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Modulation of cognition-specific cortical activity by gonadal steroids: A positron-emission tomography study in women
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There is considerable evidence from animal studies that gonadal steroid hormones modulate neuronal activity and affect behavior. To study this in humans directly, we used H 2 15 O positron-emission tomography to measure regional cerebral blood flow (rCBF) in young women during three pharmacologically controlled hormonal conditions spanning 4–5 months: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate (Lupron), Lupron plus estradiol replacement, and Lupron plus progesterone replacement. Estradiol and progesterone were administered in a double-blind cross-over design. On each occasion positron-emission tomography scans were performed during ( i ) the Wisconsin Card Sorting Test, a neuropsychological test that physiologically activates prefrontal cortex (PFC) and an associated cortical network including inferior parietal lobule and posterior inferolateral temporal gyrus, and ( ii ) a no-delay matching-to-sample sensorimotor control task. During treatment with Lupron alone (i.e., with virtual absence of gonadal steroid hormones), there was marked attenuation of the typical Wisconsin Card Sorting Test activation pattern even though task performance did not change. Most strikingly, there was no rCBF increase in PFC. When either progesterone or estrogen was added to the Lupron regimen, there was normalization of the rCBF activation pattern with augmentation of the parietal and temporal foci and return of the dorsolateral PFC activation. These data directly demonstrate that the hormonal milieu modulates cognition-related neural activity in humans.
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“E2 effects on dopaminergic striatal circuits by reducing dopamine receptors and increasing dopamine release may therefore mediate these effects (Archer, 1999; Gibbs, 2010), particularly in the prefrontal cortex (Berman et al., 1997).”
From Reproductive steroids and ADHD symptoms across the menstrual cycle (2018) · cites this paper as Berman et al., 1997
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Metadata
- Authors
- Berman, K. F., Schmidt, P. J., Rubinow, D. R., Danaceau, M. A., Van Horn, J. D., Esposito, G., Ostrem, J. L., & Weinberger, D. R.
- Affiliations
- National Institutes of Health (US)
- Clinical Brain Disorders Branch, and Behavioral Endocrinology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1997-08-05
- Volume
- 94
- Issue
- 16
- Pages
- 8836-8841
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC23156
- OpenAlex
- W2079637016
- Cited by
- 318
- References
- 35
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 9 · 2019: 4 · 2018: 7 · 2017: 10 · 2016: 12 · 2015: 17 · 2014: 11 · 2013: 11 · 2012: 15
- FWCI
- 5.68
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- sex steroids, estradiol, progesterone, ovarian suppression, leuprolide, regional cerebral blood flow, prefrontal cortex, Wisconsin Card Sorting Test, sensorimotor control, cognitive function, women
- MeSH terms
- Adult, Cerebral Cortex, Cerebrovascular Circulation, Cognition, Estradiol, Female, Humans, Gonadotropin-Releasing Hormone, Middle Aged, Progesterone, Tomography, Emission-Computed, Leuprolide
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