Institute of NeuroScience, Catholic University of Louvain, Brussels, Belgium.
Institute of NeuroScience, Catholic University of Louvain, Brussels, Belgium.
Brain Stimul. 2022 Nov-Dec;15(6):1498-1507. doi: 10.1016/j.brs.2022.11.002. Epub 2022 Nov 17.
Modulation of the locus coeruleus (LC)-noradrenergic system is a key mechanism of vagus nerve stimulation (VNS). Activation of the LC produces pupil dilation, and the VNS-induced change in pupil diameter was demonstrated in animals as a possible dose-dependent biomarker for treatment titration.
This study aimed to characterize VNS-induced pupillary responses in epileptic patients.
Pupil diameter was recorded in ten epileptic patients upon four stimulation conditions: three graded levels of VNS intensity and a somatosensory control stimulation (cutaneous electrical stimulation over the left clavicle). For each block, the patients rated the intensity of stimulation on a numerical scale. We extracted the latency of the peak pupil dilation and the magnitude of the early (0-2.5 s) and late components (2.5-5 s) of the pupil dilation response (PDR).
VNS elicited a peak dilation with longer latency compared to the control condition (p = 0.043). The magnitude of the early PDR was significantly correlated with the intensity of perception (p = 0.046), whereas the late PDR was not (p = 0.19). There was a significant main effect of the VNS level of intensity on the magnitude of the late PDR (p = 0.01) but not on the early PDR (p = 0.2). The relationship between late PDR magnitude and VNS intensity was best fit by a Gaussian model (inverted-U).
The late component of the PDR might reflect specific dose-dependent effects of VNS, as compared to control somatosensory stimulation. The inverted-U relationship of late PDR with VNS intensity might indicate the engagement of antagonist central mechanisms at high stimulation intensities.
蓝斑核（LC）-去甲肾上腺素能系统的调制是迷走神经刺激（VNS）的关键机制。LC 的激活会导致瞳孔扩大，并且已经在动物中证明 VNS 诱导的瞳孔直径变化是一种可能的剂量依赖性治疗滴定生物标志物。
本研究旨在描述癫痫患者的 VNS 诱导的瞳孔反应。
在四种刺激条件下记录了十位癫痫患者的瞳孔直径：三种不同强度的 VNS 级别和一种躯体感觉控制刺激（左锁骨上的皮肤电刺激）。对于每个刺激块，患者根据数字量表对刺激强度进行评分。我们提取了瞳孔扩张的峰值潜伏期以及瞳孔扩张反应（PDR）的早期（0-2.5 秒）和晚期（2.5-5 秒）分量的幅度。
与对照条件相比，VNS 诱发的峰值扩张具有更长的潜伏期（p = 0.043）。早期 PDR 的幅度与感知强度显著相关（p = 0.046），而晚期 PDR 则不相关（p = 0.19）。VNS 强度水平对晚期 PDR 幅度有显著的主效应（p = 0.01），但对早期 PDR 没有（p = 0.2）。晚期 PDR 幅度与 VNS 强度之间的关系最符合高斯模型（倒 U 型）。
与对照躯体感觉刺激相比，PDR 的晚期分量可能反映了 VNS 的特定剂量依赖性效应。晚期 PDR 与 VNS 强度的倒 U 关系可能表明在高刺激强度下存在拮抗的中枢机制的参与。
