Navigation performance in glaucoma: virtual-reality-based assessment of path integration.

Navigation is essential for moving between locations in our daily lives. We investigated the relationship between visual impairment in glaucoma and path-integration-based navigation. Fourteen glaucoma and 15 controls underwent ophthalmological examination (including visual acuity (logMAR), visual field sensitivity (MD: mean deviation from matched reference cohort), and peripapillary retinal nerve fiber layer (pRNFL)). Both groups navigated physically in virtual reality (VR) environments during daylight and dawn conditions. Briefly, the participants traversed a path marked by three targets, subsequently pointing back to the path's origin. Outcome measures included (i) travel-time, (ii) pointing-time, and (iii) Euclidian-distance error between indicated and starting position. Robust linear regression was conducted between visual function outcomes of the better eye and VR outcome measures. Glaucoma patients showed increase in travel-time (by 8.2 ± 1.7 s; p = 0.002) and in pointing-time (by 5.3 ± 1.6 s; p = 0.016). Predictors were MD for all outcome measures (p < 0.01) and pRNFL for travel-time (p < 0.01). The results suggest that the effect of glaucoma on the elapsed time depends on disease progression, i.e. people with stronger visual impairment need more time. This uncertainty during everyday navigation tasks may adversely affect their quality of life.

Differences between sub-second and supra-second durations for the assessment of timing deficits in amnestic mild cognitive impairment.

Previous studies have often reported timing deficits in older adults with different degrees of cognitive decline, however, the exact nature of impairments in time perception is still to be elucidated. In particular, it is unclear if the deficits are more pronounced for short or long intervals, consistent with notions that different cognitive processes and neuroanatomical areas are involved in the processing of durations of different ranges. The present study aims to further investigate timing abilities in amnestic mild cognitive impairment (aMCI) patients and age-matched controls. Participants were asked to decide whether an acoustic event occurred within the first or the second half of a reference duration. The results revealed a bias towards larger PSE values and reduced precision in aMCI patients compared to healthy controls. Further analyses showed that the bias towards larger PSE values correlated with memory performance, especially when sub-second durations were tested. Overall, the results demonstrate that memory deficits in aMCI patients coincide with changes in time perception in the sub-second interval range.

Memory traces of duration and location in the right intraparietal sulcus.

Time and space form an integral part of every human experience, and for the neuronal representation of these perceptual dimensions, previous studies point to the involvement of the right-hemispheric intraparietal sulcus and structures in the medial temporal lobe. Here we used multi-voxel pattern analysis (MVPA) to investigate long-term memory traces for temporal and spatial stimulus features in those areas. Participants were trained on four images associated with short versus long durations and with left versus right locations. Our results demonstrate stable representations of both temporal and spatial information in the right posterior intraparietal sulcus. Building upon previous findings of stable neuronal codes for directly perceived durations and locations, these results show that the reactivation of long-term memory traces for temporal and spatial features can be decoded from neuronal activation patterns in the right parietal cortex.

Repetition Suppression Reveals Cue-Specific Spatial Representations for Landmarks and Self-Motion Cues in the Human Retrosplenial Cortex.

The efficient use of various spatial cues within a setting is crucial for successful navigation. Two fundamental forms of spatial navigation, landmark-based and self-motion-based, engage distinct cognitive mechanisms. The question of whether these modes invoke shared or separate spatial representations in the brain remains unresolved. While nonhuman animal studies have yielded inconsistent results, human investigation is limited. In our previous work (Chen et al., 2019), we introduced a novel spatial navigation paradigm utilizing ultra-high field fMRI to explore neural coding of positional information. We found that different entorhinal subregions in the right hemisphere encode positional information for landmarks and self-motion cues. The present study tested the generalizability of our previous finding with a modified navigation paradigm. Although we did not replicate our previous finding in the entorhinal cortex, we identified adaptation-based allocentric positional codes for both cue types in the retrosplenial cortex (RSC), which were not confounded by the path to the spatial location. Crucially, the multi-voxel patterns of these spatial codes differed between the cue types, suggesting cue-specific positional coding. The parahippocampal cortex exhibited positional coding for self-motion cues, which was not dissociable from path length. Finally, the brain regions involved in successful navigation differed from our previous study, indicating overall distinct neural mechanisms recruited in our two studies. Taken together, the current findings demonstrate cue-specific allocentric positional coding in the human RSC in the same navigation task for the first time and that spatial representations in the brain are contingent on specific experimental conditions.

