TMS as a Tool for the Evaluation of Neuromodulatory Effects of Transcutaneous Vagus Nerve Stimulation
Condition: Epilepsy
MeSH terms: Epilepsy
Study type: Interventional

Summary: 
      Transcutaneous vagus nerve stimulation (tVNS) has been investigated as a potential treatment
      for epilepsy with inconsistent results. The combination of transcranial magnetic stimulation
      with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) allows to investigate
      the neuromodulatory effect of interventions such as tVNS by evaluating changes in motor
      evoked potentials (MEPs) and TMS-evoked potentials (TEPs). The goal of this study is to
      objectively evaluate the effect of tVNS on cortical excitability with TMS-EMG and TMS-EEG.
      These findings are expected to provide insight in the mechanism of action and help identify
      more optimal stimulation paradigms.

      In this prospective single-blind cross-over study, 15 healthy subjects will undergo active
      and sham tVNS during 60 minutes, using a maximum tolerated stimulation current. Single and
      paired pulse TMS will be delivered over the right-sided motor hotspot to evaluate MEPs and
      TEPs before and after the intervention.
    

Detailed description: 
      In the past two decades, vagus nerve stimulation (VNS)has become a valuable treatment option
      for patients with refractory epilepsy. However, VNS requires a surgical procedure associated
      with potential side effects. Therefore, the development of non-invasive devices that
      selectively target the vagus nerve fibers with a low risk profile has gained interest.
      Transcutaneous auricular VNS (tVNS) is such a non-invasive neurostimulation modality that
      targets the cutaneous receptive field of the auricular branch of the vagus nerve located in
      the outer ear. Up to date, tVNS has been investigated as a potential treatment for epilepsy
      with inconsistent results. The goal of this study is to investigate the effect of tVNS on
      cortical excitability. This will provide important insight into the underlying effects of
      this technique on brain neurophysiology. Cortical excitability will be investigated by
      combining transcranial magnetic stimulation with electromyography (TMS-EMG) and
      electroencephalography (TMS-EEG), evaluating changes in motor evoked potentials (MEPs) and
      TMS-evoked potentials (TEPs).

      In this prospective, single-blind, cross-over study, we will include 15 healthy male
      participants. They will undergo a TMS safety screening (TSS) questionnaire and clinical
      neurological examination before inclusion. Each participant will complete 2 sessions at least
      one week apart, one with active tVNS and one with sham tVNS.

      The intervention is tVNS by means of the Nemos® device which stimulates the cymba conchae at
      the outer ear. Stimulation parameters are set to a frequency of 25 Hz, a pulsewidth of 250
      µs, 7 s ON, 18 s OFF. The output current is ramped up until the user feels a tingling
      sensation at the stimulation site, but should remain subthreshold to painful stimulation.
      Stimulation is delivered during 60 min.Sham stimulation is achieved by placing the electrode
      on the earlobe instead of the cymba conchae.

      Before and after the intervention 120 single TMS pulses, 120 paired pulses with an
      interstimulus interval of 3ms and 120 paired pulses with an interstimulus interval of 100ms
      will be delivered over the right motor hotspot. MEPs will be measured at the left first
      dorsal interosseus muscle. TEPs will be measured using a 64-channel TMS-compatible electrode
      cap. MEPS and TEPS will be preprocessed offline in Matlab. TEP and MEP morphology ( amplitude
      and latency) will be evaluated before and after the intervention to investigate changes in
      cortical excitability.
    

Intervention name(s): actual tVNS; sham tVNS
Intervention type(s): Procedure; Procedure
Intervention description(s): Active tVNS (stimulation on cymba conchae --> nervus vagus stimulation); Sham tVNS (stimulation on earlobe --> no nervus vagus stimulation)
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Each participant will complete 2 sessions at least one week apart, one with active tVNS and one with sham tVNS.
Masking: Single (Participant)
Primary purpose: Treatment