Biology subjects

Hornberger, M.

Publications and source records attributed to Hornberger, M..

17 recordsLinked to original sources

bioRxiv2026

Spatial navigation impairment beyond episodic memory in autoimmune encephalitis

NMDAR and LGI1 encephalitis are the two most common forms of autoimmune encephalitis and are associated with persistent cognitive sequelae, particularly episodic memory impairment. Patients also report lasting difficulties with spatial orientation and navigation, yet these symptoms remain poorly characterized. Both disorders affect neural systems supporting spatial navigation, including prominent hippocampal pathology alongside cingulate, temporo-parietal, thalamic and cerebellar alterations identified in advanced neuroimaging studies. Here, we therefore investigated the frequency and clinical relevance of spatial navigation impairment in post-acute NMDAR and LGI1 encephalitis, its relationship with episodic memory dysfunction, and its structural correlates. We included 80 post-acute patients from the autoimmune encephalitis outpatient clinic at Charite - Universitatsmedizin Berlin: 50 with NMDAR encephalitis (mean age 35.0 years, range 19-71; 90% female; median 6.9 years from onset) and 30 with LGI1 encephalitis (mean age 63.6 years, range 33-84; 67% male; median 2.7 years from onset). Spatial navigation was assessed using a passive map-assisted task (VIENNA Young) and an active wayfinding task (Sea Hero Quest), and its relationship with verbal episodic memory was examined using the Rey Auditory Verbal Learning Test. Structural MRI analyses assessed cortical thickness, subcortical volumes and diffusion measures in preselected navigation- and memory-related regions. Patients with NMDAR and LGI1 encephalitis performed worse than matched controls on map-assisted navigation, and navigation performance showed strong convergence across the two navigation paradigms. Norm-referenced navigation impairment affected 57% of patients with NMDAR encephalitis and 70% with LGI1 encephalitis. In NMDAR encephalitis, selective navigation impairment was more common than selective memory impairment (41% versus 14%; {chi}2 = 6.26, p = .012), supporting partial dissociation. In LGI1 encephalitis, navigation and memory impairments were similarly frequent and strongly overlapping, with 53% of patients impaired in both domains. Older age was a shared risk factor for navigation impairment. Structurally, NMDAR encephalitis showed partly distinct navigation- and memory-related alteration patterns, with navigation-specific parietal-paracentral and cerebellar abnormalities and memory-specific temporal-hippocampal-thalamic involvement. LGI1 encephalitis showed more widespread, predominantly memory-related alterations without a robust navigation-specific structural signature. Our findings identify spatial navigation as a frequently affected but under-assessed cognitive domain in post-acute NMDAR and LGI1 encephalitis. They provide clinical evidence that navigation and episodic memory are partially dissociable yet overlapping functions whose degree of separability varies with the extent and distribution of network pathology. Incorporating norm-referenced navigation assessment into longitudinal follow-up could improve the characterization of cognitive profiles and related support needs, while reducing the risk that impairments relevant to everyday functioning and long-term quality of life remain undetected.

neuroscience↗

bioRxiv2024

Predicting real-world navigation performance from a virtual navigation task in older adults

Virtual reality environments presented on tablets and smartphones offer a novel way of measuring navigation skill and predicting real-world navigation problems. The extent to which such virtual tests are effective at predicting navigation in older populations remains unclear. We compared the performance of 20 older participants (54-74 years old) in wayfinding tasks in a real-world environment in London, UK, and in similar tasks designed in a mobile app-based test of navigation (Sea Hero Quest). In a previous study with young participants (18-35 years old), we were able to predict navigation performance in real-world tasks in London and Paris using this mobile app. We find that for the older cohort, virtual navigation performance predicts real-world performance for medium difficulty, but not for the easy or difficult environments. While the younger sample outperformed the older sample in the virtual task, this was not the case in the real-world task, which conflicts with the dominant view of a decline in navigation ability with age. Self-reports identifying compensatory skills and further analysis of our participants scores in the Montreal Cognitive Assessment and in the Navigation Strategy Questionnaire help give insights into the higher performance in the real world. Overall, our study supports the utility of using digital tests of spatial cognition in older age groups, while carefully adapting the task difficulty to the population.

