Biology subjects

Poletti, M.

Publications and source records attributed to Poletti, M..

14 recordsLinked to original sources

bioRxiv2026

Before the eye moves: microsaccade preparation expands spatial integration at the center of gaze

Fixation is often treated as a period of stable visual processing. Yet, fixation is often punctuated by frequent microsaccades that occur during tasks involving complex foveal stimuli. These small eye movements are preceded by changes in visual sensitivity, both at the upcoming movement goal and at the currently fixated location. However, previous work has largely focused on isolated stimuli, leaving unclear whether pre-microsaccadic modulations reflect changes in sensitivity alone or also alter the spatial interactions that govern object recognition. Visual crowding provides a direct test of this question because it depends on the integration and segregation of nearby features and constrains recognition even within the foveola. Using high-precision Dual Purkinje Image eye tracking with retinally contingent stimulus delivery, we measured acuity and crowding thresholds at the preferred locus of fixation (PLF), the starting point of the impending gaze shift, while observers either maintained fixation or prepared to execute a microsaccade to a cued location. Unflanked acuity at the PLF remained stable across conditions. In contrast, crowding strength increased during the pre-microsaccadic interval, indicating an expansion of the foveal crowding zone. These results show that microsaccade preparation alters spatial integration at the starting point of the movement, increasing crowding even when sensitivity to isolated stimuli remains unchanged. Thus, microsaccades reshape foveal vision not only by modulating visual discrimination at the movement goal, but also by changing how nearby features are integrated and segregated before the eyes move. Significance StatementVision is often assumed to be most stable when gaze is fixed. Yet the eyes are never truly still, and the brain continually prepares small movements that shape perception before they occur. This study shows that such preparation changes how visual information is organized at the very center of gaze. Upcoming eye movements do not simply alter sensitivity to isolated objects; instead, they change how nearby features are integrated. These findings reveal that fine spatial vision and object recognition depends not only on what falls on the retina or on subsequent cortical processing but also on what the eyes are preparing to do next.

neuroscience↗

bioRxiv2025

Looking for Details: Fine-Grained Visual Search at the Foveal Scale

Visual search has traditionally been conceptualized as the process by which the visual system identifies relevant objects in the extrafoveal field for subsequent foveation. Standard models implicitly assume there is no need for a finer-level search within the 1-degree foveola, as stimuli falling in this region are already viewed at high resolution. Using state-of-the-art high-precision eye tracking with arcminute level accuracy to localize the line of sight, we show that the visuomotor system is capable of implementing effective visual search strategies with striking precision within the foveated region. This active behavior, mediated by microsaccades, tiny saccades just a few arcminutes in size, allows for an efficient examination of the details falling in the central fovea. Our findings challenge the traditional visual search view and reveal that at each fixation a finer priority map of the foveal input is established, underscoring the dynamic nature of these representations.

neuroscience↗

bioRxiv2025

Temporal dynamics of peri-microsaccadic modulations within the foveola

Microsaccades are small, rapid eye movements that shift the center of gaze by less than half a degree. While they have traditionally been associated with perceptual modulations and covert attention shifts in extrafoveal vision, recent evidence indicates that microsaccades also modulate perception within the central fovea in a spatially selective manner. However, the temporal dynamics of these modulations in fine spatial discrimination remain largely unexplored. Here we used high-precision eye tracking and gaze-contingent display control to achieve accurate localization of the line of sight and to restrict visual stimulation to selective locations within the central fovea during instructed microsaccades. Our results show that visual performance peaks approximately 70 milliseconds before microsaccade onset at the target location, while perception at equally eccentric, non-target foveal locations is concurrently impaired. This is followed by a generalized suppression phase while the microsaccade is in flight, when fine spatial discrimination drops to near-chance levels. Visual performance then recovers rapidly at the target location, returning to baseline within 100 milliseconds after microsaccade landing. Our findings demonstrate that visual discrimination within the central fovea is modulated following a distinct temporal profile and in a spatially selective way around the time of microsaccade execution.

