Neuroendocrine regulation and behavior
Abstract
Abstract
Anxiety and maladaptive fear remain difficult to treat, and despite initial promising findings, evidence regarding the anxiolytic and translational potential of oxytocin (OT) remains inconsistent. In a preregistered, randomized, double-blind, placebo-controlled, parallel-group pharmaco-fMRI study in 67 healthy men, we tested whether intranasal OT reduces post-exposure subjective fear during prolonged naturalistic viewing a horror movie comprising independently defined low-, medium-, and high-fear segments. OT reduced subjective fear following naturalistic threat exposure after accounting for pre-exposure baseline ratings. Neuroimaging analyses revealed that OT attenuated recruitment of the dorsolateral prefrontal cortex particularly during higher fear, and enhanced coupling of this region with the bilateral amygdala. At the large-scale network level, OT increased communication between frontoparietal/default-mode control networks and subcortical/limbic networks during high fear indicating more integrative fear regulation. A whole-brain fear neuromarker (CAFE) further confirmed intensity-dependent OT effects. Together, these findings indicate that OT modulates post-exposure fear experience and fear-related neural dynamics in ecologically valid contexts.
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@article{Fu2026Oxytocin,
title = {Oxytocin reshapes fear control: intensity-dependent prefrontal dominance and whole-brain integration during naturalistic viewing},
author = {Kun Fu and Shuyue Xu and Dan Liu and Zheng Zhang and Qi Liu and Jingxian He and Ting Xu and Can Liu and Junjie Wang and Yuan Zhang and Feng Zhou and Xiaodong Zhang and Chunmei Lan and Mengfan Han and M. Li and Zhen Liang and Bharat Biswal and Keith M Kendrick and Weihua Zhao and Dezhong Yao and Benjamin Becker},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.08.11.26360155},
url = {https://doi.org/10.64898/2026.08.11.26360155}
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