Biology subjects

Eger, E.

Publications and source records attributed to Eger, E..

17 recordsLinked to original sources

bioRxiv2025

Numerosity Is Directly Sensed and Dynamically Transformed in the Human Brain: Evidence from MEG-MRI Fusion

Humans can estimate the number of objects in a scene within a fraction of a second, suggesting that numerosity is encoded rapidly and directly by the visual system. Yet how this encoding unfolds over time and interacts with other visual features remains unclear. Here, we combined magnetoencephalography (MEG) with time-resolved representational similarity analysis (RSA) and MEG-fMRI fusion to track how numerosity is represented in the brain over time. We also used multidimensional scaling (MDS) to visualize the evolving patterns of neural activity. Two main findings emerged. First, numerosity exhibited the hallmarks of a primary perceptual attribute: its neural signature appeared rapidly after stimulus onset, preceding the encoding of non-numeric features that could otherwise define number. Second, Visualization of the neural patterns using MDS suggested a temporal transformation in representational geometry, reflecting the engagement of two distinct coding schemes- an early, linear number line, consistent with a "summation code", dominating activity in occipital regions, and a later, curved number line, consistent with "numerosity-tuned code", emerging more strongly in associative areas along the dorsal stream. Together, these findings demonstrate that numerosity processing is encoded directly from the visual image and unfolds through a rapid hierarchical transformation, from a broad quantity signal to a finely tuned, number-specific code, linking perceptual encoding to higher-level numerical abstraction.

neuroscience↗

bioRxiv2025

Real-time genomic pathogen, resistance, and host range characterization from passive water sampling of wetland ecosystems

Wetland ecosystems provide interfaces for the transmission of microbial pathogens and antimicrobial resistances (AMR) between migratory birds, wild and domestic animals, and human populations. The efficient surveillance of wetlands is, however, challenging, since the typically low concentration of pathogens typically requires the sampling of large volumes of water and subsequent targeted detection, which is inherently limited to a few pathogens or AMR genes of interest. Here, we present a holistic, accessible, and cost-efficient framework to characterize the pathogen and resistance load of water sources together with their potential associated hosts by combining passive water sampling through torpedo-shaped devices with nanopore sequencing technology. We used this framework to characterize anthropogenically influenced and natural wetland ecosystems along the East Atlantic Flyway, where we obtained robust assessments of the microbial communities from long-read metagenomic and RNA virome data, and showed that anthropogenically impacted wetland ecosystems consistently exhibited higher relative abundances of pathogens and AMR genes. By focusing on avian influenza viruses (AIV), we finally highlight the additional need for targeted screening and whole-genome sequencing of pathogens of interest; we detected and characterized AIV at a third of the monitored sites, and used environmental DNA (eDNA) to explore potential animal hosts to better understand the role of wetland ecosystems as One Health interfaces. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=191 HEIGHT=200 SRC="FIGDIR/small/674394v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1a006f2org.highwire.dtl.DTLVardef@12824c2org.highwire.dtl.DTLVardef@8554bdorg.highwire.dtl.DTLVardef@17e800e_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Trained deep neural network models of the ventral visual pathway encode numerosity with robustness to object and scene identity

"Number sense", the ability to rapidly estimate object quantities in a visual scene without precise counting, is a crucial cognitive capacity found in humans and many other animals. Recent studies have identified artificial neurons tuned to numbers of items in biologically inspired vision models, even before training, and proposed these artificial neural networks as candidate models for the emergence of number sense in the brain. But real-world numerosity perception requires abstraction from the properties of individual objects and their contexts, unlike the simplified dot patterns used in previous studies. Using novel synthetically generated photorealistic stimuli, we show that deep convolutional neural networks optimized for object recognition encode information on approximate numerosity across diverse objects and scene types, which could be linearly read out from distributed activity patterns of later convolutional layers of different network architectures tested. In contrast, untrained networks with random weights failed to represent numerosity with abstractness to other visual properties, and instead captured mainly low-level visual features. Our findings emphasize the importance of using complex, naturalistic stimuli to investigate mechanisms of number sense in both biological and artificial systems, and suggest that the capacity of untrained networks to account for early life numerical abilities should be reassessed. They further point to a possible, so far underappreciated, contribution of the brains ventral visual pathway to representing numerosity with abstractness to other high-level visual properties.

