Transcutaneous Vagus Nerve Stimulation Does Not Affect Verbal Memory Performance in Healthy Volunteers

Abstract

Introduction: Invasive vagus nerve stimulation (VNS) improves word recognition memory in patients with epilepsy. Recent studies with transcutaneous VNS (tVNS) have also shown positive effects on various subdomains of cognitive functioning in healthy volunteers. In this randomized, controlled, crossover study, we investigated the effect of tVNS on a word recognition memory paradigm in healthy volunteers to further investigate the potential of tVNS in the treatment of cognitive disorders.

Methods: We included 41 healthy participants aged between 18 and 30 years (young age group) and 24 healthy participants aged between 45 and 80 years (older age group). Each participant completed a word recognition memory paradigm during three different conditions: true tVNS, sham, and control. During true tVNS, stimulation was delivered at the cymba conchae. Sham stimulation was delivered by stimulating the earlobe. In the control condition, no stimulation was given. In each condition, participants were asked to remember highlighted words from three test paragraphs. Accuracy scores were calculated for immediate recall after each test paragraph and for delayed recognition at the end of the paradigm. We hypothesized that highlighted words from paragraphs in the true tVNS condition would be more accurately recalled and/or recognized compared to highlighted words from paragraphs in the sham or control condition.

Results: In this randomized study, tVNS did not affect the accuracy scores for immediate recall or delayed recognition in both age groups. The younger group showed significantly higher accuracy scores than the older group. The accuracy scores improved over time, and the most recently learned words were better recognized. Participants rated true tVNS as significantly more painful; however, pain was not found to affect accuracy scores.

Conclusion: In this study, tVNS did not affect verbal memory performance in healthy volunteers. Our results could not replicate the positive effects of invasive VNS on word recognition memory in epilepsy patients. Future research with the aim of improving cognitive function should focus on the rational identification of optimized and individualized stimulation settings primarily in patients with cognitive deficits.

Keywords: cognition; delayed recognition; immediate recall; transcutaneous vagus nerve stimulation; verbal memory performance; word recognition memory paradigm.

FIGURE 1

Overview of the study. After preparation of the experimental session and one practice paragraph, the word recognition memory paradigm is conducted. Three experimental conditions are used, separated by a washout period of 30 min. Stimulation () is delivered 2 min after reading a paragraph and followed by two questions and a free recall task. This is repeated three times per condition. At the end of the paradigm, participants perform a recognition test.

FIGURE 2

Immediate recall (left) and delayed recognition (right) accuracy scores in percentage for the three experimental conditions for the young and old age group. There was no significant effect of experimental condition on immediate recall and delayed recognition scores in both age groups. Line plots represent mean scores. Error bars represent standard error.

FIGURE 3

Immediate recall (left) and delayed recognition (right) accuracy scores in percentage during the three blocks of the experimental session for the young and the old group. A significant effect of order was seen on immediate recall scores in the old age group and on delayed recognition scores in both age groups, showing significantly higher scores toward the end of the paradigm. Line plots represent mean scores. Error bars represent standard error.

FIGURE 4

(A) Correlation between immediate recall scores and stimulation intensity for the young group (left) and the old group (right). There was no correlation between stimulation intensity and immediate recall scores in both age groups. (B) Correlation between delayed recognition scores and stimulation intensity for the young group (left) and the old group (right). There was no correlation between stimulation intensity and delayed recognition scores in both age groups.