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Anterolateral entorhinal-hippocampal imbalance in older adults disrupts object pattern separation

View ORCID ProfileZachariah M. Reagh, Jessica A. Noche, Nicholas J. Tustison, Derek Delisle, Elizabeth A. Murray, View ORCID ProfileMichael A. Yassa
doi: https://doi.org/10.1101/162925
Zachariah M. Reagh
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, UC Institute for Memory Impairments and Neurological Disorders, University of California, Irvine
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Jessica A. Noche
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, UC Institute for Memory Impairments and Neurological Disorders, University of California, Irvine
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Nicholas J. Tustison
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, UC Institute for Memory Impairments and Neurological Disorders, University of California, IrvineDepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville,VA
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Derek Delisle
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, UC Institute for Memory Impairments and Neurological Disorders, University of California, Irvine
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Elizabeth A. Murray
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, UC Institute for Memory Impairments and Neurological Disorders, University of California, Irvine
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Michael A. Yassa
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, UC Institute for Memory Impairments and Neurological Disorders, University of California, Irvine
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Abstract

The entorhinal cortex (EC) is among the earliest brain areas to deteriorate in Alzheimer’s disease (AD). However, the extent to which functional properties of the EC are altered in the aging brain, even in the absence of clinical symptoms, is not understood. Recent human fMRI studies have identified a functional dissociation within the EC, similar to what is found in rodents. Here, we used high-resolution fMRI to identify a specific hypoactivity in the anterolateral EC (alEC) commensurate with major behavioral deficits on an object pattern separation task in asymptomatic older adults. Only subtle deficits were found in a comparable spatial condition, with no associated differences in posteromedial EC between young and older adults. We additionally link this condition to previously reported dentate/CA3 hyperactivity, both of which were associated with object mnemonic discrimination impairment. These results provide novel evidence of alEC-dentate/CA3 circuit dysfunction in cognitively normal aged humans.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted July 13, 2017.
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Anterolateral entorhinal-hippocampal imbalance in older adults disrupts object pattern separation
Zachariah M. Reagh, Jessica A. Noche, Nicholas J. Tustison, Derek Delisle, Elizabeth A. Murray, Michael A. Yassa
bioRxiv 162925; doi: https://doi.org/10.1101/162925
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Anterolateral entorhinal-hippocampal imbalance in older adults disrupts object pattern separation
Zachariah M. Reagh, Jessica A. Noche, Nicholas J. Tustison, Derek Delisle, Elizabeth A. Murray, Michael A. Yassa
bioRxiv 162925; doi: https://doi.org/10.1101/162925

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