Path Integration Changes as a Cognitive Marker for Vascular Cognitive Impairment?—A Pilot Study

Path integration spatial navigation processes are emerging as promising cognitive markers for prodromal and clinical Alzheimer’s disease (AD). However, such path integration changes have been less 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 early-stage AD and VCI patient groups and hypothesize 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. This 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. Results showed that egocentric integration processes are only impaired in VCI, potentially distinguishing it from AD. However, in contrast to our prediction, allocentric integration was not more impaired in AD compared to VCI. These preliminary findings suggest limited specificity of allocentric integration deficits between VCI and AD. By contrast, 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

Bedeutung der MRT und FDG-PET in der Exploration des Entorhinalen Kortex in Zusammenhang mit der räumlichen Orientierung bei Patienten mit leichter kognitiver Beeinträchtigung

Background: The entorhinal cortex (ERC) has become a center of growing interest since the description of ERC neurons especially encoding for spatial navigation and spatial memory. In rodents, those cells are particularly found in the medial side of the ERC. Studies in humans are limited, in particular there is no study clearly identifying the homolog of the rodent medial ERC in humans so far. Objective: Brodmann areas (BA) 34 and 28 are major components of the ERC in humans. The aim of this study was to evaluate whether BA 34 or BA 28 might be considered the homolog to the medial ERC in rodents with respect to spatial navigation abilities, and to evaluate the role of MRI and FDG-PET in the exploration of both regions in relation to spatial orientation in patients with mild cognitive impairment (MCI). Methods: Patients with MCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were included if they had the entire visuospatial (VISSPAT) ability scores of the Everyday Cognition (ECog) test as well as high-resolution T1-weighted MRI and brain FDG-PET performed within 30 days of the ECog test. Grey matter volume and FDG uptake in each of ERC Brodmann areas (BA 34 and BA 28) were calculated from MRI and FDG-PET using predefined standard masks of BA 34 and BA 28. Regression and multivariate analyses of covariance were employed for statistical analyses. Results: The eligibility criteria were fulfilled by 379 MCI patients. Amongst all studied subdomains assessed by the ECog test, only spatial navigation performance, as characterized by the self-reported VISSPAT sum score, was correlated with the integrity of BA 34 (grey matter volume but not FDG uptake). None of the ECog subscores was correlated with BA 28 integrity (neither grey matter volume nor FDG uptake). Conclusion: Impairment of orientation skills and spatial memory in MCI is more strongly associated with atrophy of BA 34 compared to BA 28, suggesting that BA 34 rather than BA 28 is the human homolog of the rodent medial ERC with respect to spatial orientation abilities. Spatial orientation performance was not associated with glucose metabolism in BA 34, presumably due to higher between-subjects variability of (partial volume-corrected) FDG uptake in BA 34 used to characterize its glucose metabolism.Hintergrund: Der entorhinale Kortex (ERC) ist seit der Beschreibung von ERC- Neuronen, die insbesondere für die räumliche Navigation und das räumliche Gedächtnis kodieren, von zunehmenden Interesse. Bei Nagetieren befinden sich diese Zellen insbesondere im medialen Teil des ERC. Studien am Menschen sind begrenzt, insbesondere gibt es bisher keine Studie, die das Homolog des medialen ERC von Nagern beim Menschen eindeutig identifiziert. Ziel: Die Brodmann-Areale (BA) 34 und 28 sind wesentliche Bestandteile des ERC bei Menschen. Das Ziel dieser Studie war es zu testen, ob BA 34 oder BA 28 in Bezug auf die räumlichen Navigationsfähigkeiten als Homolog des medialen ERC bei Nagetieren angesehen werden können, und die Bedeutung der MRT und FDG-PET für die Exploration der beiden Hirnareale bei Patienten mit leichter kognitiver Beeinträchtigung zu evaluieren. Methoden: Patienten mit leichter kognitiver Beeinträchtigung aus der Alzheimer's Disease Neuroimaging Initiative (ADNI) wurden eingeschlossen, wenn sie einen vollständigen visuellen (VISSPAT) Fähigkeitsscore des Everyday Cognition (ECog)-Tests sowie hochauflösende T1-gewichtete MRT und FDG-PET Bilder des Gehirns aufwiesen, die innerhalb von 30 Tagen nach dem ECog-Test erstellt wurden. Das Volumen der grauen Substanz und die FDG-Aufnahme in BA 34 und BA 28 wurden aus MRT und FDG-PET Bildern unter Verwendung vordefinierter Standardmasken von BA 34 und BA 28 berechnet. Für die statistische Analyse wurden Regressions- und multivariate Kovarianzanalysen eingesetzt. Ergebnisse: Die Auswahlkriterien wurden von 379 MCI-Patienten erfüllt. Von allen durch den ECog-Test bewerteten Subdomänen korrelierte nur die räumliche Navigationsleistung aus dem selbst berichteten VISSPAT- Summenscore mit der Integrität von BA 34 (Volumen der grauen Hirnsubstanz, aber nicht FDG-Aufnahme). Keiner der ECog-Subscores war mit der BA 28- Integrität korreliert (weder das Volumen der grauen Substanz noch die FDG- Aufnahme). Schlussfolgerung: Die Beeinträchtigung der Orientierungsfähigkeit und des räumlichen Gedächtnisses bei MCI ist stärker mit einer Atrophie von BA 34 im Vergleich zu BA 28 verbunden, was darauf hindeutet, dass BA 34 und nicht BA 28 das menschliche Homolog des medialen ERC von Nagetieren in Bezug auf räumliche Navigationsfähigkeiten ist. Die räumliche Navigationsleistung war nicht mit dem Glukosestoffwechsel in BA 34 korreliert, vermutlich aufgrund der höheren Variabilität der (teilweise volumenkorrigierten) FDG-Aufnahme in BA 34, die zur Charakterisierung des Glukosestoffwechsels verwendet wurde

