Path integration ability in humans: establishing a new diagnostic tool

Spatial navigation is more difficult and effortful for older than younger individuals, a shift which occurs for a variety of neurological, physical, and cognitive reasons associated with aging. Despite a large body of evidence documenting age-related deficits in spatial navigation, comparatively less research addresses how to facilitate more effective navigation behavior for older adults. Since navigation challenges arise for a variety of reasons in old age, a one-size-fits-all solution is unlikely to work. Here, we introduce a framework for the variety of spatial navigation challenges faced in aging, which we call LOST-Location, Orientation, Spatial mapping, and Transit. The LOST framework builds on evidence from the cognitive neuroscience of spatial navigation, which reveals distinct components underpinning human wayfinding. We evaluate research on navigational aids-devices and depictions-which help people find their way around; and we reflect on how navigation aids solve (or fail to solve) specific wayfinding difficulties faced by older adults. In summary, we emphasize a bespoke approach to improving spatial navigation in aging, which focuses on tailoring navigation solutions to specific navigation challenges. Our hope is that by providing precise support to older navigators, navigation opportunities can facilitate independence and exploration, while minimizing the danger of becoming lost. We conclude by delineating critical knowledge gaps in how to improve older adults' spatial navigation capacities that the novel LOST framework could guide to address. This article is categorized under: Psychology > Development and Aging Neuroscience > Cognition Neuroscience > Behavior.

Critical periods for alcohol-induced deficits in spatial navigation and passive avoidance learning were investigated with a rat model of fetal alcohol syndrome. Rats were exposed to alcohol prenatally (Gestational Days 1-10 or 11-22) or postnatally (Postnatal Days 2-10) or throughout all 3 periods. Offspring were tested in either a spatial navigation or an avoidance task as juveniles or adults. As juveniles, the combined exposure group took longer to learn the spatial navigation task compared with all other groups. This effect was not seen in adults. Passive avoidance performance was not affected. These results suggest that long-term exposure to alcohol during development has adverse effects on spatial learning. The lack of differences in the short-term exposure groups implies that there may not be 1 critical period of alcohol exposure, but that the adverse effects of alcohol during development may be cumulative on some behaviors.

BackgroundThe entorhinal cortex (EC) contains spatially modulated cells, so called grid cells, and plays a central role in spatial navigation. Studies show that tauopathy in the EC is already observed in the early stages of Alzheimer's disease (AD) and is responsible for impairments in spatial memory performance. Moreover, recent studies demonstrate that young, healthy volunteers with the APOE‐ε4‐allele, a genetic risk factor for AD, show impaired grid‐like representations in the EC and reduced path integration performance in environments without spatial cues. People with subjective cognitive decline (SCD) perceive a subjective deterioration in their cognitive memory performance with unimpaired performance on standardized neuropsychological tests. SCD corresponds to the recently defined stage 2 of AD and is also a risk factor for dementia. Here, we tested whether subjects with SCD show path integration impairment, presumably related to malfunctioning in the EC.Method68 participants (31 SCD patients recruited through a memory clinic, age: 68.8 ± 9.2; 37 controls without SCD, age: 69.1 ± 7.9) performed a path integration task on a laptop. In addition, a neuropsychological test (CERAD+) was carried out to rule out an objective cognitive impairment.ResultThe two groups did not differ in age, sex, medical history and number of educational years. We replicated previous findings indicating better path integration performance with spatial cues such as boundaries and landmarks (F(2,128) = 20.83, P < 0.001). In addition, we showed that women performed worse than men (F(1,64) = 6.00, P = 0.017) and that path integration performance declined with increasing age (F(1,64) = 32.14, P < 0.001). There was no significant difference in performance between SCD and controls (F(1,64) = 2.20, P = 0.143).ConclusionGenerally, SCD was not associated with lower path integration performance. We are in the process of characterizing the sample based on plasma amyloid beta 42/40, NFL, pTau and APOE genotype to test, if AD biomarkers and genetic risk factors are associated with path integration performance.