Entorhinal-based path integration selectively predicts midlife risk of Alzheimer's disease.

INTRODUCTION: Entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration (PI)-based spatial behaviors, we predicted that PI impairment would represent the first behavioral change in adults at risk of AD. METHODS: We compared immersive virtual reality (VR) PI ability to other cognitive domains in 100 asymptomatic midlife adults stratified by hereditary and physiological AD risk factors. In some participants, behavioral data were compared to 7T magnetic resonance imaging (MRI) measures of brain structure and function. RESULTS: Midlife PI impairments predicted both hereditary and physiological AD risk, with no corresponding multi-risk impairment in episodic memory or other spatial behaviors. Impairments associated with altered functional MRI signal in the posterior-medial EC. DISCUSSION: Altered PI may represent the transition point from at-risk state to disease manifestation in AD, prior to impairment in other cognitive domains.

Does sleep promote adaptation to acute stress: An experimental study.

Objectives: Evidence of the impact of chronic stress on sleep is abundant, yet experimental sleep studies with a focus on acute stress are scarce and the results are mixed. Our study aimed to fill this gap by experimentally investigating the effects of pre-sleep social stress on sleep dynamics during the subsequent night, as measured with polysomnography (PSG). Methods: Thirty-four healthy individuals (65% females, Mage = 25.76 years SD = 3.35) underwent a stress-inducing (SC) or neutral control condition (CC) in virtual reality (VR). We used overnight EEG measurements to analyze the basic sleep parameters and power spectral density (PSD) across the sleep cycles, and measured heart rate and its variability (HRV), skin electrodermal activity (EDA), and salivary cortisol to capture physiological arousal during the VR task and the pre-sleep period. Results: Following acute stress (SC), the amount of slow-wave sleep (SWS) was higher and N2 sleep lower relative to CC, specifically in the first sleep cycle. In SC, PSD was elevated in the beta-low (16-24 Hz) and beta-high (25-35 Hz) frequency ranges during both stages N2 and SWS over the entire night. Conclusions: Sleep promoted adaptation to acute social stress by a longer duration of SWS in the subsequent sleep period, especially in early sleep. A similar homeostatic effect towards restorative sleep is well-evidenced in animal model stress studies but has not been previously reported in experimental human studies. Whether the high-frequency PSD activity during stages N2 and SWS also serves in the resolution of transient stress, remains open.

Effects of estrogen on spatial navigation and memory.

RATIONALE: Animal studies suggest that the so-called "female" hormone estrogen enhances spatial navigation and memory. This contradicts the observation that males generally out-perform females in spatial navigation and tasks involving spatial memory. A closer look at the vast number of studies actually reveals that performance differences are not so clear. OBJECTIVES: To help clarify the unclear performance differences between men and women and the role of estrogen, we attempted to isolate organizational from activational effects of estrogen on spatial navigation and memory. METHODS: In a double-blind, placebo-controlled study, we tested the effects of orally administered estradiol valerate (E2V) in healthy, young women in their low-hormone menstrual cycle phase, compared to healthy, young men. Participants performed several first-person, environmentally rich, 3-D computer games inspired by spatial navigation and memory paradigms in animal research. RESULTS: We found navigation behavior suggesting that sex effects dominated any E2 effects with men performing better with allocentric strategies and women with egocentric strategies. Increased E2 levels did not lead to general improvements in spatial ability in either sex but to behavioral changes reflecting navigation flexibility. CONCLUSION: Estrogen-driven differences in spatial cognition might be better characterized on a spectrum of navigation flexibility rather than by categorical performance measures or skills.

The 3D Structural Architecture of the Human Hand Area Is Nontopographic.

The functional topography of the human primary somatosensory cortex hand area is a widely studied model system to understand sensory organization and plasticity. It is so far unclear whether the underlying 3D structural architecture also shows a topographic organization. We used 7 Tesla (7T) magnetic resonance imaging (MRI) data to quantify layer-specific myelin, iron, and mineralization in relation to population receptive field maps of individual finger representations in Brodman area 3b (BA 3b) of human S1 in female and male younger adults. This 3D description allowed us to identify a characteristic profile of layer-specific myelin and iron deposition in the BA 3b hand area, but revealed an absence of structural differences, an absence of low-myelin borders, and high similarity of 3D microstructure profiles between individual fingers. However, structural differences and borders were detected between the hand and face areas. We conclude that the 3D structural architecture of the human hand area is nontopographic, unlike in some monkey species, which suggests a high degree of flexibility for functional finger organization and a new perspective on human topographic plasticity.SIGNIFICANCE STATEMENT Using ultra-high-field MRI, we provide the first comprehensive in vivo description of the 3D structural architecture of the human BA 3b hand area in relation to functional population receptive field maps. High similarity of precise finger-specific 3D profiles, together with an absence of structural differences and an absence of low-myelin borders between individual fingers, reveals the 3D structural architecture of the human hand area to be nontopographic. This suggests reduced structural limitations to cortical plasticity and reorganization and allows for shared representational features across fingers.

