nVNS Improves Cognitive Performance Under Sleep Deprivation Stress 

Richard McKinley, MD

The use of a cervical transcutaneous vagal nerve stimulation device (ctVNS), the gammaCore noninvasive device developed by electroCore, was found to be effective in improving cognitive performance and lowering fatigue ratings compared to those not treated with ctVNS, according to recent study findings published in Communications Biology, a Nature publication.¹

The randomized, double-blind, sham-controlled trial was performed at Wright-Patterson Air Force Base and analyzed 2 groups of 20 United States Air Force personnel during 34 hours of wakefulness. Researchers concluded ctVNS may provide an alternative to pharmacological interventions when treating fatigue, as an easy-to-administer, noninvasive tool with long-lasting effects and fewer adverse effects.

“We are pleased to have successfully completed the first randomized, double-blind sham-controlled trial demonstrating the efficacy of nVNS as possible aid to cognitive performance and as a tool to counter fatigue,” Richard McKinley, MD, Air Force’s 711th Human Performance Wing, Human Effectiveness Directorate, and study investigator, said in a statement.² “Improvements in our aviators’ ability to perform tasks during the study while feeling less fatigue suggest a range of possible roles for nVNS in combating these issues in both military and civilian settings.”

A total of 40 participants, 33 men and 7 women, with an average age of 28 (± 6) years, were treated with a handheld ctVNS device, which passes a 25 Hz electrical current through the skin on the neck using 2 electrodes. The FDA-approved gammaCore product stimulated the locus coeruleus (LC) region, with the device shutting off after 2 minutes of stimulation.

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Over the course of the study, participants were asked to complete 4 performance tasks, as well as respond to a subjective mood questionnaire. Tasks included a sustained attention task (Mackworth clock test), an N-back task to assess working memory activity, a Psychomotor vigilance task to assess attention and motor responses, and an Air Force-Multi-Attribute Task Battery to evaluate throughput capacity. 

Following an initial screening, 42 participants were enrolled, with 1 participant withdrawing due to time constraints prior to data collection and another withdrawing before completion. It was determined that both the treatment group and the sham group maintained similar baselines during the first session, as a 2-tailed, 2-sample t-test found no significant difference (P <.05) between groups prior to stimulation (n = 20 for each group). 

Over a course of 8 sessions, a Bonferroni alpha-error adjustment was used, showing a per-comparison error level of 0.05/8 = 0.0063 (P <.0063). Throughput capacity was significantly higher in the group that received treatment with ctVNS, falling by 5%, compared to 15% (P <.001) in the sham group. Participants treated with ctVNS also experienced a smaller increase in subjective fatigue rating (P <.001), and it was found that 6 stimulations, totaling 12 minutes, further improved multitasking performance after 12 hours, which is when performance is anticipated to be at its worst.

“Given our positive results on various behavioral and cognitive tests related to arousal, vigilance, and attention, as measured by multitasking, reaction times, and accuracy, it is reasonable to suspect that the present method of stimulating the cervical transcutaneous vagal nerve is indeed activating the LC-NE [locus-coeruleus-norepinephrine] pathway, as hypothesized,” the authors wrote. “However, future studies are recommended to convincingly confirm this suspected link with different lines of evidence (eg, neurophysiological).”

The investigators noted several limitations to the work, primarily the sample population, which consisted of active-duty military men and women, who are general healthier and predominantly male. Additionally, there are few existing studies on the ctVNS device, creating a lack of comparison material, as the specific device has primarily been researched in clinical populations. The use of the VNS system was originally developed as a method for treating cluster headaches and migraines; however, peripheral nerve stimulation techniques generate very few adverse events, suggesting its capacity as a treatment for decreased performance associated with sleep deprivation. 

Future research should investigate different cognitive enhancements, as well as consider biomarkers and imaging analysis, investigators concluded. In doing so, a study may be able to explore the how different neural sites and regions are activated, as well as why low-current stimulation is seemingly effective. 

REFERENCES
1. McIntire LK, McKinley RA, Goodyear C, et al. Cervical transcutaneous vagal nerve stimulation (ctVNS) improves human cognitive performance under sleep deprivation stress. Commun Biol. 2021;4:624. doi:10.1038/s42003-021-02145-7
2. electroCore announces publication of study on the effect of non-invasive vagus nerve stimulation (nVNS) on cognitive performance caused by sleep deprivation. News release. electroCore, Inc. June 24, 2021. https://www.globenewswire.com/news-release/2021/06/24/2252512/0/en/electroCore-Announces-Publication-of-Study-on-the-Effect-of-non-invasive-Vagus-Nerve-Stimulation-nVNS-on-Cognitive-Performance-Caused-by-Sleep-Deprivation.html