Lateralization of Pupil dilation: a novel biomarker for VNS dose-dependent effects
(2025) 6th International Brain Stimulation Conference — Location: Kobe, Japan (23.February.2025)
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- Abstract
- VNS is an adjunctive treatment for drug-resistant epilepsy. Despite ongoing research, the mechanism of action is not fully understood and optimization is necessary. Biomarkers are extensively studied in this field, and one of them is VNS-induced pupil dilation. Acute VNS elicits a phasic increase in Locus Coeruleus (LC) firing, and a dose-dependent VNS-evoked pupil dilation response (PDR) has been demonstrated in rats, and more recently in VNS-implanted patients. Additionally, it is known from the literature that unilateral stimulation of the vagus nerve can induce bilateral pupil dilation, as observed with unilateral VNS in rats. In humans, a study using transcutaneous VNS (tVNS) reported asymmetrical pupil dilation between the eyes. This asymmetry is thought to arise because the LC–noradrenaline system has stronger effects when activated by left-sided VNS, leading to a higher lateralization ratio of pupil dilation (left vs. right). This ratio could potentially serve as an innovative biomarker to differentiate patients based on their clinical response to VNS before implantation. We recorded the pupil size of four VNS-implanted patients continuously during different stimulation conditions: high intensity (routine + 0.25 mA), mid intensity (routine), low intensity (routine - 0.5 mA), and high frequency (30 Hz), mid frequency (25 Hz), low frequency (20 Hz). Trains of 11 seconds were delivered in blocks of three trains each. Mean PDR was computed during the stimulation interval (11s ON – 18s OFF) to allow comparison between conditions. We found bilateral pupil dilation in all of the patients. A lateralization ratio was preliminarily identified, which is suggesting a potential dose-dependent effect of both intensity and frequency on this ratio. Future data will help confirm whether this lateralization ratio can be consistently observed and whether it correlates with clinical outcomes, solidifying its potential as an innovative biomarker.
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Cakiroglu, I., Boughaba, N., Danthine, V., Torres Sánchez, A., Germany Morrison, E. I., El Tahry, R., & et al. (2025). Lateralization of Pupil dilation: a novel biomarker for VNS dose-dependent effects. Brain Stimulation, 18(1), 474. https://doi.org/10.1016/j.brs.2024.12.759 (Original work published 2025)