Path integration selectively predicts midlife risk of Alzheimer's disease.

The entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration, we predicted that path integration impairment would represent the first behavioural change in adults at-risk of AD. Using immersive virtual reality, we found that midlife path integration impairments predicted both hereditary and physiological AD risk, with no corresponding impairment on tests of episodic memory or other spatial behaviours. Impairments related to poorer angular estimation and were associated with hexadirectional grid-like fMRI signal in the posterior-medial EC. These results indicate that altered path integration may represent the transition point from at-risk state to disease onset in AD, prior to impairment in other cognitive domains.

Reaching the Goal: Superior Navigators in Late Adulthood Provide a Novel Perspective into Successful Cognitive Aging.

Normal aging is typically associated with declines in navigation and spatial memory abilities. However, increased interindividual variability in performance across various navigation/spatial memory tasks is also evident with advancing age. In this review paper, we shed the spotlight on those older individuals who exhibit exceptional, sometimes even youth-like navigational/spatial memory abilities. Importantly, we (1) showcase observations from existing studies that demonstrate superior navigation/spatial memory performance in late adulthood, (2) explore possible cognitive correlates and neurophysiological mechanisms underlying these preserved spatial abilities, and (3) discuss the potential link between the superior navigators in late adulthood and SuperAgers (older adults with superior episodic memory). In the closing section, given the lack of studies that directly focus on this subpopulation, we highlight several important directions that future studies could look into to better understand the cognitive characteristics of older superior navigators and the factors enabling such successful cognitive aging.

Reducing the tendency for chronometric counting in duration discrimination tasks.

Chronometric counting is a prevalent issue in the study of human time perception as it reduces the construct validity of tasks and can conceal existing timing deficits. Several methods have been proposed to prevent counting strategies, but the factors promoting those strategies in specific tasks are largely uninvestigated. Here, we modified a classical two-interval duration discrimination task in two aspects that could affect the tendency to apply counting strategies. We removed the pause between the two intervals and changed the task instructions: Participants decided whether a short event occurred in the first or in the second half of a reference duration. In Experiment 1, both classical and modified task versions were performed under timing conditions, in which participants were asked not to count, and counting conditions, in which counting was explicitly instructed. The task modifications led to (i) a general decrease in judgment precision, (ii) a shift of the point of subjective equality, and (iii) a counting-related increase in reaction times, suggesting enhanced cognitive effort of counting during the modified task version. Precision in the two task versions was not differently affected by instructed counting. Experiment 2 demonstrates that-in the absence of any counting-related instructions-participants are less likely to engage in spontaneous counting in the modified task version. These results enhance our understanding of the two-interval duration discrimination task and demonstrate that the modifications tested here-although they do not significantly reduce the effectiveness of instructed counting-can diminish the spontaneous tendency to adopt counting strategies.

Cross-dimensional interference between time and distance during spatial navigation is mediated by speed representations in intraparietal sulcus and area hMT.

When navigating a straight path, perceived travel time and perceived traveled distance are linked via movement speed. Behavioral studies have revealed systematic interferences between the perception of travel time and distance, but the role of neuronal representations of movement speed for these effects has not been addressed to date. Using a combined fMRI-behavioral paradigm, we investigate the neuronal representations that underlie cross-dimensional interferences between travel time and traveled distance. Participants underwent fMRI while experiencing visual forward movements for either a short or a long duration, and covering either a short or a long distance. At the behavioral level, we found bi-directional interference effects between time and distance perception, which was correlated with greater representational similarity in speed-sensitive brain regions. The strength of the distance-on-time effect scaled with representational similarity in the left human middle temporal complex (hMT+), and the strength of the time-on-distance effect scaled with representational similarity in the right intraparietal sulcus (IPS). In accordance with the idea that the interference is mediated by the perception of speed, distance-on-time and time-on-distance effects were of opposing directions. Increases in traveled distance led to increases in perceived travel time, while increases in travel time led to decreases in perceived traveled distance. Together, these findings support the view that cross-dimensional interference effects between travel time and traveled distance are mediated by neuronal representations of movement speed.