neuroscience↗

bioRxiv2024

A nonlinear code for event probability in the human brain

Assessing probabilities and predicting future events are fundamental for perception and adaptive behavior, yet the neural representations of probability remain elusive. While previous studies have shown that neural activity in several brain regions correlates with probability-related factors such as surprise and uncertainty, similar correlations have not been found for probability. Here, using 7 Tesla functional magnetic resonance imaging, we uncover a representation of the probability of the next event in a sequence within the human dorsolateral prefrontal and intraparietal cortices. Crucially, univariate and multivariate analyses revealed that this representation employs a highly nonlinear code. Tuning curves for probability exhibit selectivity to various probability ranges, while the code for confidence accompanying these estimates is predominantly linear. The diversity of tuning curves we found recommends that future studies move from assuming linear correlates or simple canonical forms of tuning curves to considering richer representations whose benefits remain to be discovered.

neuroscience↗

bioRxiv2024

In-host evolution of classic to convergent Klebsiella pneumoniae sequence type 147 isolates and impact of associated capsular changes on different morphotypes

Klebsiella pneumoniae, an important opportunistic pathogen, has long been categorized into two distinct pathotypes: the often multidrug-resistant classic (cKp) and the highly virulent hypervirulent (hvKp). However, a recent global trend has witnessed the emergence of convergent strains, seamlessly combining antimicrobial resistance with hypervirulence. Our study delved into a series of K. pneumoniae isolates sourced from the same patient, all belonging to the international, high-risk clonal lineage of sequence type 147. As reported in a previous study, these isolates exhibited diverse morphotypes on blood agar, ranging from small white to normal-sized white, grey, or grey and dry (g/d) colonies. Through an interplay of omics and phenotypic experiments, we unraveled the intricate mechanisms governing these distinct colony morphologies and their implications on bacterial virulence and resilience. While the earlier isolates demonstrated modest levels of resistance and virulence, their later counterparts showed significantly heightened levels, attributed to the acquisition of additional plasmids. Bioinformatics analysis unveiled a chromosomal insertion of a hybrid plasmid in one isolate, marking an unprecedented in-host microevolution from the classic to the convergent pathotype. All morphotypes exhibited positive insertion sequences around or within the K loci, with the grey or g/d phenotypes arising from impaired K loci. Despite lower serum resistance, these morphotypes demonstrated superior adhesion to human epithelial cells. Interestingly, while capsule-deficient strains are conventionally associated with decreased virulence, our isolates displayed high mortality rates in the Galleria mellonella infection model. In conclusion, our findings not only provide unprecedented insights into in-host microevolution within a patient, transitioning from the classic to the convergent pathotype, but also contribute significantly to the understanding of the diverse morphotypes exhibited by K. pneumoniae.

microbiology↗

bioRxiv2024

Temperatures above 37°C increase virulence of a convergent Klebsiella pneumoniae sequence type 307 strain

