (either using nasal sprays or intravenous infusion) have shown beneficial effects in some disorders, with mixed results[8] Despite these recent advances, our knowledge about the neural mechanisms through which oxytocin affects human behaviour is still insufficient. Changes in perfusion provide a quantitative, non-invasive pharmacodynamic marker of the local effects of acute doses of psychoactive drugs[13,14] with high-spatial resolution and excellent temporal reproducibility[15] This approach cannot fully illuminate the effects of drugs on complex biological systems such as the brain, which are characterized by the temporal dependency of neuronal activation patterns of anatomically separated brain regions (functional connectivity) within networks[16,17]. Exceptions are some effects on the attentional and salience large-scale-networks[19,20]
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