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000157760 1001_ $$0P:(DE-2719)2811077$$aDiersch, Nadine$$b0$$eFirst author$$udzne
000157760 245__ $$aIncreased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging.
000157760 260__ $$aWashington, DC$$bSoc.$$c2021
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000157760 520__ $$aLearning 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.
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000157760 650_7 $$2Other$$aaging
000157760 650_7 $$2Other$$afMRI
000157760 650_7 $$2Other$$alearning
000157760 650_7 $$2Other$$amemory
000157760 650_7 $$2Other$$aspatial navigation
000157760 650_7 $$2Other$$avirtual reality
000157760 650_2 $$2MeSH$$aAdult
000157760 650_2 $$2MeSH$$aAged
000157760 650_2 $$2MeSH$$aAging: physiology
000157760 650_2 $$2MeSH$$aAging: psychology
000157760 650_2 $$2MeSH$$aBrain Mapping: methods
000157760 650_2 $$2MeSH$$aCognition: physiology
000157760 650_2 $$2MeSH$$aFemale
000157760 650_2 $$2MeSH$$aHippocampus: diagnostic imaging
000157760 650_2 $$2MeSH$$aHippocampus: physiology
000157760 650_2 $$2MeSH$$aHumans
000157760 650_2 $$2MeSH$$aMagnetic Resonance Imaging: methods
000157760 650_2 $$2MeSH$$aMale
000157760 650_2 $$2MeSH$$aMiddle Aged
000157760 650_2 $$2MeSH$$aParietal Lobe: diagnostic imaging
000157760 650_2 $$2MeSH$$aParietal Lobe: physiology
000157760 650_2 $$2MeSH$$aPsychomotor Performance: physiology
000157760 650_2 $$2MeSH$$aSpatial Learning: physiology
000157760 650_2 $$2MeSH$$aSpatial Navigation: physiology
000157760 650_2 $$2MeSH$$aVirtual Reality
000157760 650_2 $$2MeSH$$aYoung Adult
000157760 7001_ $$0P:(DE-2719)2811107$$aValdes Herrera, Jose Pedro$$b1$$udzne
000157760 7001_ $$aTempelmann, Claus$$b2
000157760 7001_ $$0P:(DE-2719)2810583$$aWolbers, Thomas$$b3$$eLast author$$udzne
000157760 77318 $$2Crossref$$3journal-article$$a10.1523/jneurosci.0528-20.2021$$bSociety for Neuroscience$$d2021-03-01$$n14$$p3204-3221$$tThe Journal of Neuroscience$$v41$$x0270-6474$$y2021
000157760 773__ $$0PERI:(DE-600)1475274-8$$a10.1523/JNEUROSCI.0528-20.2021$$gVol. 41, no. 14, p. 3204 - 3221$$n14$$p3204-3221$$tThe journal of neuroscience$$v41$$x0270-6474$$y2021
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