Hypermucoviscosity in Klebsiella pneumoniae is often related to the overexpression of capsular polysaccharides, regulated by complex biosynthetic mechanisms in response to external cues. However, little is known about the processes involved in hypermucoviscosity in convergent K. pneumoniae, which combine extensive drug resistance with high bacterial virulence, under pathophysiological conditions. This study aimed to fill this gap by investigating the temperature dependence of hypermucoviscosity and overall virulence in a convergent K. pneumoniae strain isolated during a clonal outbreak belonging to the high-risk sequence type (ST)307. Hypermucoviscosity, biofilm formation, and mortality rates in Galleria mellonella larvae were examined at different temperatures (room temperature, 28{degrees}C, 37{degrees}C, 40{degrees}C and 42{degrees}C) and with various phenotypic experiments including electron microscopy. The underlying mechanisms of the phenotypic changes were explored via qPCR analysis to evaluate plasmid copy numbers, and transcriptomics. Our results indicate a temperature-dependent "switch" above 37{degrees}C to a hypermucoviscous phenotype, correlating with increased biofilm formation capacity and in vivo mortality, which might be due to a bacterial response to pathophysiological conditions, i.e., fever. In addition, we detected upregulation of a hybrid plasmid encoding both carbapenemase and the mucoid regulator rmpA genes. Surprisingly, rmpA did not exhibit temperature-dependent differential gene expression, suggesting other drivers. Apparent co-regulation of hypermucoviscosity and fimbrial expression was also identified. This study not only revealed the impact that increased temperatures above 37{degrees}C have on hypermucoviscosity and virulence in a convergent K. pneumoniae strain but contributes to the understanding of previously unrecognized dimension of K. pneumoniaes behavior, emphasizing its adaptability to changing environments. Abstract importanceUnderstanding the temperature-dependent dynamics of hypermucoviscosity in Klebsiella pneumoniae is crucial for unraveling the intricacies of its hypervirulence. This study investigates a convergent K. pneumoniae strain, ST307, revealing a temperature-dependent switch to hypermucoviscosity above 37 {degrees}C. The findings showcase a correlation between increased temperature, hypermucoviscosity, enhanced attachment, and heightened in vivo mortality. Notably, a hybrid plasmid encoding carbapenemase and mucoid regulator genes was upregulated at elevated temperatures. The study sheds light on previously unexplored aspects of K. pneumoniae behavior, emphasizing its adaptability in response to changing environments. The identified temperature-associated regulatory mechanisms offer insights into the pathogens response to fever, contributing to our broader understanding of bacterial adaptation. This research contributes to addressing the global challenge of hypervirulent, drug-resistant K. pneumoniae strains, providing valuable implications for future treatment strategies.

microbiology↗

bioRxiv2024

Klebsiella pneumoniae exhibiting a phenotypic hyper-splitting phenomenon including the formation of small colony variants

In this study, we characterized a Klebsiella pneumoniae strain in a patient with shrapnel hip injury, which resulted in multiple phenotypic changes, including the formation of a small colony variant (SCV) phenotype. Although already described since the 1960s, there is little knowledge about SCV phenotypes in Enterobacteriaceae. The formation of SCVs has been recognized as a bacterial strategy to evade host immune responses and compromise the efficacy of antimicrobial therapies, leading to persistent and recurrent courses of infections. In this case, 14 different, clonally identical resisto- and morpho-types were distinguished from the patients urine and tissue samples. Whole genome sequencing revealed the K. pneumoniae high-risk clonal lineage belonging to sequence type 147. Subculturing the SCV colonies consistently resulted in the reappearance of the initial SCV phenotype and three stable normal-sized phenotypes with distinct morphological characteristics. Additionally, an increase in resistance was observed over time in isolates that shared the same colony appearance. Our findings highlight the complexity of bacterial behavior by revealing a case of phenotypic "hyper-splitting" in a K. pneumoniae SCV and its potential clinical significance.

microbiology↗

bioRxiv2023

Multi-omics investigations uncover unique pathogenic markers in clinical Klebsiella pneumoniae that could be leveraged as novel antimicrobial targets

BackgroundKlebsiella pneumoniae (KP), often multidrug-resistant (MDR), is a significant public health concern and frequently associated with various diseases including urinary-tract infection. In addition, in recent years, an increasing number of studies reports on the emergence of convergent KP that combine MDR with hypervirulence leading to severely limited treatment options and thus calling for alternative approaches. MethodsIn this study, we compared high-risk clonal KP lineages with less pathogenic Klebsiella variicola (KV) and Klebsiella quasipneumoniae (KQ) strains on multiple-omics levels and performed integrative data analysis to identify unique markers that could be subsequently leveraged as novel targets in alternative treatment strategies. ResultsOur initial genomic analysis revealed 107 genes as part of the patho-core genome in eight clinical KP that were associated with different metabolic pathways. Subsequent transcriptome and proteome analyses in infection-mimicking media demonstrated similar regulatory patterns among KP vs. other Klebsiella strains, again with metabolic responses playing a pivotal role. In total, we identified 193 KP-specific, differentially expressed genes on transcriptomic and/or proteomic levels. When then comparing these regulated genes to over 6,000 publicly available Klebsiella genomes, we identified unique markers either in KP genomes or adaptively regulated on transcriptomics and/or proteomics levels. An example for the latter was a gene cluster for the cellobiose phosphotransferase system that has been previously described in the context of bacterial virulence and biofilm formation. ConclusionIn conclusion, our study not only highlights that KP strains demonstrate metabolic flexibility in response to particular environmental conditions, which is potentially important for their success as opportunistic pathogens, but identified unique KP-markers. Subsequent studies are needed to explore whether these markers might be prospectively used as novel anti-virulence targets, providing alternatives to traditional antibiotics.