neuroscience↗

bioRxiv2025

Distinct growth regimes govern crowding in foveal and extrafoveal vision

Visual crowding--where object recognition is impaired by nearby stimuli--is a well-documented phenomenon in the visual periphery, thought to reflect fundamental processes of grouping and segmentation. A hallmark of crowding is its spatial extent increasing linearly with eccentricity, as described by Boumas law, reflecting retinal convergence and cortical magnification. Although crowding is typically studied in the periphery--and Boumas law predicts no crowding at the center of gaze--it occurs even foveally. Within the foveola, the central 1 deg of the visual field, characterized by peak visual acuity and largely one-to-one connectivity between photoreceptors and ganglion cells, the Bouma law breaks and the extent of crowding is expected to remain constant with eccentricity. Yet, whether crowding varies at this fine spatial scale remains unknown. To investigate this, we combined high-resolution eye tracking with a gaze-contingent display system to precisely localize gaze and measure crowding thresholds at multiple foveolar eccentricities. Our results reveal that crowding does increase linearly within the foveola, but at a rate significantly slower--approximately 3.5 times-than in the extrafovea. By showing that even within the highest-acuity region of the visual field, spatial integration zones are not fixed but change with eccentricity these findings challenge the view of the central fovea as a spatially uniform processing zone and demonstrate that crowding at this scale follows a distinct regime. SignificanceWhen we view objects in clutter, recognition declines--a phenomenon known as crowding. This effect increases with distance from the center of gaze, following Boumas law, which predicts little or no crowding at the foveas center. As this law breaks at the center of gaze, it has been hypothesized that around this region, crowding remains constant with eccentricity. Using high-resolution eyetracking, we show that even within the central 0.4{degrees} of the visual field, crowding increases steadily with minute stimulus offsets from the point of fixation. This growth is much slower than in peripheral vision, revealing a distinct crowding regime in the foveola, likely reflecting cortical and retinal differences. Our findings offer new insights into the fine-scale organization of spatial vision.

neuroscience↗

bioRxiv2025

Subfoveal scotomas trigger fine-scale fixation reorganization: insights from retinal imaging and retinal-contingent stimulation

Fine spatial vision relies on the foveola, the 1-degree retinal region with highest cone density. Despite its importance, the relationship between retinal anatomy, fixational behavior, and visual perception in the foveola is not fully understood. Using an Adaptive Optics Scanning Light Ophthalmoscope for high-resolution retinal imaging and stimulation, we studied the effect of a simulated subfoveolar ({approx}0.03 degrees2) scotoma on fine spatial vision and fixation behavior in healthy observers. Our findings show that the visuomotor system adapts to the scotoma with striking precision by shifting the preferred locus of fixation in a systematic fashion by minute ({approx}5 arcmin) amounts to bring stimuli into a region of visibility. These results reveal an unprecedented level of fine-scale plasticity in the human visuomotor system. Interestingly, this new retinal locus of fixation is characterized by lower cone density among those surrounding the scotoma, indicating that factors beyond spatial sampling maximization influence these fine-scale adjustments.

neuroscience↗

bioRxiv2025

Frequency-selective contrast sensitivity modulation driven by fine-tuned exogenous attention at the foveal scale

Exogenous attention is a rapid, involuntary mechanism that automatically reallocates processing resources toward salient stimuli. It enhances visual sensitivity in the vicinity of the salient stimulus, both in extrafoveal regions and within the high-acuity foveola. While the spatial frequencies modulated by exogenous attention in extrafoveal vision are well characterized, it remains unknown how this mechanism operates within the foveola, which can resolve spatial frequencies up to 30 cycles per degree (CPD). Here, we examined which spatial frequencies were enhanced by fine-grained deployments of exogenous attention within this highest-acuity region of the visual field. Using high-precision eye-tracking to precisely localize gaze during attentional allocation, we found that exogenous attention at the foveal scale selectively enhances contrast sensitivity for low- to mid-range spatial frequencies (4-8 CPD), with no significant benefits for higher spatial frequencies (12-20 CPD). In contrast, attention-related benefits on asymptotic performance at the highest contrast were observed across a wide range of spatial frequencies. These results indicate that, despite the high-resolution capacity of the foveola, exogenous attention remains an inflexible mechanism that, even at this scale, selectively enhances contrast gain for lower spatial frequencies--mirroring its behavior in extrafoveal vision.

