Abstract
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 × 10−5, 3 × 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.
Highlights
Falls in older adult populations are a significant cause of morbidity and mortality (Cameron et al, 2012) with non-fatal injuries initiating a vicious cycle leading to a fear of falling, social isolation, loss of independence, deconditioning, and a significantly greater use of health care services (Stevens et al, 2006; Williams et al, 2006).In Parkinson’s Disease (PD), gait disturbances such as decreased stride length and gait variability are associated with increased risk of falls
To determine the effect of the L-dopa equivalent daily dose (LEDD) on connectivity and to correct for the fact that some subjects had their UPDRS assessed off medication, we performed a regression analysis where connection strengths across subjects was the dependent variable, and LEDD, UPDRS score, whether or not the UPDRS was done on or off medication were independent variables
No significant differences in overall PPN connectivity were found between Galvanic vestibular stimulation (GVS) on and GVS off
Summary
Falls in older adult populations are a significant cause of morbidity and mortality (Cameron et al, 2012) with non-fatal injuries initiating a vicious cycle leading to a fear of falling, social isolation, loss of independence, deconditioning, and a significantly greater use of health care services (Stevens et al, 2006; Williams et al, 2006).In Parkinson’s Disease (PD), gait disturbances such as decreased stride length and gait variability are associated with increased risk of falls. Balance and gait deficits in PD are frequently refractory to therapy (Azevedo Coste et al, 2014; Perez-Lloret et al, 2014) and may be worsened by pharmacological and surgical interventions (Bloem et al, 1996), making falls a significant source of morbidity in PD (Schaafsma et al, 2003). FOG may be partly due to a failure to adequately scale amplitudes for the intended movement (Chee et al, 2009) and/or defective motor programming setting by the Supplemental Motor Area (SMA) and its maintenance by the basal ganglia, leading to a mismatch between intention and automation (Chee et al, 2009). Imbalance in multiple neurotransmitters (including but not limited to dopamine, acetylcholine, and GABA) is seen in basal ganglia and motor structures, and limbic circuitries (Ondo and Hunter, 2003; Perez-Lloret and Barrantes, 2016). Balance disturbance and falls in PD may be more related to disruption in cholinergic rather than dopaminergic neurotransmission (Bohnen et al, 2009)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
