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May 19, 20260 citationsOpen Access

The Pupillary Light Reflex as a Dynamical Arousal Index: A Delay-Differential Framework for Non-Invasive Locus Coeruleus Estimation

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ISIsmail Sour

Key Result

The pupillary light reflex re-dilation trajectory encodes the loop gain of a delayed negative-feedback system, enabling an exact analytical solution to estimate tonic Locus Coeruleus output.

Key Points

  • This work aims to establish a theoretical model for the pupillary light reflex as a measure of arousal tied to locus coeruleus activity.
  • Developed an analytical solution for recovery time constant using the Lambert W function.
  • Performed full nonlinear simulations of the Longtin-Milton model for validating calibration.
  • Created a three-variable instrument architecture that combines multiple measures from pupillary response.
  • Validated the constructed calibration curve through simulations and analysis.
  • Confirmed the geometry of bifurcation using spectral cross-validation techniques.
  • Identified three predictions that can be tested in empirical research.

Structured PICO

P
Population
Theoretical and computational models (Longtin-Milton model of the pupillary light reflex)
I
Intervention
Delay-differential framework using the Lambert W function
C
Comparator
Classical zero-delay approximation
O
Outcome
Recovery time constant τreturn(G) and location of the Hopf bifurcation

Provides a theoretical delay-differential framework to estimate Locus Coeruleus output from the pupillary light reflex re-dilation trajectory.

Abstract

This paper argues that the re-dilation trajectory of the Pupillary Light Reflex, which standard pupillometry discards, encodes the loop gain Gof a nonlinear delayed negative-feedback system whose operating point is set by tonic Locus Coeruleus output. The central theoretical contribution is an exact analytical solution for the recovery time constant τreturn(G) derived via the Lambert W function, which eliminates the classical zero-delay approximation and correctly locates the Hopf bifurcation at Gc. Full nonlinear simulations of the Longtin-Milton model validate the calibration curve, and a spectral cross-validation independently confirms the bifurcation geometry. From this framework a three-variable instrument architecture which combines resting diameter, recovery dynamics, and a dual-wavelength chromatic post-illumination response,is derived. The work is theoretical and computational throughout; the instrument specification is a principled design consequence of the validated framework, not a clinical prototype, and three falsifiable predictions define the bridge to empirical work.

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Cite This Study

Ismail Sour (2026) studied this question. The pupillary light reflex re-dilation trajectory encodes the loop gain of a delayed negative-feedback system, enabling an exact analytical solution to estimate tonic Locus Coeruleus output.

synapsesocial.com/papers/6a0bfdc7166b51b53d379039https://doi.org/10.5281/zenodo.20072468
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