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A Spatiotemporal Profile of In Vivo Cerebral Blood Flow Changes Following Intranasal Oxytocin in Humans
Open accessAbstract
BACKGROUND: Animal and human studies highlight the role of oxytocin in social cognition and behavior and the potential of intranasal oxytocin (IN-OT) to treat social impairment in individuals with neuropsychiatric disorders such as autism. However, extensive efforts to evaluate the central actions and therapeutic efficacy of IN-OT may be marred by the absence of data regarding its temporal dynamics and sites of action in the living human brain. METHODS: In a placebo-controlled study, we used arterial spin labeling to measure IN-OT-induced changes in resting regional cerebral blood flow (rCBF) in 32 healthy men. Volunteers were blinded regarding the nature of the compound they received. The rCBF data were acquired 15 min before and up to 78 min after onset of treatment onset (40 IU of IN-OT or placebo). The data were analyzed using mass univariate and multivariate pattern recognition techniques. RESULTS: We obtained robust evidence delineating an oxytocinergic network comprising regions expected to express oxytocin receptors, based on histologic evidence, and including core regions of the brain circuitry underpinning social cognition and emotion processing. Pattern recognition on rCBF maps indicated that IN-OT-induced changes were sustained over the entire posttreatment observation interval (25-78 min) and consistent with a pharmacodynamic profile showing a peak response at 39-51 min. CONCLUSIONS: Our study provides the first visualization and quantification of IN-OT-induced changes in rCBF in the living human brain unaffected by cognitive, affective, or social manipulations. Our findings can inform theoretical and mechanistic models regarding IN-OT effects on typical and atypical social behavior and guide future experiments (e.g., regarding the timing of experimental manipulations).
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“doubt has been cast on the extent to which intranasal OXT crosses the blood-brain barrier (Neumann et al., 2013;Paloyelis et al., 2014;Striepens et al., 2013).”
From Oxytocin increases attention to the eyes and selectively enhances self-reported affective empathy for fear (2017) · cites this paper as Paloyelis et al., 2014
In the citing paper
“Furthermore, there are uncertainties regarding the site and mechanism of action of exogenous intranasal oxytocin in humans due to lack of suitable radio tracers (Paloyelis et al., 2016).”
From Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions (2017) · cites this paper as Paloyelis et al., 2016
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“intranasal administration of oxytocin has been shown to modulate neural responses in brain regions involved in threat detection and reward processing (Ma et al., 2016b; Paloyelis et al., 2016; Wang et al., 2017; Liu et al., 2019).”
From Oxytocin promotes coordinated out-group attack during intergroup conflict in humans (2019) · cites this paper as Paloyelis et al., 2016
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“A recent elegant study using arterial spin labeling showed that IN-OT increases the levels of cerebral blood flow of key regions of the SBN such as ventral striatum, amygdala, hippocampus, caudate nucleus, anterior and middle cingulate cortices, anterior insula, ventral tegmental area (VTA), inferior frontal gyrus, inferior parietal cortex, and superior temporal gyrus (Paloyelis et al. 2016).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Paloyelis et al. 2016
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Metadata
- Authors
- Paloyelis, Y., Doyle, O. M., Zelaya, F. O., Maltezos, S., Williams, S. C., Fotopoulou, A., & Howard, M. A.
- Affiliations
- King's College London (GB)
- University College London (GB)
- Corresponding author
- Paloyelis, Yannis
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 79
- Issue
- 8
- Pages
- 693-705
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2021223630
- Cited by
- 187
- References
- 154
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 12 · 2023: 10 · 2022: 12 · 2021: 16 · 2020: 41 · 2019: 20 · 2018: 14 · 2017: 19 · 2016: 13
- FWCI
- 22.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Biological Psychiatry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Economic and Social Research Council fellowship (ES/K009400/1)
- Volkswagen Foundation “European Platform for Life Sciences, Mind Sciences and Humanities” (II/85 069)
- Institute for the Study of Affective Neuroscience/Hope for Depression Research Foundation (to AF)
- European Research Council Starting Investigator Award (ERC-2012-STG GA313755)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › 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
- intranasal oxytocin, regional cerebral blood flow, arterial spin labeling, oxytocin receptor, social cognition, emotional processing, pharmacodynamics, autism spectrum disorder, social dysfunction, spatiotemporal dynamics
- MeSH terms
- Administration, Intranasal, Brain, Brain Mapping, Central Nervous System Agents, Cerebrovascular Circulation, Humans, Magnetic Resonance Imaging, Male, Oxytocin, Pattern Recognition, Automated, Rest, Multivariate Analysis, Single-Blind Method, Young Adult
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