Electrical vestibular stimulation for Parkinson's disease treatment

Parkinson's disease (PD) is a progressive movement disorder characterized by degeneration of dopaminergic neurons and abnormal brain oscillations. While invasive deep brain stimulation can improve some motor deficits by disrupting pathological brain oscillations, achieving comparable results with non-invasive brain stimulation (NIBS) remains elusive. Previous studies have suggested that electrical vestibular stimulation (EVS) may ameliorate some motor symptoms in PD. However, the investigated effects are limited to a few domains, only a handful of stimulation waveforms have been explored, and neuroimaging studies capable of probing the mechanisms are greatly lacking. The overarching objective of this thesis is to utilize biomedical engineering approaches to fully explore the EVS technique as a potential therapeutic intervention for PD. This involves development of new stimuli, development of new artifact rejection methods, and thorough investigations of brain and behavioural responses, as outlined below. To achieve the objective, noisy EVS is firstly revisited and tested with PD and healthy subjects to investigate effects on visuomotor tracking behaviours. Next, novel EVS stimuli are developed using multisine signals in distinct frequency bands and tested in the experiment where the stimuli are applied to PD and healthy subjects during rest and task conditions while EEG are being recorded. This simultaneous EVS-EEG study aims to provide insights into modulatory effects of EVS on brain oscillations and motor behaviours altered in PD and whether the effects are a function of different stimulation types. One critical challenge involved with EVS-EEG studies is that EEG recordings are severely corrupted by the stimulation artifacts. To resolve this, a quadrature regression and subsequent independent vector analysis method is developed and its superior denoising performance to conventional methods is demonstrated. Finally, underlying mechanisms of EVS effects in PD are investigated in a resting-state functional MRI study. The results from this thesis suggest that sub-threshold EVS in PD induces widespread motor changes and brain activities that are stimulus-dependent, suggesting subject-specific stimuli may ultimately be desirable to achieve a clinically meaningful effect.Applied Science, Faculty ofGraduat