Spatial Navigation Deficits Research Articles

Identifying older adults at risk for dementia based on smartphone data obtained during a wayfinding task in the real world.

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.

Reelin differentially shapes dendrite morphology of medial entorhinal cortical ocean and island cells.

The function of medial entorhinal cortex layer II (MECII) excitatory neurons has been recently explored. MECII dysfunction underlies deficits in spatial navigation and working memory. MECII neurons comprise two major excitatory neuronal populations, pyramidal island and stellate ocean cells, in addition to the inhibitory interneurons. Ocean cells express reelin and surround clusters of island cells that lack reelin expression. The influence of reelin expression by ocean cells and interneurons on their own morphological differentiation and that of MECII island cells has remained unknown. To address this, we used a conditional reelin knockout (RelncKO) mouse to induce reelin deficiency postnatally in vitro and in vivo. Reelin deficiency caused dendritic hypertrophy of ocean cells, interneurons and only proximal dendritic compartments of island cells. Ca2+ recording showed that both cell types exhibited an elevation of calcium frequencies in RelncKO, indicating that the hypertrophic effect is related to excessive Ca2+ signalling. Moreover, pharmacological receptor blockade in RelncKO mouse revealed malfunctioning of GABAB, NMDA and AMPA receptors. Collectively, this study emphasizes the significance of reelin in neuronal growth, and its absence results in dendrite hypertrophy of MECII neurons.

Rescuing impaired hippocampal-cortical interactions and spatial reorientation learning and memory during sleep in a mouse model of Alzheimer's disease using hippocampal 40 Hz stimulation.

One of the earliest symptoms of Alzheimer's disease (AD) is getting lost in space or experiencing deficits in spatial navigation, which involve navigation computations as well as learning and memory. We investigated cross brain region interactions supporting memory formation as a potential causative factor of impaired spatial learning and memory in AD. To assess this relationship between AD pathophysiology, brain changes, and behavioral alterations, we used a targeted approach for clearing amyloid beta and tau to rescue functional interactions in the brain. This research strongly connects brain activity patterns during sleep to tau and amyloid accumulation, and will aid in understanding the mechanisms underlying cognitive dysfunction in AD. Furthermore, the results offer insight for improving early identification and treatment strategies.

Behavioral Disorders of Spatial Cognition in Patients with Mild Cognitive Impairment Due to Alzheimer's Disease (The BDSC-MCI Project): Ecological Validity of the Corsi Learning Suvra-Span Test.

Spatial navigation deficits are reported as early symptoms of Alzheimer's disease (AD) alongside episodic memory ones. The aim of the present study was to ascertain whether neuropsychological deficits of visuospatial long-term memory can predict behavioral alterations during the navigation of older adults in novel urban environments along the normal aging-dementia continuum of the Alzheimer's type. A total of 24 community-dwelling patients with Mild Cognitive Impairment (MCI) due to AD, 27 individuals with subjective cognitive decline (SCD), and 21 healthy controls were assessed in terms of their sequential egocentric and allocentric navigation abilities by using a modified version of the Detour Navigation Test, and neuropsychologically tested by the Corsi learning suvra-span (CLSS) test. Generalized linear models were adopted to verify whether the scores obtained by the three groups in the CLSS test predicted wrong turns and moments of hesitation during the navigation task, with the results presented as topographical disorientation scores. Higher scores in the CLSS test predicted fewer wrong turns (b = -0.05; z = -2.91; p = 0.004; net of between-groups differences) and moments of hesitation for patients with MCI due to AD (b = -0.14; z = -2.43; p = 0.015), and individuals with SCD (b = -0.17; z = -3.85; p < 0.001). Since the CLSS test has been reported to be a reliable measure of ecological navigational abilities in the progression towards AD dementia, we recommend its use in clinical practice and highlight implications for future research.

Age differences in spatial memory are mitigated during naturalistic navigation.

Spatial navigation deficits are often observed among older adults on tasks that require navigating virtual reality (VR) environments on a computer screen. We investigated whether these age differences are attenuated when tested in more naturalistic and ambulatory virtual environments. In Experiment 1, young and older adults navigated a variant of the Morris Water Maze task in each of two VR conditions: a desktop VR condition which required using a mouse and keyboard to navigate, and an ambulatory VR condition which permitted unrestricted locomotion. In Experiment 2, we examined whether age- and VR-related differences in spatial performance were affected by the inclusion of additional spatial cues. In both experiments, older adults navigated to target locations less precisely than younger individuals in the desktop condition. Age differences were significantly attenuated, however, when tested in the ambulatory VR environment. These findings underscore the importance of developing naturalistic assessments of spatial memory and navigation.

