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@ARTICLE{Diersch:157760,
      author       = {Diersch, Nadine and Valdes Herrera, Jose Pedro and
                      Tempelmann, Claus and Wolbers, Thomas},
      title        = {{I}ncreased {H}ippocampal {E}xcitability and {A}ltered
                      {L}earning {D}ynamics {M}ediate {C}ognitive {M}apping
                      {D}eficits in {H}uman {A}ging.},
      journal      = {The journal of neuroscience},
      volume       = {41},
      number       = {14},
      issn         = {0270-6474},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {DZNE-2021-01217},
      pages        = {3204-3221},
      year         = {2021},
      note         = {ISSN 1529-2401 not unique: **2 hits**.},
      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.},
      keywords     = {Adult / Aged / Aging: physiology / Aging: psychology /
                      Brain Mapping: methods / Cognition: physiology / Female /
                      Hippocampus: diagnostic imaging / Hippocampus: physiology /
                      Humans / Magnetic Resonance Imaging: methods / Male / Middle
                      Aged / Parietal Lobe: diagnostic imaging / Parietal Lobe:
                      physiology / Psychomotor Performance: physiology / Spatial
                      Learning: physiology / Spatial Navigation: physiology /
                      Virtual Reality / Young Adult / aging (Other) / fMRI (Other)
                      / learning (Other) / memory (Other) / spatial navigation
                      (Other) / virtual reality (Other)},
      cin          = {AG Wolbers},
      ddc          = {610},
      cid          = {I:(DE-2719)1310002},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33648956},
      pmc          = {pmc:PMC8026345},
      doi          = {10.1523/JNEUROSCI.0528-20.2021},
      url          = {https://pub.dzne.de/record/157760},
}