neuroscience↗

bioRxiv2024

Asymmetries in foveal vision

Visual perception is characterized by known asymmetries in the visual field; humans visual sensitivity is higher along the horizontal than the vertical meridian, and along the lower than the upper vertical meridian. These asymmetries decrease with decreasing eccentricity from the periphery to the center of gaze, suggesting that they may be absent in the 1-deg foveola, the retinal region used to explore scenes at high-resolution. Using high-precision eyetracking and gaze-contingent display, allowing for accurate control over the stimulated foveolar location despite the continuous eye motion at fixation, we investigated fine visual discrimination at different isoeccentric locations across the foveola and parafovea. Although the tested foveolar locations were only 0.3 deg away from the center of gaze, we show that, similar to more eccentric locations, humans are more sensitive to stimuli presented along the horizontal than the vertical meridian. Whereas the magnitude of this asymmetry is reduced in the foveola, the magnitude of the vertical meridian asymmetry is comparable but, interestingly, reversed: objects presented slightly above the center of gaze are more easily discerned than when presented at the same eccentricity below the center of gaze. Therefore, far from being uniform, as often assumed, foveolar vision is characterized by perceptual asymmetries. Further, these asymmetries differ not only in magnitude but also in direction compared to those present just [~]4deg away from the center of gaze, resulting in overall different foveal and extrafoveal perceptual fields.

neuroscience↗

bioRxiv2024

High refresh rate display for natural monocular viewing in AOSLO psychophysics experiments

By combining an external display operating at 360 frames per second with an Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) for human foveal imaging, we demonstrate color stimulus delivery at high spatial and temporal resolution in AOSLO psychophysics experiments. A custom pupil relay enables viewing of the stimulus through a 3-mm effective pupil diameter and provides refractive error correction from -8 to +4 diopters. Performance of the assembled and aligned pupil relay was validated by measuring the wavefront error across the field of view and correction range, and the as-built Strehl ratio was 0.64 or better. High-acuity stimuli were rendered on the external display and imaged through the pupil relay to demonstrate that spatial frequencies up to 54 cycles per degree, corresponding to 20/11 visual acuity, are resolved. The completed external display was then used to render fixation markers across the field of view of the monitor, and a continuous retinal montage spanning 9.4 by 5.4 degrees of visual angle was acquired with the AOSLO. We conducted eye-tracking experiments during free-viewing and high-acuity tasks with polychromatic images presented on the external display. Sub-arcminute eye position uncertainty was achieved, enabling precise localization of the line of sight on the monitor while simultaneously imaging the fine structure of the human central fovea. This high refresh rate display overcomes the temporal, spectral, and field of view limitations of AOSLO-based stimulus presentation, enabling natural monocular viewing of stimuli in psychophysics experiments conducted with AOSLO.

bioengineering↗

bioRxiv2023

FAK family proteins regulate in vivo breast cancer metastasis via distinct mechanisms.

Breast cancer is the most commonly diagnosed malignancy and the major leading cause of tumor-related deaths in women. It is estimated that the majority of breast tumor-related deaths are a consequence of metastasis, to which no cure exists at present. The FAK family proteins Proline-rich tyrosine kinase (PYK2) and focal adhesion kinase (FAK) are highly expressed in breast cancer, but the exact cellular and signaling mechanisms by which they regulate in vivo tumor cell invasiveness and consequent metastatic dissemination are mostly unknown. Using a PYK2 and FAK knockdown xenograft model we show here, for the first time, that ablation of either PYK2 or FAK decreases primary tumor size and significantly reduces Tumor MicroEnvironment of Metastasis (TMEM) doorway activation, leading to decreased intravasation and reduced spontaneous lung metastasis. Intravital imaging analysis further demonstrates that PYK2, but not FAK, regulates a motility phenotype switch between focal adhesion-mediated fast motility and invadopodia-dependent, ECM-degradation associated slow motility within the primary tumor. Furthermore, we validate our in vivo and intravital imaging results with integrated transcriptomic and proteomic data analysis from xenograft knockdown tumors and reveal new and distinct pathways by which these two homologous kinases regulate breast tumor cell invasiveness and consequent metastatic dissemination. Our findings identify PYK2 and FAK as novel mediators of mammary tumor progression and metastasis and as candidate therapeutic targets for breast cancer metastasis.