Path integration in normal aging and Alzheimer's disease.

In this review we discuss converging evidence from human and rodent research demonstrating how path integration (PI) is impaired in healthy aging and Alzheimer's disease (AD), and point to the neural mechanisms that underlie these deficits. Importantly, we highlight that (i) the grid cell network in the entorhinal cortex is crucial for PI in both humans and rodents, (ii) PI deficits are present in healthy aging and are significantly more pronounced in patients with early-stage AD, (iii) compromised entorhinal grid cell computations in healthy older adults and in young adults at risk of AD are linked to PI deficits, and (iv) PI and grid cell deficits may serve as sensitive markers for pathological decline in early AD.

Temporal context effects are associated with cognitive status in advanced age.

The perception of temporal intervals changes during the life-span, and especially older adults demonstrate specific impairments of timing abilities. Recently, we demonstrated that timing performance and cognitive status are correlated in older adults, suggesting that timing tasks can serve as a behavioral marker for the development of dementia. Easy-to-administer and retest-capable timing tasks therefore have potential as diagnostic tools for tracking cognitive decline. However, before being tested in a clinical cohort study, a further validation and specification of the original findings is warranted. Here we introduce several modifications of the original task and investigated the effects of temporal context on time perception in older adults (> 65 years) with low versus high scores in the Montreal Cognitive Assessment survey (MoCA) and a test of memory functioning. In line with our previous work, we found that temporal context effects were more pronounced with increasing memory deficits, but also that these effects are stronger for realistic compared to abstract visual stimuli. Furthermore, we show that two distinct temporal contexts influence timing behavior in separate experimental blocks, as well as in a mixed block in which both contexts are presented together. These results replicate and extend our previous findings. They demonstrate the stability of the effect for different stimulus material and show that timing tasks can reveal valuable information about the cognitive status of older adults. In the future, these findings could serve as a basis for the development of a diagnostic tool for pathological cognitive decline at an early, pre-clinical stage.

Impaired remapping of social relationships in older adults.

Social relationships are a central aspect of our everyday life, yet our ability to change established social relationships is an under-investigated topic. Here, we use the concept of cognitive mapping to investigate the plasticity of social relationships in younger and older adults. We describe social relationships within a 'social space', defined as a two-dimensional grid composed of the axis 'power' and 'affiliation', and investigate it using a 3D virtual environment with interacting avatars. We show that participants remap dimensions in 'social space' when avatars show conflicting behavior compared to consistent behavior and that, while older adults show similar updating behavior than younger adults, they show a distinct reduction in remapping social space. Our data provide first evidence that older adults show more rigid social behavior when avatars change their behavior in the dimensions of power and affiliation, which may explain age-related social behavior differences in everyday life.

Age-related changes in time perception: The impact of naturalistic environments and retrospective judgements on timing performance.

Reduced timing abilities have been reported in older adults and are associated with pathological cognitive decline. However, time perception experiments often lack ecological validity. Especially the reduced complexity of experimental stimuli and the participants' awareness of the time-related nature of the task can influence lab-assessed timing performance and thereby conceal age-related differences. An approximation of more naturalistic paradigms can provide important information about age-related changes in timing abilities. To determine the impact of higher ecological validity on timing experiments, we implemented a paradigm that allowed us to test (1) the effect of embedding the to-be-timed stimuli within a naturalistic visual scene and (2) the effect of retrospective time judgements, which are more common in real life than prospective judgements. The results show that compared with out-of-context stimuli, younger adults benefit from a naturalistic embedding of stimuli (reflected in higher precision and less errors), whereas the performance of older adults is reduced when confronted with naturalistic stimuli. Differences between retrospective and prospective time judgements were not modulated by age. We conclude that, potentially driven by difficulties in suppressing temporally irrelevant environmental information, the contextual embedding of naturalistic stimuli can affect the degree to which age influences the performance in time perception tasks.

The organizational principles of de-differentiated topographic maps in somatosensory cortex.

