Development of a Unified Cardiovascular-Pupillary Model for Interpreting Pupil Size Variability as an Autonomic...

Area of Science:

• Computational physiology
• Autonomic nervous system research
• Ocular biomechanics

Background:

• Pupil size variability (PSV) is a potential non-contact biomarker for autonomic nervous system (ANS) function.
• The precise physiological mechanisms underlying PSV and its relationship to cardiovascular autonomic balance are not fully understood.

Purpose of the Study:

• To develop a computational model investigating the physiological basis of PSV.
• To assess how frequency-domain indices of PSV relate to cardiovascular autonomic balance.

Main Methods:

• Integrated a cardiovascular regulation model with a biomechanical pupillary muscle model.
• Simulated PSV and heart rate variability (HRV) using respiratory and baroreflex inputs.
• Performed frequency-domain analyses to compare simulated PSV and HRV across various autonomic states.

Main Results:

• The model demonstrated that PSV arises from respiratory and baroreceptor inputs, naturally exhibiting range-nonlinearity (RNL) due to iris biomechanics.
• Simulated PSV mirrored key physiological responses, including inspiration-linked dilation and parasympathetic modulation.
• Frequency-domain analysis of PSV showed low- and high-frequency components analogous to HRV, but their magnitudes were sensitive to autonomic state and mean pupil size.

Conclusions:

• Established a mechanistic framework for interpreting PSV as a cardiovascular autonomic biomarker.
• Findings support the development of non-invasive, wearable, eye-based systems for ANS monitoring.