Biology subjects

Spiers, H.

Publications and source records attributed to Spiers, H..

12 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↗

bioRxiv2026

Prefrontal brain-to-brain synchrony during human group hunting: Evidence from fNIRS hyperscanning

Orca, wolves, chimpanzees and humans share a similarly impressive capacity for group hunting, where individuals coordinate behaviour together to capture prey. Studying hunting behaviours has important implications for understanding how behaviour in group contexts may be indicative of cognitive decline. Despite growing interest in brain circuits for prey capture, the brain regions involved in tracking prey during a hunt and the behaviours in group hunt linked to success remain unclear. Here we combined functional near infrared spectroscopy (fNIRS) and a virtual minecraft world to examine behaviour, brain dynamics and brain synchrony involved in group hunting behaviour. We focused on the prefrontal cortex (PFC) due to its known role in planning and social coordination and recorded from pairs of individuals as they either cooperated to hunt another person (prey) or simply followed another person. Hunters were more successful if they managed to keep a smaller distance to the prey and moved at speeds that were more synchronised with their co-predator. At high-range frequencies for fNIRS (0.1-0.2Hz), we found greater brain-to-brain synchrony in lateral and medial (frontopolar) PFC regions during hunting compared with chance levels. Together, these findings provide insights into what behaviours and brain dynamics associated with successful group hunting.

neuroscience↗

bioRxiv2026

NucleoNet and DropNet: Generalist deep learning models for instance segmentation of nuclei and lipid droplets from electron microscopy images

Automating cellular organelle segmentation is key to increasing the throughput in electron microscopy (EM) and volume EM (vEM) workflows. Deep learning (DL) has accelerated this process, but model development has predominately centered on mitochondria, partly because of a scarcity of suitable training datasets for other features. Here, we crowdsourced the manual step of labeling nuclei and lipid droplets (LDs) from complex cellular EM images and trained Panoptic DeepLab (PDL) models on these large, heterogenous annotated datasets as well as on publicly available vEM datasets. NucleoNet and DropNet, the resulting instance segmentation models for nuclei and LDs, respectively, yield high-quality results on varied benchmarks. We applied these models to quantify differences between 2D and 3D in vitro cancer models versus in vivo tumors, highlighting a path toward robust quantitation in EM. NucleoNet and DropNet are publicly available on our napari plugin, empanada v1.2, for easy point-and-click segmentation of 2D and 3D cellular EM images.

cell biology↗

bioRxiv2024

Expert Navigators Deploy Rational Hierarchical Priorization Over Predictive Maps For Large-Scale Real-World Planning

Efficient planning is a distinctive hallmark of intelligence in humans, who routinely make rapid inferences over complex world contexts. However, studies investigating how humans accomplish this tend to focus on naive participants engaged in simplistic tasks with small state-spaces, which do not reflect the intricacy, ecological validity, and human specialisation in real-world planning. In this study, we examine the street-by-street route planning of London taxi drivers navigating across more than 26,000 streets in London (UK). We explore how planning unfolded dynamically over different phases of journey construction and identify theoretic principles by which these expert human planners rationally precache decisions at prioritised environment states in an early phase of the planning process. In particular, we find that measures of path complexity predict human mental sampling prioritisation dynamics independent of alternative measures derived from the real spatial context being navigated. Our data provide real-world evidence for complexity-driven remote state access within internal models and precaching during human expert route planning in very large structured spaces. Significance statementHumans can plan efficiently in incredibly complex situations. Existing work has looked at naive participants in simple tasks, which might not be representative of how experts plan in the real world. Here, we study the real-world planning process of London taxi drivers - famous for their expert knowledge of London. By analyzing their response times as a proxy for thinking times, we reveal that at an early stage in their thought process, they store decisions at key street junctions to keep them in mind for later planning. Using computational modeling, we show that taxi drivers prioritize inference at street junctions according to normative metrics measuring how critical a particular decision is for reducing the complexity of planning across the entire city.

neuroscience↗

bioRxiv2023

A spatial map of human liver cirrhosis reveals the patho-architecture and gene signatures associated with cell state transitions during liver disease

