The potential of invasive and non-invasive vagus nerve stimulation to improve verbal memory performance in epilepsy patients

Abstract

It has been demonstrated that acute vagus nerve stimulation (VNS) improves word recognition memory in epilepsy patients. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained interest as a non-invasive alternative to improve cognition. In this prospective randomized cross-over study, we investigated the effect of both invasive VNS and taVNS on verbal memory performance in 15 patients with drug-resistant epilepsy. All patients conducted a word recognition memory paradigm in 3 conditions: VNS ON, VNS OFF and taVNS (3-period 3-treatment cross-over study design). For each condition, patients memorized 21 highlighted words from text paragraphs. Afterwards, the intervention was delivered for 30 s. Immediate recall and delayed recognition scores were obtained for each condition. This memory paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON and VNS OFF (2-period 2-treatment cross-over study design). Acute VNS and taVNS did not improve verbal memory performance. Immediate recall and delayed recognition scores were significantly improved after 6 weeks of VNS treatment irrespective of the acute intervention. We can conclude that the previously described positive effects of invasive VNS on verbal memory performance could not be replicated with invasive VNS and taVNS. An improved verbal memory performance was seen after 6 weeks of VNS treatment, suggesting that longer and more repetitive stimulation of the vagal pathway is required to modulate verbal memory performance.Clinical trial registration number: NCT05031208.

Transcutaneous auricular vagus nerve stimulation in poststroke cognitive impairment: protocol for a randomised controlled trial

“…62 Because no study to date has examined the effects of TAVNS on PSCI prevention or treatment, our design is based on assessments of verbal memory performance in patients with epilepsy. Mertens et al 29 reported improved verbal memory performance after 6 weeks of VNS. Considering that our TAVNS intervention will begin around week 4 poststroke, and that 12 weeks is widely recommended as the diagnostic time point for PSCI, it is reasonable to extend treatment to 8 weeks so that we can examine cognitive function changes.…”

“… 26 Functional brain imaging has shown that TAVNS and iVNS have similar activation patterns, suggesting that the former effectively activates vagal trajectories and has the potential to induce similar effects. 27 28 Clinical studies have also shown that TAVNS can effectively improve cognitive function in those with epilepsy 29 and depression, 30 and in healthy individuals. 31 32 However, whether TAVNS has the same effects in those with PSCI is unclear.…”

Non-invasive vagus nerve stimulation in epilepsy patients enhances cooperative behavior in the prisoner’s dilemma task

“…The investigation of effect of tVNS on social behavior in healthy participants and the associated neural networks will be subject to future studies. Nevertheless, recent studies indicate that discrepancies between the outcome of studies investigating VNS effects on cognition in epilepsy patients and healthy participants, e.g., on recognition memory 14 , 59 , are a result of different modes of VNS application, i.e., invasive vs. transcutaneous stimulation respectively, rather than the pathology 15 .…”

“…This goes in line with evidence from human imaging studies indicating that tVNS is associated with blood-oxygen-level-dependent (BOLD) changes in brain areas involved in reward-processing, such as the dopaminergic midbrain and striatum 12 , 13 . Based on current evidence, these effects are function-specific, as studies failed to observe general effects, i.e., effects across age groups, the study population and independent of emotional processing, of tVNS on other cognitive functions such as recognition memory 14 , 15 , implicit learning 16 , conflict processing 17 , 18 or response inhibition 19 .…”

Basal Forebrain Impairment: Understanding the Mnemonic Function of the Septal Region Translates in Therapeutic Advances

“…Transcutaneous vagus nerve stimulation is shown to enhance the associative memory in older individuals ( Jacobs et al, 2015 ). A recent study found that 6 weeks of VNS treatment triggered improvement in immediate recall and delayed recognition scores examined in epileptic patients ( Mertens et al, 2022 ). The authors concluded that longer and more repetitive stimulation of the vagus nerve may be required to effectively modulate memory performance.…”