Spatial navigation testing discriminates two types of amnestic mild cognitive impairment

Alzheimer’s disease (AD), as the most common form of dementia and leading cause for disability and death in old age, represents a major burden to healthcare systems worldwide. For the development of disease-modifying interventions and treatments, the detection of cognitive changes at the earliest disease stages is crucial. Recent advancements in mobile consumer technologies provide new opportunities to collect multi-dimensional data in real-life settings to identify and monitor at-risk individuals. Based on evidence showing that deficits in spatial navigation are a common hallmark of dementia, we assessed whether a memory clinic sample of patients with subjective cognitive decline (SCD) who still scored normally on neuropsychological assessments show differences in smartphone-assisted wayfinding behavior compared with cognitively healthy older and younger adults. Guided by a mobile application, participants had to find locations along a short route on the medical campus of the Magdeburg university. We show that performance measures that were extracted from GPS and user input data distinguish between the groups. In particular, the number of orientation stops was predictive of the SCD status in older participants. Our data suggest that subtle cognitive changes in patients with SCD, whose risk to develop dementia in the future is elevated, can be inferred from smartphone data, collected during a brief wayfinding task in the real world.

Prenatal cocaine effects on fear conditioning:: Exaggeration of sex-dependent context extinction

BackgroundPath integration spatial navigation processes are emerging as promising cognitive biomarkers for prodromal and clinical Alzheimer’s disease (AD). However, such path integration changes have been little explored in Vascular Cognitive Impairment (VCI),despite neurovascular change being a major contributing factor to dementia and potentially AD. In particular, the sensitivity and specificity of path integration impairments in VCI compared to AD is unclear. In the current pilot study, we explore path integration performance in AD and VCI patient groups and hypothesise that i) medial parietal mediated egocentric processes will be more affected in VCI and ii) medial temporal mediated allocentric processes will be more affected in AD.MethodThe cross‐sectional study included early stage VCI patients (n=9), AD patients (n=10) and healthy age‐matched controls (n=20). All participants underwent extensive neuropsychological testing, as well as spatial navigation testing. The spatial navigation tests included the virtual reality ‘Supermarket’ task assessing egocentric (body‐based) and allocentric (map‐based) navigation as well as the ‘Clock Orientation’ test assessing egocentric and path integration processes.ResultFindings showed that egocentric path integration processes are only impaired in VCI, potentially distinguishing it from AD. Whereas, allocentric path integration was similarly impaired for VCI and AD. Egocentric scores of Supermarket and Clock Orientation predictors explained 77% (Nagelkerke R 2 ) of variance in VCI and AD patients and correctly classified 84% of patients (7 out of 9 VCI; 9 out of 10 AD) into their respective cohorts. ROC curves were computed and similarly, Area Under the Curve (AUC) values indicated that egocentric orientation in the Supermarket (AUC = .8, SE = .12; 95% CI [.56, 1]) and Clock test (AUC= .91, SE = .06, 95% CI [.8, 1]) had strong diagnostic accuracy in distinguishing VCI from AD patients.ConclusionThese preliminary findings suggest egocentric path integration deficits emerge as more specific to VCI, potentially allowing for more specific diagnostic and treatment outcome measures for vascular impairment in dementia. By contrast, there was limited specificity of allocentric path integration deficits between VCI and AD.

