Functional Connectivity and Metabolic Alterations in Medial Prefrontal Cortex in a Rat Model of Fetal Alcohol Spectrum Disorder: A Resting-State Functional Magnetic Resonance Imaging and in vivo Proton Magnetic Resonance Spectroscopy Study
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Prenatal ethanol exposure alters brain structure, functional connectivity, and behavior in humans and rats. Behavioral changes include deficits in executive function, which requires cooperative activity between the frontal cortices and other brain regions. In this study, we analyzed the functional connectivity and neurochemical levels of the prefrontal cortex (PFC) using resting-state functional magnetic resonance imaging (rsfMRI) and proton magnetic resonance spectroscopy (1 H-MRS) in ethanol-exposed (Eth) and control (Ctr) rats. Pregnant Long-Evans rats were fed a liquid diet containing ethanol (2.1–6.46% v/v ethanol) from gestational days 6 to 21 (Eth). Ctr animals received an isocaloric, isonutritive liquid diet. In young adulthood, male and female offspring underwent in vivo MRI using a 7.0-Tesla system. 1 H-MRS from the PFC and whole brain rsfMRI were obtained on the animals. Seed-based functional connectivity analysis was performed with seeds placed in the PFC, matching the voxel of MRS. Male, but not female, Eth rats showed less functional connectivity between PFC and dorsal striatum than Ctr animals. In Eth males glucose levels were significantly lower, and in Eth females lower levels of phosphorylcholine but an increased gamma-aminobutyric acid/glutamate ratio were observed in the PFC compared with Ctr animals. Prenatal ethanol alters brain metabolism and functional connectivity of the PFC in a sex-dependent manner.
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MRI studies showed reductions in brainstem as well as cerebellum volume in a primate FAS model and a sex-dependent change in functional connectivity and metabolism in prefrontal areas in a rat FAS model.
“MRI studies showed reductions in brainstem as well as cerebellum volume in a primate FAS model and a sex-dependent change in functional connectivity and metabolism in prefrontal areas in a rat FAS model [317, 318].”
From Development of prefrontal cortex (2022) · cites this paper as [317]
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Cirafesi, C. K., Karkhanis, A. N., & Diaz, M. R. (2026) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2026.111887
- Authors
- Tang, S., Xu, S., Waddell, J., Zhu, W., Gullapalli, R. P., & Mooney, S. M.
- Affiliations
- University of Maryland, Baltimore (US)
- Venue
- Developmental Neuroscience
- Publisher
- S. Karger AG
- Published
- 2019
- Volume
- 41
- Issue
- 1-2
- Pages
- 67-78
- ISSN
- 0378-5866 (ISSN-L)
- 1421-9859
- PMC
- PMC7424565
- OpenAlex
- W2938556470
- Cited by
- 22
- References
- 80
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 1
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Developmental Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R01AA022413, UH2AA026109, R01AA024980, P50AA017823)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- fetal alcohol spectrum disorders, prenatal alcohol exposure, medial prefrontal cortex, functional connectivity, resting-state fMRI, 1H NMR, brain metabolism, sex differences, dorsal striatum, glucose, phosphorylcholine, GABA/glutamate ratio, Long-Evans rats, executive function
- MeSH terms
- Ethanol, Animals, Central Nervous System Depressants, Disease Models, Animal, Female, Magnetic Resonance Imaging, Male, Neural Pathways, Rest, Prefrontal Cortex, Rats, Long-Evans, Rats, Fetal Alcohol Spectrum Disorders, Proton Magnetic Resonance Spectroscopy
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