Fisicaro Francesco, Cortese Klizia, Bella Rita, Pennisi Manuela, Lanza Giuseppe, Yuasa Kaoru, Ugawa Yoshikazu, Terao Yasuo
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
Department of Medical Physiology, Kyorin University, Shinkawa, Tokyo, Japan.
Front Aging Neurosci. 2025 Apr 28;17:1549167. doi: 10.3389/fnagi.2025.1549167. eCollection 2025.
One of the commonly used indices of short-term memory (STM) is the digit span task. Prior studies have proposed pupil dilation as a measure of task engagement and as a promising biomarker of vagal activation. Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel non-invasive brain stimulation technique which might be used to improve cognition and modulate pupil size through its effects on the noradrenergic release in the locus coeruleus. No previous study has investigated the effects of off-line taVNS on a digit span task. With this single-blind, sham-controlled, crossover design trial, we aimed to assess whether taVNS was able to improve the digit span score, as well as to modulate the pupillary response to cognitive load in a sample of 18 elderly Japanese volunteers with no self-reported cognitive impairments.
Subjects were randomized to receive either real or sham taVNS during a digit span task while recording the pupil size, and then switched over to the other treatment group. We found that real stimulation significantly reduced the mean number of errors performed at span length 7, 8, and 9 (-0.83, -0.90, and -0.39, respectively compared to pre-stimulation values, and -0.71, -1.08, and -0.79, respectively, compared to sham stimulation). Additionally, real taVNS stimulation slightly but significantly increased the pupil size at all span lengths during the encoding period of the task, with larger effects for span 7-10 compared to pre-stimulation, and for span 5-10 compared to sham. No effect over the pupil size was found during the recall period.
Our results suggest that taVNS might selectively improve the cognitive performance during the encoding phase of the task. Although further studies are needed to better clarify the optimal stimulation parameters, findings from this study could support the use of taVNS as a safe neuromodulation technique to improve cognitive function.
数字广度任务是常用的短期记忆（STM）指标之一。先前的研究提出瞳孔扩张可作为任务参与度的衡量指标，也是迷走神经激活的一个有前景的生物标志物。经皮耳迷走神经刺激（taVNS）是一种新型非侵入性脑刺激技术，可能通过对蓝斑去甲肾上腺素能释放的影响来改善认知并调节瞳孔大小。此前尚无研究探讨离线taVNS对数字广度任务的影响。在这项单盲、假刺激对照、交叉设计试验中，我们旨在评估taVNS是否能够提高数字广度得分，以及调节18名无自我报告认知障碍的日本老年志愿者样本中瞳孔对认知负荷的反应。
在数字广度任务期间，受试者被随机分配接受真实或假taVNS刺激，同时记录瞳孔大小，然后切换到另一治疗组。我们发现，真实刺激显著减少了在数字广度为7、8和9时的平均错误次数（与刺激前值相比分别为-0.83、-0.90和-0.39，与假刺激相比分别为-0.71、-1.08和-0.79）。此外，在任务编码期，真实taVNS刺激在所有数字广度下均轻微但显著增加了瞳孔大小，与刺激前相比，数字广度为7-10时效果更大，与假刺激相比，数字广度为5-10时效果更大。在回忆期未发现对瞳孔大小有影响。
我们的结果表明，taVNS可能在任务的编码阶段选择性地改善认知表现。尽管需要进一步研究以更好地阐明最佳刺激参数，但本研究结果可能支持将taVNS作为一种安全的神经调节技术来改善认知功能。