Hexadirectional Modulation of High-Frequency Electrophysiological Activity in the Human Anterior Medial Temporal Lobe Maps Visual Space

The hippocampus, which is deeply involved in episodic memory, plays a pivotal role in spatial navigation, an essential animal behavior. Spatial navigation requires the calculation of the distance and direction from a current to the final position, i.e., a vector to a goal. Place cells in the mammalian hippocampus maximally increase their firing rates when the animal passes a particular location and then encode the animal's current location. The entorhinal cortex, one synapse upstream of the hippocampus, contains both grid and head direction cells that encode distance and direction information, respectively. However, the question of whether the hippocampus generates a vector for goal-directed navigation during the integration of distance and direction to the destination remains unclear. Mounting evidence of the cell types involved in spatial navigation has been obtained mainly in mammalian model animals such as rats and mice. Recent advances in wireless and miniaturized neural activity monitoring devices have begun to yield results not only in model organisms but also in wild mammals, birds, fish, and insects. A scrutiny of the literature examining neural correlates of spatial navigation across multiple animal species reveals that few place cells or grid cells have been found, but that head direction cells are commonly present in multiple animal species. Exceptionally, rodent-like place cells were only found in the medial pallium of tufted titmice, a food-caching bird. The medial pallium is an avian brain region homologous to the mammalian hippocampus. By contrast, rodent-like head direction cells are found in the medial pallium of quails. Head direction cells are also found in the medial pallium of streaked shearwaters, a migratory bird. The avian hippocampus contains information about the animal's current location or direction, but the neural encoding may differ depending on the ecological characteristics of the bird species. The place cells of bats, which are mammals, fly in three-dimensional space and encode vectorial information toward the goal. Training rats with an ingenious task that required them to choose a direction for each run in a maze suggested that place cells encode a vector for goal-directed spatial navigation. Thus, the scrutiny of the literature on spatial navigation-related neuronal activity across multiple animal species suggests that depending on a combination of external conditions such as the context in which the animal is situated (e.g., the context or the framework composed of landmarks in the environment) and internal conditions such as the ecological and behavioral characteristics of the animal, hippocampal neurons can be identified as place cells or head direction cells. We thus propose a conjecture that primitively, the hippocampus, or its homolog, contains information about the travel direction and that the emergence of the hippocampus during evolution has enabled the generation of vector information to the goal for advanced spatial navigation such as the search for the shortcut path and episodic memory capacity.

Transient Deregulation of Canonical Wnt Signaling in Developing Pyramidal Neurons Leads to Dendritic Defects and Impaired Behavior

P34. I slipped – Did it slip my mind? Cognitive deficits in patients with a peripheral vestibular disorder

This review delves into the entorhinal cortex (EC) as a central player in the pathogenesis of Alzheimer's Disease (AD), emphasizing its role in the accumulation and propagation of tau pathology. It elucidates the multifaceted functions of the EC, encompassing memory formation, spatial navigation, and olfactory processing, while exploring how disruptions in these processes contribute to cognitive decline in AD. The review discusses the intricate interplay between tau pathology and EC vulnerability, highlighting how alterations in neuronal firing patterns and synaptic function within the EC exacerbate cognitive impairments. Furthermore, it elucidates how specific neuronal subtypes within the EC exhibit differential susceptibility to tau-induced damage, contributing to disease progression. Early detection methods, such as imaging techniques and assessments of EC blood flow, are examined as potential tools for identifying tau pathology in the preclinical stages of AD. These approaches offer promise for improving diagnostic accuracy and enabling timely intervention. Therapeutic strategies targeting tau pathology within the EC are explored, including the clearance of pathological tau aggregates and the inhibition of tau aggregation processes. By understanding the molecular and cellular mechanisms underlying EC vulnerability, researchers can develop more targeted and effective interventions to slow disease progression. The review underscores the importance of reliable biomarkers to assess disease progression and therapeutic efficacy in clinical trials targeting the EC. Ultimately, it aims to contribute to the development of more effective management strategies for AD, emphasizing the translation of research findings into clinical practice to address the growing societal burden of the disease.

