Abstract
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.
Highlights
Parkinson’s disease (PD), the second most common neurodegenerative disease (Scandalis et al, 2001), is characterized by motor symptoms such as bradykinesia, tremor, rigidity and impaired balance and gait as well as nonmotor complications, resulting primarily from degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) (Davie, 2008)
Since the transformed phase locking value (PLV) mean was greater for the PDMOFF (Figure 3A) than the healthy controls (HC) group, the positive weights were interpreted as cortical couplings exaggerated in the PDMOFF group. 35% of the selected features were associated with Cz over a broad frequency bandwidth, and the PDMOFF group had a stronger coupling strength for the features
We found most changes in cortical coupling strength associated with PD (Figure 2A; 11 out of 17) were in key motor and parietal regions, including over the primary motor cortex (M1), supplementary motor area (SMA), premotor area (PMA), and superior parietal regions, which was in line with previous findings (Otten et al, 2012)
Summary
Parkinson’s disease (PD), the second most common neurodegenerative disease (Scandalis et al, 2001), is characterized by motor symptoms such as bradykinesia, tremor, rigidity and impaired balance and gait as well as nonmotor complications, resulting primarily from degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) (Davie, 2008). Several electrophysiology studies using local field potential (LFP) recordings demonstrated that, in the dopamine-deficient state, the neuronal synchronization in the basal ganglia (BG) is exaggerated at frequencies in the beta range (13–30 Hz) (Brown and Williams, 2005; Eusebio et al, 2009; Litvak et al, 2012; Oswal et al, 2013) These beta oscillations are highly synchronized with sensorimotor areas (Brown et al, 2001; Marsden et al, 2001; Cassidy et al, 2002; Williams et al, 2002) as well as muscle activity of upper limbs during movement (Marsden et al, 2001). Diminished interhemispheric connectivity in sensorimotor cortical regions (Seibert et al, 2012) and reduced rsFC in widespread regions including inferior frontal, superior parietal, and occipital regions (Dubbelink et al, 2014) have been shown to be implicated with disease duration and cognitive dysfunctions in PD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