animal behavior and cognition↗

bioRxiv2024

Impact of cardiometabolic factors and blood beta-amyloid on the volume of white matter hyperintensities in dementia-free subjects with cognitive complaints

IntroductionWhite matter hyperintensities (WMH) in Alzheimers disease (AD) have traditionally been associated with cerebrovascular diseases. Amyloid {beta} (A{beta}) deposition reportedly contributes to WMHs; however, this relationship remains unclear in dementia-free subjects with cognitive complaints (CC). Here, we explored the relationship between WMHs and cardiometabolic and A{beta} blood biomarkers in a community-based cohort of Latin American CC participants. MethodsWe recruited 112 individuals with CC (69 - 92 YO, 90 females) with available plasma A{beta} biomarkers and cardiometabolic markers (systolic - diastolic blood pressure and glycaemia). WMHs were quantified using a lesion segmentation tool based on SPM12 and segmented using the John Hopkins University (JHU) Atlas and ALVIN segmentation for periventricular and subcortical white matter. Linear multiple regression models were fitted to assess total WMH lesions and the segmented tract, using demographics, cardiometabolic, and A{beta} blood biomarker measures as independent variables. ResultsAfter multiple comparison corrections, diastolic blood pressure was associated with WMHs, specifically in the right anterior thalamic radiation, left cingulum, minor forceps, and subcortical ALVIN segmentation. Glycaemia was associated with WMH volume in forceps major, forceps minor, and right fronto-occipital fasciculi. Conversely, A{beta} blood biomarkers and systolic blood pressure showed no association with WMH overall or in specific tracts. ConclusionOur findings suggest that, in dementia-free CC individuals, WMH volume was more related to cardiometabolic factors, whereas A{beta} blood biomarkers might be of less relevance. Dementia prevention strategies in individuals might be a useful focus for managing high peripheral vessel resistance and endothelial damage due to hypertension and hyperglycaemia.

neuroscience↗

bioRxiv2023

Individuals learning to drive solo before age 18 have superior spatial navigation ability compared with those who learn later

A challenge associated with driving vehicles can be navigating to the destination. While driving experience would seem beneficial for improving navigation skill, it remains unclear how driving experience relates to wayfinding ability. Using the mobile video game-based wayfinding task Sea Hero Quest, which is predictive of real-world navigation, we measured wayfinding ability in US-based participants (n = 694, 291 men, 403 women, mean age = 26.8 years, range = 18-52 years). We also asked travel-related self-report questions, including the age one started learning to drive, the age one started driving solo and weekly driving hours. A multivariate linear regression model found that those who started driving solo below aged 18 had significantly better wayfinding ability than those starting to drive solo aged 18 and above. Other driving-related self-report measures were not associated with wayfinding ability. Future studies should determine the directionality of the association between driving experience and wayfinding ability.

neuroscience↗

bioRxiv2023

From overconfidence to task dropout in a spatial navigation test: evidence for the Dunning-Kruger effect across 46 countries

Overconfidence and the Dunning-Kruger effect have been reported in many cognitive domains. However, there is little examination in the field of spatial navigation. Here, we examined overconfidence in navigation ability in 376,836 participants from 46 countries. We tested navigation using our virtual wayfinding task in the app-based video game Sea Hero Quest, examined self-ratings of navigation ability and how many game levels participants had played before they dropped out. The main goal of this analysis was to investigate how performance of overconfident participants influenced the dropout rate from our experimental task embedded in a video game. First, we measured and modelled overestimation at baseline game levels. Age was found to be the strongest predictor of overestimation across the entire sample. Higher age was associated with increased overconfidence in all 46 countries and 11 distinct cultural clusters. Female participants were more likely to overestimate their performance across most of the life course (19-59 years old), however older men (60-70 years old) displayed highest overconfidence amongst all age-gender groups. Overconfidence also varied widely across countries. Secondly, we estimated performance on follow-up game levels for those who were previously identified as overconfident and we found that those who were more likely to display the Dunning-Kruger effect (i.e., poor performance while being overconfident) were predominantly female and older participants. Finally, survival analysis methods with time-dependent covariates revealed that poor wayfinding performance, while being overconfident, was one of the strongest predictors of task dropout. This Dunning-Kruger bias on participants dropout existed universally across all countries in our data.

