Purpose: The Locus Coeruleus (LC) plays a vital role by releasing norepinephrine, which contributes to the antiepileptic effects of Vagus Nerve Stimulation (VNS). LC activity…
Purpose: The Locus Coeruleus (LC) plays a vital role by releasing norepinephrine, which contributes to the antiepileptic effects of Vagus Nerve Stimulation (VNS). LC activity also influences pupil dilation. Investigating
VNS dose-dependent Pupillary Dilation Response (PDR) may provide novel neurophysiological insights into therapeutic response and allow for an objective and personalized optimization of stimulation parameters.
Methods: Fourteen VNS-implanted patients (9 responders, 5 non-responders) treated for at least 6 months were retrospectively recruited. VNS intensities were adjusted from 0.25 mA to 2.25 mA, or to the highest tolerable level. Concurrently, we tracked pupil size in the left eye and gathered patients’ subjective perception scores. Individual curve fitting was used to explore the relationship between VNS intensity and PDR.
Results: PDR increased with stimulation intensity, particularly in responders. In 6 patients, an inverted U-shaped relationship between intensity and PDR was observed 2–3 s after stimulation onset. A significant interaction was found between VNS intensity and responder status, independent of subjective perception.
Conclusions: VNS induces a dose-dependent PDR, which differs between responders and non-responders. In nearly half the patients, the dose–response relationship was characterized by an inverted U-shape with a maximal VNS effect.
Significance: We propose VNS-induced PDR as a novel biomarker of VNS response.
