Causal Multiscale Modeling of Ocular FLASH Electroretinography: Model Development, Experimental Fitting, and Spin-Glass--Percolation Predictions
- 1Howard University
Abstract
\textbf{Purpose:} To develop a causal multiscale model of retinal electroretinography (ERG) after ocular ultrahigh-dose-rate (FLASH) and conventional-dose-rate (CONV) irradiation, evaluate the framework against published ocular ERG data, and derive prospective dose-response predictions for future validation. \textbf{Methods:} The retina was coarse-grained into N=200 functional modules. Local rate equations were formulated as Hodgkin--Huxley-inspired conductance-balance/RC reductions of retinal ion-channel and synaptic pathways. Radiation generated an injury field that altered phototransduction, a-wave and b-wave dynamics and, in the network extension, inter-module coupling and bond survival. A reduced amplitude benchmark and nested M0/M1/M2 causal models were evaluated. \textbf{Results:} The reduced benchmark achieved R2=0.9721 and RMSE =11.94 μV. M0, M1, and M2 yielded R2=0.8546, 0.8559, and 0.8560, respectively, indicating limited independent identifiability of the network terms from amplitude data alone. Under an exploratory 50\% retained-gain criterion, the reduced benchmark predicted a-wave preservation thresholds of 28.6 Gy for FLASH and 23.7 Gy for CONV, and b-wave thresholds of 29.2 Gy and 24.1 Gy, respectively, corresponding to a model-based functional dose-modifying factor (DMF) of 1.21. \textbf{Conclusion:} The ERG amplitude data support the causal radiation-injury-to-ERG framework, while additional observables will be needed to distinguish the predicted collective-network contributions. The model also provides quantitative dose targets for prospective studies of the FLASH retinal-preservation window and a framework for testing how local retinal injury may propagate into collective dysfunction.
Related
- Validation of a Commercially Available Non-Woven Fabric Electrode for Mouse Electroretinography
- Development of an Experimental Protocol for Combined Electroporation and Phototherapy Treatment Against Melanoma Cells
- The C-type lectin receptor Dectin-2 is crucial for the development of experimental autoimmune skin disease
- Efficiency--Complexity Tradeoff and Constrained Percolation
- A recurrent neuronal model for the effect of predictions on sensory processes
BibTeX
@misc{abolfath2026causal,
title = {{Causal Multiscale Modeling of Ocular FLASH Electroretinography: Model Development, Experimental Fitting, and Spin-Glass--Percolation Predictions}},
author = {R. Abolfath and M. Rezaee},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762909},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762909v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Causal Multiscale Modeling of Ocular FLASH Electroretinography: Model Development, Experimental Fitting, and Spin-Glass--Percolation Predictions
AU - R. Abolfath
AU - M. Rezaee
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762909
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762909v1
AB - \textbf{Purpose:} To develop a causal multiscale model of retinal electroretinography (ERG) after ocular ultrahigh-dose-rate (FLASH) and conventional-dose-rate (CONV) irradiation, evaluate the framework against published ocular ERG data, and derive prospective dose-response predictions for future validation. \textbf{Methods:} The retina was coarse-grained into N=200 functional modules. Local rate equations were formulated as Hodgkin--Huxley-inspired conductance-balance/RC reductions of retinal ion-channel and synaptic pathways. Radiation generated an injury field that altered phototransduction, a-wave and b-wave dynamics and, in the network extension, inter-module coupling and bond survival. A reduced amplitude benchmark and nested M0/M1/M2 causal models were evaluated. \textbf{Results:} The reduced benchmark achieved R^2=0.9721 and RMSE =11.94 μV. M0, M1, and M2 yielded R^2=0.8546, 0.8559, and 0.8560, respectively, indicating limited independent identifiability of the network terms from amplitude data alone. Under an exploratory 50\% retained-gain criterion, the reduced benchmark predicted a-wave preservation thresholds of 28.6 Gy for FLASH and 23.7 Gy for CONV, and b-wave thresholds of 29.2 Gy and 24.1 Gy, respectively, corresponding to a model-based functional dose-modifying factor (DMF) of 1.21. \textbf{Conclusion:} The ERG amplitude data support the causal radiation-injury-to-ERG framework, while additional observables will be needed to distinguish the predicted collective-network contributions. The model also provides quantitative dose targets for prospective studies of the FLASH retinal-preservation window and a framework for testing how local retinal injury may propagate into collective dysfunction.
ER -