Belge Bernard, T. | Search bioRxiv

bioRxiv2026

Temporal instability weakens entorhinal grid-like coding in older adults

Entorhinal grid cell representations are thought to support spatial navigation and episodic memory, functions that decline with age. Their putative fMRI correlate, the hexadirectional signal, varies markedly among older adults, but the source of this variability is unknown. Using virtual navigation and fMRI in 85 older adults, we tested whether signal strength was related to the stability of hexadirectional signals. Hexadirectional orientation stability, the cross-run reproducibility of direction-specific activity patterns, was associated with hexadirectional signal strength in the posterior-medial-entorhinal-cortex (pmEC). In left-pmEC, higher orientation stability also predicted better object-location memory. In contrast, age and local structural measures did not account for individual differences in either measure. Finally, retrosplenial absolute-orientation stability was associated with left-pmEC orientation stability, and a mediation analysis supported an indirect association with hexadirectional signals through pmEC orientation stability. Together, these findings suggest that weaker entorhinal hexadirectional signal in aging may reflect unstable, rather than absent, entorhinal grid-cell-like representations.

neuroscience↗

bioRxiv2026

Entorhinal grid coding as a functional link between tau accumulation and episodic memory in human aging

Episodic memory decline is a common feature of cognitively normal aging, but its extent varies markedly across individuals. Although entorhinal tau pathology is thought to be a key contributor to episodic memory impairment, the neural mechanisms linking early tau accumulation to memory differences remain unclear. Grid-cell computations in the entorhinal cortex, which provide scaffolds for organizing experiences into episodic memories, offer one candidate mechanism. Here, we combined virtual-reality functional MRI, multivariate analysis, tau PET, and delayed word-list recall in cognitively normal older adults to test whether tau-related alterations in entorhinal coding are associated with worse episodic memory. Weaker left entorhinal grid-cell-like signal was associated with poorer memory performance, and individuals with higher left entorhinal tau burden showed weaker grid-cell-like signal. This association was specific to the canonical six-fold signal and was not explained by entorhinal volume, mean diffusivity, or intracortical myelination. A cross-sectional Bayesian mediation analysis further demonstrated that bilateral medial temporal tau burden is related to memory indirectly through left entorhinal grid-cell-like signal. Together, these findings provide evidence that entorhinal grid codes may constitute a functional pathway linking tau accumulation to memory variability in normal aging.

neuroscience↗