cancer biology↗

bioRxiv2023

AutophagyNet: High-resolution data source for the analysis of autophagy and its regulation

Autophagy is a highly-conserved catabolic process eliminating dysfunctional cellular components and invading pathogens. Autophagy malfunction contributes to disorders such as cancer, neurodegenerative and inflammatory diseases. Understanding autophagy regulation in health and disease has been the focus of the last decades. We previously provided an integrated database for autophagy research, the Autophagy Regulatory Network (ARN). For the last seven years, this resource has been used by thousands of users. Here, we present a new and upgraded resource, AutophagyNet. It builds on the previous database but contains major improvements to address user feedback and novel needs due to the advancement in omics data availability. AutophagyNet contains updated interaction curation and integration of over 280,000 experimentally verified interactions between core autophagy proteins and their protein, transcriptional and post-transcriptional regulators as well as their potential upstream pathway connections. AutophagyNet provides annotations for each core protein about their role: 1) in different types of autophagy (mitophagy, xenophagy, etc.); 2) in distinct stages of autophagy (initiation, elongation, termination, etc); 3) with subcellular and tissue-specific localization. These annotations can be used to filter the dataset, providing customizable download options tailored to the users needs. The resource is available in various file formats (e.g., CSV, BioPAX and PSI-MI), and data can be analyzed and visualized directly in Cytoscape. The multi-layered regulation of autophagy can be analyzed by combining AutophagyNet with tissue- or cell type-specific using (multi-)omics datasets (e.g. transcriptomic or proteomic data). The resource is publicly accessible at http://autophagynet.org.

bioinformatics↗

bioRxiv2022

Alignment, calibration, and validation of an adaptive optics scanning laser ophthalmoscope optimized for resolving human cones in the central fovea

Advances in adaptive optics scanning laser ophthalmoscope (AOSLO) technology have enabled cones in the human fovea to be reliably resolved, providing new insight into human foveal anatomy, visual perception, and retinal degenerative diseases. These high-resolution ophthalmoscopes require careful alignment of each optical subsystem to ensure diffraction-limited imaging performance, which is necessary for resolving the smallest foveal cones. This paper presents a systematic and rigorous methodology for building, aligning, calibrating, and testing an AOSLO designed for imaging the cone mosaic of the central fovea in humans with cellular resolution. This methodology uses a two-stage alignment procedure and thorough system testing to achieve diffraction-limited performance. Results from retinal imaging of healthy human subjects show that the system can resolve cones at the very center of the fovea, the region where the cones are smallest and most densely packed.

