157760 20230915092354.0 10.1523/JNEUROSCI.0528-20.2021 doi pmid:33648956 pmid pmc:PMC8026345 pmc 0270-6474 ISSN 1529-2401 ISSN altmetric:101081675 altmetric DZNE-2021-01217 English 610 Diersch, Nadine P:(DE-2719)2811077 0 First author dzne Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging. Washington, DC 2021 Soc. article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1632299114_31140 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote ISSN 1529-2401 not unique: **2 hits**. 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. 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 0 2021-10-07 Crossref https://creativecommons.org/licenses/by-nc-sa/4.0/ Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de aging Other fMRI Other learning Other memory Other spatial navigation Other virtual reality Other 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 Valdes Herrera, Jose Pedro P:(DE-2719)2811107 1 dzne Tempelmann, Claus 2 Wolbers, Thomas P:(DE-2719)2810583 3 Last author dzne 10.1523/jneurosci.0528-20.2021 Society for Neuroscience 2021-03-01 14 3204-3221 journal-article Crossref The Journal of Neuroscience 41 2021 0270-6474 10.1523/JNEUROSCI.0528-20.2021 Vol. 41, no. 14, p. 3204 - 3221 PERI:(DE-600)1475274-8 14 3204-3221 The journal of neuroscience 41 2021 0270-6474 oai:pub.dzne.de:157760 VDB Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2811077 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2811107 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2810583 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 0 2021 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2021-01-30 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2021-01-30 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2021-01-30 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-13 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-13 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-13 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-13 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-13 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-13 JCR StatID:(DE-HGF)0100 StatID J NEUROSCI : 2021 2022-11-13 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-13 Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-13 IF >= 5 StatID:(DE-HGF)9905 StatID J NEUROSCI : 2021 2022-11-13 I:(DE-2719)1310002 AG Wolbers Aging & Cognition 0 journal VDB I:(DE-2719)1310002 UNRESTRICTED 10.7554/eLife.09031 -- missing cx lookup -- Crossref 10.1016/j.nicl.2015.02.009 -- missing cx lookup -- Crossref 10.1038/40859 -- missing cx lookup -- Crossref 10.1016/j.neuroimage.2007.04.042 -- missing cx lookup -- Crossref 10.18637/jss.v031.i10 -- missing cx lookup -- Crossref 10.1002/alz.12088 -- missing cx lookup -- Crossref 10.1093/brain/awv236 -- missing cx lookup -- Crossref Brett 2002 Crossref Brett 2002 10.1073/pnas.1605719113 -- missing cx lookup -- Crossref 10.1016/j.neuroimage.2014.11.009 -- missing cx lookup -- Crossref 10.18637/jss.v076.i01 -- missing cx lookup -- Crossref 10.1016/j.cub.2014.11.001 -- missing cx lookup -- Crossref Crossref Commandeur J , Koopman SJ (2007) Introduction to state space time series analysis. Oxford: Oxford University Press. 10.1006/nimg.1998.0395 -- missing cx lookup -- Crossref 10.1016/j.neuroimage.2012.04.061 -- missing cx lookup -- Crossref 10.1016/j.neuroimage.2010.06.010 -- missing cx lookup -- Crossref 10.1242/jeb.187252 -- missing cx lookup -- Crossref 10.1016/j.neurobiolaging.2018.06.013 -- missing cx lookup -- Crossref 10.1016/j.tics.2008.07.004 -- missing cx lookup -- Crossref 10.1038/nn.4656 -- missing cx lookup -- Crossref 10.1371/journal.pone.0184661 -- missing cx lookup -- Crossref 10.1038/s41592-018-0235-4 -- missing cx lookup -- Crossref 10.3758/BRM.41.4.1149 -- missing cx lookup -- Crossref 10.1016/S0896-6273(02)00569-X -- missing cx lookup -- Crossref 10.1006/nimg.1998.0396 -- missing cx lookup -- Crossref 10.1016/j.neuroimage.2015.11.015 -- missing cx lookup -- Crossref 10.1016/j.neuroimage.2017.02.045 -- missing cx lookup -- Crossref 10.1201/b10905-7 -- missing cx lookup -- Crossref Gelman A , Shirley K (2011) Inference from simulations and monitoring convergence. In: Handbook of Markov Chain Monte Carlo ( Brooks S , Gelman A , Jones GL , Meng XL , eds), pp 163–174. Boca Raton: Chapman Hall. 10.1016/j.neuron.2015.04.023 -- missing cx lookup -- Crossref 10.1038/sdata.2016.44 -- missing cx lookup -- Crossref 10.1038/nrn3256 -- missing cx lookup -- Crossref Grinband 2017 Crossref Grinband 2017 10.1002/ana.25406 -- missing cx lookup -- Crossref 10.1038/s41586-019-1077-7 -- missing cx lookup -- Crossref 10.1016/j.bbr.2008.08.040 -- missing cx lookup -- Crossref 10.1007/s00429-016-1202-4 -- missing cx lookup -- Crossref Crossref Jones E , Oliphant T , Peterson P (2001) SciPy: open source scientific tools for Python. Available at http://www.scipy.org . 10.1002/hipo.10070 -- missing cx lookup -- Crossref 10.1002/cne.10883 -- missing cx lookup -- Crossref 10.1016/j.neuropharm.2012.06.023 -- missing cx lookup -- Crossref 10.1002/hipo.22801 -- missing cx lookup -- Crossref 10.1016/j.neuropsychologia.2015.11.013 -- missing cx lookup -- Crossref 10.1002/hipo.22181 -- missing cx lookup -- Crossref 10.7554/eLife.22978 -- missing cx lookup -- Crossref 10.1016/j.neuron.2017.06.037 -- missing cx lookup -- Crossref 10.1016/j.neuroimage.2011.01.085 -- missing cx lookup -- Crossref 10.1002/gps.2101 -- missing cx lookup -- Crossref 10.1073/pnas.1803224115 -- missing cx lookup -- Crossref 10.3389/fnhum.2014.00443 -- missing cx lookup -- Crossref 10.1016/j.neurobiolaging.2005.05.011 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.1701-17.2018 -- missing cx lookup -- Crossref 10.1002/hipo.23099 -- missing cx lookup -- Crossref 10.1111/j.1532-5415.2005.53221.x -- missing cx lookup -- Crossref 10.1016/j.neuropsychologia.2018.07.035 -- missing cx lookup -- Crossref 10.1016/0028-3932(71)90067-4 -- missing cx lookup -- Crossref 10.1093/cercor/bhz044 -- missing cx lookup -- Patai 2748 - Crossref Cereb Cortex 29 2019 10.1016/j.cpc.2010.04.018 -- missing cx lookup -- Crossref 10.1016/j.tics.2013.03.005 -- missing cx lookup -- Crossref 10.1016/j.neuron.2018.01.039 -- missing cx lookup -- Crossref 10.1002/hipo.22474 -- missing cx lookup -- Crossref 10.3389/fnagi.2012.00025 -- missing cx lookup -- Rosenbaum 25 - Crossref Front Ag Neurosci 4 2012 10.1093/acprof:oso/9780195156744.003.0006 -- missing cx lookup -- Crossref Rugg MD , Morcom AM (2005) The relationship between brain activity, cognitive performance and aging: the case of memory. In: Cognitive neuroscience of aging: linking cognitive and cerebral aging ( Cabeza R , Nyberg L , Park DC , eds), pp 132–154. New York: Oxford University Press. 10.3758/s13421-020-01089-3 -- missing cx lookup -- Segen 249 - Crossref Memory & Cognition 49 2021 10.1038/s41467-019-11802-9 -- missing cx lookup -- Crossref 10.1152/jn.00946.2006 -- missing cx lookup -- Crossref Crossref Stan Development Team (2017) PyStan: the Python interface to Stan. 2.16.0.0. edition. Available at http://mc-stan.org . 10.1038/mp.2015.160 -- missing cx lookup -- Crossref 10.1007/s11222-016-9696-4 -- missing cx lookup -- Crossref 10.1016/j.cortex.2014.12.007 -- missing cx lookup -- Crossref 10.1126/science.aau4940 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.0717-12.2013 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.1744-05.2005 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.4705-04.2005 -- missing cx lookup -- Crossref 10.3389/fnagi.2012.00014 -- missing cx lookup -- Yamamoto 14 - Crossref Front Ag Neurosci 4 2012 10.1002/hipo.20808 -- missing cx lookup -- Crossref 10.1016/j.neuroimage.2019.06.032 -- missing cx lookup -- Crossref 10.1016/j.neuroimage.2019.06.031 -- missing cx lookup -- Crossref 10.1038/nrn.2015.24 -- missing cx lookup -- Crossref