Which facets of human spatial navigation do sex and menstrual cycle influence? To answer this question, a cross-sectional online study of reproductive age women and men was conducted in which participants were asked to demonstrate and self-report their spatial navigation skills and strategies. Participants self-reported their sex and current menstrual phase [early follicular (EF), late follicular/periovulatory (PO), and mid/late luteal (ML)], and completed a series of questionnaires and tasks measuring self-reported navigation strategy use, topographical memory, cognitive map formation, face recognition, and path integration. We found that sex influenced self-reported use of cognitive map- and scene-based strategies, face recognition, and path integration. Menstrual phase moderated the influence of sex: compared to men, women had better face recognition and worse path integration, but only during the PO phase; PO women were also better at path integration in the presence of a landmark compared to EF + ML women and men. These findings provide evidence that human spatial navigation varies with the menstrual cycle and suggest that sensitivity of the entorhinal cortex and longitudinal axis of the hippocampus to differential hormonal effects may account for this variation.

Many studies have focused on navigation, spatial skills, and the olfactory system in comparative models, including those concerning the relationship between them and physical activity. Although the results are often in contrast with each other, it is assumed that physical activity can affect cognition in different ways—both indirectly and through a certain influence on some brain structures. In contrast, there is little research that focuses on the relationship between spatial abilities and olfactory abilities in humans. This research aimed to evaluate and compare the performance in working memory tasks of athletes and non-athletes who require good visual–spatial navigation, olfactory–spatial navigation, and olfactory–semantic skills. The study involved 236 participants (83 athletes) between the ages of 18 and 40. All subjects were matched by age or sex. The standard Corsi Block Tapping Test (CBTT) was administrated to investigate the visual-spatial memory. Olfactory–spatial navigation and olfactory–semantic skills were assessed with two modified versions of CBTT: Olfactory CBTT (OCBTT) and Semantic–Olfactory CBTT (SOCBTT) respectively. The results show differences between the CORSI conditions in direction of a poor performance for athletes. A gender effect in favor of men was also found, particularly in the classic version of the CBTT. Both groups performed better in the classic version of the CBTT than OCBTT and SOCBTT. The mean of SOCBTT results is markedly lower, perhaps due to the different information processing systems needed to perform this kind of task. It is possible to explain how sports practice can affect tasks that require spatial skills and olfactory perception differently, thus supporting new hypotheses and opening new scientific horizons.

BackgroundCompromised object‐based spatial navigation and spatio‐cognitive map navigation are critical early indicators of Alzheimer's Disease. Distinct neural processes, such as the interaction between posterior parietal cortices and lateral entorhinal cortex, are significant for egocentric object‐based processing, while the retrosplenial cortex (RSC) and hippocampus interaction is important for allocentric map processing. Identifying the mechanisms underlying cognitive impairment can help engage dysfunctional circuits and improve rehabilitation through closed‐loop stimulation paradigms. In this study, we explore these circuits with a passive cognitive task that evaluates cortical energy distribution and increases working memory load, while participants navigate in real‐world settings. We hypothesize that ego‐ versus allocentric navigation performance decline under high memory load may reveal early damage in relevant circuits, which could serve as clinical markers.MethodParticipants navigated five standardized paths with varying stress loads (high and low) while performing a Digit Numbering Task (DNT). An auditory mismatch negativity paradigm was also used to assess cortical energy distribution. Behavioral data were collected with electroencephalography for N = 24 (age>55, 14 males, MCI=12) subjects, screened as control or MCI using the Mini‐Mental State Exam.ResultsA significant difference was observed in DNT accuracy between groups (control: 68.9±38.8, MCI=52.3±42.1, p = 0.04*). No significant differences were found between the two groups for egocentric or allocentric performance across working memory loads. However, allocentric performance was significantly worse in MCI (67.14±54.47, 88.96±53.23, p = 0.0013**). The energy factor, measured as the difference in cortical potentials for deviant and standard trials, was higher for MCI in the parietal region (mu for control= ‐1.016, MCI= ‐2.34 microV, p = 0.0036).ConclusionThe poorer allocentric performance in MCI suggests RSC involvement, offering a potential biomarker for closed‐loop stimulation. Additionally, the increased energy factor observed in the parietal area may indicate compensatory mechanisms in MCI or inefficient resource management. Future work will validate these findings using high‐resolution source localization methodologies.