bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.06.23.661014

Healthy human eyes misaligned optical components: Binocular Listings law

Abstract

The healthy human eyes optical components are misaligned. Although important in studying vision quality, it has been overlooked in research on binocular and oculomotor vision. This study presents the construction of ocular torsion in the binocular system that incorporates the fovea displaced from the posterior pole and the lens tilted away from the eyes optical axis. When the eyes binocular posture changes, each eyes torsional position transformations, computed in the framework of Rodrigues vector, are visualized in GeoGebra simulations. Listings law, important in oculomotor control by constraining a single eye redundant torsional degree of freedom, is ab initio formulated for bifoveal fixations in the binocular system with misaligned optical components for the fixed upright head. It leads to the configuration space of binocularly constrained eyes fixations, including the noncommutativity rule. This formulation modifies the Listing plane of the straight-ahead eyes primary position by replacing it with the binocular eyes posture corresponding to the empirical horopters abathic distance fixation, a unique bifoveal fixation for which the longitudinal horopter is a straight frontal line. Notably, it corresponds to the eye muscles natural tonus resting position, which serves as a zero-reference level for convergence effort. Supported by ophthalmology studies, it revises the elusive neurophysiological significance of the Listing plane. Furthermore, the binocular constraints couple 3D changes in the eyes orientation and, hence, torsional positions during simulations with GeoGebras dynamic geometry. The binocular Listings law developed here can support this coupling, which is important in oculomotor control. The results obtained in this study should be a part of the answers to the questions posted in the literature on the relevance of Listings law to clinical practices. Author summaryOur eye optical components are misaligned: the fovea is displaced from the eyes posterior pole, and the lens is tilted away from the optical axis. Listings law, important in oculomotor control, has not only overlooked the misaligned eyes optics but was also formulated for a single eye, with a later ad hoc extension added for binocular vision. The purpose of Listings law is to constrain the eyes redundant torsional degrees of freedom, thereby supporting neural processing in the development of our spatial understanding by controlling the noncommutativity of the eyes rotations. This goal cannot be fully met because Listings law is monocular, but we acquire an understanding of the scene through bifoveal fixations on objects. In this work, I construct ocular torsion that accounts for the eyes misaligned optics and incorporate it into Listings law. It directly leads to its first ab initio consistent binocular formulation, which is visualized in a computer simulation. Supported by ophthalmological studies, it revises the still elusive neurophysiological significance of the Listing plane, the basic ingredient of Listings law. It also resolves the persistent lack of a generally accepted explanation for Listings law. The results of this study are likely to be important in the ongoing discussion in the literature regarding the relevance of Listings law to clinical practices.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Turski, J.. 2025-06-25. Healthy human eyes misaligned optical components: Binocular Listings law. https://doi.org/10.1101/2025.06.23.661014

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