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Front. Neurosci. | doi: 10.3389/fnins.2018.00101

Galvanic Vestibular Stimulation (GVS) Augments Deficient Pedunculopontine Nucleus (PPN) Connectivity in Mild Parkinson’s Disease: fMRI Effects of Different Stimuli

  • 1Department of Electrical and Computer Engineering, University of British Columbia, Canada
  • 2School of Biomedical Engineering, University of British Columbia, Canada
  • 3Pacific Parkinson's Research Centre, University of British Columbia, Canada
  • 4Division of Neurology, Department of Medicine, University of Alberta, Canada
  • 5School of Electronics and Applied Physics, Hefei University of Technology, China
  • 6Department of Medicine (Neurology), University of British Columbia, Canada

Falls and balance difficulties remain a major source of morbidity in Parkinson's Disease (PD) and are stubbornly resistant to therapeutic interventions. The mechanisms of gait impairment in PD are incompletely understood but may involve changes in the Pedunculopontine Nucleus (PPN) and its associated connections.
We utilized fMRI to explore the modulation of PPN connectivity by Galvanic Vestibular Stimulation (GVS) in healthy controls (n=12) and PD subjects even without overt evidence of Freezing of Gait (FOG) while on medication (n=23). We also investigated if the type of GVS stimuli (i.e., sinusoidal or stochastic) differentially affected connectivity. Approximate PPN regions were manually drawn on T1 weighted images and 58 other cortical and subcortical Regions of Interest (ROI) were obtained by automatic segmentation. All analyses were done in the native subject’s space without spatial transformation to a common template. We first used Partial Least Squares (PLS) on a subject-by-subject basis to determine ROIs across subjects that covaried significantly with the voxels within the PPN ROI. We then performed functional connectivity analysis on the PPN-ROI connections. In control subjects, GVS did not have a significant effect on PPN connectivity. In PD subjects, baseline overall magnitude of PPN connectivity was negatively correlated with UPDRS scores (p < 0.05). Both noisy and sinusoidal GVS increased the overall magnitude of PPN connectivity (p = 6 x 10-5, 3 x 10-4 respectively) in PD, and increased connectivity with the left inferior parietal region, but had opposite effects on amygdala connectivity. Noisy stimuli selectively decreased connectivity with basal ganglia and cerebellar regions.
Our results suggest that GVS can enhance deficient PPN connectivity seen in PD in a stimulus-dependent manner. This may provide a mechanism through which GVS assists balance in PD, and may provide a biomarker to develop individualized stimulus parameters.

Keywords: Vestibular stimulation, pedunculopontine nucleus, functional connectivity, Parkinson's disease, non-invasive neuromodulation, fMRI

Received: 16 Oct 2017; Accepted: 09 Feb 2018.

Edited by:

Takashi Hanakawa, National Center of Neurology and Psychiatry (Japan), Japan

Reviewed by:

Martijn Müller, University of Michigan, United States
Antonio Currà, Sapienza Università di Roma, Italy
Kazumi Iseki, Sakakibara Hakuho Hospital, Japan  

Copyright: © 2018 Cai, Lee, Ba, Garg, Kim, Liu, Kim, Wang and McKeown. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Aiping Liu, Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, Canada,