Oxytocin’s effect on resting-state functional connectivity varies by age and sex
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The neuropeptide oxytocin plays a role in social cognition and affective processing. The neural processes underlying these effects are not well understood. Modulation of connectivity strength between subcortical and cortical regions has been suggested as one possible mechanism. The current study investigated effects of intranasal oxytocin administration on resting-state functional connectivity between amygdala and medial prefrontal cortex (mPFC), as two regions involved in social-cognitive and affective processing. Going beyond previous work that largely examined young male participants, our study comprised young and older men and women to identify age and sex variations in oxytocin's central processes. This approach was based on known hormonal differences among these groups and emerging evidence of sex differences in oxytocin's effects on amygdala reactivity and age-by-sex-modulated effects of oxytocin in affective processing. In a double-blind design, 79 participants were randomly assigned to self-administer either intranasal oxytocin or placebo before undergoing resting-state functional magnetic resonance imaging. Using a targeted region-to-region approach, resting-state functional connectivity strength between bilateral amygdala and mPFC was examined. Participants in the oxytocin compared to the placebo group and men compared to women had overall greater amygdala-mPFC connectivity strength at rest. These main effects were qualified by a significant three-way interaction: while oxytocin compared to placebo administration increased resting-state amygdala-mPFC connectivity for young women, oxytocin did not significantly influence connectivity in the other age-by-sex subgroups. This study provides novel evidence of age-by-sex differences in how oxytocin modulates resting-state brain connectivity, furthering our understanding of how oxytocin affects brain networks at rest.
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The small number of existing rsfMRI oxytocin-administration studies use seed-based analyses that do not allow for hypothesis-free examination across the connectome.
“the small number of existing rsfMRI oxytocin-administration studies5, 13, 19, 20 use seed-based analyses that do not allow for hypothesis-free examination across the connectome.”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [13]
Sex differences in the OXTR system are documented, suggesting findings in males may not generalize to females.
“Sex differences in the OXTR system are documented,11, 12, 13 suggesting that findings in males may not generalize to females.”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [13]
Male bias can be observed in much of prior work on oxytocin in humans.
“This bias can be observed in much of the prior work on oxytocin in humans as well, with some neuroimaging studies indicating potential differences in the oxytocin system between sexes.13, 14, 47, 48, 49”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [13]
Some neuroimaging studies indicate potential differences in the oxytocin system between sexes.
“This bias can be observed in much of the prior work on oxytocin in humans as well, with some neuroimaging studies indicating potential differences in the oxytocin system between sexes.13, 14, 47, 48, 49”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [13]
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- Authors
- Ebner, N. C., Chen, H., Porges, E., Lin, T., Fischer, H., Feifel, D., & Cohen, R. A.
- Affiliations
- University of Florida (US)
- University of Florida Health (US)
- Stockholm University (SE)
- University of California San Diego (US)
- Corresponding author
- Ebner, Natalie C.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 69
- Pages
- 50-59
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC4942126
- OpenAlex
- W2298685505
- Cited by
- 84
- References
- 73
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 10 · 2021: 5 · 2020: 9 · 2019: 16 · 2018: 9 · 2017: 7 · 2016: 3
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Florida
- National Institutes of Health (UL1TR001427, UL1TR000064, KL2TR001429)
- National Institute on Aging (R24AG039350, P30AG028740)
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- oxytocin, resting-state functional connectivity, amygdala, medial prefrontal cortex, age differences, sex differences, intranasal administration, social cognition, emotional processing, brain networks
- MeSH terms
- Administration, Intranasal, Adult, Age Factors, Amygdala, Brain, Double-Blind Method, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Membrane Potentials, Middle Aged, Neural Pathways, Oxytocin, Sex Factors, Prefrontal Cortex
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