High-resolution structural and functional MRI of hippocampal CA3 and dentate gyrus in patients with amnestic mild cognitive impairment
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Functional magnetic resonance imaging (fMRI) studies have observed hyperactivity in the hippocampal region in individuals with Mild Cognitive Impairment (MCI). However, the actual source of such hyperactivity is not well understood. Studies of aged rats observed similar hyperactive signals in the CA3 region of the hippocampus that correlated with spatial memory deficits and, in particular, with their ability to represent novel environments as being distinct from familiar ones (pattern separation). In this study, we tested the hypothesis that patients with amnestic MCI (aMCI) have deficits in pattern separation, along with hyperactive fMRI BOLD activity in the CA3 region of the hippocampus. We used high-resolution fMRI during a continuous recognition task designed to emphasize pattern separation. We conducted hippocampal subfield-level region of interest analyses to test for dysfunctional activity in aMCI patients. We found that patients showed impaired performance on trials that taxed their pattern separation abilities. We also observed hyperactive BOLD signals in the CA3/dentate and hypoactive signals in the entorhinal cortex during the separation condition. In a high-resolution morphometric analysis of hippocampal subfields, aMCI patients also had smaller CA3/dentate and CA1 volumes (no difference in the subiculum). The CA3/dentate region bilaterally also exhibited the largest shape deformations in aMCI patients, suggesting that this locus is affected early in the course of the disease. These findings suggest that structural and functional changes in the CA3/dentate region of the hippocampus contribute to the deficits in episodic memory that are observed in patients with aMCI. The functional hyperactivity may be evidence for a dysfunctional encoding mechanism, consistent with the predictions of computational models of hippocampal learning.
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Patients with amnestic mild cognitive impairment (MCI) showed an impaired ability to distinguish between a previously seen object and a very similar but unobserved object.
“Patients with amnestic mild cognitive impairment (MCI), for instance, showed an impaired ability to distinguish between a previously seen object and a very similar but unobserved object [68].”
From Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development (2012) · cites this paper as [68]
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- Authors
- Yassa, M. A., Stark, S. M., Bakker, A., Albert, M. S., Gallagher, M., & Stark, C. E. L.
- Affiliations
- University of California, Irvine (US)
- Johns Hopkins University (US)
- Corresponding author
- Stark, Craig E.L.
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 51
- Issue
- 3
- Pages
- 1242-1252
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC2909476
- OpenAlex
- W1989019473
- Cited by
- 523
- References
- 11
- Citations by year
- 2026: 24 · 2025: 34 · 2024: 31 · 2023: 39 · 2022: 21 · 2021: 38 · 2020: 39 · 2019: 36 · 2018: 31 · 2017: 46 · 2016: 33 · 2015: 31 · 2014: 37 · 2013: 27 · 2012: 27
- FWCI
- 17.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging/National Institutes of Health (P50AG05146, 2P01 AG09973)
- Glenn Foundation Award
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- amnestic mild cognitive impairment, hippocampal CA3, dentate gyrus, pattern separation, hippocampal hyperactivity, entorhinal cortex, hippocampal subfields, hippocampal morphometry, episodic memory, recognition memory, Alzheimer's disease
- MeSH terms
- Aged, Amnesia, Brain Mapping, Cognition Disorders, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Nerve Net
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