Abstract
IntroductionInvasive 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.MethodsWe 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.ResultsIn 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.ConclusionIn 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.
Highlights
Invasive vagus nerve stimulation (VNS) improves word recognition memory in patients with epilepsy
The effect of transcutaneous VNS (tVNS) on memory function was investigated in healthy volunteers belonging to two different age groups: young individuals between 18 and 30 years and older individuals between 45 and 80 years
While VNS was previously shown to improve performance on memory paradigms, we did not find a significant effect of tVNS on verbal memory performance in young and older healthy participants
Summary
Invasive vagus nerve stimulation (VNS) improves word recognition memory in patients with epilepsy. The brain is able to reorganize itself during aging, learning, and following damage, a process defined as neural plasticity This concept has stimulated the development of new treatment options for cognitive decline, aiming to enhance this plastic potential (Duffau, 2006). It has been well documented that arousal shortly following a learning experience, during the process of memory consolidation, can modulate the storage of information (Cahill and McGaugh, 1996; McGaugh, 1966; McGaugh, 2015) This process has not been fully elucidated, preclinical research suggests that the vagus nerve plays a crucial role in transmitting the signals of peripheral neuromodulators associated with arousal to brain structures involved in memory storage (Williams and McGaugh, 1993; Nogueira et al, 1994; Hassert et al, 2004)
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