Effects of off-line auricular transcutaneous vagus nerve stimulation (taVNS) on a short-term memory task: a pilot study

Francesco Fisicaro^1,2Klizia Cortese³Rita Bella⁴Manuela Pennisi¹Giuseppe Lanza^5,6Kaoru Yuasa²Yoshikazu Ugawa⁷Yasuo Terao^2*

• ¹Department of Biomedical and BIotechnology Science, University of Catania, Catania, Sicily, Italy
• ²Department of Medical Physiology, Kyorin University, Tokyo, Japan
• ³Department of Education Sciences, University of Catania, Catania, Sicily, Italy
• ⁴Department of Medical, Surgical Sciences and Advanced Technologies G.F. Ingrassia, University of Catania, Catania, Sicily, Italy
• ⁵Department of Surgery and Medical-Surgical Specialities, University of Catania, Catania, Italy
• ⁶Clinical Neurophysiology Research Unit, Oasi Research Institute-IRCCS, Catania, Italy
• ⁷Department of Neurophysiology, School of Medicine, Fukushima Medical University, Fukushima, Fukushima, Japan

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. Subject 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 to 10 compared to pre stimulation and for span 5 to 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.