neuroscience↗

bioRxiv2023

Shorter reported sleep duration in men is associated with worse virtual spatial navigation performance

Sleep has been shown to impact navigation ability. However, it remains unclear how different sleep-related variables may be independently associated with spatial navigation performance, and as to whether gender may play a role in these associations. We used a mobile video game app, Sea Hero Quest (SHQ), to measure wayfinding ability in US-based participants. Wayfinding performance on SHQ has been shown to correlate with real-world wayfinding. Participants were asked to report their sleep duration, quality, daytime sleepiness and nap frequency and duration on a typical night (n = 737, 409 men, 328 women, mean age = 27.1 years, range = 18-59 years). A multivariate linear regression was used to identify which self-reported sleep variables were independently associated with wayfinding performance. For men, longer self-reported sleep durations were associated with better wayfinding performance. For women, no such association was found. While other self-reported sleep variables showed trends of association with wayfinding performance, none of these were significantly associated with wayfinding performance in our regression model. These findings from younger U.S.-based participants suggest that a longer self-reported sleep duration may be an important contributor to successful navigation ability in men.

neuroscience↗

bioRxiv2023

Video gaming, but not reliance on GPS, is associated with spatial navigation performance

Recent evidence suggests that greater reliance on GPS-assisted devices is associated with poorer navigation ability. Contrastingly, studies have shown that video gaming can enhance navigation ability. While gender differences in navigation ability in favour of men are well-reported, it remains unclear if the effects of reliance on GPS and video gaming on navigation performance are influenced by gender. We investigated whether gender would influence the effect of gaming experience and reliance on GPS on navigation ability using the mobile app Sea Hero Quest, which has been shown to predict real-world wayfinding performance. Alongside navigation performance assessment we asked a series of self-report questions relating to reliance on GPS, navigation strategies and gaming experience with a group of US-based participants (n = 822, 280 men, 542 women, mean age = 26.3 years, range = 18-52 years). A multivariate linear regression model found no significant association between reliance on GPS and navigation performance for either gender. There was a significant association between weekly hours of video gaming and navigation performance which was not moderated by gender. After accounting for video game experience, gender was no longer significantly associated with navigation performance. These findings have implications for which daily activities may enhance or disrupt specific cognitive abilities. Future studies applying an interventional design and real-world navigation testing would be useful to determine whether video games playing increases navigation skill, or whether those who are good at navigating tend to play more video games.

neuroscience↗

bioRxiv2023

Handedness and its association with education and spatial navigation assessed in over 400,000 participants across 41 countries

There is an active debate concerning the association of handedness and spatial ability. Past studies used small sample sizes within a single country. Determining the effect of handedness on spatial ability requires a large, cross-cultural sample of participants, and a navigation task with real-world validity. Here, we overcome these challenges via the mobile app Sea Hero Quest. We analysed the navigation performance from 422,772 participants from 41 countries and found no reliable evidence for any difference in spatial ability between left- and right-handers across all countries. Using 749,037 participants from the larger sample, we replicate previous findings that age, gender, and country of residence have an impact on the prevalence of left-handedness, and found an effect of education on left-handedness prevalence in China, Indonesia, India, Taiwan, and Hong Kong. Our study clarifies the factors associated with spatial ability and outlines new ways in which cultural patterns influence handedness. Statement of RelevanceWhat is the relation between handedness and navigation ability? Evidence so far has been mixed, and findings from small-scale and large-scale tasks seem to point in opposite directions. Part of the reason is that cultural and sociodemographic differences have a significant impact on both spatial ability and handedness. Tackling the question requires a large, cross-cultural sample of participants performing an ecologically valid navigation task. Here, we employ a mobile app, Sea Hero Quest, to test the navigation ability of a large number of participants across many different countries. What we find is that there is no reliable connection between handedness and navigation ability. Then, we use our data to explore the prevalence of left-handedness across countries, and find that age, gender, and country of residency all have an effect on the ratio of left-handedness. Moreover, we find an effect of education on left-handedness in China, Indonesia, India, Taiwan, and Hong Kong.