Geospatial environmental complexity, spatial brain volume, and spatial behavior across the Alzheimer's disease spectrum.

Understanding impact of environmental properties on Alzheimer's disease (AD) is paramount. Spatial complexity of one's routinely navigated environment is an important but understudied factor. A total of 660 older adults from National Alzheimer's Coordinating Center (NACC) dataset were geolocated and environmental complexity index derived from geospatial network landmarks and points-of-interest. Latent models tested mediation of spatial navigation-relevant brain volumes and diagnosis (cognitively-healthy, mild cognitive impairment [MCI], AD) on effect of environmental complexity on spatial behavior. Greater environmental complexity was selectively associated with larger allocentric (but not egocentric) navigation-related brain volumes, lesser diagnosis of MCI and AD, and better spatial behavioral performance, through indirect hierarchical mediation. Findings support hypothesis that spatially complex environments positively impact navigation neural circuitry and spatial behavior function. Given the vulnerability of these very circuits to AD pathology, residing in spatially complex environments may be one factor to help stave off the brain atrophy that accompanies spatial navigation deficits across the AD spectrum.

Spatial navigation performance differentiates Alzheimer´s disease biomarker positive and biomarker negative cognitively impaired older adults

AbstractBackgroundSpatial navigation deficits including egocentric (body‐centered) and allocentric (world‐centered) navigation impairment are present early in Alzheimer´s disease (AD). We evaluated a potential of a realistic‐looking spatial navigation task to differentiate older adults with amnestic mild cognitive impairment (aMCI) who have positive AD biomarkers (AD aMCI) from those with negative AD biomarkers (non‐AD aMCI).MethodParticipants with AD aMCI (n = 24), non‐AD aMCI (n = 25), mild AD dementia (n = 14) and cognitively normal (CN) older adults (n = 35) underwent spatial navigation assessment in the virtual Supermarket task. Participants passively travelled through the supermarket and followed different routes to reach specific locations. In the final location, the participants had to indicate their starting location (egocentric heading) and their current location and final heading orientation on an aerial spatial map of the supermarket (distance from the correct location and allocentric heading, respectively, both measures of allocentric navigation).ResultIn the egocentric heading, the AD aMCI and mild AD dementia groups indicated their original starting location less accurately than the CN group (p&lt;0.001) and with similar accuracy as the non‐AD aMCI group (p&gt; = 0.219). The non‐AD aMCI group did not significantly differ from the CN group (p = 0.055). In the first allocentric task (distance from the correct location), the AD aMCI group and mild AD dementia groups indicated their positions on a paper aerial map of the supermarket with greater distance errors compared to the non‐AD aMCI group (p&lt; = 0.013) and CN (p&lt;0.001) groups. The non‐AD aMCI group had comparable performance to the CN group (p = 0.172). In the second allocentric task (allocentric heading), both the AD aMCI and mild AD dementia groups made more errors indicating final heading orientation than the non‐AD aMCI (p&lt; = 0.040) and the CN (p&lt;0.001) groups. The non‐AD aMCI group had worse performance than the CN group (p = 0.004). The sensitivity and specificity for discriminating AD aMCI and non‐AD aMCI was 72% and 71%, respectively.ConclusionBoth, egocentric and allocentric spatial navigation tasks detected spatial navigation impairment in older adults with AD aMCI. However, only the allocentric tasks differentiated AD aMCI from non‐AD aMCI. The virtual Supermarket task has a potential to become a screening tool for early AD‐related spatial navigation deficits.