The Aging Navigational System

The discovery of neuronal systems dedicated to computing spatial information, composed of functionally distinct cell types such as place and grid cells, combined with an extensive body of human-based behavioral and neuroimaging research has provided us with a detailed understanding of the brain's navigation circuit. In this review, we discuss emerging evidence from rodents, non-human primates, and humans that demonstrates how cognitive aging affects the navigational computations supported by these systems. Critically, we show 1) that navigational deficits cannot solely be explained by general deficits in learning and memory, 2) that there is no uniform decline across different navigational computations, and 3) that navigational deficits might be sensitive markers for impending pathological decline. Following an introduction to the mechanisms underlying spatial navigation and how they relate to general processes of learning and memory, the review discusses how aging affects the perception and integration of spatial information, the creation and storage of memory traces for spatial information, and the use of spatial information during navigational behavior. The closing section highlights the clinical potential of behavioral and neural markers of spatial navigation, with a particular emphasis on neurodegenerative disorders

Measurement of allocentric processing in mild cognitive impairment and early Alzheimer’s disease using a virtual reality object location paradigm

Aim: Mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) are major contributors to disability in old age and defined in the early stages by spatial memory deficits associated with hippocampal (HC) and entorhinal (EC) atrophy. Currently diagnosis occurs late in the process which limits efficacy of interventions. This study investigated the neural correlates of a novel object location task (OLT) in immersive virtual reality (iVR). Methods: Twenty amnestic MCI (aMCI) patients and twenty two healthy controls were tested on the iVR OLT, underwent neuropsychological testing and structural MRI scanning. OLT performance and HC, EC subfield volumetric data were compared between groups, and correlational analyses of HC/EC volumes and performance were conducted. Results: Participants with aMCI were significantly impaired in object location recall and object recognition compared to controls. They had significantly smaller total HC, subiculum, CA1, EC and perirhinal volumes. There was a significant interaction of group in analysis of neural correlates: OLT performance was strongly predicted by total HC and subiculum volumes in patients only. EC subfields were not significant predictors of performance. Conclusion: Performance on the novel OLT in immersive VR is a good indicator of HC integrity in older adults with amnestic MCI and can improve the diagnostic process for people with MCI and AD in the future

Foregrounding accessibility for user experience design

textI am interested in creating generative tools and techniques for designing accessible user experiences for end users. As a user experience designer, I am working on embracing the web accessibility standards and guidelines and including them from the beginning of the User Experience (UX) design process. My projects are directed at facilitating design students and professionals to understand two things: that the broad concept of web accessibility is important, and how they can embed web accessibility into the UX design process at a very early stage. To do this, I used different media (website, posters and videos etc.) to create awareness and educate designers in an interesting, simple and engaging way. In this report, I will discuss the definition and role of accessible design, identify limitations in existing tools and methods, and demonstrate how future designers might research, prototype, analyze, and implement their designs for all users.Desig