animal behavior and cognition↗

bioRxiv2023

The relationship between object-based spatial ability and virtual navigation performance

Spatial navigation is a multi-faceted behaviour drawing on many different aspects of cognition. Visuospatial abilities, such as spatial working memory and mental rotation, in particular, may be key factors. A range of tests have been developed to assess visuospatial processing and memory, but how such tests relate to navigation ability remains unclear. This understanding is important to advance tests of navigation for disease monitoring in Alzheimers Disease, where disorientation is an early symptom. Here, we report the use of an established mobile gaming app, Sea Hero Quest, as a measure of navigation ability. We used three separate tests of navigation embedded in the game: wayfinding, path integration and spatial memory in a radial arm maze. In the same participants, we also collected measures of mental rotation (Mental Rotation Test), visuospatial processing (Design Organization Test) and visuospatial working memory (Digital Corsi). We found few strong correlations across our measures. Being good at wayfinding in a virtual navigation test does not mean an individual will rate themself as a confident navigator, be good at path integration, or have a superior memory in a radial arm maze. However, those good at wayfinding tend to perform well on the three visuospatial tasks examined here, and to also use a landmark strategy in the radial maze task. These findings help clarify the inter-relationships between different abilities supporting visuospatial and navigation skills. HighlightsO_LIThree navigation tests embedded in the game Sea Hero Quest were examined in relation to three object-based visuospatial tasks, and self-ratings of navigation ability and stress during navigation. C_LIO_LINo associations were observed among performance on wayfinding, path integration and radial arm maze levels of Sea Hero Quest. C_LIO_LIObject-based visuospatial abilities were selectively correlated with performance on wayfinding levels of Sea Hero Quest. C_LIO_LIGameplay stress and navigation strategy were not associated with performance on Sea Hero Quest navigation tasks. C_LI

neuroscience↗

bioRxiv2022

Cultural determinants of the gap between self-estimated navigation ability and wayfinding performance: evidence from 46 countries.

Cognitive abilities can vary widely. Some people excel in certain skills, others struggle. However, not all those who describe themselves as gifted are. One possible influence on self-estimates is the surrounding culture. Some cultures may amplify self-assurance and others cultivate humility. Past research has shown that people in different countries can be grouped into a set of consistent cultural clusters with similar values and tendencies, such as attitudes to masculinity or individualism. Here we explored whether such cultural dimensions might relate to the extent to which populations in 46 countries overestimate or underestimate their cognitive abilities in the domain of spatial navigation. Using the Sea Hero Quest navigation test and a large sample (N=383,187) we found cultural clusters of countries tend to be similar in how they self-rate ability relative to their actual performance. Across the world population sampled, higher self-ratings were associated with better performance. However, at the national level, higher self-ratings as a nation were not associated with better performance as a nation. Germanic and Near East countries were found to be most overconfident in their abilities and Nordic countries to be most under-confident in their abilities. Gender stereotypes may play a role in mediating this pattern, with larger national positive attitudes to male stereotyped roles (Hofstedes masculinity dimension) associated with a greater overconfidence in performance at the national level. We also replicate, with higher precision than prior studies, evidence that older men tend to overestimate their navigation skill more than other groups. These findings give insight into how culture and demographics may impact self-estimates of our abilities.

neuroscience↗

bioRxiv2020

Memory precision of object-location binding is unimpaired in APOE ε4-carriers with spatial navigation deficits