Transcranial direct current stimulation of the right temporoparietal junction facilitates hippocampal spatial learning in Alzheimer’s disease and mild cognitive impairment

ObjectiveSpatial memory deficits are an early symptom in Alzheimer’s disease (AD), reflecting the neurodegenerative processes in the neuronal navigation network such as in hippocampal and parietal cortical areas. As no effective treatment options are available, neuromodulatory interventions are increasingly evaluated. Against this backdrop, we investigated the neuromodulatory effect of anodal transcranial direct current stimulation (tDCS) on hippocampal place learning in patients with AD or mild cognitive impairment (MCI). MethodsIn this randomized, double-blind, sham-controlled study with a cross-over design anodal tDCS of the right temporoparietal junction (2 mA for 20 minutes) was applied to 20 patients diagnosed with AD or MCI and in 22 healthy controls while they performed a virtual navigation paradigm testing hippocampal place learning. ResultsWe show an improved recall performance of hippocampal place learning after anodal tDCS in the patient group compared to sham stimulation but not in the control group. ConclusionsThese results suggest that tDCS can facilitate spatial memory consolidation via stimulating the parietal-hippocampal navigation network in AD and MCI patients. SignificanceOur findings suggest that tDCS of the temporoparietal junction may restore spatial navigation and memory deficits in patients with AD and MCI.

Multisensory input modulates memory-guided spatial navigation in humans

Efficient navigation is supported by a cognitive map of space. The hippocampus plays a key role for this map by linking multimodal sensory information with spatial memory representations. However, in human navigation studies, the full range of sensory information is often unavailable due to the stationarity of experimental setups. We investigated the contribution of multisensory information to memory-guided spatial navigation by presenting a virtual version of the Morris water maze on a screen and in an immersive mobile virtual reality setup. Patients with hippocampal lesions and matched controls navigated to memorized object locations in relation to surrounding landmarks. Our results show that availability of multisensory input improves memory-guided spatial navigation in both groups. It has distinct effects on navigational behaviour, with greater improvement in spatial memory performance in patients. We conclude that congruent multisensory information shifts computations to extrahippocampal areas that support spatial navigation and compensates for spatial navigation deficits.

Getting LOST: A conceptual framework for supporting and enhancing spatial navigation in aging.

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.

Unraveling the Twist: Spatial Navigational Challenges in Cervical Dystonia.

Cervical dystonia (CD) is an intricate neurological condition with motor and nonmotor symptoms. These include disruptions in visual perception, self-orientation, visual working memory, and vestibular functions. However, the specific impact of CD on perceiving self-motion direction, especially with isolated visual or vestibular stimuli, remains largely unexplored. This study aimed to examine the effects of CD on linear motion perception, hypothesizing impaired heading discrimination in both vestibular and visual tasks, and that such deficits correlate with the disease severity. We employed a cutting-edge motion platform to precisely control whole-body linear motion. Through repeated two-alternative forced-choice tasks, we assessed vestibular heading direction discrimination. Participants observed dynamic star clouds in immersive virtual reality and indicated their perceived self-motion direction, evaluating visual heading direction discrimination. Sensitivity to direction variations and response accuracy errors were analyzed using robust Gaussian cumulative distribution psychometric functions. Heading perception is impaired in individuals with CD, particularly evident in vestibular heading discrimination. CD severity correlated with elevated thresholds for both vestibular and visual heading discrimination. Surprisingly, lateralized CD did not introduce bias in either system, suggesting widespread disruption over localized effects. Contrary to previous beliefs, our findings challenge the idea that CD-related heading discrimination issues mainly arise from peripheral vestibular effects. Instead, abnormal proprioceptive input from dystonic neck muscles introduces noise into the central mechanism integrating visual, vestibular, and proprioceptive signals. These insights into spatial navigation deficits have implications for future CD research. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Search Strategy Analysis of 5xFAD Alzheimer Mice in the Morris Water Maze Reveals Sex- and Age-Specific Spatial Navigation Deficits

Spatial disorientation and navigational impairments are not only some of the first memory deficits in Alzheimer's disease, but are also very disease-specific. In rodents, the Morris Water Maze is used to investigate spatial navigation and memory. Here, we examined the spatial memory in the commonly used 5xFAD Alzheimer mouse model in a sex- and age-dependent manner. Our findings show first spatial learning deficits in 7-month-old female 5xFAD and 12-month-old male 5xFAD mice, respectively. While the assessment of spatial working memory using escape latencies provides a global picture of memory performance, it does not explain how an animal solves a spatial task. Therefore, a detailed analysis of swimming strategies was performed to better understand the behavioral differences between 5xFAD and WT mice. 5xFAD mice used a qualitatively and quantitatively different search strategy pattern than wildtype animals that used more non-spatial strategies and showed allocentric-specific memory deficits. Furthermore, a detailed analysis of swimming strategies revealed allocentric memory deficits in the probe trial in female 3-month-old and male 7-month-old 5xFAD animals before the onset of severe reference memory deficits. Overall, we could demonstrate that spatial navigation deficits in 5xFAD mice are age- and sex-dependent, with female mice being more severely affected. In addition, the implementation of a search strategy classification system allowed an earlier detection of behavioral differences and therefore could be a powerful tool for preclinical drug testing in the 5xFAD model.

