Functional Connectome of the Fetal Brain
Open accessAbstract
Large-scale functional connectome formation and reorganization is apparent in the second trimester of pregnancy, making it a crucial and vulnerable time window in connectome development. Here we identified which architectural principles of functional connectome organization are initiated before birth, and contrast those with topological characteristics observed in the mature adult brain. A sample of 105 pregnant women participated in human fetal resting-state fMRI studies (fetal gestational age between 20 and 40 weeks). Connectome analysis was used to analyze weighted network characteristics of fetal macroscale brain wiring. We identified efficient network attributes, common functional modules, and high overlap between the fetal and adult brain network. Our results indicate that key features of the functional connectome are present in the second and third trimesters of pregnancy. Understanding the organizational principles of fetal connectome organization may bring opportunities to develop markers for early detection of alterations of brain function. SIGNIFICANCE STATEMENT The fetal to neonatal period is well known as a critical stage in brain development. Rapid neurodevelopmental processes establish key functional neural circuits of the human brain. Prenatal risk factors may interfere with early trajectories of connectome formation and thereby shape future health outcomes. Recent advances in MRI have made it possible to examine fetal brain functional connectivity. In this study, we evaluate the network topography of normative functional network development during connectome genesis in utero. Understanding the developmental trajectory of brain connectivity provides a basis for understanding how the prenatal period shapes future brain function and disease dysfunction.
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Fetal resting-state networks form clusters or modules; this modularity decreases with advancing gestational age.
“Fetal resting-state networks also tend to form clusters or modules; this tendency, called modularity, decreases with advancing gestational age [69, 70].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [70]
The Modular organization section reports that the fetal connectome has four functional modules, supporting the claim that fetal resting-state networks form clusters. It does not report that modularity decreases with advancing gestational age; the Discussion notes that group-level comparisons averaged across a wide age range. (LLM, conf=0.86)
Experimental — accuracy not yet measuredFetal networks exhibit efficient small-world organization.
“Fetal networks, like adults, exhibit efficient small-world organization, suggesting that regions are simultaneously well integrated with topologically distant regions of the brain while forming specialized clusters with their close-by neighbors [69, 70].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [70]
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Global Network Organization of the Fetal Functional Connectome
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- Authors
- Turk, E., van den Heuvel, M. I., Benders, M. J., de Heus, R., Franx, A., Manning, J. H., Hect, J. L., Hernandez-Andrade, E., Hassan, S. S., Romero, R., Kahn, R. S., Thomason, M. E., & van den Heuvel, M. P.
- Affiliations
- Utrecht University (NL)
- University Medical Center Utrecht (NL)
- United States Department of Health and Human Services (US)
- Icahn School of Medicine at Mount Sinai (US)
- NYU Langone Health (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2019-11-04
- Volume
- 39
- Issue
- 49
- Pages
- 9716-9724
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6891066
- OpenAlex
- W2985941729
- Cited by
- 176
- References
- 68
- Citations by year
- 2026: 18 · 2025: 31 · 2024: 37 · 2023: 21 · 2022: 30 · 2021: 21 · 2020: 18
- FWCI
- 10.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- Research portal (Tilburg University) (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- U.S. Department of Health and Human Services (HHSN275201300006C)
- Australian Government
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (452-16-015)
- National Institutes of Health (HHSN 275201300006C)
- National Institute of Mental Health (R01MH110793)
- National Institute on Drug Abuse (R34DA050287)
- National Institute of Environmental Health Sciences (P30ES020957, R21ES026022)
- National Institute of Child Health and Human Development (HHSN275201300006C)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275201300006C)
- NHLBI Division of Intramural Research
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- fetal brain, functional connectome, fetal brain development, resting-state functional connectivity, network topology, network efficiency, functional modules, prenatal risk factors, brain development, second trimester
- MeSH terms
- Adult, Atlases as Topic, Brain, Female, Fetus, Gestational Age, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Nerve Net, Pregnancy, Pregnancy Trimester, Second, Fetal Development, Connectome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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