Effects of Noninvasive Cervical Vagal Nerve Stimulation on Cognitive Performance But Not Brain Activation in Healthy Adults

Abstract

Objectives: While preliminary evidence suggests that noninvasive vagal nerve stimulation (nVNS) may enhance cognition, to our knowledge, no study has directly assessed the effects of nVNS on brain function and cognitive performance in healthy individuals. The aim of this study was therefore to assess whether nVNS enhances complex visuospatial problem solving in a normative sample. Functional magnetic resonance imaging (fMRI) was used to examine underlying neural substrates.

Material and methods: Participants received transcutaneous cervical nVNS (N = 15) or sham (N = 15) stimulation during a 3 T fMRI scan. Stimulation lasted for 2 min at 24 V for nVNS and at 4.5 V for sham. Subjects completed a matrix reasoning (MR) task in the scanner and a forced-choice recognition task outside the scanner. An analysis of variance (ANOVA) was used to assess group differences in cognitive performance. And linear mixed effects (LMEs) regression analysis was used to assess main and interaction effects of experimental groups, level of MR task difficulty, and recall accuracy on changes in blood oxygen level-dependent (BOLD) signal.

Results: Subjects who received nVNS showed higher accuracy for both easy (p = 0.017) and hard (p = 0.013) items of the MR task, slower reaction times for hard items (p = 0.014), and fewer false negative errors during the forced-choice recognition task (p = 0.047). MR task difficulty related to increased activation in frontoparietal regions (p < 0.001). No difference between nVNS and sham stimulation was found on BOLD response during performance of the MR task.

Conclusions: We hypothesize that nVNS increased attention compared to sham, and that this effect led to enhanced executive functions, and consequently to better performance on visuospatial reasoning and recognition tasks. Results provide initial support that nVNS may be a low-risk, low-cost treatment for cognitive disorders.

Keywords: Attention; cervical noninvasive vagal nerve stimulation; cognition; functional magnetic resonance imaging.

Figure 1.

Timeline of study illustrating order and timing of stimulation and tasks. Graphic adapted with permission from Lerman et al. 2019.

Figure 2.

Hard and easy sample items of Matrix Reasoning task. Task would automatically advance upon selection or when time had expired (easy=16.8s, hard=26s). Task were separated by an intertrial interval (ITI) of 1.5s and fixation time was provided sporatically through the task.

Figure 3.

Lateral view of the brain showing main effect for task activation for easy items. L = left hemisphere, R = right hemisphere. Color bar represents t statistic.