Influence of Non-invasive Neurostimulation (Transcutaneous Vagus Nerve Stimulation) on 1. the Noradrenergic Release in the Brain and 2. a Neuropsychological Memory Task
Condition: Epilepsy; Cognitive Decline
MeSH terms: Cognitive Dysfunction
Study type: Interventional

Summary: 
      The goal of this study is to investigate the influence of transcutaneous vagus nerve
      stimulation 1. on the noradrenergic system in the brain and 2. on memory, in healthy
      volunteers.

      Preclinical and clinical studies indicate that noradrenaline plays a role in the working
      mechanism of vagus nerve stimulation. This study will investigate if the effects of invasive
      vagus nerve stimulation can be replicated with transcutaneous vagus nerve stimulation.

      The release of noradrenaline in the brain will be measured non-invasively by the P300
      component of event-related potentials in the electro-encephalogram (EEG) via an auditory
      oddball paradigm.

      Research to elucidate the working mechanism of non-invasive neurostimulation can help to
      identify subpopulations who will respond well to a treatment and can provide insights that
      could contribute to the optimalisation of the stimulation parameters, with as possible
      consequence a better clinical outcome.

      Some studies indicate that stimulation of the vagus nerve can optimally influence memory,
      possibly via the noradrenergic system. This study will investigate if the effects of invasive
      vagus nerve stimulation on memory can be replicated with transcutaneous vagus nerve
      stimulation.

      The influence of transcutaneous vagus nerve stimulation on memory will be measured via a
      neuropsychological memory task that investigates the ability to focus attention. The
      correlation between the performance on the memory task and the signal analysis of the
      auditory oddball task could give an indication about the underlying working mechanism of
      transcutaneous vagus nerve stimulation on memory.

      This will be the first step to investigate whether transcutaneous vagus nerve stimulation can
      be used as innovative intervention for cognitive decline.
    

Detailed description: 
      First a sympathetic skin response (SSR) will be measured to investigate whether the SSR could
      be used as a method to measure the activity of the locus coeruleus non-invasively.

      There are 3 conditions:

        1. transcutaneous vagus nerve stimulation

        2. sham stimulation

        3. no stimulation

      The conditions will be randomized.

      In each condition the participant will do the oddball task and then the memory task. Between
      the conditions there is a wash-out period of 30 minutes. After completion of all 3 conditions
      and after a wash-out period of 30 minutes, the participant will do a final recognition task
      (part of the memory task in total).

      During the oddball task EEG will be measured. An electro-cardiogram (ECG), electro-oculogram
      (EOG) and larynx electromyogram (EMG) will also be recorded for easy filtering of artefacts.
    

Intervention name(s): Transcutaneous vagus nerve stimulation (Nemos®, Cerbomed GmbH); Sham stimulation (Nemos®, Cerbomed GmbH)
Intervention type(s): Device; Device
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Transcutaneous vagus nerve stimulation; P300; Memory task