Utility of Environmental Complexity as a Predictor of Alzheimer’s Disease Diagnosis: A Big-Data Machine Learning Approach

BackgroundRural-urban differences and spatial navigation deficits have received much attention in Alzheimer’s Disease research. While individual environmental and neighborhood factors have been independently investigated, their integrative, multifactorial effects on Alzheimer’s diagnosis have not. Here we explore this “environmental complexity” for predictive power in classifying Alzheimer’s from cognitively-normal status.MethodsWe utilized data from the National Alzheimer’s Coordinating Center (NACC) uniform data set containing annual visits since 2005 and selected individuals with multiple visits and who remained in their zipcode (N = 22,553). We georeferenced each subject with 3-digit zipcodes of their residences since entering the program. We calculated environmental complexity measures using geospatial tools from street networks and landmarks for spatial navigation in subjects’ zipcode zones. Zipcode zones were grouped into two cognitive classes (Cognitively-Normal and Alzheimer’s-inclined) based on the ratios of AD and dementia subjects to all subjects in an individual zipcode zone. We randomly selected 80% of the data to train a neural network classifier model on environmental complexity measures to predict the cognitive class for each zone, controlling for salient demographic variables. The remaining 20% served as the test set for performance evaluation.ResultsOur proposed model reached excellent classification ability on the testing data: 83.87% accuracy, 95.23% precision, 83.33% recall, and 0.8889 F1-score (F1-score=1 for perfect prediction). The most salient features of “Alzheimer’s-inclined” zipcode zones included longer street-length average, higher circuity, and slightly fewer points of interest. Most “cognitively-normal” zipcode zones appeared in or near urban areas with high environmental complexity measures.ConclusionEnvironmental complexity, reflected in frequency and density of street networks and landmarks features, predicted with high precision the cognitive status of 3-digit zipcode zones based on the etiologic diagnoses and observed cognitive impairment of NACC subjects residing in these zones. The zipcode zones vary widely in size (1.6 km2 to 35,241 km2), and large zipcode zones suffer high spatial heterogeneity. Other proven AD risk factors, such as PM2.5, disperse across zones, and so do individual’s activities, leading to spatial uncertainty. Nevertheless, the model classifies diagnosis well, establishing the need for prospective experiments to quantify effects of environmental complexity on Alzheimer’s development.

Spatial memory deficits in Alzheimer's disease and their connection to cognitive maps' formation by place cells and grid cells.

Whenever we navigate through different contexts, we build a cognitive map: an internal representation of the territory. Spatial navigation is a complex skill that involves multiple types of information processing and integration. Place cells and grid cells, collectively with other hippocampal and medial entorhinal cortex neurons (MEC), form a neural network whose activity is critical for the representation of self-position and orientation along with spatial memory retrieval. Furthermore, this activity generates new representations adapting to changes in the environment. Though there is a normal decline in spatial memory related to aging, this is dramatically increased in pathological conditions such as Alzheimer's disease (AD). AD is a multi-factorial neurodegenerative disorder affecting mainly the hippocampus-entorhinal cortex (HP-EC) circuit. Consequently, the initial stages of the disease have disorientation and wandering behavior as two of its hallmarks. Recent electrophysiological studies have linked spatial memory deficits to difficulties in spatial information encoding. Here we will discuss map impairment and remapping disruption in the HP-EC network, as a possible circuit mechanism involved in the spatial memory and navigation deficits observed in AD, pointing out the benefits of virtual reality as a tool for early diagnosis and rehabilitation.

A cortico-collicular circuit for orienting to shelter during escape.