Topographic maps are a fundamental feature of cortex architecture in the mammalian brain. One common theory is that the de-differentiation of topographic maps links to impairments in everyday behavior due to less precise functional map readouts. Here, we tested this theory by characterizing de-differentiated topographic maps in primary somatosensory cortex (SI) of younger and older adults by means of ultra-high resolution functional magnetic resonance imaging together with perceptual finger individuation and hand motor performance. Older adults' SI maps showed similar amplitude and size to younger adults' maps, but presented with less representational similarity between distant fingers. Larger population receptive field sizes in older adults' maps did not correlate with behavior, whereas reduced cortical distances between D2 and D3 related to worse finger individuation but better motor performance. Our data uncover the drawbacks of a simple de-differentiation model of topographic map function, and motivate the introduction of feature-based models of cortical reorganization.

Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging.

Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas. With advancing age, the ability to learn spatial environments deteriorates substantially but the underlying neural mechanisms are not well understood. Here, we report findings from a behavioral and a fMRI experiment where healthy human older and younger adults of either sex performed a spatial learning task in a photorealistic virtual environment (VE). We modeled individual learning states using a Bayesian state-space model and found that activity in retrosplenial cortex (RSC)/parieto-occipital sulcus (POS) and anterior hippocampus did not change systematically as a function learning in older compared with younger adults across repeated episodes in the environment. Moreover, effective connectivity analyses revealed that the age-related learning deficits were linked to an increase in hippocampal excitability. Together, these results provide novel insights into how human aging affects computations in the brain's navigation system, highlighting the critical role of the hippocampus.SIGNIFICANCE STATEMENT Key structures of the brain's navigation circuit are particularly vulnerable to the deleterious consequences of aging, and declines in spatial navigation are among the earliest indicators for a progression from healthy aging to neurodegenerative diseases. Our study is among the first to provide a mechanistic account about how physiological changes in the aging brain affect the formation of spatial knowledge. We show that neural activity in the aging hippocampus and medial parietal areas is decoupled from individual learning states across repeated episodes in a novel spatial environment. Importantly, we find that increased excitability of the anterior hippocampus might constitute a potential neural mechanism for cognitive mapping deficits in old age.

Spatial Updating Depends on Gravity.

As we move through an environment the positions of surrounding objects relative to our body constantly change. Maintaining orientation requires spatial updating, the continuous monitoring of self-motion cues to update external locations. This ability critically depends on the integration of visual, proprioceptive, kinesthetic, and vestibular information. During weightlessness gravity no longer acts as an essential reference, creating a discrepancy between vestibular, visual and sensorimotor signals. Here, we explore the effects of repeated bouts of microgravity and hypergravity on spatial updating performance during parabolic flight. Ten healthy participants (four women, six men) took part in a parabolic flight campaign that comprised a total of 31 parabolas. Each parabola created about 20-25 s of 0 g, preceded and followed by about 20 s of hypergravity (1.8 g). Participants performed a visual-spatial updating task in seated position during 15 parabolas. The task included two updating conditions simulating virtual forward movements of different lengths (short and long), and a static condition with no movement that served as a control condition. Two trials were performed during each phase of the parabola, i.e., at 1 g before the start of the parabola, at 1.8 g during the acceleration phase of the parabola, and during 0 g. Our data demonstrate that 0 g and 1.8 g impaired pointing performance for long updating trials as indicated by increased variability of pointing errors compared to 1 g. In contrast, we found no support for any changes for short updating and static conditions, suggesting that a certain degree of task complexity is required to affect pointing errors. These findings are important for operational requirements during spaceflight because spatial updating is pivotal for navigation when vision is poor or unreliable and objects go out of sight, for example during extravehicular activities in space or the exploration of unfamiliar environments. Future studies should compare the effects on spatial updating during seated and free-floating conditions, and determine at which g-threshold decrements in spatial updating performance emerge.

Sources of path integration error in young and aging humans.

Path integration plays a vital role in navigation: it enables the continuous tracking of one's position in space by integrating self-motion cues. Path integration abilities vary widely across individuals, and tend to deteriorate in old age. The specific causes of path integration errors, however, remain poorly characterized. Here, we combine tests of path integration performance in participants of different ages with an analysis based on the Langevin equation for diffusive dynamics, which allows us to decompose errors into distinct causes that can corrupt path integration computations. We show that, across age groups, the dominant error source is unbiased noise that accumulates with travel distance not elapsed time, suggesting that the noise originates in the velocity input rather than within the integrator. Age-related declines are primarily traced to a growth in this noise. These findings shed light on the contributors to path integration error and the mechanisms underlying age-related navigational deficits.