Prenatal lead exposure impacts cross-hemispheric and long-range connectivity in the human fetal brain
Open accessAbstract
Lead represents a highly prevalent metal toxicant with potential to alter human biology in lasting ways. A population segment that is particularly vulnerable to the negative consequences of lead exposure is the human fetus, as exposure events occurring before birth are linked to varied and long-ranging negative health and behavioral outcomes. An area that has yet to be addressed is the potential that lead exposure during pregnancy alters brain development even before an individual is born. Here, we combine prenatal lead exposure information extracted from newborn bloodspots with the human fetal brain functional MRI data to assess whether neural network connectivity differs between lead-exposed and lead-naïve fetuses. We found that neural connectivity patterns differed in lead-exposed and comparison groups such that fetuses that were not exposed demonstrated stronger age-related increases in cross-hemispheric connectivity, while the lead-exposed group demonstrated stronger age-related increases in posterior cingulate cortex (PCC) to lateral prefrontal cortex (PFC) connectivity. These are the first results to demonstrate metal toxicant-related alterations in human fetal neural connectivity. Remarkably, the findings point to alterations in systems that support higher-order cognitive and regulatory functions. Objectives for future work are to replicate these results in larger samples and to test the possibility that these alterations may account for significant variation in future child cognitive and behavioral outcomes.
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Lead and other pollutants are damaging to the developing brain and PFC.
“Similarly, we can find lead and other pollutants to be damaging to the developing brain and PFC [331–334].”
From Development of prefrontal cortex (2022) · cites this paper as [331]
The Discussion reports that lead-exposed fetuses deviated from typical brain-development patterns, and the Results identify altered connectivity involving a frontal region. This supports a concern about prenatal lead and the developing brain, including prefrontal circuitry, but the study did not test other pollutants or demonstrate direct damage to the PFC. (LLM, conf=0.86)
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- Authors
- Thomason, M. E., Hect, J. L., Rauh, V. A., Trentacosta, C., Wheelock, M. D., Eggebrecht, A. T., Espinoza-Heredia, C., & Burt, S. A.
- Affiliations
- University of Michigan (US)
- Wayne State University (US)
- Columbia University Irving Medical Center (US)
- Washington University in St. Louis (US)
- Michigan State University (US)
- Corresponding author
- Thomason, Moriah E.
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 191
- Pages
- 186-192
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC6451829
- OpenAlex
- W2913441973
- Cited by
- 94
- References
- 67
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 21 · 2023: 12 · 2022: 17 · 2021: 10 · 2020: 12 · 2019: 2
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (T32 MH100019, ES026022, MH110793, K01 MH103594)
- National Alliance for Research on Schizophrenia and Depression
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- prenatal lead exposure, fetal brain development, neural network connectivity, long-range connectivity, posterior cingulate cortex, lateral prefrontal cortex, developmental neurotoxicity, cognitive and behavioral outcomes
- MeSH terms
- Brain, Female, Fetus, Humans, Lead, Magnetic Resonance Imaging, Neural Pathways, Pregnancy, Prenatal Diagnosis, Prenatal Exposure Delayed Effects, Lead Poisoning, Nervous System, Childhood
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