microbiology↗

bioRxiv2023

Neural codes for visual numerosity independent of other quantities are present both in the dorsal and in the ventral stream of the human brain

Visual numerosity, a feature of visual sets traditionally associated with the parietal cortex, has recently been suggested to be encoded in a broader range of cortical regions, including early visual and associative cortices of both streams. However, a clear picture of how numerosity information is represented alongside other non-numeric features across the cortex is still lacking. To address this, we conducted a whole-brain 3T fMRI study with thirty-one adult subjects (eighteen females) engaged in a numerosity estimation task involving visual sets varying in number, item size, total item area, total field area, and density, thus allowing us to perform a tight control of the stimulus properties. Using model-based semipartial correlation representational similarity analyses, we found that numerosity is represented independently of other visual properties already in early visual areas and amplified in both retinotopic and non-retinotopic associative areas along both the dorsal and ventral streams. Dimensionality reduction analyses of BOLD activity patterns revealed clearly distinct neural representational geometries of numerosity across brain regions: a one-dimensional representation of numerical rank in early visual and in associative retinotopic regions of the ventral stream, and a curved structure encoding rank-order together with distance to end-point in associative regions of both the dorsal and ventral stream. These findings indicate that numerosity is represented over and above other visual features broadly in the brain but with substantially different neural coding schemes across regions, and are discussed in light of two non necessarily exclusive interpretations.

neuroscience↗

bioRxiv2023

Human brain representations of internally generated outcomes of approximate calculation revealed by ultra-high-field brain imaging

Much of human cultures advanced technology owes its existence to the ability to mentally manipulate quantities. Neuroscience has described the brain regions overall recruited by numerical tasks and the neuronal codes representing individual quantities during perceptual tasks. Nevertheless, it remains unknown how quantity representations are combined or transformed during mental computations and how specific quantities are coded in the brain when generated as the result of internal computations rather than evoked by a stimulus. Here, we imaged the brains of adult human subjects at 7 Tesla during an approximate calculation task designed to disentangle in- and outputs of the computation from the operation itself. While physically presented sample numerosities were distinguished in activity patterns along the dorsal visual pathway and within frontal and occipito-temporal regions, a representation of the internally generated result was most prominently detected in higher order regions such as angular gyrus and lateral prefrontal cortex. Behavioral precision in the task was related to cross-decoding performance between sample and result representations in medial IPS regions. This suggests the transformation of sample into result may be carried out within dorsal stream sensory-motor integration regions, and resulting outputs maintained for task purposes in higher-level regions in a format possibly detached from sensory-evoked inputs.

neuroscience↗

bioRxiv2023

Carbapenem- and cefiderocol-resistant Enterobacterales in surface waters in Kumasi, Ashanti Region, Ghana

This study investigated the presence of extended-spectrum {beta}-lactamase-producing Enterobacterales in selected surface waters in the Ashanti Region in Ghana. Subsequent genomic analysis revealed that one-fifth of the isolates were genotypically carbapenem-resistant. Phenotypic susceptibility testing not only confirmed their carbapenem resistance, but also uncovered two cefiderocol-resistant isolates.

microbiology↗

bioRxiv2022

A characterization of the neural representation of confidence during probabilistic learning

