Exploring the Possible Beneficial Impact of Non-invasive and Invasive Neuromodulation on Freezing of Gait in Parkinson's Disease During Different Ambulatory Complexities: An Electrophysiological and fMRI Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Electromyography recording before and after the tDCS session
研究概览
简要总结
Freezing of gait (FOG) stands out as a devastating symptom of Parkinson's disease (PD), where patients may become momentarily glued to the ground, rendering them incapable of walking efficiently. The pathogenesis of FOG remains uncertain but is likely attributed to functional perturbations in superficial cortical and deep locomotion regions. FOG tends to manifest more prominently during complex walking, such as turning, than during simple straight forward walking, and the reasons for this phenomenon remain unclear. Unfortunately, effective methods for overcoming this ambulatory issue has yet to be identified, and quantifying paroxysmal gait spells proves challenging with clinical rating alone; thus, a scientific tool is warranted. In this 3-year proposal, the investigators plan to address these challenges comprehensively.
详细描述
First, the investigators aim to develop an artificial intelligence algorithm for the identification and quantification of FOG episodes using Red-Green-Blue (RGB) and walkway pressure data. PD patients experiencing FOG will undergo a standardized walking protocol on the PKMAS System, acquiring simultaneous data from two angles of video recording and foot pressure. Labeled videos of FOG incidents will be inputted into an algorithm, Adaptive Fusion Algorithm for Spam Detection (AFSD), utilizing raw RGB data, optical flow data (DualTVL), and their combination for temporal segmentation.
Second, the investigators intend to pinpoint sources of FOG in PD patients through electrophysiological methods during unconstrained walking, employing a high-density 64-channel electroencephalographic ambulatory recording and motor imagery fMRI to delve into the pathophysiology of FOG under different ambulatory conditions. Effective connectivity among higher neural regions, including the basal ganglia, cerebellum, and cortical regions, will be explored. The resulting connectivity map will be overlaid with electric recording data to examine neurovascular coupling or uncoupling.
Third, the investigators plan to conduct non-invasive interventions (transcranial direct current stimulation: tDCS, magnetic resonance-guided focused ultrasound: MRgFUS) and Deep Brain Stimulation (DBS) to assess their impact on gait and FOG in PD patients. Motor imagery fMRI and electrophysiological investigations will be performed before and after treatment using the mentioned methods. Our multi-modal approach aims to unravel the complexities of FOG in PD patients, providing valuable insights and potentially benefiting those enduring the challenges posed by this debilitating symptom.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients meet the diagnosis of PD based on the established consensus criteria
- •Age above 20 years old and below 90 years
- •For MRgFUS patients: a. At least one of the 3 cardinal symptoms (akinesia, tremor, rigidity) reaches an intensity of at least 2/
- •b. Parkinsonian symptoms cannot be satisfactorily controlled by optimal pharmacological treatment including L-dopa and other antiparkinsonian drugs. c. stable medication for PD ≥ 30 days.
- •DBS patients must meet Taiwan Health Insurance criteria: PD duration exceeding 5 years, positive response to levodopa (≥33% UPDRS motor score improvement), and presence of motor complications (e.g., wearing off, on-off, levodopa-related dyskinesia, or medically intractable tremor).
排除标准
- •Congestive heart failure (Functional III or above) or advanced cancer with distant metastasis.
- •PD at Hoehn and Yahr Stage
- •DBS exclusion criteria: overt dementia or major depression.
结局指标
主要结局
Electromyography recording before and after the tDCS session
时间窗: baseline / 2 days, 2 and 4 weeks after the end of the tDCS session
The 4 pairs of leg EMG recording during 50 meters walking. The EMG signals will be filtered with a band pass ranging from 0.05 to 70 Hz. Variables in gait analysis: 1.Gait initiation, 2.Level walking, 3.Gait termination.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III before and after the tDCS session UPDRS contains four parts, the third part of which is reported in this outcome.
时间窗: baseline / 2 days, 2 and 4 weeks after the end of the tDCS session
UPDRS contains four parts, the third part of which is reported in this outcome. Part III is clinician-scored monitored motor evaluation (14 questions, ranges from 0=normal to 4= Severe). The scoring of Part III varies between 0-56. The higher score indicates the worse motor function. Negative change from baseline values indicate improvement.
Functional magnetic resonance images examination before and after the tDCS session
时间窗: baseline / 2 days after the end of the tDCS session
fMRI scan will be performed on a 3.0T MR imager to detect the brain BOLD signal change in FOG. When fMRI was conducted, four different video tapes will be presented to the subjects#1.normal walking, 2.normal turning, 3.FOG during forward straight walking and 4.FOG during turning.
Electroencephalogram recording before and after the tDCS session
时间窗: baseline / 2 days, 2 and 4 weeks after the end of the tDCS session
Gait recording by 64 channels EEG device. Four different frequency bands ( theta, alpha, beta, and gamma) will be investigated. Variables in gait analysis: 1.Gait initiation, 2.Level walking, 3.Gait termination.
次要结局
- Change in New freezing of gait questionnaire (NFOG-Q) before and after the tDCS session(baseline / 2 days, 2 and 4 weeks after the end of the tDCS session)
- Change in Gait and Falls Questionnaire (GFQ) before and after the tDCS session(baseline / 2 days, 2 and 4 weeks after the end of the tDCS session)