When faced with predatory threats, escape towards shelter is an adaptive action that offers long-term protection against the attacker. Animals rely on knowledge of safe locations in the environment to instinctively execute rapid shelter-directed escape actions1,2. Although previous work has identified neural mechanisms of escape initiation3,4, it is not known how the escape circuit incorporates spatial information to execute rapid flights along the most efficient route to shelter. Here we show that themouse retrosplenial cortex (RSP) and superior colliculus (SC) form a circuit that encodes the shelter-direction vector and is specifically required for accurately orienting to shelter during escape. Shelter direction is encoded in RSP and SC neurons in egocentric coordinates and SC shelter-direction tuning depends on RSP activity. Inactivation of the RSP-SC pathway disrupts the orientation to shelter and causes escapes away from the optimal shelter-directed route, but does not lead to generic deficits in orientation or spatial navigation. We find that the RSP and SC are monosynaptically connected and form a feedforward lateral inhibition microcircuit that strongly drives the inhibitory collicular network because of higher RSP input convergence and synaptic integration efficiency in inhibitory SC neurons. This results in broad shelter-direction tuning in inhibitory SC neurons and sharply tuned excitatory SC neurons. These findings are recapitulated by a biologically constrained spiking network model in which RSP input to the local SC recurrent ring architecture generates a circular shelter-direction map. We propose that this RSP-SC circuit might be specialized for generating collicular representations of memorized spatial goals that are readily accessible to the motor system during escape, or more broadly, during navigation when the goal must be reached as fast as possible.

Intuitive assessment of spatial navigation beyond episodic memory: Feasibility and proof of concept in middle-aged and elderly individuals.

Deficits in spatial navigation in three-dimensional space are prevalent in various neurological disorders and are a sensitive cognitive marker for prodromal Alzheimer's disease, but are also associated with non-pathological aging. However, standard neuropsychological tests used in clinical settings lack ecological validity to adequately assess spatial navigation. Experimental paradigms, on the other hand, are often too difficult for seniors or patients with cognitive or motor impairments since most require operating a human interface device (HID) or use complex episodic memory tasks. Here, we introduce an intuitive navigation assessment, which is conceptualized using cognitive models of spatial navigation and designed to account for the limited technical experience and diverging impairments of elderly participants and neurological patients. The brief computer paradigm uses videos of hallways filmed with eye tracking glasses, without employing an episodic memory task or requiring participants to operate a HID. Proof of concept data from 34 healthy, middle-aged and elderly participants (56-78 years) provide evidence for the assessment's feasibility and construct validity as a navigation paradigm. Test performance showed normal distribution and was sensitive to age and education, which needs to be considered when investigating the assessment's psychometric properties in larger samples and clinical populations. Correlations of the navigation assessment with other neuropsychological tests confirmed its dependence on visuospatial skills rather than visual episodic memory, with age driving the association with working memory. The novel paradigm is suitable for a differentiated investigation of spatial navigation in elderly individuals and promising for experimental research in clinical settings.

Different Profiles of Spatial Navigation Deficits In Alzheimer's Disease Biomarker-Positive Versus Biomarker-Negative Older Adults With Amnestic Mild Cognitive Impairment.

BackgroundSpatial navigation impairment is a promising cognitive marker of Alzheimer’s disease (AD) that can reflect the underlying pathology.ObjectivesWe assessed spatial navigation performance in AD biomarker positive older adults with amnestic mild cognitive impairment (AD aMCI) vs. those AD biomarker negative (non-AD aMCI), and examined associations between navigation performance, MRI measures of brain atrophy, and cerebrospinal fluid (CSF) biomarkers.MethodsA total of 122 participants with AD aMCI (n = 33), non-AD aMCI (n = 31), mild AD dementia (n = 28), and 30 cognitively normal older adults (CN) underwent cognitive assessment, brain MRI (n = 100 had high-quality images for volumetric analysis) and three virtual navigation tasks focused on route learning (body-centered navigation), wayfinding (world-centered navigation) and perspective taking/wayfinding. Cognitively impaired participants underwent CSF biomarker assessment [amyloid-β1–42, total tau, and phosphorylated tau181 (p-tau181)] and amyloid PET imaging (n = 47 and n = 45, respectively), with a subset having both (n = 19).ResultsIn route learning, AD aMCI performed worse than non-AD aMCI (p < 0.001), who performed similarly to CN. In wayfinding, aMCI participants performed worse than CN (both p ≤ 0.009) and AD aMCI performed worse than non-AD aMCI in the second task session (p = 0.032). In perspective taking/wayfinding, aMCI participants performed worse than CN (both p ≤ 0.001). AD aMCI and non-AD aMCI did not differ in conventional cognitive tests. Route learning was associated with parietal thickness and amyloid-β1–42, wayfinding was associated with posterior medial temporal lobe (MTL) volume and p-tau181 and perspective taking/wayfinding was correlated with MRI measures of several brain regions and all CSF biomarkers.ConclusionAD biomarker positive and negative older adults with aMCI had different profiles of spatial navigation deficits that were associated with posterior MTL and parietal atrophy and reflected AD pathology.

