In this prospective, randomized, cross-over study, we investigated the effect of both invasive vagus nerve stimulation (VNS) and transcutaneous auricular vagus nerve stimulation (tavNS) on verbal memory performance in epilepsy patients.

Fifteen drug-resistant epilepsy patients conducted a word recognition paradigm in 3 conditions: VNS ON, VNS OFF and tavNS.  For each condition, patients were instructed to memorize the highlighted words from 3 text paragraphs. The intervention was delivered during 30 seconds after each paragraph during the consolidation phase of memory formation. Immediate recall scores after each paragraph and delayed recognition scores at the end of the paradigm were obtained for each condition. The word recognition paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON  and VNS OFF. VNS ON stimulation current was set to 0.5mA in the first session and 1.0mA in the second session. tavNS was delivered with the maximum tolerated stimulation current. We hypothesized to find an intensity-dependent effect of VNS and tavNS on verbal memory performance.

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.

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.