Transcutaneous VNS shows greater cognitive and psychological benefits than invasive VNS: a meta-analysis of vagus nerve stimulation studies

This is the authors' abstract. We don't add key points for this paper.

Vagus nerve stimulation (VNS) is increasingly investigated for modulating cognition and psychological function, but the magnitude and determinants of its effects remain unclear. We systematically synthesised 222 effect sizes from 59 studies (1,491 participants) to compare invasive cervical VNS (iVNS) with transcutaneous VNS (tVNS) across executive control, memory, attention, perception, affect and general cognition. Across modalities, VNS produced a small but robust improvement in cognitive and psychological outcomes (Hedges’ g = 0.22, s.e. = 0.04, P < 0.001), which persisted after exclusion of outliers and restriction to sham-controlled studies. tVNS showed consistent benefits across executive control, working memory and affect, whereas the evidence for iVNS was more limited. The magnitude of the effect varied substantially across participant populations, from no detectable benefit in epilepsy to a large effect in other clinical populations (g = 0.69; subgroup difference χ² = 28.79, P < 0.0001). Population characteristics accounted for greater variation in treatment effects than stimulation frequency, intensity, site or duration. The efficacy of VNS is determined not solely by how the nerve is stimulated, but critically by whom it is stimulated in, making patient selection an important consideration for the clinical translation of both invasive and non-invasive VNS.