Research suggests that tests of memory fidelity, feature binding and spatial navigation are promising for early detection of subtle behavioural changes related to Alzheimers disease (AD). In the absence of longitudinal data, one way of testing the early detection potential of cognitive tasks is through the comparison of individuals at different genetic risk for AD. Most studies have done so using samples aged 70 years or older. Here, we tested whether memory fidelity of long-term object-location binding may be a sensitive marker even among cognitively healthy individuals in their mid-60s by comparing participants at low and higher risk based on presence of the {varepsilon}4-allele of the apolipoprotein gene (n=26 {varepsilon}3{varepsilon}3, n=20 {varepsilon}3{varepsilon}4 carriers). We used a continuous report paradigm in a visual memory task that required participants to recreate the spatial position of objects in a scene. We employed mixture modelling to estimate the two distinct memory processes that underpin the trial-by-trial variation in localisation errors: retrieval success which indexes the proportion of trials where participants recalled any information about an objects position and the precision with which participants retrieved this information. Prior work has shown that these memory paradigms that separate retrieval success from precision are capable of detecting subtle differences in mnemonic fidelity even when retrieval success could not. Nonetheless, a Bayesian analysis found good evidence that {varepsilon}3{varepsilon}4 carriers did not remember fewer object locations (F(1, 42)=.450, p=.506, BF01 =3.02), nor was their precision for the spatial position of objects reduced compared to {varepsilon}3{varepsilon}3 carriers (F(1, 42)=.12, p=.726, BF01 =3.19). Because the participants in the sample presented here were a subset of a study on APOE effects on spatial navigation in the Sea Hero Quest game (Coughlan et al., 2019. PNAS, 116(9)), we obtained these data to contrast APOE effects on the two tasks within the same sample (n=33). Despite the smaller sample size, wayfinding deficits among {varepsilon}3{varepsilon}4 could be replicated (F(1, 33) =5.60, p=.024, BF10 =3.44). Object-location memory metrics and spatial navigation scores were not correlated (all r<.25, p>.1, 0<BF10 <3). These findings show spared object-location binding in the presence of a detrimental APOE {varepsilon}4 effect on spatial navigation. This suggests that the sensitivity of memory fidelity and binding tasks may not extend to individuals with one {varepsilon}4-allele in their early to mid-60s. The results provide further support to prior proposals that spatial navigation may be a sensitive marker for the earliest AD-dependent cognitive changes, even before episodic memory.

neuroscience↗

bioRxiv2020

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 Alzheimers 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. This retrospective 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 path integration processes are only impaired in VCI, potentially distinguishing it from AD. However, in contrast to our prediction, allocentric path integration was similarly impaired for VCI and AD. These preliminary findings suggest limited specificity of allocentric path 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.

neuroscience↗

bioRxiv2020

Cities have a negative impact on navigation ability: evidence from 38 countries

Cultural and geographical properties of the environment have been shown to deeply influence cognition and mental health[1-6]. While living near green spaces has been found to be strongly beneficial [7-11], urban residence has been associated with a higher risk of some psychiatric disorders [12-14] (although see [15]). However, how the environment one grew up in impacts later cognitive abilities remains poorly understood. Here, we used a cognitive task embedded in a video game[16] to measure non-verbal spatial navigation ability in 397,162 people from 38 countries across the world. Overall, we found that people who grew up outside cities are better at navigation. More specifically, people were better at navigating in environments topologically similar to where they grew up. Growing up in cities with low Street Network Entropy (e.g. Chicago) led to better results at video game levels with a regular layout, while growing up outside cities or in cities with higher Street Network Entropy (e.g. Prague) led to better results at more entropic video game levels. This evidences the impact of the environment on human cognition on a global scale, and highlights the importance of urban design on human cognition and brain function.

neuroscience↗

bioRxiv2019

Functional connectivity between the entorhinal and posterior cingulate cortices associated with navigation impairment following path integration in at-genetic-risk Alzheimer’s disease

Navigation processes mediated selectively by the entorhinal cortex (EC) may be impaired in individuals with suspected preclinical Alzheimers disease (AD), but the clinical utility of navigation tests to detect such impairments remains to be established. In a sample of 64 individuals (32 e3e3 and 32 e3e4), we tested whether an existing paradigm, the Virtual Supermarket Test (VST), can reliably detect the presence or absence of the APOE e4 allele which accelerates amyloid plaque deposition in the brain. The present study assessed four major navigational processes that are subserved by functionally specialised cell groups located in AD vulnerable regions including the EC and examined the relationship between navigation process and regional functional connectivity (FC) given FC is a marker early AD-related tau seeding. While heading direction and spatial memory were unaffected by at-risk AD, clear altered navigational strategies following path integration were found on the VST in the e3e4 group. The APOE-sensitive VST measure correctly classified 77% of the APOE cohort. Including resting-state FC between the EC and the posterior cingulate cortex, a correlate of the path integration deficit in the APOE e4 group, the classification model increased the accuracy to 85%. Our findings show that at-genetic-risk AD selectively impairs path integration and biases self-reported spatial locations away from the centre and towards the boundary of a virtual environment. Importantly, this impairment is associated with reduced FC between the EC and the posterior cingulate cortex, which in turn informs the neurobiological mechanisms of at-genetic-risk of AD.