Learning in a stochastic and changing environment is a difficult task. Models of learning typically postulate that observations that deviate from the learned predictions are surprising and used to update those predictions. Bayesian accounts further posit the existence of a confidence-weighting mechanism: learning should be modulated by the confidence level that accompanies those predictions. However, the neural bases of this confidence are much less known than the ones of surprise. Here, we used a dynamic probability learning task and high-field MRI to identify putative cortical regions involved in the representation of confidence about predictions during human learning. We devised a stringent test based on the conjunction of four criteria. We localized several regions in parietal and frontal cortices whose activity is sensitive to the confidence of an ideal observer, specifically so with respect to potential confounds (surprise and predictability), and in a way that is invariant to which item is predicted. We also tested for functionality in two ways. First, we localized regions whose activity patterns at the subject level showed an effect of both confidence and surprise in qualitative agreement with the confidence-weighting principle. Second, we found neural representations of ideal confidence that also accounted for subjective confidence. Taken together, those results identify a set of cortical regions potentially implicated in the confidence-weighting of learning.

neuroscience↗

bioRxiv2020

Excessive visual crowding effects in developmental dyscalculia

Visual crowding refers to the inability to identify objects when surrounded by other similar items. Crowding-like mechanisms are thought to play a key role in numerical perception by determining the sensory mechanisms through which ensembles are perceived. Enhanced visual crowding might hence prevent the normal development of a system involved in segregating and perceiving discrete numbers of items and ultimately the acquisition of more abstract numerical skills. Here, we investigated whether excessive crowding occurs in developmental dyscalculia (DD), a neurodevelopmental disorder characterized by difficulty in learning the most basic numerical and arithmetical concepts, and whether it is found independently of associated major reading and attentional difficulties. We measured spatial crowding in two groups of adult individuals with DD and control subjects. In separate experiments, participants were asked to discriminate the orientation of a Gabor patch either in isolation or under spatial crowding. Orientation discrimination thresholds were comparable across groups when stimuli were shown in isolation, yet they were much higher for the DD group with respect to the control group when the target was crowded by closely neighbouring flanking gratings. The difficulty in discriminating orientation (as reflected by the combination of accuracy and reaction times) in the DD compared to the control group persisted over several larger target flanker distances. Finally, we found that the degree of such spatial crowding correlated with impairments in mathematical abilities even when controlling for visual attention and reading skills. These results suggest that excessive crowding effects might be a characteristic of DD, independent of other associated neurodevelopmental disorders. Bullet pointsO_LIPeople with DD have difficulty learning about numbers and arithmetics. C_LIO_LIPerception of non-symbolic number seems to be modulated by visual crowding. C_LIO_LICan stronger than normal crowding effects contribute to the origin of DD? C_LIO_LIWe measured crowding with orientation discrimination tasks using Gabor gratings. C_LIO_LIAbnormal crowding characterizes DD independently of other developmental deficits. C_LI

neuroscience↗

bioRxiv2019

Mapping numerical perception and operations in relation to functional and anatomical landmarks of human parietal cortex

Human functional imaging has identified the middle part of the intraparietal sulcus (IPS) as an important brain substrate for different types of numerical tasks. This area is often equated with the macaque ventral intraparietal area (VIP) where neuronal selectivity for non-symbolic numbers is found. However, the low spatial resolution and whole-brain averaging analysis performed in most fMRI studies limit the extent to which an exact correspondence of activation in different numerical tasks with specific sub-regions of the IPS can be established. Here we disentangled the functional neuroanatomy of numerical perception and operations (comparison and calculation) by acquiring high-resolution 7T fMRI data in a group of human adults, and relating the activations in different numerical contrasts to anatomical and functional landmarks on the cortical surface. Our results reveal a functional heterogeneity within human intraparietal cortex where the visual field map representations in superior/medial parts of IPS and superior parietal gyrus are involved predominantly in numerosity perception, whereas numerical operations predominantly recruit lateral/inferior parts of IPS. Since calculation and comparison-related activity fell mainly outside the field map representations considered the functional equivalent of the monkey VIP/LIP complex, the areas most activated during such numerical operations in humans are likely different from VIP.

neuroscience↗

bioRxiv2019

Attentional amplification of neural codes for number independent of other quantities along the dorsal visual stream