bioengineering↗

bioRxiv2022

Individual differences in eye drift predict visual acuity

Visual acuity is commonly assumed to be determined by the eye optics and spatial sampling in the retina. Unlike a camera, however, the eyes are never stationary during the acquisition of visual information, a jittery motion known as ocular drift, incessantly displaces stimuli over many photoreceptors. Previous studies have shown that acuity is impaired in the absence of retinal image motion caused by eye drift. However, the relation between individual drift characteristics and acuity remains unknown. Here we show that (a) healthy emmetropes exhibit a large variability in their amount of drift; and (b) that these differences profoundly affect the structure of spatiotemporal signals to the retina. We further show that (c) the spectral distribution of the resulting luminance modulations strongly correlates with individual visual acuity; and (d) that natural inter-trial fluctuations in the amount of drift modulate acuity. As a consequence, in healthy emmetropes acuity can be predicted from the motor behavior elicited by a simple fixation task, without directly measuring it. These results shed new light on how oculomotor behavior contributes to fine spatial vision. SignificanceHealthy humans can visually resolve extremely fine patterns, in some cases with the relevant features spanning less than a single photoreceptor on the retina. This accomplishment is particularly remarkable considering that the eyes are never stationary. Ocular drift--a motion that eludes human awareness--shifts the stimulus across many photoreceptors during the acquisition of visual information. Here we show that visual acuity depends on ocular drift. Natural variations in the amount of drift are associated with acuity both within and across subjects, so that individual acuity limits can be directly inferred from the amount of motion during fixation on a marker. Results closely follow the strength of the luminance modulations caused by ocular drift, providing support to long-standing dynamic theories of visual acuity.

neuroscience↗

bioRxiv2021

Reprogramming of the intestinal epithelial-immune cell interactome during SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents an unprecedented worldwide health problem. Although the primary site of infection is the lung, growing evidence points towards a crucial role of the intestinal epithelium. Yet, the exact effects of viral infection and the role of intestinal epithelial-immune cell interactions in mediating the inflammatory response are not known. In this work, we apply network biology approaches to single-cell RNA-seq data from SARS-CoV-2 infected human ileal and colonic organoids to investigate how altered intracellular pathways upon infection in intestinal enterocytes leads to modified epithelial-immune crosstalk. We point out specific epithelial-immune interactions which could help SARS-CoV-2 evade the immune response. By integrating our data with existing experimental data, we provide a set of epithelial ligands likely to drive the inflammatory response upon infection. Our integrated analysis of intra- and inter-cellular molecular networks contribute to finding potential drug targets, and suggest using existing anti-inflammatory therapies in the gut as promising drug repurposing strategies against COVID-19.

bioinformatics↗

bioRxiv2020

ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways

The SARS-CoV-2 pandemic of 2020 has mobilised scientists around the globe to research all aspects of the coronavirus virus and its infection. For fruitful and rapid investigation of viral pathomechanisms, a collaborative and interdisciplinary approach is required. Therefore, we have developed ViralLink: a systems biology workflow which reconstructs and analyses networks representing the effect of viruses on intracellular signalling. These networks trace the flow of signal from intracellular viral proteins through their human binding proteins and downstream signalling pathways, ending with transcription factors regulating genes differentially expressed upon viral exposure. In this way, the workflow provides a mechanistic insight from previously identified knowledge of virally infected cells. By default, the workflow is set up to analyse the intracellular effects of SARS-CoV-2, requiring only transcriptomics counts data as input from the user: thus, encouraging and enabling rapid multidisciplinary research. However, the wide-ranging applicability and modularity of the workflow facilitates customisation of viral context, a priori interactions and analysis methods. Through a case study of SARS-CoV-2 infected bronchial/tracheal epithelial cells, we evidence the functionality of the workflow and its ability to identify key pathways and proteins in the cellular response to infection. The application of ViralLink to different viral infections in a cell-type specific manner using different available transcriptomics datasets will uncover key mechanisms in viral pathogenesis. The workflow is available on GitHub (https://github.com/korcsmarosgroup/ViralLink) in an easily accessible Python wrapper script, or as customisable modular R and Python scripts.Author summary Collaborative and multidisciplinary science provides increased value for experimental datasets and speeds the process of discovery. Such ways of working are especially important at present due to the urgency of the SARS-CoV-2 pandemic. Here, we present a systems biology workflow which models the effect of viral proteins on the infected host cell, to aid collaborative and multidisciplinary research. Through integration of gene expression datasets with context-specific and context-agnostic molecular interaction datasets, the workflow can be easily applied to different datasets as they are made available. Application to diverse SARS-CoV-2 datasets will increase our understanding of the mechanistic details of the infection at a cell type specific level, aid drug target discovery and help explain the variety of clinical manifestations of the infection.Competing Interest StatementThe authors have declared no competing interest.View Full Text

systems biology↗