Compromised Grid-Cell-like Representations in Old Age as a Key Mechanism to Explain Age-Related Navigational Deficits

老年人网格状细胞表征受损是解释与年龄相关的导航障碍的关键机制

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Abstract

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.

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