Biology subjects

Segen, V.

Publications and source records attributed to Segen, V..

6 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↗

bioRxiv2025

Altered coding of environmental boundaries in human aging: an fMRI study

Aging is associated with changes in spatial memory and navigation, yet the mechanisms underlying these changes are not yet fully understood. Environmental boundaries are among the most salient and reliable spatial cues, supporting both spatial memory and orientation. Here, we investigated how aging affects the use and the neural representation of boundary information during a virtual object location memory task. Healthy young and older adults navigated a square virtual environment while undergoing functional magnetic resonance imaging, allowing us to assess moment-to-moment encoding of distance to environmental boundaries in the entorhinal cortex and subiculum. Behaviorally, both age groups showed more accurate memory for objects located near boundaries, but this effect was amplified in older adults, whose spatial precision declined more steeply with increasing distance from boundaries. Older adults also exhibited a stronger bias to recall objects closer to boundaries. Analysis of navigation behaviour revealed that older adults followed boundary-oriented paths regardless of target location, whereas young adults flexibly adapted their navigation based on spatial context. Neurally, older adults--but not young adults--showed significant blood-oxygen-level-dependent modulation by boundary distance in the entorhinal cortex and subiculum, with activity decreasing as participants moved farther from boundaries. This effect was most pronounced in low-performing older adults and was associated with stronger behavioral boundary bias, suggesting a maladaptive reliance on proximity-based cues. Together, our results provide converging behavioral and neural evidence that aging alters the use and representation of boundary information, with downstream effects on spatial memory. Altered boundary processing may represent a key mechanism contributing to age-related declines in spatial cognition.

neuroscience↗

bioRxiv2025

Path integration impairments reveal early cognitive changes in Subjective Cognitive Decline

Path integration, the ability to track ones position using self-motion cues, is critically dependent on the grid cell network in the entorhinal cortex, a region vulnerable to early Alzheimers disease pathology. In this study, we examined path integration performance in individuals with subjective cognitive decline (SCD), a group at increased risk for Alzheimers disease, and healthy controls using an immersive virtual reality task. We developed a Bayesian computational model to decompose path integration errors into distinct components. SCD participants exhibited significantly higher path integration error, primarily driven by increased memory leak, while other modelling-derived error sources, such as velocity gain, sensory and reporting noise, remained comparable across groups. Our findings suggest that path integration deficits, specifically memory leak, may serve as an early marker of neurodegeneration in SCD and highlight the potential of self-motion-based navigation tasks for detecting pre-symptomatic Alzheimers disease-related cognitive changes. TeaserVirtual reality, modelling, and plasma biomarkers reveal path integration deficits in pre-symptomatic Alzheimers vs normal aging.

neuroscience↗

bioRxiv2025

rTCT: Rodent Triangle Completion Task to facilitate translational study of path integration

Path integration is navigation in the absence of environmental landmarks and is a primary cognitive mechanism underlying spatial memory. Path integration performance is primarily assessed in humans using the Triangle Completion Task (TCT). In humans, TCT has shown promise for the early diagnosis of Alzheimers disease. In rodents, however, path integration is assessed using a wide variety of tasks but none of which currently provide a homologue for the TCT. As rodents are routinely used as preclinical models, homologous path integration tasks that result in comparable performance metrics between species are important. In the present study we developed and tested a novel rodent version of the triangle completion task to enhance cross species comparability of path integration performance. Rats were able to comprehend and perform the task. A group of Alzheimers disease model rats (TgF344-AD) exhibited similar path integration performance to their wild-type littermates; however, analysis of behavioural structure suggests use of differing behavioural strategies. This work establishes a novel rodent homologue of the triangle completion task, facilitating enhanced reverse translational study of human path integration.

neuroscience↗

bioRxiv2021

The role of memory and perspective shifts in systematic biases during object location estimation

Our previous research highlighted a systematic bias in a spatial memory task, with participants correctly detecting object movements in the same direction as the perspective shift, whilst misjudging the direction of object movements if those were in the opposite direction to the perspective shift. The aim of the current study was to investigate if the introduction of perspective shifts results in systematic biases in object location estimations. To do so, we asked participants to encode the position of an object in a virtual room and to then estimate the objects position following a perspective shift. In addition, by manipulating memory load (perception and memory condition) we investigated if the bias in object position estimates results from systematic distortions introduced in spatial memory. Overall, our results show that participants make systematic errors in estimating object positions in the same direction as the perspective shift. This bias was present in both the memory and the perception condition. We propose that the systematic bias in the same direction as the perspective shift is driven by difficulties in understanding the perspective shifts that may lead participants to use an egocentric representation of object positions as an anchor when estimating the object location following a perspective shift, thereby giving rise to a systematic shift in errors in the same direction as the perspective shift.

neuroscience↗