Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex
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The neuropeptide oxytocin (OXT) plays an important role in complex socio-affective behaviours such as affiliation, attachment, stress and anxiety. Previous studies have focused on the amygdala as an important target of OXT's effects. However, the effects of OXT on connectivity of the amygdala with cortical regions such as medial frontal cortex, an important mediator of social cognition and emotion regulation, remain unexplored. In a randomized, double-blind, cross-over design, 15 volunteers received intranasal OXT or placebo prior to resting-state functional magnetic resonance imaging. OXT significantly increased connectivity between both amygdalae and rostral medial frontal cortex (rmFC), while having only negligible effects on coupling with other brain regions. These results demonstrate that OXT is a robust and highly selective enhancer of amygdala connectivity with rmFC, a region critical to social cognition and emotion regulation, and add to our understanding of the neural mechanisms by which OXT modulates complex social and cognitive behaviours.
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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 [19]
The authors had previously shown that oxytocin enhances amygdala connectivity to rostral anterior cingulate cortex at rest in healthy volunteers.
“We had previously shown that OXT enhances amygdala connectivity to rostral ACC at rest in healthy volunteers (Sripada et al, 2013).”
From Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder (2014) · cites this paper as Sripada et al, 2013
Evidence suggests that oxytocin mitigates prefrontal cortex-amygdala dysregulation in healthy samples and in individuals with PTSD.
“evidence suggests that oxytocin mitigates prefrontal cortex-amygdala dysregulation in healthy samples (Sripada et al., 2013) and in individuals with PTSD (Koch et al., 2016).”
From Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial (2018) · cites this paper as Sripada et al., 2013
During resting state fMRI, IN-OT enhances functional connectivity between amygdala and rostral medial frontal areas.
“During resting state fMRI, IN-OT enhances the functional connectivity between amygdala and rostral medial frontal areas, regions that are crucial for social cognition and emotion regulation (Sripada et al. 2013).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Sripada et al. 2013
Intranasal oxytocin dampens the central fear response by lowering amygdala activity and potentially enhancing fear regulation by increasing top-down control of the prefrontal cortex over the amygdala.
“In addition, intranasal oxytocin also dampened the central fear response by lowering amygdala activity [44-46] and potentially enhancing fear regulation by increasing top-down control of the prefrontal cortex over the amygdala [47].”
From Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial (2014) · cites this paper as [47]
OT administration resulted in increased resting-state functional connectivity between the amygdala and vmPFC in healthy males and in patients with GSAD.
“Furthermore, OT administration resulted in increased resting-state functional connectivity between the amygdala and vmPFC in healthy males (Sripada et al, 2013) and in patients with GSAD (Dodhia et al, 2014), possibly enhancing top-down control over the fear response.”
From Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients (2016) · cites this paper as Sripada et al, 2013
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- Authors
- Sripada, C. S., Phan, K. L., Labuschagne, I., Welsh, R., Nathan, P. J., & Wood, A. G.
- Affiliations
- University of Michigan (US)
- Monash University (AU)
- University of Cambridge (GB)
- Murdoch Children's Research Institute (AU)
- ORCID
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05-30
- Volume
- 16
- Issue
- 2
- Pages
- 255-260
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W1983458543
- Cited by
- 197
- References
- 24
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 30 · 2019: 14 · 2018: 15 · 2017: 20 · 2016: 17 · 2015: 22 · 2014: 18 · 2013: 11 · 2012: 2
- FWCI
- 25.50
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- cc-by
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Aston Publications Explorer (Aston University) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- National Institute of Mental Health (MH076198, K23MH076198)
- National Center for Research Resources (UL1RR024986)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, amygdala, resting-state functional connectivity, intranasal administration, social cognition, emotion regulation, neuropeptides
- MeSH terms
- Adult, Amygdala, Double-Blind Method, Frontal Lobe, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Oxygen, Oxytocin, Rest, Young Adult
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