17 Stangl, Matthias Achtzehn, Johannes Huber, Karin Dietrich, Caroline Tempelmann, Claus Wolbers, Thomas AG Wolbers Current biology Current biology Current Biology Ltd. London 0960-9822 10.1016/j.cub.2018.02.038 English 1108-1115.e6 7 28 A progressive loss of navigational abilities in old age has been observed in numerous studies, but we have only limited understanding of the neural mechanisms underlying this decline [1]. A central component of the brain's navigation circuit are grid cells in entorhinal cortex [2], largely thought to support intrinsic self-motion-related computations, such as path integration (i.e., keeping track of one's position by integrating self-motion cues) [3-6]. Given that entorhinal cortex is particularly vulnerable to neurodegenerative processes during aging and Alzheimer's disease [7-14], deficits in grid cell function could be a key mechanism to explain age-related navigational decline. To test this hypothesis, we conducted two experiments in healthy young and older adults. First, in an fMRI experiment, we found significantly reduced grid-cell-like representations in entorhinal cortex of older adults. Second, in a behavioral path integration experiment, older adults showed deficits in computations of self-position during path integration based on body-based or visual self-motion cues. Most strikingly, we found that these path integration deficits in older adults could be explained by their individual magnitudes of grid-cell-like representations, as reduced grid-cell-like representations were associated with larger path integration errors. Together, these results show that grid-cell-like representations in entorhinal cortex are compromised in healthy aging. Furthermore, the association between grid-cell-like representations and path integration performance in old age supports the notion that grid cells underlie path integration processes. We therefore conclude that impaired grid cell function may play a key role in age-related decline of specific higher-order cognitive functions, such as spatial navigation. PUB:(DE-HGF)16, ; 0, ; Adult Aged Aging: pathology Cognition: physiology Entorhinal Cortex: physiology Female Grid Cells: physiology Humans Male Spatial Memory: physiology Spatial Navigation: physiology Journal Article 2018 DZNE-2020-06209 2018 pmc:PMC5887108 pmid:29551413 https://pub.dzne.de/record/139887 https://doi.org/10.1016/j.cub.2018.02.038