Humans and other animals base important decisions on estimates of number, and intraparietal cortex is thought to provide a crucial substrate of this ability. However, it remains debated whether an independent neuronal processing mechanism underlies this 'number sense', or whether number is instead judged indirectly on the basis of other quantitative features. We performed high-resolution 7 Tesla fMRI while adult human volunteers attended either to the numerosity or to an orthogonal dimension (average item size) of visual dot arrays. Numerosity explained a significant amount of variance in activation patterns, above and beyond non-numerical dimensions. Its representation was progressively enhanced along the dorsal visual pathway and was selectively amplified by attention when task relevant. These results reveal a dedicated extraction mechanism for numerosity that operates independently of other quantitative dimensions of the stimuli, and suggest that later stages along the dorsal stream are most important for the explicit manipulation of numerical quantity.

neuroscience↗

bioRxiv2018

Asymmetrical interference between number and item size perception provide evidence for a domain specific impairment in dyscalculia

Dyscalculia, a specific learning disability that impacts arithmetical skills, has previously been associated to a deficit in the precision of the system that estimates the approximate number of objects in visual scenes (the so called number sense system). However, because in tasks involving numerosity comparisons dyscalculics judgements appears disproportionally affected by continuous quantitative dimensions (such as the size of the items), an alternative view linked dyscalculia to a domain-general difficulty in inhibiting task-irrelevant responses.\n\nTo arbitrate between these views, we evaluated the degree of reciprocal interference between numerical and non-numerical quantitative dimensions in adult dyscalculics and matched controls. We used a novel stimulus set orthogonally varying in mean item size and numerosity, putting particular attention into matching both features perceptual discriminability. Participants compared those stimuli based on each of the two dimensions. While control subjects showed no significant size interference when judging numerosity, dyscalculics numerosity judgments were strongly biased by the unattended size dimension. Importantly however, both groups showed the same degree of interference from number when judging mean size. Moreover, only the ability to discard the irrelevant size information when comparing numerosity (but not the reverse) significantly predicted calculation ability across subjects.\n\nOverall, our results show that numerosity discrimination is less prone to interference than discrimination of another quantitative feature (mean item size) when the perceptual discriminability of these features is matched, as here in control subjects. By quantifying, for the first time, dyscalculic subjects degree of interference on another orthogonal dimension of the same stimuli, we are able to exclude a domain-general inhibition deficit as explanation for their poor / biased numerical judgement. We suggest that enhanced reliance on non-numerical cues during numerosity discrimination can represent a strategy to cope with a less precise number sense.

neuroscience↗

bioRxiv2017

Discriminability of numerosity-evoked fMRI activity patterns in human intra-parietal cortex reflects behavioral numerical acuity

Areas of the primate intraparietal cortex have been identified as an important substrate of numerical cognition. In human fMRI studies, activity patterns in these and other areas have allowed researchers to read out the numerosity a subject is viewing, but the relation of such decodable information with behavioral numerical proficiency remains unknown.\n\nHere, we estimated the precision of behavioral numerosity discrimination (internal Weber fraction) in twelve adult subjects based on psychophysical testing in a delayed numerosity comparison task outside the scanner. FMRI data were then recorded during a similar task, to obtain the accuracy with which the same sample numerosities could be read out from evoked brain activity patterns, as a measure of the precision of the neuronal representation. Sample numerosities were decodable in both early visual and intra-parietal cortex with approximately equal accuracy on average. In parietal cortex, smaller numerosities were better discriminated than larger numerosities of the same ratio, paralleling smaller behavioral Weber fractions for smaller numerosities. Furthermore, in parietal but not early visual cortex, fMRI decoding performance was correlated with behavioral number discrimination acuity across subjects (subjects with a more precise behavioral Weber fraction measured prior to scanning showed greater discriminability of fMRI activity patterns in intraparietal cortex, and more specifically, the right LIP region).\n\nThese results suggest a crucial role for intra-parietal cortex in supporting a numerical representation which is explicitly read out for numerical decisions and behavior.

neuroscience↗