Biology subjects

Bahrd, P.

Publications and source records attributed to Bahrd, P..

3 recordsLinked to original sources

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↗

bioRxiv2024

Evaluating the position of the uncal apex as a predictor of episodic memory across the adult lifespan

Structural decline of the hippocampus follows heterogeneous spatial patterns, and is an important determinant of episodic memory dysfunction in aging. However, evidence indicate that the anatomical landmark uncal apex, used to demarcate anterior and posterior hippocampal subregions, changes position as the hippocampus atrophies. This risks misclassifying gray matter into the incorrect subregion when using standard demarcation methods, potentially contributing to over- and underestimation of age-related anterior and posterior hippocampal volume loss, respectively. Yet, it remains unexplored whether inter-individual differences in uncal apex position itself predict episodic memory performance. Here, we manually identified the uncal apex in anatomical MRI data from a healthy adult-lifespan sample (n=180; 20-79 years), analyzed age differences in its position, and examined associations with word recall performance. Increasing age was linked to a more anteriorly located uncal apex (retracting [~]0.04 mm/year), and this anterior shift was linked to lower memory performance. Using the manually identified uncal apex for subregion segmentation in native space revealed a lower proportion of anterior hippocampal volume compared to segmentation in MNI space (y = -21), with effects of age on volumes differing between methods. Memory performance was not predicted by hippocampal subregion volumes, but the ratio of posterior to anterior volume was significantly linked to memory when accounting for tissue misclassification due to uncal apex variation. These results indicate that uncal apex position may provide an estimate of hippocampal integrity sensitive to inter-individual differences in memory, independent of limitations associated with different segmentation methods.

neuroscience↗