Behavioural and neural characteristics of navigation impairments in preclinical Alzheimer’s disease

Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk preclinical individuals. This thesis focuses on spatial navigation deficits, which are increasingly shown to be present in atrisk individuals, because the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Experimental chapters 2 and 3, show that a novel test battery captures navigation deficits that precede the onset of verbal and non-verbal episodic memory deficits in preclinical disease and that resting-state functional connectivity between the EC and the PCC underpins such deficits. Evidence for moderate test re-test reliability in the same non-clinical sample is presented in chapter 4. Moving beyond detection of preclinical disease, and towards prevention, in chapter 5 we examined whether marine fish oils help preserve the volume of AD vulnerable brain regions and found that low circulating DHA blood concentration predicts preservation of hippocampal and entorhinal volume in preclinical AD. This is potentially due to increased DHA uptake from the blood to the brain due to preclinical disease. Taken together, the research advances our conceptual understanding of the pathological and compensatory changes that characterise preclinical AD and offers important information toward generating more accurate risk profiles for AD vulnerable adults

Testing Spatial Cognition in Mild Cognitive Impairment Using Immersive Virtual Reality

The prodromal stage of dementia is known as mild cognitive impairment (MCI). Currently, cognitive tests are unable to correctly characterize the MCI type, and specifically, whether it will develop into Alzheimer's disease (AD). This means that cognitive deficits are detected long after the onset of pathological changes. More sensitive and specific tests, which can non-invasively detect the subtle, early signs of AD in MCI, would facilitate investigation of its early development and potentially permit early treatments. This thesis aims to develop a diagnostic tool to target the cognitive functions – and engage the corresponding brain regions – typically affected during the prodromal stages of AD. Pathological changes start in the hippocampal formation, a critical area for episodic memory and navigation. The tasks are developed from previous work demonstrating hippocampal dependence and make use of recent advances in immersive virtual reality, providing an ecologically valid improvement on standard tests of cognitive function. The first experimental chapter presents a test of navigation by path integration, a function specifically associated with processing by grid cells in the medial entorhinal cortex (mEC). The second experiment presents a test of object-location memory, believed to involve place cells in the hippocampus proper, combining inputs from mEC and object-identity information from the lateral entorhinal cortex (lEC). The third experiment tests object-location memory in a way that enables the contribution of self-motion to be assessed. Results show that the immersive virtual reality paradigms developed to test spatial cognition in prodromal AD are able to differentiate MCI patients from healthy age-matched older controls. Additionally, in combination with CSF biomarkers, navigation testing has proven the ability to stratify between MCI with different levels of biomarkers, identifying the patients who are most likely going to develop the disease. Finally, the last experiment, in an attempt to summarize different aspects of spatial cognition tested in the previous experiments, can detect subtle changes starting from ageing that may further decline with the onset of cognitive decline due to AD neuropathology. In conclusion within this thesis, we demonstrated the use of immersive virtual reality tests as an ecological valid tool for assessing the behavioural changes associated with the early progression of AD

Coaching Imagery to Athletes with Aphantasia

We administered the Plymouth Sensory Imagery Questionnaire (Psi-Q) which tests multi-sensory imagery, to athletes (n=329) from 9 different sports to locate poor/aphantasic (baseline scores <4.2/10) imagers with the aim to subsequently enhance imagery ability. The low imagery sample (n=27) were randomly split into two groups who received the intervention: Functional Imagery Training (FIT), either immediately, or delayed by one month at which point the delayed group were tested again on the Psi-Q. All participants were tested after FIT delivery and six months post intervention. The delayed group showed no significant change between baseline and the start of FIT delivery but both groups imagery score improved significantly (p=0.001) after the intervention which was maintained six months post intervention. This indicates that imagery can be trained, with those who identify as having aphantasia (although one participant did not improve on visual scores), and improvements maintained in poor imagers. Follow up interviews (n=22) on sporting application revealed that the majority now use imagery daily on process goals. Recommendations are given for ways to assess and train imagery in an applied sport setting

Unmasking selective path integration deficits inAlzheimer’s disease risk carriers

Alzheimer’s disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE4-carriers during a virtual navigation task. We report a selective impairment in APOE4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations when no compensatory strategies were available, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE4-carriers. Furthermore, posterior cingulate/retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset