Development of Electrophysiological Biomarkers and Their Therapeutic Cortical Electrical Stimulation for Improving Neuroplasticity and Motor Function in Parkinsonian Rats

Parkinson's disease (PD) is the second most common neurodegenerative disease of the elderly, affecting more than seven million people worldwide and thirty thousand individuals in Taiwan. Current diagnosis in PD is mainly based on the behavioral symptoms, and there is still lack of biomarkers that can be used to track the disease progression in clinical application. Electrophysiological techniques, such as electroencephalography (EEG), have been reported to have abnormal rhythms in PD. However, a rapid, recurrent and individualized EEG as the biomarkers to identify early pathophysiological alterations in PD has not been established. One possible reason may be that earlier approaches to analyze EEG data are inappropriate, because the tool used is based on the linear and stationary additive Fourier analysis, which is not suitable for brain signal analysis as these signals are nonlinear and non-stationary. Currently, a novel analysis method, called Holo-Hilbert Spectral Analysis (HHSA), has a particular strength in analyzing nonlinear and nonstationary data for getting more information than conventional means. Thus, we would like to learn whether EEG can be a biomarker for the staging of PD by using the novel HHSA analytical approach. If EEG profile identified through this investigation does serve as a prognosis marker (or differentiate the stages of disease), it will have a tremendous impact on the basic and translational researches, along with a great commercial value to medical device industry. Besides, functional impairments of the motor cortex-basal ganglia loop may occur in the brain of PD before the onset of clinical signs, it is thus important to develop the interventions that will delay disease progression before tremendous neurons loss. The cortical electrical stimulation (CES) has been developed for modulating cortical plasticity in our previous study which are considered having therapeutic potential in PD. This proposed project is aimed to identify a novel and capable EEG biomarker for the detection of disease onset and progression and to establish a protocol of CES approach for therapeutic intervention of PD. To achieve these goals, the neurotoxic PD rats and transgenic PD mice will be used to monitor the changes of EEG data through disease progression and for further CES treatment. The EEG signal will be applied and quantified by HHSA analytical method for getting more information than conventional means. Furthermore, the obtained EEG results will provide detailed guidance that can help to determine the parameters of the CES therapy for PD. The PD animals with long-term treatment of CES will be assessed for their degeneration in motor and cognitive functions, along with pathological analysis of brain tissues for determining the neuroprotection and neurogenesis effects. Through this investigation, a electrophysiological biomarker for early diagnosis of PD, which is useful in clinical setting and development of novel therapeutic brain stimulation approach, will be identified. In addition, with basic neurological studies, we plan to provide the physiological evidences which can facilitate the translational use of novel brain stimulation therapies aimed at delaying disease progression and improving motor dysfunctions in PD.

Project ID:PC10507-0252
External Project ID:MOST105-2314-B182-016