Biology subjects

Seitz, A.

Publications and source records attributed to Seitz, A..

7 recordsLinked to original sources

bioRxiv2026

PLFest: A Multi-Site Validation of an Open Platform for Visual and Cognitive Assessment

PurposeTo evaluate the feasibility, validity, and scalability of PLFest, an open-source, Unity-based, cross-platform application designed for standardized, multi-site visual and cognitive assessment and training. MethodsTwo hundred sixty participants (mean age = 23 years) were recruited across four university sites in the United States. Participants completed a battery of five visual assessments administered through PLFest, including visual acuity, contrast sensitivity, spatial frequency cutoff, contrast sensitivity at spatial-frequency cutoff, and visual search. Five cognitive assessments measuring visuospatial working memory, verbal working memory, fluid reasoning, inhibitory control, and selective attention were also administered. Descriptive statistics and performance distributions were examined and compared with normative data. ResultsVisual acuity and contrast sensitivity measures closely matched previously reported normative values obtained using established clinical and psychophysical methods. Spatial frequency cutoff and visual search tasks produced stable threshold estimates while showing substantial inter-individual variability. Performance across all cognitive assessments was consistent with published validation studies of the corresponding tasks. Across the full battery, adaptive procedures demonstrated reliable convergence and generated well-distributed performance measures without evidence of substantial floor or ceiling effects. Importantly, these findings were observed across four geographically distributed testing sites using standardized consumer-grade tablet hardware. ConclusionsPLFest provides reliable and scalable assessment of visual and cognitive function using portable consumer devices. The platform supports standardized data collection across distributed research settings while maintaining performance characteristics consistent with established laboratory and clinical benchmarks. These findings support the use of PLFest as a reliable framework for large-scale studies of vision and cognition. Translational RelevanceBy reducing dependence on specialized laboratory infrastructure and trained personnel, PLFest may facilitate broader access to visual and cognitive assessment, enabling large-scale research, screening, and future rehabilitation applications.

neuroscience↗

bioRxiv2025

CASPR facilitates clearance of degenerating axons by Schwann cells and macrophages after peripheral nerve injury

In the peripheral nervous system (PNS) debris of injured axons is efficiently removed by Schwann cells (SCs) and macrophages (Mphs) - a process which is vital for nerve regeneration. Molecular so-called "eat-me" signals, mediating axon-SC/axon-Mph crosstalk and debris clearance after injury are just at the beginning of being identified. Herein, we describe the axonal node protein contactin-associated protein (CASPR) as a potential novel signal for axonal debris removal in peripheral nerve injury. In healthy nerves, CASPR is restricted to Ranviers nodes interacting with glia-derived partner proteins to assure saltatory action potential propagation. In injured murine and human nerves, we describe upregulation and re-localization of CASPR protein along the axons. Enhanced CASPR presence after injury appears to involve local axonal translation rather than transcriptional regulation. Of note, CASPR overexpression in murine central and peripheral neurons in vitro has a growth inhibitory effect. More importantly, axonal debris deriving from injured nerves - and hence having increased CASPR content - are phagocytosed more efficiently than debris of healthy nerves. Interfering with CASPR by function-blocking antibodies strongly reduces axonal debris uptake. This finding demonstrates a functional relevance of CASPR as a potential "eat me" signal in this process.

neuroscience↗

bioRxiv2025

Examining oculomotor behavior in central vision loss with a gaze-contingent display

Patients with central vision loss due to macular degeneration (MD) must rely on their peripheral vision for tasks normally performed by the fovea. Many patients develop a preferred retinal locus (PRL), an eccentric retinal location used as a substitute for the damaged fovea in tasks such as face recognition, navigation, and reading. However, the mechanisms underlying PRL development remain elusive, and no single hypothesis fully explains its characteristics. Investigations into PRL development are hindered by oculomotor assessments, which often focus on fixation ability while neglecting other eye movement characteristics and potentially conflating different behaviors over time. In previous work, we introduced a series of oculomotor metrics in cases of simulated central vision loss, demonstrating that complex profiles of eye movement behavior can be extracted from a simple visual task. Here we present longitudinal data from 10 patients with MD as evidence of the feasibility of using these metrics to characterize different profiles of eye movements following central vision loss. Consistent with findings in healthy individuals using artificial scotoma, the metrics reveal substantial individual differences in behavior, both at baseline and after visual training. Overall, patients exhibit significantly higher saccadic re-referencing than controls, despite larger inter-individual differences. These metrics provide a detailed evaluation of oculomotor behavior in patients with central vision loss and offer a valuable tool for assessing progress in training protocols.