neuroscience↗

bioRxiv2018

Virtual navigation tested on a mobile app (Sea Hero Quest) is predictive of real-world navigation performance: preliminary data

Virtual reality environments presented on smart-phone and tablet devices have potential to aid the early diagnosis of conditions such as Alzheimers dementia by quantifying impairments in navigation performance. However, it is unclear whether performance on mobile devices can predict navigation errors in the real-world. In a preliminary study we tested 30 participants (15 female, 18-30 years old) on their wayfinding ability in our mobile app Sea Hero Quest and on novel real-world wayfinding task in London (UK). We find a significant correlation between virtual and real-world navigation performance and a male advantage on both tasks, although smaller in the real-world environment. These results are consistent with prior studies which have reported navigation in the virtual environments are predictive of real-world navigation performance and a consistent male advantage. Future research will need to test a larger sample size and older participants.

neuroscience↗

bioRxiv2018

Impact of Sex and APOE Status on Spatial Navigation in Pre-symptomatic Alzheimer’s disease

INTRODUCTIONSpatial navigation is emerging as a critical factor in identifying pre-symptomatic Alzheimer pathophysiology, with the impact of sex and APOE status on spatial navigation yet to be established.\n\nMETHODSWe estimate the effects of sex on navigation performance in 27,308 individuals (50-70 years [benchmark population]) by employing a novel game-based approach to cognitive assessment using Sea Hero Quest. The effects of APOE genotype and sex on game performance was further examined in a smaller lab-based cohort (n = 44).\n\nRESULTSBenchmark data showed an effect of sex on wayfinding distance, duration and path integration. Importantly in the lab cohort, performance on allocentric wayfinding levels was reduced in{varepsilon} 4 carriers compared to{varepsilon} 3 carriers, and effect of sex became negligible when APOE status was controlled for. To demonstrate the robustness of this effect and to ensure the quality of data obtained through unmonitored at-home use of the Sea Hero Quest game, post-hoc analysis was carried out to compare performance by the benchmark population to the monitored lab-cohort.\n\nDISCUSSIONAPOE {varepsilon}4 midlife carriers exhibit changes in navigation pattern before any symptom onset. This supports the move towards spatial navigation as an early cognitive marker and demonstrates for the first time how the utility of large-scale digital cognitive assessment may hold future promise for the early detection of Alzheimers disease. Finally, benchmark findings suggest that gender differences may need to be considered when determining the classification criteria for spatial navigational deficits in midlife adults.

neuroscience↗

bioRxiv2017

Global determinants of navigation ability

Countries vary in their geographical and cultural properties. Only a few studies have explored how such variations influence how humans navigate or reason about space [1-7]. We predicted that these variations impact human cognition, resulting in an organized spatial distribution of cognition at a planetary-wide scale. To test this hypothesis we developed a mobile-app-based cognitive task, measuring non-verbal spatial navigation ability in more than 2.5 million people, sampling populations in every nation state. We focused on spatial navigation due to its universal requirement across cultures. Using a clustering approach, we find that navigation ability is clustered into five distinct, yet geographically related, groups of countries. Specifically, the economic wealth of a nation was predictive of the average navigation ability of its inhabitants, and gender inequality was predictive of the size of performance difference between males and females. Thus, cognitive abilities, at least for spatial navigation, are clustered according to economic wealth and gender inequalities globally, which has significant implications for cross-cultural studies and multi-centre clinical trials using cognitive testing.

neuroscience↗