TY  - JOUR
AU  - Diersch, Nadine
AU  - Valdes Herrera, Jose Pedro
AU  - Tempelmann, Claus
AU  - Wolbers, Thomas
TI  - Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging.
JO  - The journal of neuroscience
VL  - 41
IS  - 14
SN  - 0270-6474
CY  - Washington, DC
PB  - Soc.
M1  - DZNE-2021-01217
SP  - 3204-3221
PY  - 2021
N1  - ISSN 1529-2401 not unique: **2 hits**.
AB  - 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.
KW  - Adult
KW  - Aged
KW  - Aging: physiology
KW  - Aging: psychology
KW  - Brain Mapping: methods
KW  - Cognition: physiology
KW  - Female
KW  - Hippocampus: diagnostic imaging
KW  - Hippocampus: physiology
KW  - Humans
KW  - Magnetic Resonance Imaging: methods
KW  - Male
KW  - Middle Aged
KW  - Parietal Lobe: diagnostic imaging
KW  - Parietal Lobe: physiology
KW  - Psychomotor Performance: physiology
KW  - Spatial Learning: physiology
KW  - Spatial Navigation: physiology
KW  - Virtual Reality
KW  - Young Adult
KW  - aging (Other)
KW  - fMRI (Other)
KW  - learning (Other)
KW  - memory (Other)
KW  - spatial navigation (Other)
KW  - virtual reality (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33648956
C2  - pmc:PMC8026345
DO  - DOI:10.1523/JNEUROSCI.0528-20.2021
UR  - https://pub.dzne.de/record/157760
ER  -