Exploit the Functional Higher Neural Connectivity and Electrophysiological Intervention of Freezing of Gait in PD and PSP During Different Ambulatory Complexities

Overview

In the current proposal, investigators will investigate three crucial issues of FOG. Firstly, investigators will identify the possible source(s) of FOG in PD and PSP patients during unconstrained walking using a 64-channel ambulatory recorder. The investigators will explore the electric neural sources of FOG and brain connectivity. Secondarily, fMRI during motor imagery will be performed to examine the brain regions involved in the FOG patients. The investigators will merge the electrophysiological and imaging findings to detect the possible neurovascular coupling or uncoupling. Thirdly, electric intervention with transcranial direct current stimulation (tDCS) will be conducted to see whether the FOG situation can be ameliorated in PD and PSP patients. The investigators will deliver a 5-day session of tDCS to the leg motor cortex of the FOG patients to examine whether the intervention will benefit the patients in a double blind randomized design. Six assessments with different combinations of clinical scaling, gait analysis, electrophysiological investigation and fMRI examinations before and after tDCS will be conducted. Besides, there is no long-term cohort investigation of tDCS on neurodegenerative patients with FOG. The investigators will have a 3-year follow-up with a 1-month interval open-label stimulation paradigm for the patients who remained voluntarily after the termination of the initial short-term trials.

The main goal of the first part of the 3-year project is to identify the source(s) of FOG with electrophysiological recording. The investigators will conduct concomitant high density Electroencephalographic and leg electromyographic recording to investigate subjects with and without FOG under unrestrained walking in the gait laboratory. The acquisitive signals from 64 montages will be decomposed first by independent component analysis (ICA) for further source localization of FOG. The event (FOG) related synchronization and desynchronization of different frequency bands of EEG will also be investigated to understand the neurophysiological implications of brain wave oscillations for the generation of FOG. In addition, the cerebello-thalamo-cortical pathway function will be assessed with magnetic paired associative stimulation in patients to probe the role of cerebellum in the pathogenesis of FOG. In the second part of the project, fMRI study will be adopted by having the subjects perform video-guided motor imagery of simple and complex walking situations. Block design paradigms will be delivered for signal acquisition. The signals will be analyzed by ICA before further processing for activation analysis. The connectivity map will beoverlaid with that of electric recording to examine the neurovascular coupling or uncoupling. In the third part of the project, investigators will deliver a 5-day session of transcranial direct current stimulation (tDCS) to the leg motor cortex of the FOG patients to examine whether the intervention will benefit the patients in a doubleblind randomized cross-over design.