Abnormal Phase Coupling in Parkinson’s Disease and Normalization Effects of Subthreshold Vestibular Stimulation

The human brain is a highly dynamic structure requiring dynamic coordination between different neural systems to perform numerous cognitive and behavioral tasks. Emerging perspectives on basal ganglia (BG) and thalamic functions have highlighted their role in facilitating and mediating information transmission among cortical regions. Thus, changes in BG and thalamic structures can induce aberrant modulation of cortico-cortical interactions. Recent work in deep brain stimulation (DBS) has demonstrated that externally applied electrical current to BG structures can have multiple downstream effects in large-scale brain networks. In this work, we identified EEG-based altered resting-state cortical functional connectivity in Parkinson’s disease (PD) and examined effects of dopaminergic medication and electrical vestibular stimulation (EVS), a non-invasive brain stimulation (NIBS) technique capable of stimulating the BG and thalamus through vestibular pathways. Resting EEG was collected from 16 PD subjects and 18 age-matched, healthy controls (HC) in four conditions: sham (no stimulation), EVS1 (4–8 Hz multisine), EVS2 (50–100 Hz multisine) and EVS3 (100–150 Hz multisine). The mean, variability, and entropy were extracted from time-varying phase locking value (PLV), a non-linear measure of pairwise functional connectivity, to probe abnormal cortical couplings in the PD subjects. We found the mean PLV of Cz and C3 electrodes were important for discrimination between PD and HC subjects. In addition, the PD subjects exhibited lower variability and entropy of PLV (mostly in theta and alpha bands) compared to the controls, which were correlated with their clinical characteristics. While levodopa medication was effective in normalizing the mean PLV only, all EVS stimuli normalized the mean, variability and entropy of PLV in the PD subject, with the exact extent and duration of improvement a function of stimulus type. These findings provide evidence demonstrating both low- and high-frequency EVS exert widespread influences on cortico-cortical connectivity, likely via subcortical activation. The improvement observed in PD in a stimulus-dependent manner suggests that EVS with optimized parameters may provide a new non-invasive means for neuromodulation of functional brain networks

The Electrophysiological Effects of Vestibular Stimulation in Parkinson's Disease

A recent study showed that vestibular stimulation can produce long-lasting alleviation of motor and non-motor features in Parkinson’s disease (PD). The improvements observed in motor symptoms were of particular note and may provide an indication as to one of the underlying physiological mechanisms of action for vestibular stimulation. An electrophysiological marker known to be abnormal in PD is the Bereitschaftpotential (BP) of the movement-related cortical potentials (MRCPs). One aim of this thesis was to observe the effects of galvanic vestibular stimulation (GVS) on MRCPs in PD to better understand its underlying physiological mechanisms. Many studies measuring the electrophysiological response to GVS have employed pre- versus post-GVS protocols, limiting observations to only after stimulation. The investigation of the mechanisms during GVS is limited by the large artifacts that contaminate the electroencephalograph (EEG). Previous studies have described pre-processing strategies to remove the GVS-related artifact, but these have many limitations. Thus, another aim of this thesis was to describe an artifact removal strategy using a novel approach of employing Independent Components Analysis (ICA) to identify, quantify and eliminate the GVS-related artifact from the EEG data. Study 1 (n = 11) validated this strategy by successfully removing the GVS-related artifact from MRCP data when manipulating the GVS frequency. Study 2 (n = 9) provided further validation by showing successful removal of the GVS-related artifact associated with a higher GVS intensity. Study 3 applied the methodology validated in the first two studies to a PD sample and found a significant increase in the early BP associated with GVS. This suggests that vestibular stimulation may improve motor features in PD through modulation of underlying pathological oscillations associated with motor dysfunction