Transcutaneous Auricular Vagal Electrostimulation and Its Effect in Parkinson’s Disease Patients

Abstract

Introduction

Parkinson's disease (PD) is a progressive disease caused by the deterioration of dopaminergic neurons. It is associated by motor symptoms that are usually adequately treated with drugs in early PD. Patients also suffer from non-motor symptoms. Their cause is not fully understood, but one hypothesis is that they arise from degeneration of other diffuse neuromodulatory systems (DNMS) involved in motor and cognitive function, mood and metabolism.

Although certain drugs are able to modulate the DNMS, they are often associated with side effects. A new treatment option is vagal nerve stimulation. Recent studies show its ability to alter DNMS through different nuclei in the brainstem. Transcutaneous auricular vagus stimulation (taVNS) is a non-invasive technique applied at the auricular branch of the vagus nerve. An electrode is placed on the outer part of the ear. The frequency of stimulation appears to be the determining factor in its efficacy [1]. Not much is known about regions actually stimulated with taVNS. Our study is the first to examine the effect of taVNS in early and late PD patients using fMRI to compare the difference between two commonly studied frequencies on strictly defined regions of interest (ROI) to avoid multiple comparison problem.

Knowledge about effects of stimulation of DMNS could lead to broader understanding of various cognitive disorders.

We have two main hypotheses:

• taVNS will stimulate predetermined nuclei of DNMS in the brainstem (ROI);          
• the response to stimulation will vary depending on the stage of disease.

Methods

25 Hz (the most commonly studied), 100 Hz (most efficient) and a sham frequency of taVNS are used on each participant. Stimulation is delivered in randomized order during the same session of fMRI recording with pauses in between. fMRI is used to measure the response of ROI. We aim to enroll 20 participants in early stage of disease and 20 patients in progressive stage.

Expected Results

Given the early stage of the research, we can only speculate on the results. We believe that taVNS will activate the DNMS, but the extent of the response may vary depending on the stage of the disease and the frequency used.

Limitations

Major limitations lie in the small number of participants, the heterogeneity of the group and lack of healthy controls - early stage PD patients are used as one. Having only neuroimaging data, we can see the correlation between stimulation and activation of certain structures, but clinical interpretation is limited.

References

[1] R. Sclocco, R. G. Garcia, N. W. Kettner, H. P. Fisher, K. Isenburg, M. Makarovsky, J. A. Stowell, J. Goldstein, R. Barbieri, and V. Napadow, “Stimulus frequency modulates brainstem response to respiratory-gated transcutaneous auricular vagus nerve stimulation,” Brain Stimulation, vol. 13, no. 4, pp. 970–978, 2020.