Search strategy analysis of Tg4-42 Alzheimer Mice in the Morris Water Maze reveals early spatial navigation deficits

Spatial disorientation is one of the earliest symptoms in Alzheimer’s disease and allocentric deficits can already be detected in the asymptomatic preclinical stages of the disease. The Morris Water Maze (MWM) is used to study spatial learning in rodent models. Here we investigated the spatial memory of female 3, 7 and 12 month-old Alzheimer Tg4-42 mice in comparison to wild-type control animals. Conventional behavior analysis of escape latencies and quadrant preference revealed spatial memory and reference memory deficits in female 7 and 12 month-old Tg4-42 mice. In contrast, conventional analysis of the MWM indicated an intact spatial memory in 3 month-old Tg4-42 mice. However, a detailed analysis of the swimming strategies demonstrated allocentric-specific memory deficits in 3 month-old Tg4-42 mice before the onset of severe memory deficits. Furthermore, we could show that the spatial reference memory deficits in aged Tg4-42 animals are caused by the lack of allocentric and spatial strategies. Analyzing search strategies in the MWM allows to differentiate between hippocampus-dependent allocentric and hippocampus-independent egocentric search strategies. The spatial navigation impairments in young Tg4-42 mice are well in line with the hypometabolism and synaptic deficits in the hippocampus. Therefore, analyzing search strategies in the Tg4-42 model can be a powerful tool for preclinical drug testing and identifying early therapeutic successes.

Different strategies in pointing tasks and their impact on clinical bedside tests of spatial orientation

Deficits in spatial memory, orientation, and navigation are often early or neglected signs of degenerative and vestibular neurological disorders. A simple and reliable bedside test of these functions would be extremely relevant for diagnostic routine. Pointing at targets in the 3D environment is a basic well-trained common sensorimotor ability that provides a suitable measure. We here describe a smartphone-based pointing device using the built-in inertial sensors for analysis of pointing performance in azimuth and polar spatial coordinates. Interpretation of the vectors measured in this way is not trivial, since the individuals tested may use at least two different strategies: first, they may perform the task in an egocentric eye-based reference system by aligning the fingertip with the target retinotopically or second, by aligning the stretched arm and the index finger with the visual line of sight in allocentric world-based coordinates similar to using a rifle. The two strategies result in considerable differences of target coordinates. A pilot test with a further developed design of the device and an app for a standardized bedside utilization in five healthy volunteers revealed an overall mean deviation of less than 5° between the measured and the true coordinates. Future investigations of neurological patients comparing their performance before and after changes in body position (chair rotation) may allow differentiation of distinct orientational deficits in peripheral (vestibulopathy) or central (hippocampal or cortical) disorders.

An Appraisal of the Role of the Neocerebellum for Spatial Navigation in Healthy Aging

Spatial navigation is an intricate ability, requiring multisensory and motor integration, that is particularly impacted in aging. The age-related decline in navigational capabilities is known to be associated with changes in brain regions such as the frontal, temporal, and cerebellar cortices. Age-related cerebellar differences in spatial navigation have generally been ascribed to motor impairments, omitting the central role of this structure in several cognitive processes. In the present voxel-based morphometric study, we investigated gray matter volume loss in older adults across cognitive and motor subregions of the cerebellum. Specifically, we hypothesized that age-related gray matter differences would occur mainly in cerebellar regions involved in cognitive processing. Our results showed a significant age-related atrophy in the left neocerebellum of healthy older adults that includes Crus I and lobule VI. The latter are important nodes in the network that subtends cognitive abilities such as object recognition and spatial cognition. This exploratory work sets the ground for future research to investigate the extent of the neocerebellum’s contribution to spatial navigation deficits in aging.