Journal Article DZNE-2021-01217

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Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging.

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2021
Soc. Washington, DC

The journal of neuroscience 41(14), 3204-3221 () [10.1523/JNEUROSCI.0528-20.2021]

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Abstract: Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas. With advancing age, the ability to learn spatial environments deteriorates substantially but the underlying neural mechanisms are not well understood. Here, we report findings from a behavioral and a fMRI experiment where healthy human older and younger adults of either sex performed a spatial learning task in a photorealistic virtual environment (VE). We modeled individual learning states using a Bayesian state-space model and found that activity in retrosplenial cortex (RSC)/parieto-occipital sulcus (POS) and anterior hippocampus did not change systematically as a function learning in older compared with younger adults across repeated episodes in the environment. Moreover, effective connectivity analyses revealed that the age-related learning deficits were linked to an increase in hippocampal excitability. Together, these results provide novel insights into how human aging affects computations in the brain's navigation system, highlighting the critical role of the hippocampus.SIGNIFICANCE STATEMENT Key structures of the brain's navigation circuit are particularly vulnerable to the deleterious consequences of aging, and declines in spatial navigation are among the earliest indicators for a progression from healthy aging to neurodegenerative diseases. Our study is among the first to provide a mechanistic account about how physiological changes in the aging brain affect the formation of spatial knowledge. We show that neural activity in the aging hippocampus and medial parietal areas is decoupled from individual learning states across repeated episodes in a novel spatial environment. Importantly, we find that increased excitability of the anterior hippocampus might constitute a potential neural mechanism for cognitive mapping deficits in old age.

Keyword(s): Adult (MeSH) ; Aged (MeSH) ; Aging: physiology (MeSH) ; Aging: psychology (MeSH) ; Brain Mapping: methods (MeSH) ; Cognition: physiology (MeSH) ; Female (MeSH) ; Hippocampus: diagnostic imaging (MeSH) ; Hippocampus: physiology (MeSH) ; Humans (MeSH) ; Magnetic Resonance Imaging: methods (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Parietal Lobe: diagnostic imaging (MeSH) ; Parietal Lobe: physiology (MeSH) ; Psychomotor Performance: physiology (MeSH) ; Spatial Learning: physiology (MeSH) ; Spatial Navigation: physiology (MeSH) ; Virtual Reality (MeSH) ; Young Adult (MeSH) ; aging ; fMRI ; learning ; memory ; spatial navigation ; virtual reality

Classification:

Note: ISSN 1529-2401 not unique: **2 hits**.

Contributing Institute(s):
  1. Aging & Cognition (AG Wolbers)
Research Program(s):
  1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021
Database coverage:
Medline ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Document types > Articles > Journal Article
Institute Collections > MD DZNE > MD DZNE-AG Wolbers
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 Record created 2021-09-22, last modified 2023-09-15


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