Liver fibrosis is a major cause of death worldwide. As a progressive step in chronic liver disease, fibrosis is almost always diagnosed too late with limited treatment options. Here, we uncover the spatial transcriptional landscape driving human liver fibrosis using single nuclei RNA and Assay for Transposase-Accessible Chromatin (ATAC) sequencing to deconvolute multi-cell spatial transcriptomic profiling in human liver cirrhosis. Through multi-modal data integration, we define molecular signatures driving cell state transitions in liver disease and define an impaired cellular response and directional trajectory from hepatocytes to cholangiocytes associated with disease remodelling. We identify pro-fibrogenic signatures in non-parenchymal cell subpopulations co-localised within the fibrotic niche and localise transitional cell states at the scar interface. This combined approach provides a spatial atlas of gene regulation and defines molecular signatures associated liver disease for targeted therapeutics or as early diagnostic markers of progressive liver disease.

genomics↗

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↗

bioRxiv2021

Automatic instance segmentation of mitochondria in electron microscopy data

We present a new method for rapid, automated, large-scale 3D mitochondria instance segmentation, developed in response to the ISBI 2021 MitoEM Challenge. In brief, we trained separate machine learning algorithms to predict (1) mitochondria areas and (2) mitochondria boundaries in image volumes acquired from both rat and human cortex with multi-beam scanning electron microscopy. The predictions from these algorithms were combined in a multi-step post-processing procedure, that resulted in high semantic and instance segmentation performance. All code is provided via a public repository.

bioinformatics↗

bioRxiv2020

Citizen science, cells and CNNs - deep learning for automatic segmentation of the nuclear envelope in electron microscopy data, trained with volunteer segmentations

Advancements in volume electron microscopy mean it is now possible to generate thousands of serial images at nanometre resolution overnight, yet the gold standard approach for data analysis remains manual segmentation by an expert microscopist, resulting in a critical research bottleneck. Although some machine learning approaches exist in this domain, we remain far from realising the aspiration of a highly accurate, yet generic, automated analysis approach, with a major obstacle being lack of sufficient high-quality ground-truth data. To address this, we developed a novel citizen science project, Etch a Cell, to enable volunteers to manually segment the nuclear envelope of HeLa cells imaged with Serial Blockface SEM. We present our approach for aggregating multiple volunteer annotations to generate a high quality consensus segmentation, and demonstrate that data produced exclusively by volunteers can be used to train a highly accurate machine learning algorithm for automatic segmentation of the nuclear envelope, which we share here, in addition to our archived benchmark data.

cell biology↗

bioRxiv2018

Spotting the path that leads nowhere: Modulation of human theta and alpha oscillations induced by trajectory changes during navigation

The capacity to take efficient detours and exploit novel shortcuts during navigation is thought to be supported by a cognitive map of the environment. Despite advances in understanding the neural basis of the cognitive map, little is known about the neural dynamics associated with detours and shortcuts. Here, we recorded magnetoencephalography from humans as they navigated a virtual desert island riven by shifting lava flows. The task probed their ability to take efficient detours and shortcuts to remembered goals. We report modulation in event-related fields and theta power as participants identified real shortcuts and differentiated these from false shortcuts that led along suboptimal paths. Additionally, we found that a decrease in alpha power preceded back-tracking where participants spontaneously turned back along a previous path. These findings help advance our understanding of the fine-grained temporal dynamics of human brain activity during navigation and support the development of models of brain networks that support navigation.

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↗

bioRxiv2017

5-Hydroxymethylcytosine Is Highly Dynamic Across Human Fetal Brain Development

BackgroundEpigenetic processes play a key role in orchestrating transcriptional regulation during the development of the human central nervous system. We previously described dynamic changes in DNA methylation (5mC) occurring during human fetal brain development, but other epigenetic processes operating during this period have not been extensively explored. Of particular interest is DNA hydroxymethylation (5hmC), a modification that is enriched in the human brain and hypothesized to play an important role in neuronal function, learning and memory. In this study, we quantify 5hmC across the genome of 71 human fetal brain samples spanning 23 to 184 days post-conception.\n\nResultsWe identify widespread changes in 5hmC occurring during human brain development, notable sex-differences in 5hmC in the fetal brain, and interactions between 5mC and 5hmC at specific sites. Finally, we identify loci where 5hmC in the fetal brain is associated with genetic variation.\n\nConclusionsThis study represents the first systematic analysis of dynamic changes in 5hmC across neurodevelopment and highlights the potential importance of this modification in the human brain. A searchable database of our fetal brain 5hmC data is available as a resource to the research community at http://epigenetics.essex.ac.uk/fetalbrain2/.

genomics↗