neuroscience↗

bioRxiv2025

Connectome-based predictive modelling predicts frailty levels in older adults

Frailty is characterized by a persistent and progressive decline in physiological reserves, leading to increased vulnerability to stressors and a heightened risk of adverse health outcomes, both physically and mentally. Despite frailtys prevalence in older adults, there is limited research on its neural substrates, especially using task-based brain functional connectivity. In this study, we used connectome-based predictive modelling (CPM) to find a linear relationship between task-based connectomes -- taken from tasks that involved similar handgrip manipulations -- and a separate measure of frailty: the maximum grip strength in older adults. We observed that the task-based connectomes were able to explain individual differences in grip strength, with the Subcortical and Cerebellum network, particularly the caudate nucleus, functional connectivity being the strongest predictor. These findings demonstrate that task-based functional connectomes can serve as personalized markers that can predict individual behavioral measures, including handgrip strength, and point to involvement of the caudate nucleus in frailty. Key pointsO_LIWe used connectome-based predictive modeling on task-based fMRI to predict grip strength in older adults, a key marker of physical frailty. C_LIO_LIThe model significantly explained inter-individual differences in contraction strength using functional connectivity patterns. C_LIO_LISubcortical regions, especially the caudate nucleus, played a major role in prediction, highlighting their relevance in frailty assessment and potential interventions. C_LI

neuroscience↗

bioRxiv2024

ABBA, a novel tool for whole-brain mapping, reveals brain-wide differences in immediate early genes induction following learning

Unbiased characterization of whole-brain cytoarchitecture represents an invaluable tool for understanding brain function. For this, precise mapping of histological markers from 2D sections onto 3D brain atlases is pivotal. Here, we present two novel software tools facilitating this process: Aligning Big Brains and Atlases (ABBA), designed to streamline the precise and efficient registration of 2D sections to 3D reference atlases, and BraiAn, an integrated suite for multi-marker automated segmentation, whole-brain statistical analysis, and data visualisation. Combining these tools, we performed a comprehensive comparative study of the whole-brain expression of three of the most widely used immediate early genes (IEGs). Thanks to their neural activity-dependent expression, IEGs have been used for decades as a proxy of neural activity to generate unbiased mapping of activity following behaviour, but their respective induction in response to neuronal activation across the entire brain remains unclear. To address this question, we systematically compared the brain-wide expression cFos, Arc and NPAS4, three abundantly used IEGs, across three different behavioural conditions related to memory. Our results highlight major differences in both their distribution and induction patterns, indicating that they do not represent equivalent markers across brain areas or activity states, but can provide instead complementary information.

neuroscience↗

bioRxiv2023

S100A1's single cysteine is an indispensable redox-switch for the protection against diastolic calcium leakage in cardiomyocytes

The EF-hand calcium (Ca2+) sensor protein S100A1 combines inotropic with antiarrhythmic potency in cardiomyocytes (CM). Oxidative posttranslational modification (ox-PTM) of S100A1s conserved, single cysteine residue (C85) via reactive nitrogen species (i.e. S-nitrosylation or glutathionylation) was proposed to modulate conformational flexibility of intrinsically disordered sequence fragments and to increase the molecules affinity towards Ca2+. In light of the unknown biological functional consequence, we aimed to determine the impact of the C85 moiety of S100A1 as a potential redox-switch. We first uncovered that S100A1 is endogenously glutathionylated in the adult heart in vivo. To prevent glutathionylation of S100A1, we generated S100A1 variants that were unresponsive to ox-PTMs. Overexpression of wildtype (WT) and C85-deficient S100A1 protein variants in isolated CM demonstrated equal inotropic potency, as shown by equally augmented Ca2+ transient amplitudes under basal conditions and {beta}-adrenergic receptor ({beta}AR) stimulation. However, in contrast ox-PTM defective S100A1 variants failed to protect against arrhythmogenic diastolic sarcoplasmic reticulum (SR) Ca2+ leak and ryanodine receptor (RyR2) hypernitrosylation during {beta}-AR stimulation. Despite diastolic performance failure, C85-deficient S100A1 protein variants exerted similar Ca2+-dependent interaction with the RyR2 than WT-S100A1. Dissecting S100A1s molecular structure-function relationship, our data indicate for the first time that the conserved C85 residue potentially acts as a redox-switch that is indispensable for S100A1s antiarrhythmic but not its inotropic potency in CM. We therefore propose a model where C85s ox-PTM determines S100A1s ability to beneficially control diastolic but not systolic RyR2 activity.

molecular biology↗

bioRxiv2022

Locus coeruleus neuromelanin predicts ease of attaining and maintaining neural states of arousal

The locus coeruleus (LC), a small subcortical structure in the brainstem, is the brains principal source of norepinephrine. It plays a primary role in regulating stress, the sleep-wake cycle, and attention, and its degradation is associated with aging and neurodegenerative diseases associated with cognitive deficits (e.g., Parkinsons, Alzheimers). Yet precisely how norepinephrine drives brain networks to support healthy cognitive function remains poorly understood - partly because LCs small size makes it difficult to study noninvasively in humans. Here, we characterized LCs influence on brain dynamics using a hidden Markov model fitted to functional neuroimaging data from healthy young adults across four attention-related brain networks and LC. We modulated LC activity using a behavioral paradigm and measured individual differences in LC magnetization transfer contrast. The model revealed five hidden states, including a stable state dominated by salience-network activity that occurred when subjects actively engaged with the task. LC magnetization transfer contrast correlated with this states stability across experimental manipulations and with subjects propensity to enter into and remain in this state. These results provide new insight into LCs role in driving spatiotemporal neural patterns associated with attention, and demonstrate that variation in LC integrity can explain individual differences in these patterns even in healthy young adults.

neuroscience↗